Preservation of the mesureter to reduce urinary complications: analysis of data from the observational Leipzig School MMR study.

OBJECTIVE: To evaluate the feasibility and effect of mesureteral preservation on urinary complications in the context of total mesometrial resection (TMMR), a surgical treatment for cervical cancer. DESIGN: Retrospective cohort study with historic control. SETTING: Single tertiary academic centre. POPULATION: Women older than 18 with primary cervical cancer staged FIGO IB1-IIB enrolled in the prospective Leipzig School MMR study and underwent total mesometrial resection (TMMR) without adjuvant radiation. METHOD: We retrospectively analysed 100 consecutive TMMR procedures which were performed for cancer of the uterine cervix and in which the mesureter was preserved (intervention group, 01/2014-06/2017). We compared this group with the previous 100 consecutive TMMRs, which were performed before the introduction of mesureteral preservation (control group, 09/2010-01/2014). MAIN OUTCOME MEASURES: The occurrence of urological and specifically ureteral complications. RESULTS: Mesureteral preservation was feasible and was associated with a significant decrease in ureteral complications (11% without mesureteral preservation versus 3% with mesureteral preservation, P = 0.049). Furthermore, we found a significant decrease in the number of postoperative percutaneous nephrostomies and re-operations (7% versus none, P = 0.014). There was also a trend towards a decrease in other urinary complications such as postoperative bladder atony and uretero-vaginal fistulas. CONCLUSION: The mesureter constitutes a convenient dissection plane enabling the preservation of lateral ureteral blood supply during TMMR. In our study, maintenance of mesureteral integrity was associated with a significant reduction in ureteral complications. Mesureteral preservation might also be useful in other types of pelvic surgeries that carry a high risk of ureteral damage. TWEETABLE ABSTRACT: Surgical preservation of the mesureter in cervical cancer patients was associated with a reduction in urinary complications.

[Un- and dedifferentiated endometrial carcinoma : A rare entity with a wide range of differential diagnosis]. / Das un- und dedifferenzierte Endometriumkarzinom : Eine seltene Entität mit breitem differenzialdiagnostischem Spektrum.

Dedifferentiated endometrial carcinomas (ECs) are composed of undifferentiated EC and a FIGO grade 1 or 2 endometrioid carcinoma. The undifferentiated component represents a malignant epithelial neoplasm with no obvious differentiation and immunohistochemical loss of PAX8, E­cadherin and focal expression of EMA and/or CK18 and the predominant presence of nuclear staining for INI1 (SMARCB1) and BRG1 (SMARCA4). The main differential diagnoses include poorly differentiated endometrioid EC, neuroendocrine carcinoma, lymphoma, plasmocytoma, high-grade endometrial stromal sarcomas, undifferentiated uterine sarcomas (UUS), carcinosarcomas, and metastases to the endometrium. The histogenesis is not yet fully understood and molecular data are still limited. Some tumors represent a loss of MHL1 and PMS2 staining due to MLH1-promotor methylation. Rare cases are associated with Lynch syndrome or POLE mutation. The un- or dedifferentiated EC represents a high-grade endometrial carcinoma that requires extended surgery and indicates a poor prognosis. In cases with mismatch repair protein deficiency or POLE mutation, immuno-oncological treatment with checkpoint inhibitors are a therapeutic option.

[The 2019 FIGO classification for cervical carcinoma-what's new?] / FIGO-Klassifikation für das Zervixkarzinom 2019 ­ was ist neu?

Numerous therapeutic and prognostic studies of cervical carcinoma have necessitated a revision of the FIGO classification.For microinvasive carcinomas, the horizontal dimension is no longer considered and diagnosis and staging will solely be made by the depth of cervical stromal invasion. Lymphovascular invasion beyond the deepest point of stromal infiltration by tumor cells does not alter the stage.There will be a new subclassification of macroinvasive carcinoma confined to the uterine cervix, which will be made by largest tumor extension as follows: FIGO IB1/T1b1 - invasive carcinoma >0.5 cm depth of stromal invasion and ≤2 cm in largest dimension, FIGO IBII/T1b2: - invasive carcinoma >2 cm and ≤4 cm, FIGO IBII/T1b3 - invasive carcinoma >4 cm. Pelvic as well as para-aortic lymph nodes will be defined as regional nodes. Pelvic lymph node metastases only will be categorised as FIGO IIIC1/pN1a and para-aortic lymph node involvement with or without concomitant pelvic involvement will be FIGO IIIC2/pN1b. Uterine corpus as well as adnexal involvement are not relevant for staging purpose.

[TNM classification of gynecologic malignancies : What remains to be done beyond 2017?] / TNM-Klassifikation gynäkologischer Tumoren : Was bleibt über 2017 hinaus zu tun?

For some gynecologic malignancies, there are disagreements between the most recent WHO and TNM classifications and the recommendations of the International Collaboration of Cancer Reporting. These discrepancies are addressed and discussed in this paper. The WHO definition for primary vaginal cancer does not match the TNM definition. The paper also discusses and provides TNM classifications for rare gynecologic tumors like primary malignant vulvar melanomas, sarcomas of the vulva, perivascular epithelioid cell tumor (PECom) of the uterus, undifferentiated uterine sarcomas, and extra-intestinal gastrointestinal stromal tumors (GIST), and provides some recommendations for the reporting and categorization of regional lymph nodes in nonuterine serous pelvic cancer.

[S3 guidelines on the diagnosis and treatment of carcinoma of the endometrium : Requirements for pathology]. / S3-Leitlinie Diagnostik und Therapie des Endometriumkarzinoms : Anforderungen an die Pathologie.

The present article summarises the relevant aspects of the S3 guidelines on endometrioid carcinomas. The recommendations include the processing rules of fractional currettings as well as for hysterectomy specimens and lymph node resections (including sentinel lymph nodes). Besides practical aspects, the guidelines consider the needs of the clinicians for appropriate surgical and radiotherapeutic treatment of the patients. Carcinosarcomas are assigned to the endometrial carcinoma as a special variant. For the first time, an algorithmic approach for evaluation of the tumour tissue for Lynch syndrome is given. Prognostic factors based on morphologic findings are summarised.

[Histopathology and clinical aspects of extrauterine pregnancy]. / Histopathologie und Klinik der Extrauteringravidität.

Ectopic pregnancies are the main sources of pregnancy-related morbidity and mortality in the first trimester. They are usually located in the ampullary part of the fallopian tube and the incidence increases in the setting of assisted reproductive techniques, older age at the time of the first pregnancy, and prior adnexal procedures. The clinical aspects and diagnostic challenges of an ectopic pregnancy for the pathologist are to be outlined. A review of the relevant literature was performed. Proof of gestational tissue is of utmost importance in the pathological-anatomical evaluation of an ectopic pregnancy. A complete evaluation of the specimen of a presumed tubal abruption or after milking out should be performed. Abnormal placentations (blighted ovum, embryonal molar pregnancy) as well as gestational trophoblastic disease (GTD, e.g., partial/complete molar pregnancy, choriocarcinoma) can occur in the setting of an ectopic pregnancy. Caution must be taken to differentiate a trophoblast hyperplasia secondary to the tubal microenvironment from GTD. p57 immunohistochemistry can help exclude a molar pregnancy. Only 50% of ectopic pregnancies are associated with tubal pathologies (e. g. inflammation, tubal adhesions). Chorionic villi and trophoblast epithelia can demonstrate regressive changes after prior methotrexate treatment. Rarely, immunohistochemistry with GATA-3, p63, ß­HCG, PAX-8, and WT-1 can be used in the differential diagnosis of trophoblastic epithelium. Ectopic pregnancies are associated with significant morbidity and mortality. A thorough evaluation of the specimen can help guide management and follow-up.

[Categorization of uterine cervix tumors : What's new in the 2014 WHO classification]. / Kategorisierung der Tumoren der Cervix uteri : Neues in der WHO-Klassifikation 2014.

In the 2014 WHO classification, squamous cell precursor lesions are classified as low-grade and high-grade intraepithelial lesions. LSIL corresponds to CIN1, HSIL includes CIN2 and CIN3. Only adenocarcinoma in situ (AIS) is accepted as precursor of adenocarcinoma and includes the stratified mucin-producing intraepithelial lesion (SMILE). Although relatively rare, adenocarcinoma and squamous cell carcinoma can be mixed with a poorly differentiated neuroendocrine carcinoma. Most cervical adenocarcinomas are low grade and of endocervical type. Mucinous carcinomas show marked intra- and extracellular mucin production. Almost all squamous cell carcinomas, the vast majority of adenocarcinomas, and many rare carcinoma types are HPV related. For low grade endocervical adenocarcinomas, the pattern-based classification according to Silva should be reported. Neuroendocrine tumors are rare and are classified into low-grade and high-grade, whereby the term carcinoid is still used.

[Grading of gynecological tumors : Current aspects]. / Grading gynäkologischer Tumoren : Aktuelle Aspekte.

Histopathological assessment of the tumor grade and cell type is central to the management and prognosis of various gynecological malignancies. Conventional grading systems for squamous carcinomas and adenocarcinomas of the vulva, vagina and cervix are poorly defined. For endometrioid tumors of the female genital tract as well as for mucinous endometrial, ovarian and seromucinous ovarian carcinomas, the 3­tiered FIGO grading system is recommended. For uterine neuroendocrine tumors the grading system of the gastrointestinal counterparts has been adopted. Uterine leiomyosarcomas are not graded. Endometrial stromal sarcomas are divided into low and high grades, based on cellular morphology, immunohistochemical and molecular findings. A chemotherapy response score was established for chemotherapeutically treated high-grade serous pelvic cancer. For non-epithelial ovarian malignancies, only Sertoli-Leydig cell tumors and immature teratomas are graded. At this time molecular profiling has no impact on the grading of tumors of the female genital tract.

[Cervical cancer : Update on morphology]. / Zervixkarzinom : Aktuelles zur Morphologie.

The World Health Organization (WHO) classification from 2014 differentiates between different subtypes of mucinous adenocarcinoma of the uterine cervix. A gastric subtype was recently described that showed no association with high-risk human papillomavirus (HPV) infections, has a poor prognosis, is mainly diagnosed in women of Asian origin and can occur in patients with Peutz-Jeghers syndrome. Although no clear grading system has been recommended in the WHO classification, it is likely that grading of adenocarcinomas of the uterine cervix will partly be based on the different patterns of invasion. Deep stromal infiltration of macroinvasive carcinomas is defined as an infiltration of >66 % of the cervical stroma. In the near future a maximum tumor size of 2 cm could act as a discriminator for planning of less radical surgery. Parameters of the histopathological report that are relevant for the prognostic assessment as well as the choice of adjuvant treatment and function as quality indicators during certification are described. The histological type of an adenocarcinoma alone is of no predictive or prognostic relevance for patients undergoing primary surgical treatment, neoadjuvant chemotherapy, combined chemo-radiotherapy or treatment with angiogenesis inhibitors. Currently, molecular parameters and biomarkers are of no relevance.

[Nomenclature of squamous cell precursor lesions of the lower female genital tract : Current aspects]. / Nomenklatur der plattenepithelialen Präkanzerosen des unteren weiblichen Genitales : Aktuelle Aspekte.

The majority of precancerous lesions of the lower female genital tract (intraepithelial neoplasia, IN) are caused by human papillomavirus (HPV) infections resulting in cellular atypia and in turn an altered tissue architecture. Depending on the pathogenesis, a distinction is made between vulvar intraepithelial neoplasia (VIN) classified as classical VIN associated with high-risk HPV infections (u-VIN) and differentiated VIN (d-VIN), which is associated with lichen sclerosus et atrophicus and p53 alterations. In the current World Health Organization (WHO) classification a novel grading system for squamous cell precancerous lesions of the lower female genital tract has been proposed, differentiating low grade squamous intraepithelial lesions (L-SIL) including condyloma and HPV-associated alterations plus VIN 1, vaginal intraepithelial neoplasia (VaIN 1) and cervical intraepithelial neoplasia (CIN 1) from high grade squamous intraepithelial lesions (H-SIL) with VIN 2 and 3, VaIN 2 and 3 as well as CIN 2 and 3. The use of p16 immunohistochemistry can assist the differentiation. The new binary classification, however, contradicts the German cytological nomenclature (Munich nomenclature III), which differentiated three grades of dysplasia in order to avoid overtreatment of patients with moderate IN. The individual nomenclatures are compared to each other. It is recommended to report the grade of precancerous lesions in addition to the SIL classification of the WHO.

[S3 guidelines on diagnostics and treatment of cervical cancer: Demands on pathology]. / S3-Leitlinie Diagnostik und Therapie des Zervixkarzinoms.

Between 2011 and the end of 2014 the former consensus S2k guidelines for the diagnostics and treatment of cervical cancer were updated and upgraded to S3 level, methodologically based on the regulations of the German Cancer Society (DKG). The present article summarizes the relevant aspects for the sectioning, histopathological workup, diagnostics and reporting for the pathology of invasive cancer of the uterine cervix. The recommendations are based on the most recent World Health Organization (WHO) and TNM classification systems and consider the needs of the clinician for appropriate surgical and radiotherapeutic treatment of patients. Detailed processing rules of colposcopy-guided diagnostic biopsies, conization and trachelectomy as well as for radical hysterectomy specimens and lymph node resection (including sentinel lymph node resection) are given. In the guidelines deep stromal invasion in macroinvasive cervical cancer is defined for the first time as tumor infiltration of > 66% of the cervical stromal wall. Furthermore, morphological prognostic factors for microinvasive and macroinvasive cervical cancer are summarized.

Tumors and tumor-like lesions in the mammary gland of 24 pet rabbits: a histomorphological and immunohistochemical characterization.

The aim of this retrospective study (2004-2011) was to examine mammary tumors and tumor-like lesions in 24 pet rabbits by histopathology and immunohistochemistry. Rabbits were aged 2 to 8 years. Seventeen were female and 7 female-spayed. Diagnosed tumor-like lesions were lobular hyperplasia (2 rabbits) and multiple cysts (10 rabbits). Tumors included cystadenoma (7 tumors; 3 rabbits), intraductal papilloma (2 tumors; 1 rabbit), intraductal papillary carcinoma (1 tumor), adenocarcinoma (14 tumors; 13 rabbits), adenosquamous carcinoma (2 tumors; 2 rabbits), and matrix-producing carcinoma (1 tumor). The most frequently diagnosed lesion was invasive carcinoma (n = 17). Ten rabbits had several lesions. Immunohistochemistry for calponin and p63 showed that the diagnosed tumor-like lesions, benign tumors, and noninvasive carcinoma had a peripheral myoepithelial layer that was lacking in the invasive carcinomas. In 13 of 14 (93%) of the invasive carcinomas, however, there were variable numbers of calponin- and/or p63-immunopositive cells ranging from 0.1% to 40% with morphological features of either retained nonneoplastic myoepithelial cells or neoplastic epithelial cells with a myoepithelial differentiation. Tumor recurrence was reported in the rabbit with the matrix-producing carcinoma and in 3 rabbits with mammary adenocarcinomas displaying ≥20 mitotic figures in 10 high-power fields and high numbers of neoplastic cells with a myoepithelial differentiation (19%-39%). The rabbit with the matrix-producing mammary carcinoma developed cutaneous metastases confirmed by histopathology. This study shows that different types of mammary tumor-like lesions and tumors can occur in pet rabbits.

[Importance of the tumor stem cell hypothesis for understanding ovarian cancer]. / Bedeutung der Tumorstammzellhypothese für das Verständnis des Ovarialkarzinoms.

BACKGROUND: Despite complex surgical and systemic therapies epithelial ovarian cancer has a poor prognosis. A small quantity of tumorigenic cells termed cancer stem cells (CSC) are responsible for the development of chemoresistance and high rates of recurrence. OBJECTIVES: This review presents the CSC hypothesis and describes methods of identification and enrichment of CSCs as well as approaches for the therapeutic use of these findings. MATERIAL AND METHODS: A systematic literature review based on PubMed and Web of Science was carried out. RESULTS: The CSC model is based on a hierarchical structure of tumors with few CSCs and variably differentiated tumor cells constituting the tumor bulk. Only the CSCs possess tumorigenic potential. Other essential functional characteristics of CSCs are their potential for self-renewal and their ability to differentiate into further cell types. The CSCs are structurally characterized by different surface markers and changes in certain signaling pathways. Currently there are phase I and II studies in progress investigating specific influences on CSCs. CONCLUSION: Various clinical characteristics of the course of disease in ovarian cancer are aptly represented by the tumor stem cell model. In spite of precisely defined functional characteristics of CSCs, surface markers and signaling pathways show individual differences and vary between tumor entities. This complicates identification and enrichment. Current experimental findings in various approaches and even first clinical studies raise hopes for a personalized cancer therapy targeting CSCs.

[New FIGO classification of ovarian, fallopian tube and primary peritoneal cancer]. / Neue FIGO-Klassifikation des Ovarial-, Tuben und primären Peritonealkarzinoms.

During recent years paramount changes have occurred in the pathogenesis of ovarian cancer and recent clinical studies identified new prognostic factors. Consequently, the FIGO has established a new staging system collectively covering carcinomas derived from the ovaries, the fallopian tubes and primary peritoneal cancers as well as malignant ovarian germ cell and sex-cord stromal tumors. The new staging system started on 01 January 2014. Major changes occurred in the FIGO IC/T1c stage with surgical spill (FIGO IC1/T1c1) versus capsule ruptured before surgery or tumor on ovarian or fallopian tube surface (FIGO IC2/T1c2) versus malignant cells in the ascites or peritoneal washings (FIGO IC3/T1c3). The regional lymph node metastases were subcategorised using a cut-off value of 10 mm as the largest dimension of the metastatic deposits. Distant metastases (excluding peritoneal metastases) were substaged as FIGO IVA/M1a in cases of cytologically or histologically proven pleural involvement and as FIGO IVB/M1b in cases of parenchymal metastases and metastases in extra-abdominal organs (including lymph nodes outside the peritoneal cavity and the inguinal lymph nodes).

[Morphology of secondary ovarian tumors and metastases]. / Morphologie sekundärer Ovarialtumoren/Ovarmetastasen.

The distinction between primary and secondary (metastatic) ovarian tumors is essential for the selection of appropriate surgical interventions, chemotherapeutic treatment and prognostic evaluation for the patient. Metastatic tumors of the ovary range between 5 % and 30 %. The majority of ovarian metastases in Europe and North America derive from colorectal (25-50 %) and breast cancers (8-25 %). A major issue is the differential diagnosis of mucinous tumors. Major features favoring metastasis include bilaterality, size < 10 cm, ovarian surface involvement, extensive intra-abdominal spread, and infiltrative growth within the ovary involving the corpus albicans and corpora lutea. An algorithm using bilaterality and tumor size (cut-off 10 cm) allows correct categorization in approximately 85 % of the cases. Although immunohistochemistry (especially CK7 and CK20 in mucinous tumors) using a panel of antibodies plays a valuable role and is paramount in the diagnosis, the results must be interpreted with caution and within the relevant clinical and histopathological context. It is necessary to note that the correct diagnosis of ovarian metastases always needs interdisciplinary and multidisciplinary approaches.

Lacking hypoxia-mediated downregulation of E-cadherin in cancers of the uterine cervix.

BACKGROUND: Experimental studies have established a causal connection between tumour hypoxia, hypoxia-associated proteome changes and downregulation of E-cadherin, the final common pathway of epithelial-to-mesenchymal transition (EMT). Our study aimed at elucidating the interrelationship of these processes in cancers of the uterine cervix in vivo. METHODS: Tumour oxygenation was assessed in 48 squamous cell carcinomas (SCC) of the uterine cervix using polarographic needle electrodes. The expression pattern of E-cadherin was investigated by immunohistochemistry and western blotting, and was compared with that of the hypoxia-inducible proteins glucose transporter (GLUT)-1 and carbonic anhydrase (CA) IX in biopsy specimens of the oxygenation measurement tracks. RESULTS: The majority of cervical cancers (52%) were E-cadherin positive, with a complete absence of the antigen in only 10% of the tumours. No correlation was found between the level of E-cadherin expression and the oxygenation status (mean pO(2), median pO(2) and hypoxic fractions). In patients showing partial expression of E-cadherin (38%), staining was not preferentially diminished in GLUT-1- or CA IX-positive areas, and loss of E-cadherin occurred independently of tumour cell scattering. CONCLUSION: Our data provide no evidence in favour of a hypoxia-induced EMT as a mechanistic basis of cervical cancer invasiveness.

c-kit/CD 117 positive cells in the myometrium of pregnant women and those with uterine endometriosis.

PURPOSE: Abnormal myometrial motility may play a role in the pathogenesis of endometriosis. Uterine contractility is a major contribution to labour. Myometrial motility might be controlled by CD 117-positive uterine smooth muscle cells. METHODS: Myometrial tissues from 8 cases with uterine endometriosis, 9 pregnant uteri (31.1 ± 8.7 weeks of gestation), 10 cases from non-pregnant pre-menopausal and 9 cases from post-menopausal women were immunohistochemically evaluated using a polyclonal antibody against c-kit/CD 117. The number of CD 117 positive cells was counted within 10 microscopic high power fields (× 400) and compared with the clinical diagnoses. RESULTS: Overall, a mean number of 15.7 (range 0-43) CD 117-positive cells within the myometrium was seen. Significant highest count occurred in the myometrium of non-pregnant pre-menopausal women without uterine endometriosis (30.78 ± 9.52), followed by post-menopausal women (15.5 ± 8.37) and those with uterine endometriosis (9.98 ± 4.9; p ≤ 0.01). The lowest count of CD 117-positive cells was seen in pregnant uteri (4.09 ± 2.33; p < 0.001). CONCLUSIONS: The lowest count of CD 117-positive cells was seen in the myometrium of pregnant women suggesting a role of preventing premature uterine contractility. There is no increase of CD 117-positive cells in the myometrium of women affected by uterine endometriosis.

[Precancerous lesions of the uterine cervix: morphology and molecular pathology]. / Präkanzerosen der Cervix uteri: Morphologie und Molekularpathologie.

HPV-induced alterations of the uterine cervix are frequently biopsied because of suspicious findings on a Pap smear and/or colposcopy. Precancerous lesions occur at the so called transformation zone. For those representing squamous differentiation, the traditional three-tier grading system in CIN 1 to 3 is used. CIN 1 and CIN 2 represent (spontaneous) regression in 60-90% and 50%, respectively. In CIN 3 lesions progression is seen in 20-50%. For appropriate grading, improvement of inter- and intraobserver correlation as well as the exclusion of non-precancerous lesions, p16 immunohistochemistry might be helpful. The terms endocervical glandular dysplasia and low-grade glandular intraepithelial neoplasia have been suggested for glandular lesions less than adenocarcinoma in situ (AIS). Until now reproducible histological criteria have not been established. Additional studies using HPV analysis, p16 and Ki-67 immunohistochemistry have not been proved for these lesions. In accordance with international consensus meetings, these diagnostic terms are not recommended for use in practice. AIS, characterised by the replacement of glandular epithelium by cytologically malignant cells, has been established as the precancerous lesion of the endocervix. AIS is much less common than CIN 3 with a reported range of 1:50-100. But, AIS is found in association with CIN 3 with 25-75%. The differential diagnosis between AIS and non-neoplastic glandular lesion may be aided by immunohistochemistry (e.g. p16, Ki-67, bcl-2, vimentin). All specimens obtained after the clinical diagnosis of cervical precancerous lesions should be examined using step sectioning to rule out microinvasive growth. Important information for clinicians includes the quality of the specimen (cautery artefacts, transformation zone enclosed within the probe), exact grading of CIN lesions, identification of other lesions responsible for suspicious findings of a Pap smear or at colposcopy, and in the case of conisation the distance of the lesion from the resection margins (endo- and ectocervical and circumferential margin).

[Current TNM/FIGO classification for cervical and endometrial cancer as well as malignant mixed müllerian tumors. Facts and background]. / Aktuelle TNM/FIGO-Stadieneinteilung für das Zervix- und Endometriumkarzinom sowie maligne Müller-Mischtumoren. Fakten und Hintergründe.

Numerous recent studies of endometrial and cervical carcinomas as well as malignant mixed müllerian tumors (MMMT) of the uterus have made a revision of the FIGO/TNM classification necessary, effective as of January 1st, 2010. There will be a new subclassification of carcinoma of the uterine cervix with proximal vaginal infiltration, using the same cut-off for the tumor extension as used for stage FIGOIB/T1b (≤/>4 cm), resulting in stage FIGO IIA1/T2a1 and FIGO IIA2/T2a2. In endometrial carcinoma, the previous FIGO IA/pT1a and FIGO IB/pT1b will be merged to FIGO IA/pT1a. The former category FIGO IC/T1c will be changed into FIGO IB/T1b. The category FIGO IC/pT1c will not longer been used. Additionally, there will be no separate classification for the involvement of the endocervical glands by endometrial carcinoma. This feature will be incorporated in stage FIGO I/T1 disease. The new category FIGO II/T2 will be defined as endocervical stromal involvement. There will be a new category, termed T3c/IIIC, which includes regional lymph node involvement. Stage T3c1/IIIC1 will be defined as pelvic lymph node involvement and stage T3c2/IIIC2 para-aortal lymph node involvement with or without pelvic lymph node disease. In the TNM system, regional lymph node involvement can alternatively be classified as N1. The MMMT will be staged like endometrial carcinoma.

[HPV-associated alterations of the vulva and vagina. Morphology and molecular pathology]. / HPV-assoziierte Veränderungen an Vulva und Vagina. Morphologie und Molekularpathologie.

Non-neoplastic HPV-induced alterations of the vulva and vagina are frequent. The traditional three-tier grading system of vulvar intraepithelial neoplasia (VIN) will be replaced by the definition of usual and simplex type of VIN. The usual type is characterized by a strong association to high-risk HPV infections, the occurrence at younger age and multifocality, mostly associated with non-keratinizing squamous cell carcinoma. The differentiated (or simplex) type is rare and shows an association to older age and p53 alterations and is typically diagnosed co-incidentally with keratinizing squamous cell carcinoma. Vaginal intraepithelial neoplasia (VAIN) is still graded into VAIN 1-3 where VAIN 1 and 2 are mostly associated with low-risk HPV infections and a high spontaneous regression rate whereas VAIN 3 represents a high-risk HPV-associated lesion with capable progression into (micro-)invasive carcinoma. The differential diagnosis between a non-neoplastic condylomatous lesion and VIN common type and VAIN may be aided by p16 immunohistochemistry. The HPV-associated invasive vulvo-vaginal cancers are verrucous carcinoma (low-risk HPV) and the high-risk HPV-induced (non-keratinizing) squamous cell carcinoma (NOS), the condylomatous (warty) carcinoma and the very rare vaginal squamo-transitional carcinoma.