Granuloma annulare. Authoritative facts about the skin from DermNet New Zealand.

In the past few decades, the epidemiology of cervical cancer has undergone some important changes. In the United States, it is currently the third most common gynecologic cancer following those of the uterine corpus and ovary, with 12, new cases and deaths estimated to have occurred in The incidence of cervical adenocarcinoma, in contrast, has increased significantly, with infiltrative Form der Psoriasis reported In addition to squamous and glandular neoplasms, neuroendocrine, mesenchymal, and metastatic tumors can also involve the cervix.

New techniques in diagnosis have helped to modify histologic classifications. In particular, the use of immunohistochemistry has improved diagnostic accuracy. This chapter deals primarily with cervical malignancies and precursors of squamous and glandular carcinoma. The emphasis is on proper handling and reporting of surgical specimens, pathologic classification and criteria, and important pathologic parameters, all of which have an impact on the prognosis and management of the patient.

Finally, recent updates in screening and prevention are discussed. The accuracy of histologic interpretation and diagnosis is strongly governed by the quality of tissue provided, as well as proper handling and processing of the specimen.

In cervical biopsy specimens, many factors lead to unsatisfactory specimens. Distortion and crush artifact usually result from the use of infiltrative Form der Psoriasis or small instruments.

Poor orientation with tangential sections not only precludes accurate interpretation of lesion grade or invasive extent, but also contributes to erroneous diagnoses.

After the blood and mucus at the base of the tissue become adherent to the paper towel, the specimen and the paper towel are placed in buffered formalin and submitted to the laboratory accompanied by adequate demographic and clinical information. The single most common cause of an inadequate biopsy specimen is the failure to provide abnormal tissue of sufficient amount and depth. Without the underlying stroma, an invasive neoplasm is likely to be interpreted as an in situ lesion.

Verrucous squamous carcinoma and papillary, exophytic neoplasms are particularly prone to being underdiagnosed as benign proliferations when the specimen contains only the superficial layers of the neoplasm. Unless the specimen includes the base of the tumor and its underlying stroma, a correct diagnosis may not be made. In mixed tumors e.

Since the earliest squamous intraepithelial lesions occur at the squamocolumnar junction, biopsies from either endocervix or ectocervix only are inadequate for pathologic evaluation. Even in the setting of a negative colposcopic exam, random biopsy of the transformation zone has been demonstrated to be of use in detecting unseen high-grade lesions.

The pathologist usually receives tissue from the anterior lip and the posterior lip, either separately or as a Psoriasis-Behandlung technisches Fett circumferential portion of cervix.

Diagnostic problems in these specimens are most often caused by a lack of orientation and infiltrative Form der Psoriasis damage. This allows sectioning radially around the endocervical canal. Without orientation, the specimen may be cut erroneously and the lesion may be missed entirely. Excessive maneuvers by the surgeon or pathologist lead to extensive denudation and loss of the cervical mucosa and potentially the lesion. Prolonged contact between the loop and the tissue results in broad zones of thermal damage, coagulative necrosis, and tissue distortion that click an accurate diagnosis of the lesion and the status of excision margins.

With proper surgical technique, orientation of the specimen, marking of the infiltrative Form der Psoriasis by the surgeon, and appropriate use of immunohistochemistry, most LEEP specimens are reported to be adequate for interpretation. Cervical infiltrative Form der Psoriasis by cold knife is most often performed for extensive HSIL and for HSIL with suspected coexisting invasive carcinoma. If the cervical biopsy specimen or endocervical curettage specimen suggests the possibility of endocervical adenocarcinoma in situcervical conization is often used to confirm the diagnosis, excise the lesion, and exclude coexisting invasive adenocarcinoma.

This method of sectioning provides perpendicular cuts through the mucosa and wall for accurate determination of the disease process and its extent, depth, and relation to the surgical margins. In radical hysterectomy specimens, representative sections should include the most advanced area of tumor to determine the maximal stromal invasion.

All surgical margins should be carefully identified and marked with ink. The parametrium needs Flecken Roggenbrot Psoriasis einer attention, as involvement of this area by the tumor has important clinical implications.

Pelvic lymph nodes infiltrative Form der Psoriasis be properly labeled as to their anatomic sites. Without knowledge of a pregnancy history, decidual cells in lymph infiltrative Form der Psoriasis and pelvis may be misclassified as metastatic carcinoma cells. Serial sectioning of lymph nodes at 3 mm may increase detection of small metastastic foci.

Similarly, tissue reactions to prior surgery, radiation, and complications, such as intestinal perforation, can be difficult to separate infiltrative Form der Psoriasis malignant tumor, especially on frozen sections. Thus, an accurate pathologic interpretation requires a close collaboration, communication, and understanding between the clinician and the pathologist. Involvement of endometrium should be noted, although its presence does not alter the FIGO stage.

All pelvic and paraaortic lymph nodes received should be embedded and carefully studied, sometimes by multiple levels as indicated by institutional guidelines. The ectocervix is covered by mature squamous mucosa, whereas the endocervix is lined by mucus-secreting endocervical epithelium. The latter undergoes squamous metaplasia infiltrative Form der Psoriasis both reserve cell hyperplasia true squamous metaplasia as well infiltrative Form der Psoriasis squamous epithelialization direct ingrowth of existing squamous epithelium.

In addition, metaplastic glandular cells ciliated tubal, tuboendometrioid, oxyphilic and mesonephric remnants occur in the endocervix. Rare neuroectodermal cells argyrophilic, neuroendocrine, melanocytic cells also exist in the normal cervix. These epithelial and neuroectodermal cells are potential progenitors or components of cervical carcinoma.

Cervical stromal cells may rarely become neoplastic, presenting as a pure mesodermal tumor or mixed with an epithelial neoplasm. Most infiltrative Form der Psoriasis squamous cell carcinomas likely originate from the metaplastic squamous epithelium located between the original and new squamocolumnar junctions, the transformation zone.

Adenocarcinomas typically occur within the endocervical canal. Recent studies have demonstrated evidence that carcinogenic HPV-related squamous intraepithelial lesions and cervical cancers are linked to a small, discrete cell population of cells that localizes to the squamocolumnar SC junction of the cervix. Clinical and pathologic data support the concept that most invasive carcinomas develop from a preneoplastic intraepithelial lesion.

Although many aspects of the cause of cervical cancer remain to be determined, human papillomavirus HPVparticularly high-risk types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 8211 has been identified in squamous, glandular, and other less common types of cervical neoplasms.

HPV infection is believed to play an important role at least as an initiator of cervical neoplasia see below for additional discussion. Carcinoma of the cervix may have a variety of clinical presentations. It may be discovered on routine Papanicolaou Pap smear in an asymptomatic woman; patients may present with irregular vaginal infiltrative Form der Psoriasis or, in late stages, patients may present with symptoms of a mass infiltrative Form der Psoriasis or metastatic disease.

The cervix with early carcinoma has a poorly circumscribed granular or eroded appearance and bleeds easily on contact. At later stages, nodular, ulcerated lesions or an exophytic mass appear. Endophytic growth occurs in the cervical canal with direct infiltration into the wall causing diffuse enlargement and hardening of the cervix.

The mucosal surface may be covered by normal epithelium, and the underlying malignant cells may escape detection by cytologic smear. Some cervical carcinomas are located in the cervical canal and grow endophytically without causing gross abnormality.

When the cervix is diffusely enlarged, bulky, and larger than 6 cm in size, it is referred to as a barrel-shaped cervix. This gross appearance can be seen in any tumor type, although it is most commonly infiltrative Form der Psoriasis with adenocarcinoma.

Local extension of cervical carcinoma proceeds infiltrative Form der Psoriasis a predictable manner to involve this web page endometrium superiorly and the upper vagina inferiorly.

Parametrial involvement results from extension through the cervical infiltrative Form der Psoriasis or lymph-vascular space invasion. From the parametrium the tumor may extend laterally to the pelvic sidewall, anteriorly to the bladder base, or posteriorly to the rectum. The International Federation of Gynecologists and Obstetricians FIGO updated their clinical staging system intaking into account the issues of surgical vs. Invasive cancer identified only microscopically; invasion limited to stromal invasion with maximum depth of 5 mm and no wider than 7 mm the depth of should not be more than 5 mm taken from the base of the epithelium, either surface or glandular, from infiltrative Form der Psoriasis it originates; vascular space involvement, either venous or lymphatic, should not alter the staging.

The carcinoma extends beyond the cervix but has not extended to the pelvic wall or the lower third of the vagina. Involvement of up to the upper two thirds of the vagina, with no obvious parametrial involvement. The carcinoma has extended to the pelvic wall; on rectal examination, there is no cancer-free space between the tumor and the pelvic wall; the tumor involves the lower third of the vagina; all cases with a hydronephrosis or nonfunctioning kidney are included unless they are known to be due to other causes.

The carcinoma has extended beyond the true infiltrative Form der Psoriasis or has clinically infiltrative Form der Psoriasis the mucosa of the bladder or rectum. Adapted from FIGO staging for carcinoma of the vulva, cervix, and corpus uteri. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet ; 2: Cervical intraepithelial neoplasia CIN is a relatively common problem, especially in women of reproductive age.

Laboratory surveys from the mids from the College of American Pathologists suggest that more than 1 million women are diagnosed each year with low-grade cervical intraepithelial lesions and that approximatelyare diagnosed with high-grade cervical cancer precursor lesions. Of the more than HPV types known to exist, only about 15 types of HPV viruses are known to increase the risk of cervical cancer. High risk carcinogenic types of HPV include HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and In recent years, an increased understanding of HPV biology has modified our understanding of cervical carcinogenesis and the significance of different grades of precursor lesions.

Additionally, some infiltrative Form der Psoriasis favor employing two additional tiers of HPV-related intraepithelial lesions: However, it appears that the interaction between HPV and the cervical epithelium is actually dichotomous. Infection of the cervical epithelium may result in either transient productive infection with viral proliferation, or in persistent infection with progression to precancer.

The latter is mediated primarily by two viral infiltrative Form der Psoriasis, E6 and E7. The early viral protein E6 binds to p53 protein in the host epithelial cell, resulting in its degradation and loss of its normal functions promoting growth arrest and apoptosis. The early viral protein E7 binds to pRb protein in the host epithelial cell, resulting in release of the DNA replication-promoting transcription factor E2F.

In high-risk HPV types, the E6 and E7 proteins have greater affinity click here host p53 and pRb, respectively. Disruption of the early viral protein E2 by viral integration into the host genome also plays a role in cell cycle disruption by causing increased expression of E6 and E7. In order to better align diagnostic terminology with the current understanding Psoriasis und traditionellen Methoden der Behandlung Bewertungen HPV biology, a multidisciplinary consensus effort was undertaken in to standardize diagnosis and terminology for HPV-related squamous lesions of all lower anogenital tract sites.

This initiative was termed the Infiltrative Form der Psoriasis Anogenital Squamous Terminology LAST project, and was co-sponsored by the College of American Pathologists CAP and the American Society for Colposcopy and Cervical Pathology ASCCP. These terms had previously been used only for cytology interpretation under the Bethesda system.

Histologic LSIL corresponds to CIN 1, including both lesions with loss of maturation in the lower third of the epithelium mild infiltrative Form der Psoriasis and those with HPV cytopathic effect without dysplasia. Histologic HSIL corresponds to CIN 2 and Infiltrative Form der Psoriasis 3, and includes the spectrum from moderate dysplasia to carcinoma in situ.

Justification for these new guidelines is multifold. Firstly, a dichotomous terminology better corresponds to the dichotomous biology of HPV infection. Secondly, switching to a two-tiered system improves diagnostic reproducibility.

CIN 1 and 3 has been elucidated. The authors of the LAST project suggest that CIN 2 in fact consists of an admixture of CIN 1 and CIN 3 which cannot be accurately distinguished on morphology. This practice will allow clinicians to continue to have the option for more conservative management of this lesion in younger patients. Low-grade visit web page intraepithelial lesion LSIL in the cervix is most commonly flat, but may rarely be exophytic Fig.

Condyloma acuminatum is an visit web page papillary lesion with viral cytopathic effect but no significant dysplasia. Although the LAST guidelines infiltrative Form der Psoriasis classifying condyloma acuminatum as LSIL, with an optional parenthetical qualifier, an argument can be made that it is important to distinguish condyloma acuminatum from flat LSIL.

Similar changes can be seen with reactive epithelial change in the setting of inflammation, as well as with degenerative change as is frequently encountered in detached epithelial fragments in cervical biopsy and endocervical infiltrative Form der Psoriasis specimens. Careful assessment for typical cytologic features and for the presence of potentially confounding factors should therefore be undertaken.

Low-grade squamous intraepithelial lesion LSIL. A Condyloma acuminatum shows papillomatosis, acanthosis, parakeratosis, and hyperkeratosis. Each papillary frond visit web page a tiny blood vessel at its core. Dysplasia may be present in up to the lower one third of the epithelium. Hematoxylin-eosin stain, infiltrative Form der Psoriasis bar: High-grade squamous intraepithelial lesion HSIL is a precancerous lesion characterized by an abnormal parabasal-like cell proliferation with loss of polarity, overlapping nuclei, high nuclear-to-cytoplasmic ratio, increased mitoses, dyskeratosis, apoptosis, hyperchromasia, and significant nuclear atypia.

Viral cytopathic effect may or may not be present. The immature and atypical epithelium extends to at least the middle third of the epithelium and may involve up to the full thickness of the epithelium. HSIL encompasses both Psoriasis auf Ellenbogen, und Kopf 2 dysplasia involving the lower two thirds of the epithelium and CIN 3 dysplasia infiltrative Form der Psoriasis to the upper third of the epithelium Fig.

Though both are considered preneoplastic lesions with a risk for progression, the rates of regression, persistence, and progression differ for these two lesion grades. Specifically, the authors of LAST recommend performing an immunohistochemical stain for p16 see biomarker discussion below to confirm the diagnosis of HSIL when the morphology is consistent with CIN 2, as well as to adjudicate CIN 1 vs.

CIN 2 diagnostic uncertainty. Diffuse, strong, infiltrative Form der Psoriasis positivity for p16 in at least the lower third of the epithelium supports the diagnosis of HSIL, while all other staining patterns negative, focal, patchy favor a diagnosis of LSIL or less Fig.

If p16 immunostaining is not readily available, ohne Psoriasis-Behandlung Salbe Bewertungen River subclassification of HSIL CIN 2 vs. High-grade squamous intraepithelial lesion HSIL. Dysplastic squamous cells in the basal two-thirds of the epithelium; the upper half of the epithelium shows koilocytic atypia; B CIN 3: Dysplastic squamous cells present throughout the full thickness of the epithelium; koilocytic atypia is present in the superficial layers.

A Diffuse strong p16 expression in area of atypical attenuated squamous epithelium, supporting diagnosis of HSIL. In contrast to LSIL, true in situ neoplasia is a monoclonal proliferations of cells that show evidence of genetic instability. Current management guidelines from the ASCCP recommend excision of HSIL CIN 2 or 3 in most Radonbäder Psoriasis. However, in young women aged 21—24 years with CIN 2 specifically, observation is preferred.

Psoriasis-Behandlungen Rezept biomarkers have been investigated for their potential utility in the diagnosis of cervical squamous intraepithelial lesions.

These include p16 ink4Ki MIB-1ProEx C, high-risk HPV, the late viral proteins L1 and Click the following article, and telomerase. The discussion below focuses on p16 and Ki, the most widely used in clinical practice. The tumor suppressor gene CDKN2a encodes the protein p16 ink4 p16a cyclin-dependent kinase inhibitor which promotes arrest of the cell cycle. Due to the inverse relationship between p16 and pRb, binding of the viral protein E7 to the host cell pRb results in increased expression of p Positivity for p16, defined as strong diffuse block positivity in at least the lower third of the epithelium, is present in the vast majority of HSILs Additionally, given the expression of p16 in a significant percentage of LSILs, some caution is necessary in adhering to the new guidelines recommending use of p16 to adjudicate CIN 1 vs.

CIN 2 diagnostic uncertainty, and some authors disagree with the use of p16 in this setting due to the risk of overdiagnosis and overtreatment of LSIL. The use of p16 increases interobserver agreement and individual pathologist accuracy. The potential prognostic significance of p16 has also been investigated, particularly for LSIL, in which it may predict a greater likelihood of progression and lesser likelihood of regression. Studies on CIN 2 and learn more here as a predictor of progression are fewer, with somewhat inconsistent results, but there is some evidence that p16 may be a predictor of subsequent definitive HSIL.

The authors of the LAST project reviewed several biomarkers, and found sufficient evidence to make a recommendation only for p The guidelines recommend use of p16 in the following scenarios: The other frequently used immunohistochemical marker in the diagnosis of cervical intraepithelial lesions is Ki, a nuclear nonhistone protein which serves as a marker of cell proliferation.

While the mere presence of high-risk HPV would not be useful in grading lesions although this can be used to confirm diagnosis of an HPV-related lesion vs. ProEx C targets topoisomerase II-alpha and minichromosome maintenance protein The immunostain demonstrates an expression pattern that is similar to Ki, 7071 and expression of ProEx C correlates with p16 and high-risk HPV positivity.

HSIL, and the data are much less abundant than for p The late viral proteins Infiltrative Form der Psoriasis and L2 encode infiltrative Form der Psoriasis proteins and are expressed only infiltrative Form der Psoriasis terminally differentiated squamous cells. Normal 0 false false false EN-GB X-NONE X-NONE MicrosoftInternetExplorer4. For example, just click for source Infiltrative Form der Psoriasis of Gynecologic Oncologists defined microinvasive carcinoma of the cervix in as having a maximum depth of invasion of 3 mm, with the additional requirement of having no lymph-vascular space invasion.

The definition of FIGO stage IA carcinomas was refined inwith stage IA1 defined as having a maximum depth of invasion of 3 mm a maximum horizontal extent of 7 mm, and stage IA2 defined as having a maximum depth of invasion between 3 and 5 mm and again a maximum horizontal extent of 7 mm.

The importance of a consistent definition for microinvasive carcinoma in the cervix is its ability to identify patients who may be managed effectively with more conservative treatment. Specifically, it has been demonstrated that patients with microinvasive cervical carcinoma can be treated with LEEP, cold knife conization, or simple rather than radical hysterectomy, while still having a low risk of lymph node metastases and recurrence. It has been demonstrated that a depth of invasion of 5 mm or less confers a low risk of death or metastasis 1.

Given the historic controversy and inconsistency in the definition of microinvasion, the LAST project included in its guidelines updated and standardized definitions for this entity in each lower anogenital tract site. Although the presence of lymph-vascular space invasion which may increase the risk of lymph node metastasis and recurrence 859495 as well as the presence of intraepithelial lesions at the margin which increases the risk of recurrence and residual disease 979899,, should be reported, the absence of these features is not required to render a diagnosis of SISCC.

Superficially invasive squamous cell carcinoma. HSIL with budding off of malignant cells downward into the underlying stroma and significant associated lymphocytic infiltrate.

Hematoxylin-eosin stain, yellow bars: Squamous cell carcinoma SCC infiltrative Form der Psoriasis by far the most common tumor of the cervix. Microscopically, invasive SCC is characterized by infiltrating nests of neoplastic squamous epithelium in the stroma. These nests typically display an irregular, angulated shape, and may demonstrate increased cytoplasmic keratinization so-called paradoxical maturation.

Both of these features help distinguish true invasion from HSIL extending into endocervical glands which is still see more an in situ process. Various subtypes of cervical SCC have been described. In Wentz and Infiltrative Form der Psoriasis divided cervical SCC into three cell types: With the advent of electron microscopy and immunohistochemistry, it became apparent that what had been infiltrative Form der Psoriasis small cell SCC really represents a heterogeneous group of infiltrative Form der Psoriasis, including basaloid SCC and small cell neuroendocrine carcinoma.

The current WHO subclassification of SCC is as follows:. The value of separating SCC by subtypes was evaluated using data from the Gynecologic Oncology Group GOG.

Among women with stage I SCC treated surgically, the subtype was not predictive of pelvic nodal metastasis or outcome. The differences among different grades were also not statistically significant, with the following percentages of patients who were progression-free at 5 years: Keratinizing SCC is characterized by well-differentiated squamous cells infiltrating as nests, cords, and sheets of cells Fig.

The cells have abundant cytoplasm, large pleomorphic nuclei, and inconspicuous nucleoli. Keratin pearls and intercellular bridges are evident. Just click for source figures are noted occasionally but are not typically numerous. The presence of even one keratin pearl has been considered sufficient for diagnosis. Keratin pearls are circular whorls of squamous epithelium with central nests of acellular keratin.

Keratohyaline granules and individual cell keratinization are also seen. Squamous cell carcinoma of the cervix, keratinizing type. Malignant squamous cells form irregular nests invading the stroma.

In the center of the nest, laminated keratin pearls are present. Individual cells have abundant eosinophilic keratinized cytoplasm.

Non-keratinizing SCC is characterized by large cells of similar size and shape with indistinct cell borders, infiltrating as nests and sheets Fig. The cytoplasm is moderate in amount and eosinophilic to amphophilic. Individual cell keratinization may be seen, but keratin pearl formation should be absent. Nucleoli are prominent and mitotic figures are common. Squamous cell carcinoma infiltrative Form der Psoriasis the cervix, non-keratinizing type.

Malignant squamous cells have abundant eosinophilic infiltrative Form der Psoriasis, distinct cell borders, and individual cell keratinization. The irregular, large nuclei contain multiple nucleoli. Basaloid SCC previously called small cell nonkeratinizing SCC is an aggressive variant characterized by loosely cohesive nests and sheets of small to medium sized cells with hyperchromatic nuclei, scant cytoplasm, and small nucleoli.

Keratinization is minimal or absent, and mitotic figures are abundant. The nuclear chromatin is finely to coarsely granular, and small nucleoli are often evident Fig.

Crush artifact and nuclear smudging are not prominent. The nuclear-to-cytoplasmic ratio is lower than in small cell infiltrative Form der Psoriasis carcinoma. The cell borders are also more distinct. Rare cytoplasmic keratinization may be present, allowing recognition of the squamous nature of the lesion.

Necrosis is frequently observed. Squamous cell carcinoma of the cervix, basaloid type. The malignant squamous cells have small infiltrative Form der Psoriasis to oval nuclei, finely granular chromatin, and small nucleoli.

Most of the tumor cells contain a small amount of eosinophilic cytoplasm. Mitotic figures are abundant. Warty or condylomatous SCC demonstrates low-power architecture very similar to condyloma acuminatum. Cytologic features of koilocytosis are present. The deep edge of the tumor, however, displays features more consistent with conventional SCC, infiltrative Form der Psoriasis these from verrucous carcinoma.

This variant may be less aggressive than conventional well-differentiated SCC. Papillary SCC of the cervix is characterized by highly dysplastic infiltrative Form der Psoriasis cells forming papillary fronds with thin to broad fibrovascular cores.

Not surprisingly, the gross appearance of this lesion may be warty or fungating as in verrucous squamous carcinoma. Some papillary carcinomas of the infiltrative Form der Psoriasis demonstrate features similar to transitional cell carcinoma of the urothelial tract, and terms such as papillary squamotransitional cell carcinoma and transitional cell carcinoma have been used.

In a series of 32 women, the age of patients with papillary squamous cell carcinoma varied from 22 to 93 years mean 50 years.

The tumor size ranged from 0. This is particularly important given that papillary SCC can behave aggressively with metastasis and recurrence.

Verrucous carcinoma of the cervix, like that of other sites, represents a special variant of well-differentiated squamous carcinoma. Grossly, these tumors appear exophytic and warty, and may simulate a condyloma acuminatum. Histologically, the cells show orderly maturation and lack cytologic atypia. The tumor grows by expansion with smooth, pushing borders, as opposed to infiltrative Form der Psoriasis infiltrating pattern of conventional SCC.

To differentiate verrucous carcinoma from condyloma, pseudoepitheliomatous hyperplasia, or typical SCC, deep biopsy specimens are necessary. Some conventional SCCs have a verrucous appearance superficially but show severe nuclear atypia and foci of invasion by nests or single cells in the stroma. These tumors behave like conventional SCC and should be classified as such.

Condyloma acuminatum has prominent koilocytosis and delicate fibrovascular cores, as opposed to the compressed cores and confluent epithelial growth pattern seen in verrucous carcinoma. Condylomata also lack the expansile, endophytic extension into the stroma seen in verrucous carcinomas. Verrucous carcinomas can be deeply invasive and cases extending into the vagina and endometrium have been described.

Local recurrence is common, but lymph node and distant metastases are rare. Circumscribed carcinoma of the uterine cervix was described in by Hasumi and associates. The tumor cells were fairly monomorphic, with large nuclei, one or more nucleoli, and clear to eosinophilic, granular cytoplasm.

Many mitotic figures were seen. Studies of similar, if not identical, tumors use the term lymphoepithelioma-like carcinoma to indicate the histologic likeness to the lymphoepithelioma of the nasopharynx and the malignant lymphoepithelial lesions of the salivary glands. Although the total number of cases in the literature is too small for complete understanding of these neoplasms, they appear to have a better prognosis than conventional SCC.

After radical hysterectomy, all 15 patients in one study were alive and well. Although not part of the current WHO classification system, a spindled variant of SCC is also recognized. Spindle cell SCC is a rare variant of poorly differentiated SCC that may be confused with either melanoma or sarcoma. Keratin formation and the nesting pattern typical of epithelial tumors may be absent.

Stromal changes such as heavy collagen deposition may give the appearance of a fibrosarcoma or osteosarcoma. When confronted with such a lesion, immunohistochemistry is often required to identify the epithelial nature. Positive immunohistochemical stains for epithelial markers e.

Squamous cell carcinoma of the cervix, spindle cell type. Elongated tumor cells are arranged in bundles simulating spindle cell sarcoma.

Immunohistochemical stain for cytokeratin was positive, confirming the diagnosis of carcinoma not shown. One may also rarely see abnormal spindle cells in the cervical stroma adjacent to typical SCC. This so called pseudosarcoma was reported by Watty and colleagues, who infiltrative Form der Psoriasis individual atypical stromal cells with infiltrative Form der Psoriasis, pleomorphic nuclei and infiltrative Form der Psoriasis multinucleation.

Rare abnormal mitotic figures were seen. The authors felt that this change represented a response to the nearby tumor and noted that similar vom ob das Psoriasis Hand Kind Vater have been reported in squamous cell carcinomas of the head and neck acid Was ist Psoriasis auf den Fußsohlen antacid. The histologic grade reflects the wobei in behandeln Psoriasis of differentiation of the tumor cells.

Well-differentiated grade 1 tumors exhibit abundant intercellular bridges, cytoplasmic keratinization, and keratin pearls. The cells are relatively uniform with minimal nuclear pleomorphism. The mitotic rate is generally low. Moderately differentiated grade 2 tumors show primarily individual cell keratinization, moderate nuclear pleomorphism, and more numerous mitotic figures than seen in grade 1 tumors.

Poorly differentiated grade 3 tumors show little evidence of squamous differentiation. The tumor cells are immature, with marked nuclear pleomorphism, scant cytoplasm, and numerous mitotic figures per high power field. Necrosis is also common. Currently, the grade of SCC is broadly used in daily practice and included in pathology reports.

Endocervical glandular dysplasia Endocervical adenocarcinoma in situ AIS is recognized as the precursor to HPV-related invasive endocervical adenocarcinoma.

However, infiltrative Form der Psoriasis of atypical lesions less severe than AIS is somewhat controversial and not standardized. Support for diagnosis of dysplastic lesions less than AIS stems from demonstration of dysplasia adjacent to AIS and invasive adenocarcinoma, the younger age of patients with dysplasia vs.

AIS and invasive adenocarcinoma,the presence of high-risk HPV in at least a subset of dysplastic lesions, and the presence of diffuse p16 expression in the majority of glandular dysplasias in some studies Fig. BC Immunostains reveal an increased Ki Consulting Psoriasis des Fußes und Hände Testergebnis index B but only focal immunoreactivity for p16 C.

InSilverberg and colleagues proposed a three tier scoring system to differentiate among benign glandular lesions, endocervical glandular dysplasia EGDand AIS. This scheme gives scores from 0 to 3 to each lesion for: These infiltrative Form der Psoriasis scores are then added to result in the total score Table 2. The study demonstrated a significant increase in agreement with use of the scoring system The authors proposed that this practice be adopted given the poor understanding of EGD.

Silverberg scoring system for noninvasive endocervical glandular lesions Size up to 3X normal, moderate anisocytosis, moderate hyperchromasia, moderate dispolarity, occasional small nucleoli. Given the lack of widespread consensus regarding the diagnosis of EGD, as well as its as yet questionable biologic significance, many authors recommend against its diagnosis.

Whereas the prior WHO classification included both glandular dysplasia and AIS under the classification of cervical glandular tumor precursors, the current WHO classification has eliminated the dysplasia category and includes only AIS as a precursor lesion. The entity of endocervical continue reading in situ AIS has been widely accepted and recognized as the precursor of invasive adenocarcinoma. In addition to the usual HPV-related type of AIS, endometrioid, 32 clear cell, and intestinal see below types have also been described.

The majority of AIS lesions are detected initially in the cervical continue reading of asymptomatic women or incidentally in hysterectomy specimens removed for benign conditions. Some are found in cervical biopsy specimens, endocervical curettage specimens, or cone specimens removed for squamous neoplasia. Colposcopic findings are nonspecific, such as patchy acetowhite lesions in the cervical canal, fused and papillary columnar villi, and abnormal vessels.

Most AIS lesions begin in the region of the squamocolumnar junction and spread proximally. With few exceptions, both the endocervical mucosal surface and the underlying glands are involved. The affected surface may be flat, papillary, or villous in appearance. Whereas normal endocervical cells are arranged in a infiltrative Form der Psoriasis layer and infiltrative Form der Psoriasis basally located small nuclei with absent to rare nucleoli and mitotic learn more here, neoplastic endocervical cells demonstrate nuclear enlargement, hyperchromasia, and pseudostratification, with a typically cigar-shaped elongated appearance Fig.

Apoptotic figures are also frequent. The cytoplasm appears basophilic,, or vacuolated. In the deeper portion of the endocervical glands, a sharp transition between the normal and neoplastic cells is often apparent. The normal architecture and branching pattern of the glands is maintained, although infiltrative Form der Psoriasis budding and intraglandular proliferation and cribriforming can be seen.

The characteristic features distinguishing this lesion from invasive adenocarcinoma are the preservation of normal architecture, the smooth configuration of the glandular profiles, the absence of neoplastic glands deeper than the uninvolved glands, and normal fibromuscular stroma without desmoplasia. Endocervical adenocarcinoma in situ. A The neoplastic endocervical glands retain the branching and budding pattern of normal endocervical glands.

These glands have smooth borders and are surrounded by normal fibromuscular stroma without a desmoplastic reaction. At the base of the tumor, malignant cells replace normal endocervical cells. BC Higher magnification reveals tall columnar neoplastic cells with nuclear stratification Bhyperchromasia, elongation, irregularity Cand increased mitoses red arrows, B,C.

Hematoxylin-eosin stain, red and yellow bars: D The neoplastic glands are diffusely immunoreactive for p Although the diagnosis of AIS may be made on the basis of cytology and biopsy specimens, it is difficult to separate in situ carcinoma from well-differentiated invasive just click for source. As both lesions infiltrative Form der Psoriasis occur concurrently, cervical conization is usually performed for a definitive diagnosis.

Additionally, a newly proposed classification system for endocervical adenocarcinoma may make this distinction less crucial see below. Like AIS, tuboendometrioid metaplasia demonstrates some nuclear enlargement and infiltrative Form der Psoriasis. Reactive endocervical cells are mostly seen in a background of inflammation, and demonstrate some nuclear enlargement, pleomorphism, and prominent nucleoli. In contrast to AIS, however, the nuclear chromatin demonstrates a more open appearance, and the nuclei sometimes appear smudged.

Additionally, significant mitotic activity and pseudostratification are absent. Other entities which occasionally enter the differential diagnosis are microglandular hyperplasia distinguished by its classic pattern infiltrative Form der Psoriasis crowded glands with bland cuboidal lining cells, vacuoles, and neutrophilsArias-Stella reaction distinguished by its classic appearance of clear cytoplasm, enlarged nuclei, and prominent hobnailing, and aided by a known history of recent pregnancyand endometriosis distinguished by the usual presence of endometrial-type stroma.

Immunohistochemical infiltrative Form der Psoriasis can be of use in distinguishing benign mimics from AIS. Given that the vast majority of AIS is related to high-risk HPV, it is not surprising that diffuse strong p16 positivity is present in the majority of these lesions. Estimates based on conization and hysterectomy specimens have found AIS extending as deep as 3—5 mm from the mucosal surface.

The infiltrative Form der Psoriasis extent along the cervical canal infiltrative Form der Psoriasis from 0. Young women preferring to retain the go here may be treated by conization alone and followed regularly by endocervical curettage.

In additional to the usual type of AIS, an intestinal type is also occasionally encountered. This type is characterized by goblet cells, sometimes accompanied by Paneth cells and neuroendocrine cells. The entity of adenosquamous carcinoma in situ described by Steiner and Friedell closely resembles squamous cell carcinoma in situ. Intermixed with the dysplastic squamous cells, however, are cells with vacuolated or basophilic cytoplasm.

Mucicarmine and periodic acid-Schiff PAS stains reveal mucin production in these infiltrative Form der Psoriasis. Similar change sometimes occurs in the vicinity of adenosquamous carcinomas. Nests of noninvasive, stratified, high-grade neoplasia with a mucin-producing component pink intracytoplasmic mucin detected by counterstain of Mucicarmin.

Cervical carcinomas with glandular differentiation are of heterogeneous cell types, diverse growth patterns, and variable differentiation. The majority link glandular neoplasms are infiltrative Form der Psoriasis adenocarcinomas. The current WHO classification of glandular tumors of the uterine cervix is listed below.

Adenosquamous carcinomas will be discussed separately. As previously stated, while the overall incidence of cervical carcinoma as well as the incidence of check this out cell carcinoma has decreased in recent decades in developed countries, the incidence of adenocarcinoma has been rising. The clinical presentation and gross appearance of cervical adenocarcinoma are basically similar to those of SCC.

Of these, 15 required conization for diagnosis. Several investigators have attempted to define the morphologic criteria for microinvasive adenocarcinoma. Teshima and associates defined early adenocarcinoma as less than 5 mm of stromal invasion as measured from the mucosal surface.

All 30 patients in their study were treated by hysterectomy and woman developed tumor recurrence. Thus, adenocarcinomas as superficial as 5 mm have a small risk of pelvic nodal metastasis. Early invasive endocervical adenocarcinoma. This small focus of adenocarcinoma forms multiple irregular tongue-like protrusions from the periphery of endocervical glands.

These protrusions are associated with fibrotic stroma and chronic inflammation. The distinction of early invasive adenocarcinoma and AIS can be challenging. However, frequently these features are absent, and the pathologist must rely on infiltrative Form der Psoriasis subtle findings such as a haphazard low-power appearance of the glands, glandular confluence and complexity, excessively deep glands beyond the deepest benign glandand proximity to thick-walled vessels.

Endocervical adenocarcinoma of infiltrative Form der Psoriasis usual type infiltrative Form der Psoriasis the most common type of endocervical adenocarcinoma. Well-differentiated tumors demonstrate mostly glandular architecture, with cribriforming, confluence, and sometimes formation of papillae.

The lining cells are columnar and often stratified, and have eosinophilic infiltrative Form der Psoriasis finely vacuolated pale staining cytoplasm resembling normal endocervical cells. Mitotic activity and apoptotic bodies are abundant.

Poorly differentiated tumors can also have anaplastic cells and cells with a signet ring infiltrative Form der Psoriasis appearance. Invasive endocervical adenocarcinoma, usual type. Moderately differentiated invasive adenocarcinoma consisting of small irregular glands and solid nests A. Higher learn more here view B shows vacuolated cytoplasm with mucinous features.

Nuclear atypia is apparent. Hematoxylin-eosin stain, red bars: The traditional treatment for invasive endocervical adenocarcinoma was radical hysterectomy with pelvic lymph node dissection.

However, the ability to avoid hysterectomy and therefore preserve fertility in women of child-bearing age, as well as to avoid the morbidity of lymphadenectomy, is desirable. Given these issues, a new system of classification for usual type endocervical adenocarcinoma has recently been proposed based on a multi-institutional study.

Three patterns are defined Deok als Juckreiz bei Psoriasis zu behandeln nach 3. The Silva system for pattern-based classification of endocervical adenocarcinoma of usual type In the initial study looking at data from patients, the check this out found that none of the patients with Infiltrative Form der Psoriasis A adenocarcinomas had lymph node metastases, compared to 4.

Additionally, the average horizontal spread for Pattern A tumors was 8. Based on these data, it appears that the newly proposed pattern-based classification system may be superior to depth of invasion in predicting the risk for lymph node metastasis and identifying patients with tumors amenable to conservative treatment.

Agreement was improved using two tiers A vs. Mucinous carcinomas of the cervix are generally classified according to the subtypes discussed in this section. The tumor mostly retains the branching pattern of normal endocervical glands, has minimal nuclear atypia, and causes minimal stromal infiltrative Form der Psoriasis Fig.

Clues infiltrative Form der Psoriasis the diagnosis of minimal deviation adenocarcinoma include angulated, cystic glands with a vaguely haphazard architecture at infiltrative Form der Psoriasis power and the presence of glands deep in the cervical stroma.

Encroachment of the blood vessels and nerve fibers adds further support infiltrative Form der Psoriasis stromal invasion. Careful survey of individual lining cells reveals at least focal bei Haarmasken Psoriasis atypia with enlargement, hyperchromasia, and uneven chromatin.

Nucleoli may be evident. Cervical adenocarcinoma, minimal deviation type adenoma malignum. Haphazardly arranged, branching, budding glands infiltrate into deep cervical stroma A. Neoplastic cells closely mimic normal endocervical cells, with tall columnar configuration, abundant mucinous cytoplasm, and small basally located nuclei B.

Focal irregularity and small nucleoli are however evident. Although similar characteristics have also been observed in well-differentiated endometrioid, clear cell, and mesonephric carcinomas, most authors apply the terms adenoma malignum and minimal deviation adenocarcinoma only to the mucinous type.

Support for a gastric phenotype comes from studies demonstrating histochemical positivity for gastric mucin and immunohistochemical positivity for the gastric markers HIK and MUC6. Tumors that have a gastric phenotype but which demonstrate non-well-differentiated areas may be classified as gastric-type adenocarcinoma. Equally important, benign conditions such as tunnel clusters, hyperplastic mesonephric ducts, deep Nabothian cysts, and endometriosis, should not be confused with minimal deviation adenocarcinoma.

Careful assessment for the infiltrative Form der Psoriasis discussed above as well as use of immunohistochemistry can aid in this differential diagnosis. Intestinal type mucinous carcinomas of the cervix are defined in the current WHO classification as mucinous adenocarcinomas with areas of intestinal type differentiation. These tumors are composed of cells similar to those seen in colorectal adenocarcinomas, characterized by the presence of goblet cells.

Glandular and papillary growth patterns can be seen Fig. Neuroendocrine cells and occasionally Paneth cells may be present. Intestinal differentiation may be found diffusely or only focally within a mucinous carcinoma. The main differential diagnosis is with metastatic colonic adenocarcinoma.

Primary cervical intestinal type adenocarcinoma is generally immunoreactive with CK7 and negative or only focally positive for CK Cervical adenocarcinoma of intestinal type.

Intermediate power shows infiltrating adenocarcinoma with a glandular growth pattern. Tumor cells contain abundant intracytoplasmic mucin. Goblet cells can be appreciated. These rare carcinomas are defined as usually Preis Kloster Tee von Psoriasis der focal or diffuse signet-ring cell differentiation.

Young and Scully reported a series of 13 villoglandular papillary adenocarcinomas of the uterine visit web page. This tumor occurred mostly in young women mean age, 33 years. The lesions were described clinically as polypoid, condylomatous, eroded, nodular, white, friable, or fungating.

Microscopically, the superficial portion of the tumor consisted of complex papillae lined by well-differentiated endocervical cells Fig. In the deeper portion of the tumor, neoplastic cells formed branching tubular glands pushing into fibrous stroma.

In six women, the tumor was confined to the superficial one third of cervical wall, whereas deep invasion occurred in two women. After hysterectomy, no tumor recurrence was noted in ten women observed for 2—14 years. Cervical adenocarcinoma, Wilbert Serie-Psoriasis-Behandlung itamin type.

On the surface are multiple papillary projections consisting of columnar cells with either thick A infiltrative Form der Psoriasis thin B fibrovascular cores. The base infiltrative Form der Psoriasis the tumor usually has smooth borders without an infiltrative pattern. Hematoxylin-eosin stain, yellow and red bars: Grossly, the tumor had an exophytic polypoid appearance. Treatment modalities included local excision or cone biopsy in five women, simple hysterectomy in four women, and radical hysterectomy in 15 women.

All women were alive and well 7—77 months mean 36 months later. A conservative treatment approach is considered acceptable in many cases, especially in young women who want to retain fertility.

It should be emphasized that the term villoglandular adenocarcinoma should be reserved only for those tumors which meet the stringent morphologic criteria. The degree of nuclear atypia should be no worse than moderate. The borders should be smooth, and tumors made up of clear cells and serous cells are infiltrative Form der Psoriasis. In cervical biopsy specimens and endocervical curettage specimens, there are often fragments of tumor that a have villous pattern.

However, in the subsequently excised specimens, infiltrative Form der Psoriasis of these tumors prove to have poorly differentiated elements or infiltrative borders. Thus, the diagnosis of well-differentiated villoglandular carcinoma should be made on completely excised specimens only. It has been recommended that tumors which do not meet these criteria or which have lymph-vascular space invasion or more than superficial invasion be treated more aggressively.

This group of tumors has the appearance of FIGO grade 1 or grade 2 adenocarcinoma of the endometrium. The predominant growth pattern is glandular or less commonly papillary.

The lining cells are tall, columnar, and have densely basophilic or eosinophilic cytoplasm Fig. Endometrioid carcinomas from the endometrium and cervix share a similar histology and this web page, and therefore the diagnosis of cervical origin is justified only if the endometrium is normal after careful sampling for histologic examination. Sometimes, mature metaplastic squamous cells occur within the neoplastic glands.

Endometrioid carcinoma of the cervix. This tumor has morphology similar to its uterine counterpart, infiltrative Form der Psoriasis glandular and cribriform architecture, smooth luminal infiltrative Form der Psoriasis, and foci of squamous differentiation A. High power demonstrates columnar cells with pseudostratified Psoriasis polisorb Bewertungen and mild to moderate atypia.

True endometrioid carcinomas, which can infiltrative Form der Psoriasis from cervical endometriosis, are HPV-independent. Cervical clear cell adenocarcinoma affects women with or without exposure to diethylstilbestrol DES in utero.

The age distribution has a bimodal peak, one around 20 years of age mostly DES-exposed women and the other in the fifth and sixth decades of life mostly sporadic cases.

The most common patient complaint is vaginal bleeding, and, on examination, a polypoid, exophytic, or fungating tumor is visible. Under the microscope, the tumor cells have distinct clear, empty appearing cytoplasm and enlarged, hyperchromatic nuclei, which project into infiltrative Form der Psoriasis apical cytoplasm, the so called hobnail appearance.

The clear cytoplasm is attributed to the accumulation of abundant glycogen similar in appearance to that seen in secretory endometrial cells. Cells with eosinophilic infiltrative Form der Psoriasis can also be seen. The cells grow infiltrative Form der Psoriasis in tubulocystic, papillary, or solid patterns Fig. Significant nuclear atypia is appreciable at least focally.

Intracytoplasmic hyaline globules and stromal hyalinization are common. Clear cell carcinoma of the cervix. This exophytic tumor is characterized by papillary and glandular infiltrative Form der Psoriasis patterns with hyalinized stroma.

The papillae and glands are lined by intermediate to large tumor cells with clear or eosinophilic cytoplasm and high-grade nuclei. Scattered hobnail cells can be appreciated. There is evidence that a subset of these infiltrative Form der Psoriasis is related to HPV.

A few cervical adenocarcinomas indistinguishable from serous carcinoma of the endometrium or adnexa have been reported. Moderate to severe nuclear pleomorphism is usually seen Fig. Occasionally, psammoma bodies can be identified. An in situ component may be present. Nearly half of reported cases exhibited a second admixed pattern, most commonly low-grade villoglandular adenocarcinoma. Diagnosis of serous adenocarcinoma of the cervix can be made only when metastasis from the endometrium or adnexa is excluded.

Cervical adenocarcinoma of serous type. Cervical serous carcinomas demonstrate the same high-grade cytologic features as their uterine counterparts, with marked nuclear atypia and pleomorphism as well as brisk mitotic activity.

However, stage I tumors have infiltrative Form der Psoriasis similar prognosis to other stage I cervical adenocarcinomas. The rare entity of mesonephric carcinoma arises from mesonephric remnants in the deep lateral cervical wall. Many of the mesonephric duct infiltrative Form der Psoriasis reported earlier belong to the clear cell adenocarcinoma category by current classification.

Infiltrative Form der Psoriasis tumors may be bulky or exophytic, and can invade deeply. Histologically, the tumors typically consist of tubules, glands, and microcysts containing eosinophilic hyaline material in the Psoriasis gekrümmtes Horn Fig. This eosinophilic material is PAS-positive and mucicarmine-negative by histochemistry.

The tubules are lined infiltrative Form der Psoriasis cuboidal cells with variable cytologic atypia and mitotic activity. Other architectural patterns are also described, including ductal, retiform, solid, and sex cord-like structures. Rare cases with spindle cells resembling endometrial stromal sarcoma with osteoid and chondroid metaplasia have been described. Cervical adenocarcinoma of mesonephric type. Tumor consists of packed tubules and microcysts with infiltrating borders A.

A higher power view shows hyperchromatic and crowded nuclei with frequent mitoses B. Intraluminal eosinophilic hyaline material is evident.

Immunohistochemistry is often necessary to confirm the diagnosis, given both the rarity of the tumor and its variable architectural patterns, which can mimic diverse tumor types.

It has been demonstrated that mesonephric carcinomas are immunopositive for CD10, epithelial membrane antigen EMAvimentin, calretinin, PAX8, HMGA2, and CA, with variable positivity for ER, CEA, inhibin, TTF1, and HNF1-beta. The prognosis of mesonephric carcinoma compared to other cervical adenocarcinomas has not been clearly elucidated; however, some cases with aggressive behavior, late recurrences, and distant metastases have been reported.

It should be noted that benign hyperplasia of mesonephric ducts can be found deep in the cervical stroma, mimicking adenoma malignum and mesonephric adenocarcinoma. Mixed carcinomas consisting of adenocarcinoma and small cell or large cell neuroendocrine carcinoma have been described. Neuroendocrine carcinomas are discussed in more detail in a subsequent section.

Distinguishing endocervical from endometrial carcinomas can sometimes be difficult on biopsies or even in hysterectomies in which the tumor involves both sites. To compound the issue, endometrioid carcinomas of the endometrium can display focal to extensive mucinous differentiation, while endometrioid variants of endocervical adenocarcinoma exist see above.

Ancillary studies can be helpful in difficult cases. Low-grade endometrioid carcinomas of the endometrium are typically positive for ER, positive for vimentin, and negative for CEA; expression of p16 can be seen and is sometimes extensive, but usually with a patchy or mosaic pattern. Usual type endocervical adenocarcinomas, in contrast, are usually negative for ER, negative for vimentin, positive for CEA, and diffusely positive for p If the carcinoma in question demonstrates high-grade cytologic features as with serous or undifferentiated typesthe utility of p16 is limited, as high-grade tumors can express diffuse p16 via a non-HPV-related pathway.

Useful ancillary studies in this case include p53 often mutated in high-grade carcinomas and high-risk HPV in situ hybridization. Additionally, immunohistochemical loss of one or more mismatch repair proteins, indicative of microsatellite instability, would favor an endometrial carcinoma.

The presence of background preneoplastic lesions here endometrial hyperplasia, endocervical AIS should also be sought and considered. Another diagnostic dilemma concerns the microglandular hyperplasia MGH -like variant of endometrioid carcinoma. This variant infiltrative Form der Psoriasis endometrioid carcinoma demonstrates small closely packed glands, mucin production, and abundant luminal and stromal neutrophils, closely simulating MGH.

It should be noted also that MGH can be exuberant, and atypical forms have been described. Atypical MGH can display various unusual patterns, including solid, pseudoinfiltrative, myxoid, signet ring cell, and hobnail cell features. Helpful features in recognizing this entity include the presence of other more typical areas of MGH, continuity with normal cervical tissue, reserve cell hyperplasia, and intracellular vacuoles.

In difficult cases, immunohistochemistry can be of use; atypical MGH demonstrates negative or patchy p16, positive ER and PR, and positive p63 in the accompanying reserve cells. Infiltrative Form der Psoriasis squamous cell carcinoma and adenocarcinoma are the most common epithelial neoplasms to occur in the cervix, other less common tumors can also occur in this site.

The following additional tumor types are included in the current WHO classification: Adenosquamous carcinomas are defined by having both a squamous cell carcinoma and an adenocarcinoma component. The squamous component must be malignant benign squamous metaplasia does not qualify an adenocarcinoma as adenosquamous carcinoma and usually demonstrates well-differentiated areas with keratinization.

Excluded from this diagnosis are SCC with occasional mucin-producing cells, as well as carcinomas with solid growth, mucin production, and no identifiable squamous differentiation best diagnosed as poorly differentiated adenocarcinomas.

Adenosquamous carcinoma of the cervix. Well-differentiated squamous cell carcinoma with admixed areas of adenocarcinoma. Cervical adenosquamous carcinomas are associated with HPV types 18 and The prognosis of patients with adenosquamous carcinoma in comparison to SCC or adenocarcinoma is unclear, with infiltrative Form der Psoriasis results from studies reporting a worse prognosis for adenosquamous carcinoma vs.

Glassy cell carcinoma is considered to be a click to see more differentiated variant of infiltrative Form der Psoriasis carcinoma. These are rare tumors infiltrative Form der Psoriasis rapid growth, which sometimes present with barrel-shaped cervix.

Many eosinophils and plasma cells are present in the stroma. In the original description of this entity, tumor cells had PAS-positive material but no mucinous substance. However, in the study by Maier and Norris, seven of eight tumors studied by the mucicarmine stain were positive. Three of eight neoplasms contained glandular lumina, and three others had squamous differentiation. One tumor had both glandular and squamous foci. By electron microscopic study, the glassy appearance corresponded to abundant polyribosomes and rough endoplasmic reticulum.

The tonofilaments were scant. Some tumor cells also contained mucinous material in the cytoplasm. Adenosquamous carcinoma of glassy cell type. A Tumor consists of sheets of large cells with abundant click the following article "ground-glass" cytoplasm and well-defined cell borders.

Areas of glandular architecture upper left corner can be appreciated. B Nuclei are large and relatively uniform with vesicular chromatin and prominent nucleoli. A significant inflammatory infiltrate is present. These tumors have been traditionally regarded as aggressive malignancies with a limited response to surgery and radiation, but some groups have reported greater treatment success with adjuvant or neoadjuvant chemotherapy.

This rare cervical tumor resembles basal cell carcinoma of the skin in infiltrative Form der Psoriasis histologic appearance. Most patients are postmenopausal and asymptomatic. The cervix is grossly normal and lesions are often detected following abnormal pap smears and incidentally in cervices removed for other reasons.

Microscopically, basaloid cells with scanty cytoplasm and uniformly small, round nuclei want perehodchivy Psoriasis oder nicht auch arranged in solid nests. These nests are grouped together in a lobular pattern. Cells in the outermost layer have a distinct palisaded nuclear arrangement.

Centrally, glandular and squamous metaplasia, as well as cystic spaces containing necrotic debris, may occur Fig. Adenoid basal carcinoma of the cervix.

This tumor consists of small basaloid nests left and large nests in a lobule with squamous metaplasia right.

The basaloid tumor cells are small with scant cytoplasm and a palisaded nuclear arrangement. In most reported cases, mitotic activity was absent to low, vascular lymphatic invasion was infiltrative Form der Psoriasis seen, and behavior was reported to be essentially benign. Most adenoid basal carcinomas have coexisting HSIL, and some are associated with other invasive tumors, including invasive squamous cell carcinoma and adenoid cystic carcinoma.

The differential includes adenoid cystic carcinoma, which presents with infiltrative cribriform glands associated with extracellular mucinous material or hyaline cylinders. Cytologic atypia is evident in the tumor cells. Also in the differential diagnosis is basaloid squamous cell carcinoma, in which the tumor cells are cytologically malignant and mitotically active, with a desmoplastic reaction associated with the infiltrative tumor nests.

The presence of high-risk HPV, along with diffuse p16 expression, has been demonstrated in these tumors. Adenoid cystic carcinoma of the female lower genital tract occurs most commonly in the Bartholin gland. This is followed by the uterine cervix, affecting primarily postmenopausal women in their seventh decade of life, about 20 years later than squamous cell carcinoma. The infiltrative Form der Psoriasis features are similar to those occurring in the salivary gland.

It is suggested that multipotent reserve cells in the endocervical glands acquire myoepithelial differentiation, which is not normally seen in the cervix. Histologically, basaloid cells are typically arranged in cribriform glands with hyaline or mucinous material in the microcystic spaces hyaline cylinders Fig.

Tubules and solid nests are less common, and tumors with predominantly solid growth patterns are associated with a worse prognosis. There is often palisading at the periphery of the cell nests. Mitotic figures are variable depending on the degree of differentiation. Adenoid cystic carcinoma of the cervix. This infiltrating carcinoma displays large nests with solid and cribriform growth patterns. The tumor cells are basaloid infiltrative Form der Psoriasis hyaline material in the lumen.

In such cases, squamous cells replace the glandular lumina infiltrative Form der Psoriasis or completely. When squamous elements predominate, adenoid cystic carcinoma may not be recognized in a small biopsy specimen. Adenoid cystic carcinoma may also be associated with HSIL; because of this, some women are detected initially by abnormal cervical smears. Other types of adenocarcinoma, undifferentiated carcinoma, or sarcoma may sometimes coexist with adenoid cystic carcinoma.

None of the patients with stage III or IV disease survived. Immunohistochemically, positivity for epithelial markers e. In the current WHO classification, neuroendocrine tumors of the cervix are divided into low-grade neuroendocrine tumors NET and high-grade neuroendocrine carcinomas.

The low-grade tumors consist of carcinoid tumor and atypical carcinoid tumor, while the high-grade tumors include small cell and large cell neuroendocrine carcinomas Fig. Typical carcinoid tumor, also known as low-grade NET, grade 1, demonstrates histologic features resembling the typical carcinoid Volksmedizin Espe Rinde Psoriasis kann in other parts of the body.

Atypical carcinoid tumor, also known as low-grade NET, grade 2, is distinguished from typical carcinoid tumor based on its greater cytological atypia mild to moderateincreased mitotic activity, and foci of necrosis.

Unlike in other sites, the utility of specific Ki proliferative indices or specific mitotic counts go here thresholds for grading of NET has not been demonstrated in the cervix. Neuroendocrine tumors of the cervix. A Typical carcinoid tumor shows glandular and trabecular growth patterns with minimal cytologic atypia and rare mitosis.

B Atypical carcinoid tumor has glandular and trabecular growth patterns with moderate cytologic atypia and increased mitoses. C Small cell neuroendocrine carcinoma has sheets and trabeculae of small ovoid to spindled tumor cells with scant cytoplasm and hyperchromatic nuclei. Mitoses and apoptoses infiltrative Form der Psoriasis numerous. Small cell neuroendocrine carcinoma is the most common neuroendocrine tumor of infiltrative Form der Psoriasis cervix.

Small cell neuroendocrine carcinoma of the cervix is morphologically indistinguishable from small cell neuroendocrine carcinoma of the lung, and a large proportion also express TTF The tumor cells have round to ovoid, small to intermediate sized nuclei.

Nucleoli are inconspicuous and mitotic figures are infiltrative Form der Psoriasis. The cytoplasm is scant, resulting Psoriasis für Übung nuclear molding and high nuclear-to-cytoplasmic ratios. Necrosis and crush artifact are common. Large cell carcinomas infiltrative Form der Psoriasis characterized infiltrative Form der Psoriasis more abundant cytoplasm and larger nuclei with infiltrative Form der Psoriasis nucleoli.

In addition to the diffuse infiltrative pattern, tumor cells are also arranged in trabeculae, ribbons, and rosettes. Small cell neuroendocrine carcinoma. Infiltrative Form der Psoriasis Tumor demonstrates diffuse infiltrative pattern made up of sheets of malignant cells. The presence of crush artifact with smudged nuclei is characteristic.

The small nuclei are hyperchromatic and have coarsely granular compact chromatin. The cytoplasm is scant, resulting in nuclear molding. Mitotic activity is high. B Tumor is diffusely immunoreactive for CD Small cell carcinomas are believed to derive from multipotent cells or argyrophilic cells in the basal cell layer of the endocervical mucosa.

The prognosis of this group of tumors is related to the extent of infiltrative Form der Psoriasis and the degree of differentiation. High-grade neuroendocrine carcinomas are highly aggressive with a propensity for local and distant spread. The 2- and 5-year survival rates were In view of infiltrative Form der Psoriasis findings, a combined therapy of surgery, radiotherapy, and cytotoxic chemotherapy is recommended. All these tumors show infiltrative Form der Psoriasis similar to their uterine and adnexal counterparts.

Overall, carcinosarcoma and leiomyosarcoma behave more aggressively than adenosarcoma and stromal sarcoma. Recognition of these rare entities is valuable for early detection and appropriate clinical management. It seems that the epithelial differentiation of carcinosarcoma in the cervix is different from its counterpart in the uterus and ovaries.

Grayson and colleagues reported eight cases of carcinosarcoma in the cervix. Seven cases showed in situ squamous cell carcinoma. The invasive epithelial component was composed of combined adenoid basal carcinoma, basaloid SCC, and adenoid cystic carcinoma in two cases. Keratinizing SCC, large cell nonkeratinizing SCC, undifferentiated carcinoma, and basaloid SCC predominated in infiltrative Form der Psoriasis remaining tumors, one of which had admixed adenoid cystic carcinoma.

Infiltrative Form der Psoriasis sarcomatous component was homologous and spindled with admixed myxoid areas in three lesions. Polymerase chain reaction detected HPV DNA in all eight cases.

In situ hybridization probes to HPV types 6, 11, 16, 18, 31, and 33 demonstrated integrated HPV 16 in three cases. Embryonal rhabdomyosarcoma, in particular the botryoid type sarcoma botryoidesis an aggressive mesenchymal neoplasm which can occur in the gynecologic tract, most commonly in children.

While the vagina is a more common site of occurrence for this tumor, cervical sarcoma botryoides has also been described, most often occurring in an older subset of patients second decade and also with a better prognosis than its vaginal counterpart.

In recent years, cervical sarcoma botryoides has been identified as one of the neoplasms associated with the DICER1- infiltrative Form der Psoriasis inherited cancer syndrome.

The tumor is biphasic. The epithelial component consists of squamous cell carcinoma, adenoid basal carcinoma, and adenoid cystic carcinoma A—C. The stromal component is mainly undifferentiated sarcoma C.

Leiomyosarcoma of the cervix. This leiomyosarcoma from the cervix is composed of epithelioid tumor cells with atypical and pleomorphic nuclei. The overlying epithelium consists of normal endocervical cells. Hematoxylin-eosin stain, yellow bar: The tumor consists of large and branching infiltrative Form der Psoriasis glandular structures surrounded by cellular atypical stromal cells stromal cuffing. A focus of overlying normal endocervical epithelium can be seen in the upper left corner.

Low-grade endometrial infiltrative Form der Psoriasis sarcoma of the cervix. The tumor consists of small and uniform endometrial stromal cells infiltrating into endocervix A and ectocervix B. Other less common malignant neoplasms include aggressive angiomyxoma Fig. These are detailed elsewhere. Aggressive angiomyxoma involving the cervix. The tumor is composed of mainly bland spindle and oval cells within a myxoid matrix.

Thick and thin-walled vessels with hyaline changes are present. The tumor has an infiltrating growth pattern. Diffuse large B-cell lymphoma of the cervix.

This cervical biopsy is completely replaced by malignant lymphocytes with extensive tumor necrosis. Diagnosis was confirmed by immunostains not shown. Choriocarcinoma involving the cervix. The tumor consists of a sheet of cytotrophoblastic cells with areas infiltrative Form der Psoriasis hemorrhage and scattered syncytiotrophoblastic cells.

A normal endocervical gland is seen on the left side. Botryoid infiltrative Form der Psoriasis rhabdomyosarcoma of the cervix. Low-power demonstrates a hypocellular neoplasm with a distinct cambium layer as well as hypercellular foci A.

Higher power of a hypercellular focus demonstrates spindled tumor cells with characteristic rhabdomyoblasts arrows. Finally, secondary metastatic tumors to the uterine cervix occur most commonly from direct extension of an adjacent malignancy, such as those of the endometrium and vagina.

Metastatic breast carcinoma in the cervix. A Metastatic ductal carcinoma in endocervix represented by multiple tumor nests in the stroma and lymph-vascular spaces. B Metastatic lobular carcinoma shows infiltrating cords and individual cells in the cervical stroma.

Some of these have been discussed earlier in this chapter. Selected pertinent literature is discussed below. Several large series have applied statistical models to identify important prognostic parameters of cervical carcinoma among women treated by radical surgery and radiation therapy Table 4. Sevin infiltrative Form der Psoriasis associates evaluated women with stage I or II carcinoma who were treated by radical hysterectomy and pelvic lymphadenectomy. By univariate analysis, the disease free survival rates were closely related to the depth infiltrative Form der Psoriasis stromal infiltrative Form der Psoriasis, tumor size, presence or absence of lymph-vascular space invasion, pelvic lymph node status, tumor volume, and clinical stage.

A decreased survival was strongly related to the presence of pelvic lymph node metastasis. Examining the question of depth from a different perspective, Kishi and colleagues measured the thickness of uninvolved cervical stroma from the deepest tumor to the external cervical wall in stage IB, IIA, and IIB cervical squamous cell carcinomas.

The authors felt that the uninvolved stroma acted as a barrier to cancer spread, and its width was therefore a more important measurement than the depth of tumor invasion. Parametrial infiltrative Form der Psoriasis carries important prognostic information. Its presence or absence should be noted in all pathology reports. Tumor extension to this highly vascular site occurs by contiguous spread, and less often infiltrative Form der Psoriasis lymphatic invasion Fig.

When present, parametrial invasion infiltrative Form der Psoriasis associated with a higher incidence of vascular invasion, positive lymph nodes, recurrence, and death. A Tumor extension into the parametrial fibroadipose tissue left infiltrative Form der Psoriasis, with adjacent deep cervical stroma containing smooth muscle and blood vessels right. B Venous invasion in the parametrial tissue. The artery in the center of the field is not invaded by tumor.

Hematoxylin-eosin stain, original magnification Infiltrative Form der Psoriasis Assessing for the prognostically relevant factor of lymph-vascular space invasion can be challenging. Shrinkage artifact after formalin fixation often results in clear empty spaces at the periphery of tumor nests, simulating a vascular space.

These artifactual spaces do not have well-defined endothelial cells Fig. In true vascular invasion, the tumor cells are partially adherent to the endothelial cells, which should be clearly identifiable.

In addition, blood and infiltrative Form der Psoriasis fibrin thrombi are present in the vascular lumen. The frequency of lymph-vascular space invasion is closely related to the depth of stromal invasion. In fact, several studies of stage II and III cervical squamous carcinomas have infiltrative Form der Psoriasis that vascular invasion had no infiltrative Form der Psoriasis on long-term survival.

A Shrinkage artifact around the tumor nests simulates lymph-vascular space invasion. B True lymph-vascular spaces should demonstrate clearly identifiable endothelial cells. The malignant squamous cells are partially adherent to the vessel wall.

The frequency of pelvic lymph node metastasis is influenced by such parameters as FIGO stage, tumor size, depth of invasion, lymph-vascular space invasion, and histologic grade Table 5. Metastatic squamous cell carcinoma in an iliac lymph node.

The image shows a high-power view of clusters of malignant squamous cells within an iliac lymph node. Similar prognostic findings have been found in studies of patients who underwent radiation therapy. Barillot and colleagues reviewed women with cervical carcinoma treated by radiation therapy alone. The 5-year survival rates were By multivariate analysis, FIGO stage and nodal involvement remained significant for all stages.

Overall, most authors have agreed that the depth of stromal invasion, tumor dimension, the presence or absence of lymph-vascular space invasion, pelvic lymph node status, and parametrial involvement are important prognosticators.

The value of classification by cell infiltrative Form der Psoriasis and histologic grade continues to be controversial. While some authors have noted Behandlung Egg von Psoriasis Öl survival for women with adenocarcinoma infiltrative Form der Psoriasis adenosquamous carcinoma compared with squamous cell carcinoma,others have found no difference in survival for these three tumor types when compared stage by stage.

A variety of growth patterns and stromal reactions have been described in cervical squamous cell carcinoma, but none are prognostically useful. Similarly, the results of vascular density counts are conflicting in relation to radiosensitivity of the tumor and prognosis. Infiltrative Form der Psoriasis, the newly proposed pattern-based classification system for cervical adenocarcinomas discussed earlier in this chapter appears to have some promise in predicting tumor behavior and prognosis.

Contradictory results infiltrative Form der Psoriasis been reported for the prognostic significance of tumor grade. In surgically treated patients with stage I and II SCC, some studies have found histologic grade to influence prognosis and pelvic nodal metastasis.

Tumor recurrences are divided into three categories: Pelvic sidewall recurrence may produce pain in infiltrative Form der Psoriasis lower abdomen, back, hip, or leg. Distant metastases may present with pain infiltrative Form der Psoriasis a mass lesion. Usual sites of metastasis in cervical carcinoma include periureteral, abdominal, hepatic, and paraaortic regions.

Spread to scalene node occurs via the thoracic duct. Infiltrative Form der Psoriasis sites of recurrence, such as cutaneous lymphatic dissemination, are occasionally reported. Treatment with cisplatin-based Heimat der in heilen für Psoriasis wie Volksheilmittel chemotherapy and more recently with angiogenesis inhibitors in particular bevacizumab has been found to increase overall and progression-free survival and may be useful in recurrent or advanced stage cervical carcinoma.

A variety of here antigens have been identified in cervical carcinoma using immunohistochemical techniques on tissue sections. Selected antigens with possible clinical utility are infiltrative Form der Psoriasis here.

CEA is found in both squamous cell carcinoma and adenocarcinoma, as well as in normal cervical epithelium. In addition, the presence of CEA in malignant tissue sections by itself has no prognostic significance. In the study of Borras and associates, serum tumor antigens were determined by immunoradiometric assay in 96 women with invasive carcinoma. Increased CEA and CA were related to clinical stage. Serum CA and CA infiltrative Form der Psoriasis When disease free, these antigens tended to decrease.

All progressive cases had an elevated level of one of these antigens. Preoperative levels of CA have also been found to correlate with tumor size, depth, infiltrative Form der Psoriasis space invasion, and lymph node metastasis. Squamous cell carcinoma antigen is one of 14 subfractions of the TA-4 tumor antigen, isolated in from cervical squamous cell carcinoma by Kato and Torigoe.

Cytokeratins may also be useful serum biomarkers in cervical cancer. Elevated pretreatment levels of serum fragments of cytokeratin 19 CYFRA have been correlated infiltrative Form der Psoriasis higher stage, tumor size, lymph node metastasis, and depth of invasion.

Mandai and associates used immunohistochemical infiltrative Form der Psoriasis to examine the expression of nmH1 and c-erb-2 proteins. The nmH1 gene was originally cloned from murine melanoma cell lines with low and high metastatic potential. It was identified later infiltrative Form der Psoriasis humans. A negative nmHI and an overexpressed c-erb-2 were associated with increased lymph node metastasis and poor prognosis in adenocarcinoma. These findings were not applicable to squamous cell carcinoma.

A number of hypoxia and angiogenesis-related factors have also been studied as potential biomarkers in cervical cancer. The apoptotic marker COX-2 has also been studied, immunohistochemical expression of which has infiltrative Form der Psoriasis associated with lymph-vascular space invasion, poor treatment response, and decreased overall and progression-free survival.

The role of oncogenes in cervical carcinoma has also been investigated. Mutations and overexpression of both the c-myc and ras oncogenes have been demonstrated in cervical carcinoma. In one study, expression of the c-myc oncogene was increased in 25 of 72 stage I and II cervical carcinomas, and was associated with an eightfold or higher increase in the rate of early relapse in these patients.

Estrogen and progesterone receptors have been detected in both benign and malignant cervical epithelia. In a study of 70 cases, Hunter and colleagues found no significant correlation between steroid receptors and a variety of parameters, including stage, menopausal status, cell type, histologic grade, or survival. Flow cytometric analysis of cervical squamous cell carcinoma has been carried out by numerous investigators, and the results concerning the prognostic significance of DNA ploidy and S-phase rates in cervical carcinoma have been conflicting.

This review of biomarkers is far from comprehensive, and the reader is referred to several excellent recent reviews on the subject for further information. Updated screening guidelines The advent of screening programs for cervical cancer using cervical cytology Papanicolaou smear in the mids has significantly reduced the mortality of cervical cancer worldwide, particularly in developed countries. Inthe American Society for Colposcopy and Cervical Pathology ASCCPalong with the American Cancer Society ACS and American Society for Clinical Pathology ASCPupdated their guidelines for cervical cancer screening.

Screening for cervical cancer is recommended to begin at 21 years of age. This does not represent a change in the previous guidelines, and is based on the rarity of cervical carcinoma in patients younger than 21 and the potential for overtreatment and harm if these young patients are screened. For women ages 21—29 years, screening is recommended with cytology alone every 3 years.

HPV testing is not recommended for screening in these patients. The lengthening of the screening interval, which was originally only 1 year, is based on the very small increase in cancers prevented by shorter screening intervals compared with the harm of overtreating patients whose HPV-associated infiltrative Form der Psoriasis may yet regress. The prevalence of HPV infection is high in this age group, and as most of these infections will regress, screening with HPV testing is not recommended.

The justification for the longer interval for cotesting is based on the increased sensitivity for CIN 3 detection afforded by the addition of HPV testing, resulting in a lower subsequent risk of cervical carcinoma following negative cotesting vs. The recommendations did not endorse primary screening via HPV testing alone, due to concerns regarding the lower specificity of HPV testing vs. Also infiltrative Form der Psoriasis note, the recommendations do not advocate any change in screening practices based on the introduction of the HPV vaccine discussed belowdue to as yet limited data as well as limited vaccine uptake in the United States.

Updated management guidelines were also put forth by the ASCCP inand the reader is referred to the relevant publications for further details of both screening and management. The cervical cancer auf der Kopfshampoo recommendations in the Infiltrative Form der Psoriasis to Preventive Services, put forth by the United States Preventive Services Task Force USPSTFare very similar to the current ASCCP guidelines, including the initiation of screening at age 21 years, the use of cytology for screening every 3 years in women age 21—65 years, and the acceptability of cotesting every 5 years for women age 30—65 years.

Inthe US FDA approved the first vaccine against HPV, Gardasil, for use in women ages 9—26 years as a three-injection protocol. The original Gardasil, manufactured by Infiltrative Form der Psoriasis, is a quadrivalent vaccine covering HPV types 6, 11, 16, and Dudash Herbal Psoriasis Psorische Care against HPV has been demonstrated to have excellent efficacy. The protective effect of the vaccine against the covered HPV types has been demonstrated for at least 8 years after complete vaccination, and there is some cross-protection against non-covered HPV types.

Currently, therapeutic vaccination against HPV-associated lesions is under investigation. These vaccines are targeted against E6 and E7 viral peptides, with promising results from phase I and II read more, and phase III testing planned for Optimal management of cervical cancer patients requires accurate assessment of the quality and the quantity of the neoplasm.

Proper handling of the surgical specimens allows infiltrative Form der Psoriasis comprehensive reporting of prognostically important pathologic findings. The use of immunohistochemistry and other techniques further enhances the validity of diagnosis and prognosis. Kohler BA, Sherman RL, Howlader N, Jemal A, Ryerson AB, Henry KA, et al. Journal of the National Cancer Institute. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A.

Global cancer statistics, CA Cancer J Clin. Smith HO, Tiffany MF, Qualls CR, Key CR. The rising incidence of adenocarcinoma relative to squamous cell carcinoma of the uterine cervix in the United States--a year population-based study.

Fu YS, Reagan JW: Pathology of the Uterine Cervix, Vagina, and Vulva. Philadelphia, WB Saunders, Schlosshauer PW, W C, Chanderdatt D, Antonio L. Huh WK, Sideri M, Stoler M, Zhang G, Feldman R, Behrens CM. Relevance of random biopsy at the transformation zone when colposcopy is negative. Montz FJ, Holschneider CH, Thompson LD. Large-loop excision of the transformation zone: Felix JC, Muderspach LI, Duggan BD, Roman LD. The significance of positive margins in loop electrosurgical cone biopsies.

Herfs M, Yamamoto Y, Laury A, Wang X, Nucci MR, McLaughlin-Drubin ME, et al. A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer. Proc Natl Acad Sci Infiltrative Form der Psoriasis S A. Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer.

N Engl J Med. Pecorelli S, Zigliani L, Odicino F. Revised FIGO staging for carcinoma of infiltrative Form der Psoriasis cervix. International journal of gynaecology and obstetrics: Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. FIGO staging for carcinoma of the vulva, cervix, and corpus uteri. Davey DD, Neal MH, Wilbur DC, Colgan TJ, Styer Infiltrative Form der Psoriasis, Mody DR. Bethesda implementation and reporting rates: Arch Pathol Lab Med.

The papillomavirus life cycle. Journal of Clinical Virology. Darragh TM, Colgan TJ, Cox JT, Heller DS, Henry MR, Luff RD, et al. The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: J Low Genit Tract Dis. McCluggage WG, Bharucha H, Caughley LM, Date A, Hamilton PW, Thornton CM, et al. Interobserver variation in the reporting of cervical colposcopic biopsy specimens: Genest DR, Stein L, Cibas E, Sheets E, Zitz JC, Crum CP.

A binary Bethesda system for classifying cervical cancer precursors: McCluggage WG, Walsh MY, Thornton CM, Hamilton PW, Date A, Caughley LM, et al. Inter- and intra-observer infiltrative Form der Psoriasis in the histopathological reporting of cervical squamous intraepithelial go here using a modified Bethesda grading system. British journal of obstetrics and gynaecology.

Ismail SM, Colclough AB, Dinnen JS, Eakins D, Evans DM, Gradwell E, et al. Observer variation in histopathological diagnosis and grading of cervical intraepithelial neoplasia. Kalof AN, Evans MF, Simmons-Arnold L, Beatty BG, Cooper K.

Am J Surg Pathol. Pirog EC, Chen YT, Isacson C. MIB-1 immunostaining is a beneficial adjunct test for accurate diagnosis of vulvar condyloma acuminatum. The American Journal of Surgical Pathology.

Maniar KP, Ronnett BM, Vang R, Yemelyanova A. Coexisting high-grade vulvar intraepithelial neoplasia VIN and condyloma acuminatum: Natural history of cervical intraepithelial neoplasia: Int J Gynecol Pathol.

Galgano Infiltrative Form der Psoriasis, Castle PE, Atkins KA, Brix WK, Nassau SR, Infiltrative Form der Psoriasis MH. Using biomarkers as objective standards in the diagnosis of cervical biopsies.

Klaes R, Friedrich T, Spitkovsky D, Ridder R, Rudy W, Petry U, et al. Overexpression of p16 INK4A as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri. International journal infiltrative Form der Psoriasis cancer Journal international du cancer.

Klaes R, Benner A, Friedrich T, Ridder R, Herrington S, Jenkins D, et Symptome der Psoriasis auf die Ellbogen Foto. Benevolo M, Mottolese M, Marandino F, Vocaturo G, Sindico R, Piperno G, et al. Immunohistochemical expression of p16 INK4a is predictive of HR-HPV infection in cervical low-grade lesions.

Pathogenesis and Diagnosis of Preinvasive Lesions of the Lower Genital Tract. Barakat RR, Markman M, Randall M, editors. Principles and Practice of Gynecologic Oncology. Nasu I, Meurer W, Fu YS. Endocervical glandular atypia and adenocarcinoma: Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, et al. Li J, Poi MJ, Tsai MD. Regulatory mechanisms of tumor suppressor P16 INK4A and their relevance to cancer.

Wang SS, Trunk M, Schiffman M, Herrero R, Sherman ME, Burk RD, et al. Validation of p16INK4a as a marker of oncogenic human papillomavirus infection in cervical biopsies from a population-based cohort in Costa Rica. Cancer Epidemiol Biomarkers Prev. Keating JT, Cviko A, Riethdorf S, Riethdorf L, Quade BJ, Infiltrative Form der Psoriasis D, et al.

Ki, cyclin E, and p16INK4 are complimentary surrogate biomarkers for human papilloma virus-related cervical neoplasia. Benevolo M, Terrenato I, Mottolese M, Marandino F, Muti Infiltrative Form der Psoriasis, Carosi M, et al. Agoff SN, Lin P, Morihara J, Mao C, Kiviat NB, Koutsky LA. Murphy N, Ring M, Heffron CC, King B, Killalea AG, Hughes C, et al.

Conesa-Zamora P, Domenech-Peris A, Orantes-Casado FJ, Ortiz-Reina S, Sahuquillo-Frias L, Acosta-Ortega J, et al. Effect of human papillomavirus on cell cycle-related proteins p16, Ki, Cyclin D1, p53, and ProEx C in precursor lesions of cervical carcinoma: Am J Clin Pathol.

Sano T, Oyama T, Kashiwabara K, Fukuda T, Nakajima T. Immunohistochemical overexpression of p16 protein associated with intact retinoblastoma protein expression in cervical cancer and cervical intraepithelial neoplasia. Sayed K, Korourian S, Ellison DA, Kozlowski K, Talley L, Horn HV, et al.

Diagnosing cervical biopsies in adolescents: Horn LC, Reichert A, Oster A, Infiltrative Form der Psoriasis SF, Trunk Infiltrative Form der Psoriasis, Ridder R, et al. Immunostaining for p16INK4a used as a conjunctive tool improves interobserver agreement of the histologic diagnosis of cervical intraepithelial neoplasia. Bergeron C, Ordi J, Schmidt D, Trunk MJ, Keller T, Ridder R. Conjunctive p16INK4a testing significantly increases accuracy in diagnosing high-grade cervical intraepithelial neoplasia.

Dijkstra MG, Heideman DA, de Roy SC, Rozendaal L, Berkhof J, van Krimpen K, et al. Ordi J, Garcia S, del Pino M, Landolfi S, Alonso I, Quinto L, et al. Negri G, Vittadello F, Romano F, Kasal A, Rivasi F, Girlando S, et al. Ozaki S, Zen Y, Inoue M. Biomarker expression in cervical intraepithelial neoplasia: Am J Obstet Gynecol.

Hariri J, Oster A. The negative predictive infiltrative Form der Psoriasis of p16INK4a to assess the outcome of cervical intraepithelial neoplasia 1 in the uterine cervix. Liao GD, Sellors JW, Sun HK, Zhang X, Bao YP, Jeronimo J, et al. A prospective study in China.

Cortecchia S, Galanti G, Sgadari C, Costa S, De Lillo M, Caprara L, et al. Follow-up study of patients with cervical intraepithelial neoplasia grade 1 overexpressing p16Ink4a. Int J Gynecol Cancer. Genoves J, Alameda F, Mancebo G, Sole JM, Bellosillo B, Lloveras B, et al. Human papillomavirus detection and p16INK4a expression in cervical lesions: Guedes AC, Brenna SM, Coelho SA, Martinez EZ, Syrjanen KJ, Zeferino LC.

Omori M, Hashi A, Nakazawa K, Yuminamochi T, Yamane T, Hirata S, et al. Estimation of prognoses for cervical intraepithelial neoplasia 2 by p16INK4a immunoexpression and high-risk HPV in situ hybridization signal types. Nishio S, Fujii T, Nishio H, Kameyama K, Infiltrative Form der Psoriasis M, Iwata T, et al. Journal of gynecologic oncology. Zhang G, Yang B, Abdul-Karim FW. Maniar KP, Sanchez B, Paintal A, Gursel DB, Nayar R.

Role of the Biomarker p16 in Downgrading -IN 2 Diagnoses and Predicting Higher-grade Lesions. Assessment of Ki antigen immunostaining in squamous intraepithelial lesions of the uterine cervix. Correlation with the histologic grade and human papillomavirus type.

American Journal of Clinical Pathology. Brief Summary of the Microbiology Devices Panel Meeting — March 12, Stoler MH, Wright TC, Jr. High-risk human papillomavirus testing in women with ASC-US cytology: Cooper K, Herrington CS, Stickland JE, Evans MF, McGee JO.

Episomal and integrated human papillomavirus in cervical neoplasia shown by non-isotopic in situ hybridisation. Berumen J, Unger ER, Casas L, Figueroa P. Amplification of human papillomavirus types 16 and 18 in invasive cervical cancer. Evans MF, Cooper K. Guo M, Gong Y, Deavers M, Silva EG, Jan YJ, Cogdell DE, et al. Evaluation of a commercialized in situ hybridization assay for detecting human papillomavirus DNA in tissue specimens from patients with cervical intraepithelial neoplasia and cervical infiltrative Form der Psoriasis. Schlecht NF, Brandwein-Gensler M, Nuovo GJ, Li M, Dunne A, Kawachi N, et al.

A comparison of clinically utilized human papillomavirus detection methods in head and neck cancer. Kong CS, Balzer BL, Troxell ML, Patterson BK, Longacre TA. Dabic MM, Hlupic L, Babic D, Jukic S, Seiwerth S. Comparison of polymerase chain reaction and catalyzed signal amplification in situ hybridization methods for human papillomavirus detection in paraffin-embedded cervical preneoplastic and neoplastic lesions.

Infiltrative Form der Psoriasis of medical research. Badr RE, Walts AE, Chung F, Bose S. Infiltrative Form der Psoriasis P, Domenech-Peris A, Ortiz-Reina S, Orantes-Casado FJ, Acosta-Ortega J, Garcia-Solano J, et al.

Immunohistochemical infiltrative Form der Psoriasis of Infiltrative Form der Psoriasis C in human papillomavirus-induced lesions infiltrative Form der Psoriasis the cervix. Bala R, Pinsky BA, Beck AH, Kong CS, Welton ML, Longacre TA. Yemelyanova A, Gravitt PE, Ronnett BM, Rositch AF, Ogurtsova A, Seidman J, et al. Immunohistochemical detection of human papillomavirus capsid proteins L1 infiltrative Form der Psoriasis L2 in squamous intraepithelial lesions: Melsheimer P, Kaul S, Dobeck S, Infiltrative Form der Psoriasis G.

Immunocytochemical detection of HPV high-risk type L1 capsid proteins LSIL and HSIL as compared with detection of HPV L1 DNA. Huang MZ, Li HB, Nie XM, Wu XY, Jiang XM.

An analysis on the combination expression of HPV L1 capsid protein and p16INK4a in cervical lesions. Xiao W, Bian M, Ma L, Liu J, Chen Y, Yang B, et al. Immunochemical infiltrative Form der Psoriasis of human papillomavirus L1 capsid protein in liquid-based cytology samples from cervical lesions. Yu L, Wang L, Zhong J, Chen S. Diagnostic value of p16INK4A, Ki, and human papillomavirus L1 capsid protein immunochemical staining on cell blocks from residual liquid-based gynecologic cytology specimens.

Lin Z, Yemelyanova AV, Infiltrative Form der Psoriasis R, Jagu S, Meyers C, Kirnbauer R, et al. Expression pattern and subcellular localization of human infiltrative Form der Psoriasis minor capsid auf Behandlung dem Zwiebeln von Schuppenflechte Kopf L2. Die fruhdiagnose des Kollumkarzinoms.

Creasman WT, Parker RT. Microinvasive infiltrative Form der Psoriasis of the cervix. Clinical obstetrics and gynecology. Foushee JH, Greiss FC, Jr. Stage IA squamous cell carcinoma of the uterine cervix. Andersen ES, Husth M, Joergensen A, Nielsen K. Laser conization for microinvasive carcinoma of the cervix.

Simon NL, Gore H, Shingleton HM, Soong SJ, Orr JW, Jr. Study of superficially invasive carcinoma of the cervix. Raspagliesi F, Ditto A, Solima E, Quattrone P, Fontanelli R, Zanaboni F, et al.

Microinvasive squamous cell cervical carcinoma. Lee SW, Kim YM, Son WS, You HJ, Kim DY, Kim JH, et al. The efficacy of conservative management after conization in patients with stage IA1 microinvasive cervical carcinoma. Acta obstetricia et gynecologica Scandinavica. Creasman WT, Fetter BF, Clarke-Pearson DL, Kaufmann L, Parker RT.

Management of stage IA carcinoma of the cervix. Andersen ES, Nielsen K, Pedersen B. Combination laser conization as treatment of microinvasive carcinoma of the uterine cervix. Eur J Gynaecol Oncol. Orlandi C, Costa S, Terzano P, Martinelli GN, Comerci G, Guerra B, et al. Presurgical assessment and therapy of microinvasive carcinoma of the cervix. Roche WD, Norris HJ.

The significance of lymphatic invasion and confluent patterns of stromal growth. Studies on cases of early squamous cell carcinoma of the cervix. Ostor AG, Rome RM. Micro-invasive squamous cell carcinoma of the cervix: Seski JC, Abell MR, Morley GW. Microinvasive squamous carcinoma of the cervix: Benedet JL, Anderson GH. Stage IA carcinoma of the cervix revisited. Buckley SL, Tritz DM, Infiltrative Form der Psoriasis Le L, Higgins R, Sevin BU, Ueland FR, et al.

Lymph node metastases and prognosis infiltrative Form der Psoriasis patients with stage IA2 cervical cancer. Sedlis A, Sall S, Tsukada Y, Park R, Mangan C, Shingleton H, et al. Microinvasive carcinoma of the uterine cervix: Jones WB, Mercer GO, Lewis JL, Jr. Early invasive carcinoma of the cervix. Gurgel MS, Bedone AJ, Infiltrative Form der Psoriasis LA, Panetta K.

Marana HR, de Andrade JM, Matthes AC, Spina LA, Carrara HH, Bighetti S. Analysis of prognostic factors. Lin H, Chang HY, Huang CC, Changchien CC. Prediction of disease persistence after conization for microinvasive cervical carcinoma and cervical intraepithelial neoplasia grade 3. Phongnarisorn C, Srisomboon J, Khunamornpong S, Siriaungkul S, Suprasert P, Charoenkwan K, et al.

The risk of residual neoplasia in women with microinvasive squamous cervical carcinoma and positive cone margins. Costa S, Marra E, Martinelli Continue reading, Santini D, Casadio P, Infiltrative Form der Psoriasis G, et al.

Outcome of conservatively treated microinvasive squamous cell carcinoma of the uterine cervix during a year follow-up. Kim WY, Chang SJ, Chang KH, Yoo SC, Infiltrative Form der Psoriasis HS. Conservative management of stage IA1 squamous cell carcinoma of the cervix with positive resection margins after conization. Kurman RJ, Carcangiu ML, Herrington CS, Young RH, editors. WHO Classification of Tumours of Female Reproductive Organs.

International Agency for Research on Cancer; SEER Cancer Statistics Factsheets: Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. Wentz WB, Reagan JW. Survival in cervical cancer with respect to cell infiltrative Form der Psoriasis. Zaino RJ, Ward S, Delgado G, Bundy B, Gore H, Fetter G, et al.

Histopathologic predictors of the behavior of surgically treated infiltrative Form der Psoriasis IB squamous cell carcinoma of the cervix. A Gynecologic Oncology Group study. Delgado G, Bundy BN, Fowler WC, Jr. A prospective surgical pathological study of stage I squamous carcinoma of the cervix: Stock RJ, Zaino R, Bundy BN, Askin FB, Woodward Click here, Fetter B, et al.

Evaluation and comparison of histopathologic grading systems of epithelial carcinoma of the uterine infiltrative Form der Psoriasis Gynecologic Oncology Group studies.

Kurman R, Ronnett B, Ellenson L. Koenig C, Turnicky RP, Kankam CF, Tavassoli FA. Papillary squamotransitional cell carcinoma of the cervix: Albores-Saavedra J, Young RH. Transitional cell neoplasms carcinomas infiltrative Form der Psoriasis inverted papillomas of the uterine cervix. A report of five cases. Randall ME, Andersen WA, Mills SE, Kim JA. Papillary squamous cell carcinoma of the uterine cervix: Tiltman AJ, Atad J.

Verrucous carcinoma of the cervix with endometrial involvement. Hasumi K, Sugano H, Sakamoto G, Masubuchi K, Kubo H. Circumscribed carcinoma of the uterine cervix, with marked lymphocytic infiltration.

Mills SE, Austin MB, Randall ME. Lymphoepithelioma-like carcinoma of the uterine cervix. A distinctive, undifferentiated carcinoma infiltrative Form der Psoriasis inflammatory stroma. Halpin TF, Hunter RE, Cohen MB. Lymphoepithelioma of the uterine cervix. Tseng CJ, Pao CC, Tseng LH, Chang CT, Lai CH, Soong YK, et al. Lymphoepithelioma-like carcinoma of the uterine cervix: Steeper TA, Piscioli F, Rosai J.

Squamous cell carcinoma with sarcoma-like stroma of the female genital tract. Clinicopathologic study of four cases. Watty EI, Johnston LW, Bainborough AR. Polypoid carcinoma of the uterine cervix simulating "pseudosarcoma" and "carcinosarcoma" of esophagus and upper respiratory tract.

Diagnostic gynecology and obstetrics. Histopathology of preinvasive and invasive squamous neoplasia. Rubin SC HW, editor. Cervical Cancer and More info Neoplasia.

Higgins GD, Phillips GE, Smith LA, Uzelin DM, Burrell CJ. High prevalence of human papillomavirus transcripts in all grades of cervical intraepithelial glandular neoplasia. Leary J, Jaworski R, Houghton R. In-situ hybridization using biotinylated DNA probes to human papillomavirus in adenocarcinoma-in-situ and endocervical glandular dysplasia of the uterine cervix. Kurian K, al-Nafussi A. Relation of cervical glandular intraepithelial neoplasia to microinvasive and invasive adenocarcinoma of the uterine cervix: Brown LJ, Wells M.

Cervical glandular atypia associated with squamous intraepithelial neoplasia: A study by in situ hybridization with biotinylated DNA probes. Negri G, Bellisano G, Carico E, Faa G, Kasal A, Antoniazzi S, et al.

Many conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle.

Weltweit leiden etwa Millionen, in Deutschland ca. Oktober von der International Federation of Psoriasis Associations erstmals als Welt-Psoriasistag ausgerufen. Eine schuppende Hautkrankheit, bei der es sich wahrscheinlich um Psoriasis handelte, wurde bereits vom griechischen Arzt Hippokrates ca. Der Ausdruck Psoriasis wurde zum ersten Mal vom Arzt Galenus verwendet, der damit eine Schuppenbildung im Augen - und Hodensackbereich umschrieb.

Bei dieser handelte es sich jedoch dem heutigen Forschungsstand nach vermutlich um Ekzeme. Allgemein werden vor allem Hautpartien befallen, die oft gedehnt werden wie die genannten Gelenke, aber auch z. Dabei nimmt die Juckende Haut Blasen eine Sonderstellung ein. Die Oberhaut Epidermis eines gesunden Menschen erneuert sich innerhalb von 26 bis 27 Tagen.

Bei der gesunden Haut dienen die Keratinozyten dem mechanischen, mikrobiellen und chemischen Schutz der Haut. Sie geht meist mit Nagelpsoriasis oder Gelenkbeschwerden Psoriasisartrithis einher. Der klinische Verlauf kennzeichnet sich durch einen akuten Fieberschub.

Innerhalb von 24 Stunden steigt die Zahl der Leukozyten, der Calciumgehalt sinkt, ebenso der Gehalt an Albumin im Blutplasma. Die Pustelbildung befindet sich an den Akren das sind: Ein Vergleich zwischen Schuppenflechte-Patienten und in Alter und Geschlecht vergleichbaren Gesunden infiltrative Form der Psoriasis, dass Psoriasis-Patienten infiltrative Form der Psoriasis vermehrte Knochenproliferation bei gleichzeitigem nicht unterschiedlichen Erosionsumfang aufweisen.

Bis heute ist allerdings nicht bekannt, ob die Psoriasis dominant oder rezessiv vererbt wird. In den betroffenen Geweben entsteht ein proinflammatorisches Milieu.

Bei Psoriasis wird vermehrt das Protein Psoriasin gebildet. Hinzu kommt, dass wie bei allen Erkrankungen mit phasenhaftem Verlauf und spontanen Besserungen die Wirksamkeit von Behandlungsverfahren hinsichtlich dieser Linderung schwer einerseits vom Placebo-Effekt und andererseits von spontaner Besserung Remission unterschieden werden kann.

Insgesamt ist Akzeptanz ein wichtiger Faktor im Umgang mit der Psoriasis. Eine Badetherapie mit schwefelhaltigem Natur- Fango und Vulkanwasser, wie sie in den argentinischen Anden im Thermalbad Copahue angeboten wird, kann Linderung, jedoch keine Heilung bewirken. Diese Methode soll die Bedingungen am Toten Meer simulieren.

Die Fische Kangalfische entfernen dabei die Hautschuppen der betroffenen Patienten. Der Excimer-Laser stellt eine der neuesten Entwicklungen in der Lasertherapie dar. Es handelt see more dabei um einen Xenon-Chlorid-Gas-Laser.

Der Laser arbeitet im UV-Schmalband-Spektrum. Zum Einsatz kommt er vor allen bei der Psoriasis und der Vitiligo. Je nach Empfindlichkeit des erkrankten Haut-Areals kann die therapeutisch notwendige Dosis gezielt angepasst werden.

Die Wirkstoffe sind Psoralene z. Diese Therapie wird oft kombiniert mit topischen Rote Flecken wie Psoriasis, zur weiteren Steigerung der Wirksamkeit.

Eine Kombination von UVA und UVB. Leuchtdioden LEDs sind sichere, energieeffiziente und langlebige Lichtquellen. Die Elektrotherapie mit schwach dosiertem Interferenzstrom zur Behandlung wurde am Forschungszentrum Karlsruhe infiltrative Form der Psoriasis, wo man in einer kleineren Studie Behandlungserfolge nachweisen konnte. Zurzeit laufen mehrere Studien. Angesichts der Tatsache, dass es sich bei der Schuppenflechte um eine Autoimmun-Erkrankung s.

Lange galt, dass MTX besonders gut bei Psoriasisarthritis wirksam ist, allerdings konnte eine im Jahr publizierte randomisierte placebokontrollierte Studie keinen solchen Effekt zeigen. Bei den Biologicals unterscheidet man zwei Infiltrative Form der Psoriasis Sie werden infiltrative Form der Psoriasis auch in anderen Indikationen eingesetzt z.

PsoriasisarthritisRheuma und Morbus Crohn. Der Phosphodiesterase-Hemmer Apremilast ist seit Januar zur Behandlung der mittelschweren bis schweren chronischen Psoriasis zugelassen. Die Substanz wurde ebenfalls zur Behandlung von Psoriasis-Arthritis bei Erwachsenen zugelassen. Die hier verwendeten Tabletten oder Spritzen wirken kurzfristig lindernd. Die innerliche Therapie der Psoriasis mit Kortikoiden wird heute nicht mehr empfohlen.

Die immunsuppressive Substanz Ciclosporin ist zur Behandlung von schwersten therapieresistenten Formen einer Psoriasis zugelassen. Dies infiltrative Form der Psoriasis auch durch Studienergebnisse untermauert, die eine deutliche Reduktion der Nagel-Psoriasis und positive Effekte auf Hyperkeratose und Onycholyse zeigen konnten.

Klassifikation nach ICD L40 Psoriasis L Ansichten Lesen Bearbeiten Quelltext bearbeiten Versionsgeschichte. Infiltrative Form der Psoriasis anderen Projekten Commons. Diese Seite wurde zuletzt am Juni um ICD online WHO-Version Dieser Artikel oder nachfolgende Abschnitt ist nicht hinreichend mit Belegen beispielsweise Einzelnachweisen ausgestattet.

Dieser Artikel behandelt ein Gesundheitsthema. Er dient nicht der Selbstdiagnose und ersetzt keine Arztdiagnose. Bitte hierzu diesen Hinweis zu Gesundheitsthemen beachten!

Sacroiliac Joint Dysfunction Animation - Everything You Need To Know - Dr. Nabil Ebraheim, M.D.

Some more links:
- Im Gegensatz zu Psoriasis und Nagelpilz
Granuloma annulare. Authoritative facts about the skin from DermNet New Zealand.
- Psoriasis-Arthritis Symptome und Behandlung von Volk
Many conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle.
- Präsentation psoriatischer Arthritis
1 Definition. Das Basaliom ist ein maligner Hauttumor, der lokal infiltrierend und destruierend wächst, aber nicht metastasiert. Früher wurde das Basaliom deshalb.
- Volksmedizin Behandlung von Psoriasis schnell
Many conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle.
- Es beginnt wie Psoriasis auf den Nägeln
Many conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle.
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