To improve the precision of epithelial ovarian cancer histotyping, Köbel et al. (2016) developed immunohistochemical decision-tree algorithms. These included a six- and four-split algorithm, and separate six-split algorithms for early- and advanced stage disease. In this study, we evaluated the efficacy of these algorithms. A gynecological pathologist determined the hematoxylin and eosin (H&E)-based histotypes of 230 patients. Subsequently, the final histotypes were established by re-evaluating the H&E-stained sections and immunohistochemistry outcomes. For histotype prediction using the algorithms, the immunohistochemical markers Napsin A, p16, p53, progesterone receptor (PR), trefoil factor 3 (TFF3), and Wilms\' tumor 1 (WT1) were scored. The algorithmic predictions were compared with the final histotypes to assess their precision, for which the early- and advanced stage algorithms were assessed together as six-split-stages algorithm. The six-split algorithm demonstrated 96.1% precision, whereas the six-split-stages and four-split algorithms showed 93.5% precision. Of the 230 cases, 16 (7%) showed discordant original and final diagnoses; the algorithms concurred with the final diagnosis in 14/16 cases (87.5%). In 12.4%-13.3% of cases, the H&E-based histotype changed based on the algorithmic outcome. The six-split stages algorithm had a lower sensitivity for low-grade serous carcinoma (80% versus 100%), while the four-split stages algorithm showed reduced sensitivity for endometrioid carcinoma (78% versus 92.7-97.6%). Considering the higher sensitivity of the six-split algorithm for endometrioid and low-grade serous carcinoma compared with the four-split and six-split-stages algorithms, respectively, we recommend the adoption of the six-split algorithm for histotyping epithelial ovarian cancer in clinical practice.

Sexsomnia is a rare, male-predominant, non-rapid eye movement parasomnia characterized by complex sexual behaviors occurring without conscious awareness during sleep. The biopsychosocial consequences of sexsomnia on both those diagnosed and their bed partners have not yet been fully elucidated. We present the case of an adult, a heterosexual female who developed vaginitis following sexual intercourse that occurred secondary to her partner\'s diagnosed sexsomnia. To our knowledge, this is the first reported case of gynecological pathology occurring because of sexsomnia, and it serves to highlight the importance of thorough history-taking and the need for further research on the effects of sexsomnia on both parties involved.

Background: Inflammatory lesions and cysts are the most common Bartholin glands pathologic diagnoses. There have been very few reports of benign solid lesions of Bartholin glands such as nodular hyperplasia. Materials and methods: Thirty-two lesions diagnosed as Bartholin duct cyst in the gynecologic specialized institute were reviewed by two expert gynecological pathologists. Results: Using specific criteria, 7 qualified as nodular hyperplasia, 25 as Bartholin duct cyst. The average age of the patients with nodular hyperplasia was 31 years (range, 24 to 43). These lesions were solid, solid and cystic or purely cystic, had a mean maximal dimension of 3.3 cm, and were frequently thought to be Bartholin cysts on clinical examination. Four lesions were diagnosed as Bartholin duct cysts, while in the review they were considered as nodular hyperplasia. Conclusion: Nodular hyperplasia of Bartholin gland may be more common than is reported in the literature. This study showed that the diagnosis of nodular hyperplasia has been overlooked due to limited literature sources.

Historically known as a \"silent killer\", ovarian cancer is often diagnosed at an advanced stage. We describe an unusual case of stage I, ovarian, high-grade serous carcinoma detected by a routine Papanicolaou (PAP) smear, with no abnormal physical, imaging, or laboratory findings. A 53-year-old woman with newly diagnosed triple-negative breast cancer received a screening Pap smear, which showed malignant cells not coming from the breast or uterine cervix. Pelvic examination, cervical biopsy, and gynecologic ultrasonography found no abnormality. Endometrial curettage yielded free-floating adenocarcinoma cells. The immunohistochemical stain result indicated ovary or fallopian tube cancer. Complete cytoreductive surgery was performed, and high-grade serous carcinoma of bilateral ovaries, FIGO stage IB, was diagnosed. Although extremely rare, when malignant cells not originating from the uterine cervix are detected on a Pap smear, it may lead to an early diagnosis of ovarian cancers, and this warrants further comprehensive workup.

Mucous membrane pemphigoid (MMP), also known as cicatricial pemphigoid (CP), is a heterogeneous group of subepidermal blistering diseases that affect the mucous membranes, most frequently in the eye and oral cavity. MMP is often unrecognized or misdiagnosed in its early stages due to its rarity and nonspecific presentation. We present the case of a 69-year-old female in which MMP of the vulva was not initially suspected. The first biopsy, from lesional tissue for routine histology, revealed fibrosis, late-stage granulation tissue, and nonspecific findings. A second biopsy, from perilesional tissue for direct immunofluorescence (DIF), revealed DIF findings typical of MMP. Scrutiny of both the first and second biopsies revealed a subtle but telling histologic feature: subepithelial clefts along adnexae in the context of a scarring process with neutrophils and eosinophils, which can be an important clue to MMP. This histologic clue has been previously described; reinforcing its importance may prove useful for future cases, especially those for which DIF is not feasible. Our case demonstrates the protean presentations of MMP, the need for persistence in sampling unusual cases, and the relevance of inconspicuous histologic features. The report highlights this underrecognized yet potentially decisive histologic clue to MMP, reviews current biopsy guidelines when MMP is suspected, and delineates the clinical and morphological features of vulvar MMP.

BACKGROUND: In the last two decades, there has been marked development in virtual slide technology as well as its application in various subspecialties of pathology. In particular, there have been several studies examining the utility of whole slide imaging (WSI) in breast and gynecological pathology. The aim of this systematic review is to analyse published evidence regarding validation studies of WSI applied specifically to the female genital tract and breast pathology.
METHODS: A systematic search was carried out in Pubmed and Embase databases and studies dealing with the validation of a WSI system for breast and gynaecological pathology. The topics evaluated concerned expertise of engaged pathologists, varied specimens, scanners, washout period, experience viewing WSI, and diagnostic concordance of WSI to traditional light microscopic diagnoses.
RESULTS: Of 1467 publications retrieved, 23 studies were included. Most of these studies concerned breast pathology. Validation guidelines recommended by the College of American Pathologists pertaining to a dataset of at least 60 cases, washout period, and recording intra-observer variability were followed by most studies. Major challenges encountered with WSI included difficulty identifying high-grade nuclear atypia and mitotic count for borderline ovarian tumors, interpretation of squamous intraepithelial lesions in liquid-based cervical cytology, and grading breast cancer.
CONCLUSIONS: Published data demonstrates the value of utilizing WSI in breast and gynecological pathology. Key issues reported with WSI systems were problems related to focus, resolution and the contrast and brightness of immunohistochemical staining patterns. Grading breast cancer and mitotic count remained challenging in WSI as in conventional microscopy.

Understanding whether human papillomavirus (HPV) may establish latency in the uterine cervix is important. A better understanding of HPV natural history is useful for clinical counseling of women attending screening and to accurately inform health prevention strategies such as screening and HPV vaccination. We evaluated the extent of latent HPV infections in older women with a history of abnormal cytology.
We conducted a cross-sectional study in Aarhus, Denmark, from March 2013 through April 2015. Women were enrolled if they underwent cervical amputation or total hysterectomy because of benign disease. Prior to surgery, women completed a questionnaire and a cervical smear was collected for HPV testing and morphological assessment. For evaluation of latency (i.e., no evidence of active HPV infection, but HPV detected in the tissue), we selected women with a history of abnormal cervical cytology or histology, as these women were considered at increased risk of harboring a latent infection. Cervical tissue underwent extensive HPV testing using the SPF10-DEIA-LipA25 assay.
Of 103 women enrolled, 26 were included in this analysis. Median age was 55 years (interquartile range [IQR] 52-65), and most women were postmenopausal and parous. The median number of sexual partners over the lifetime was six (IQR 3-10), and 85% reported no recent new sexual partner. Five women (19.2%) had evidence of active infection at the time of surgery, and 19 underwent latency evaluation. Of these, a latent infection was detected in 11 (57.9%), with HPV16 being the most prevalent type (50%). Nearly 80% (n = 14) of the 18 women with a history of previous low-grade or high-grade cytology with no treatment had an active or latent HPV infection, with latent infections predominating. HPV was detected in two of the six women with a history of high-grade cytology and subsequent excisional treatment, both as latent infections.
HPV can be detected in cervical tissue specimens without any evidence of an active HPV infection, indicative of a latent, immunologically controlled infection. Modeling studies should consider including a latent state in their model when estimating the appropriate age to stop screening and when evaluating the impact of HPV vaccination.

Mesonephric adenocarcinomas are rare tumors of the female genital tract, thought to arise from embryonic mesonephric remnants, primarily in the cervix and vagina. Conversely, endometrial and ovarian mesonephric adenocarcinomas may have a different pathogenesis, probably originating from transdifferentiated Müllerian carcinomas, as demonstrated by the association of these neoplasms with endometriosis and ovarian serous tumors. For this reason, in the endometrium and in the ovary, they are defined as \"mesonephric-like adenocarcinomas\". Some cases of mesonephric carcinomas of the female genital tract have been reported to show a sarcomatous component and have been defined as \"mesonephric carcinosarcomas\", characterized by poor prognosis and high metastatic behavior, but this entity has never been described in the ovary. The case herein presented is of a 74-year-old female with abdominal discomfort and a complex ovarian mass. Histological and immunohistochemical analysis showed features of ovarian mesonephric-like carcinoma combined with a low-grade serous component, in support of the theory of a Müllerian origin of these neoplasms. The tumor also revealed foci of chondrosarcomatous differentiation, never before reported in the ovary, showing a similar immunohistochemical profile to the mesonephric-like elements. This work thus describes the first reported case of ovarian mesonephric-like carcinosarcoma.

OBJECTIVE: The purpose of the present study was to elucidate the presence of human herpesvirus 6A (HHV-6A), HHV-6B and HHV-7 in samples of the uterine cervix through detection of viral DNA. We analysed normal tissues, samples with low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs). We correlated the presence of HHV-6 and HHV-7 with the finding of human papillomavirus (HPV) in mucosal samples.
METHODS: Cervical samples were examined and grouped as follows: group 1 (n=29), normal cytology; group 2 (n=61), samples with LSIL; group 3 (n=35), samples with HSIL. Molecular biology examinations were performed in all samples to detect HHV-6, HHV-7 and HPV DNA and to typify HHV-6 species.
RESULTS: Group 1: normal cytology and HPV (-): HHV-6: 6.8% (2/29), HHV-7: 79.3% (23/29); group 2: LSIL and HPV (-): HHV-6: 93.1% (27/29), HHV-7: 96.5% (28/29); LSIL and HPV (+): HHV-6: 0% (0/32), HHV-7: 90.6% (29/32); group 3: HSIL and HPV (-): HHV-6: 20% (2/10), HHV-7: 70% (7/10); HSIL HPV (+): HHV-6: 12% (3/25), HHV-7: 68% (17/25). HHV-6A DNA was not detected in any samples.
CONCLUSIONS: (1) Both HHV-6 and HHV-7 infect the mucosal cells of the cervix with higher prevalence of HHV-7. (2) The higher prevalence of HHV-6 in LSIL HPV (-) samples compared with those with normal cytology indicates that it constitutes a possible risk factor for atypia production. (3) The presence of HHV-7 in all samples questions its role in the production of atypia. (4) The finding of HHV-6 and HHV-7 suggests that the cervical mucosa is a possible transmission pathway for these viruses.

OBJECTIVE: The International Endocervical Adenocarcinoma Criteria and Classification (IECC) was recently proposed as an improved method for categorising endocervical adenocarcinoma (EA) into human papillomavirus (HPV)-associated adenocarcinomas (HPVAs) and non-HPV-associated adenocarcinomas (NHPVAs). Such categorisation correlates with patient age and tumour size; however, its association with patient outcome remains to be established.
METHODS: Institutional cases of EA with histological material available were selected. Three gynaecological pathologists independently classified all tumours according to the IECC with consensus review used when necessary. Clinicopathologic variables were recorded for each case.
RESULTS: Of a total of 87 EAs, 71 (82%) were classified as HPVA and 16 (18%) as NHPVA. Among HPVA, most were usual type (51/71, 72%) followed by mucinous not otherwise specified (10/71, 14%) and invasive stratified mucin-producing carcinoma (ISMC, 8/71, 11%). Most NHPVAs were of gastric type (12/16, 71%) followed by clear cell and mesonephric (two each, 12%). Compared with HPVAs, NHPVAs were significantly associated with older age (p<0.001), larger horizontal extent (p=0.013), greater depth of invasion (p=0.003), lymphovascular space invasion (p<0.001), advanced stage (p<0.001) and invasive pattern C (p<0.001). On univariate analysis, worse disease-free survival (DFS) and disease-specific survival (DSS) correlated with NHPVA group. Among the HPVA subtypes, ISMC showed worse DFS and DSS compared with other HPVA types.
CONCLUSIONS: The simple morphological approach of the IECC appears to be prognostically valuable. NHPVA (in particular gastric type) and ISMC (a recently recognised subset of HPVA) have an adverse outcome and their recognition following the IECC is important. We provide further evidence to replace the current WHO classification with the IECC.