Moderately-differentiated Ovarian Sertoli-Leydig Cell Tumor With a Concurrent Serous Borderline Tumor in a 16-year-old Girl.

Sertoli-Leydig cell tumors (SLCT) are rare tumors of the ovary with a peak incidence in the second to third decade of life. Serous borderline tumors (SBT) are epithelial ovarian neoplasms which occur at a median age of 50 years. A co-occurrence of SLCT and SBT has not yet been reported. Here, we describe a case of a 16-year-old girl who presented with irregular menses, virilization, and an abdominopelvic mass. The mass was surgically removed and an intraoperative consultation revealed an 18.5 cm solid and cystic ovarian mass with the presence of co-existing SLCT and SBT. The diagnosis was confirmed on permanent sections after extensive sampling and immunohistochemical stains. The SLCT showed positive staining for calretinin, inhibin, CD99, and androgen receptor. MART-1 immunostain highlighted the Leydig cells. The SBT showed classic features including hierarchically branching papillae lined by stratified serous epithelium. This pediatric case is the first reported case of a Sertoli-Leydig cell tumor arising in association with a serous borderline tumor.

Gynecologic Pathology Journal Club: A 2-year, Worldwide Virtual Learning Experience With a Focus on Mentorship and Inclusion.

Journal clubs (JCs) are a common format used in teaching institutions to promote trainee engagement and develop skills in seeking out evidence-based medicine and critically evaluating literature. Digital technology has made JC accessible to worldwide audiences, which allows for increased inclusion of globally diverse presenters and attendees. Herein we describe the experience of the first 2 years of a virtual gynecologic pathology JC designed with the goal of providing mentorship and increasing inclusivity. JC began in a virtual format in April 2020 in response to the need for remote learning during the coronavirus disease 2019 pandemic. Each JC had 1 moderator, lasted 1 hour, featured up to 3 trainees/early-career pathologists, and covered articles on gynecologic surgical pathology/cytopathology. Trainees were recruited through direct contact with moderators and advertising through social media (eg, Twitter). A template was used for all presentations, and before presenting, live practice sessions were conducted with the moderator providing constructive feedback and evaluations were provided to presenters and attendees for feedback. Recordings of the meetings were made publicly available after the event through YouTube, a society website, and emails to registrants. Fifty-nine presenters participated, covering 71 articles. Most were trainees (53/59; 89%) from North America (33/59; 56%), with additional presenters from Asia (14/59; 24%), Australia/Oceania (5/59; 8%), Africa (4/59; 7%), and Europe (3/59; 5%). An average of 20 hours were spent per month by moderators on the selection of papers, meeting preparation, and provision of mentorship/feedback. Live events had a total of 827 attendees, and 16,138 interactions with the recordings were noted. Among those who self-identified on provided surveys, the attendees were most commonly from Europe (107/290; 37%) and were overwhelmingly practicing pathologists (275/341; 81%). The experience, including mentorship, format, and content, was positively reviewed by attendees and presenters. Virtual JC is an inclusive educational opportunity to engage trainees and early-career pathologists from around the world. The format allowed for the JC to be widely viewed by attendees from multiple countries, most being practicing pathologists. Based on feedback received, virtual JC appears to expand the medical knowledge of the attendees and empower presenters to develop their expertise and communication skills.

Evaluation of Saccharomyces cerevisiae -like 1 (SEC14L1) in Gynecologic Malignancies Shows Overexpression in Endometrial Serous Carcinoma.

Saccharomyces cerevisiae -like 1 ( SEC14L1 ) is a member of the SEC14 family and is involved in liposoluble vitamin transfer, and in a large cohort of breast cancer cases, was one of the genes most significantly associated with lymphovascular invasion (LVI), and had a significant relationship with human epidermal growth factor receptor 2 status, survival, and histologic grade. In this study, 111 separate gynecologic tumors were studied for SEC14L1 protein expression, including: uterine adenosarcoma, ovarian clear cell carcinoma, endometrial stromal sarcoma, endometrioid carcinoma of the uterus, high-grade serous carcinoma, ovarian endometrioid carcinoma, uterine leiomyosarcoma, low-grade serous carcinoma, uterine carcinosarcoma, and uterine serous carcinoma (USC). Overall, LVI was noted in 31/111 (28%) cases, highest in uterine carcinosarcoma (5/11; 45%), high-grade serous carcinoma (9/21; 43%), and ovarian clear cell carcinoma (4/10; 40%). SEC14L1 was positive in 25/111 (23%) cases; the highest percentage and only statistically significant finding by tumor type was USC at 9/12 (75%) cases positive. No relation between LVI or survival and SEC14L1 expression was noted. The relation between USC, a tumor known to show human epidermal growth factor receptor 2 overexpression and SEC14L1 is a novel finding, the significance of which warrants further study.

Inflammatory Myofibroblastic Tumor of the Placenta With Subsequent Successful Pregnancy and Benign Hysterectomy: A Case Report With 59-Month Follow-up.

Inflammatory myofibroblastic tumors (IMT) are rare neoplasms of intermediate malignant potential which have been described in the gynecologic tract, predominantly in the myometrial wall, but also in association with the placenta. Like those in other organs, IMT of the placenta are characterized by molecular abnormalities, most commonly anaplastic lymphoma kinase gene rearrangements, and are often positive for anaplastic lymphoma kinase immunohistochemically. Although the clinical behavior of placental IMTs has so far proven benign, a successful intrauterine pregnancy with subsequent negative hysterectomy following a placental IMT has not been documented. Herein is presented a case of a 27-yr-old noted to have a 2 cm IMT of the extraplacental membranes at delivery, after which the patient received no further treatment. After 56 mo, the patient experienced a subsequent normal delivery in a pregnancy complicated by gestational diabetes. No longer desiring fertility, the patient elected to have a hysterectomy to confirm the absence of IMT at 59 mo and the uterus was unremarkable. This case provides insight into possible outcomes for patients with a rare tumor who may desire future fertility and may otherwise be advised to undergo hysterectomy in the setting of an unclear clinical course.

Yolk Sac Tumor Arising in Uterine Carcinosarcoma With Endometrioid and Serous Components: A Case Report With Immunohistochemical Analysis.

Yolk sac tumor of the endometrium is an uncommon neoplasm. Here we report a case of yolk sac tumor arising in a uterine carcinosarcoma, with the carcinomatous component showing both endometrioid and serous components, and the sarcomatous component showing homologous (spindled) differentiation. The yolk sac tumor showed predominant glandular configuration and was present admixed with the epithelial components. Extensive immunostaining was performed to narrow the differential diagnosis, including potentially therapeutic testing for HER-2. To our knowledge, this is the first case of carcinosarcoma with this mix of epithelial components and corresponding reporting of these immune and therapeutic markers.

Dermatofibrosarcoma protuberans with fibrosarcomatous transformation arising at the site of breast implant.

Fibrosarcomatous transformation of dermatofibrosarcoma protuberans (DFSP) is a rare variant with higher risk of recurrence and metastasis, and no known associations with breast implants. We report a rare case of fibrosarcomatous dermatofibrosarcoma protuberans arising at the site of breast implant in a 33-year-old patient followed by brief discussion on fibrosarcomatous DFSP.

Clinical and histopathologic characteristics of patients undergoing surgical excision with Essure coils: Longitudinal experience at a women's specialty hospital.

The introduction of the Essure (Bayer AG, Leverkusen, Germany) device made possible a less invasive approach for patients desiring sterilization. Following FDA approval in 2002, problems were reported in some patients with these devices including most commonly pain. Labeling changes were mandated in 2016, and as of late 2018, the devices are no longer being sold in the United States. A comprehensive description of Pathologic findings in patients with these devices has not been reported. This study characterizes pathologic findings in patients undergoing surgery who had Essure in place, regardless of the indication for surgery. 137 cases were found, 126 of which had submitted tissue, 121 of which had fallopian tube(s) submitted. Duration for coils being in place was available for 104/137 patients (mean 48 months; median 43 months, range 0-166 months). Cases ranged from 2009 to 19, with a peak in cases noted in 2016. A chief complaint relating to the phrase "pelvic pain" was the most common, noted in 72/137 cases. Obliteration, defined as loss of the fallopian tube epithelium with filling of the lumen with fibrotic material, was noted in 33/121 cases. Inflammation was noted in 59/126 cases, 31/59 showed with giant cells, chronic inflammation (lymphocytes and/or plasma cells) in 37/59 cases, and acute inflammation 19/59 cases, with 14/19 showing eosinophils. Acute inflammation was noted in those with a shorter duration of coil implantation, while chronic inflammation, including giant cells, were noted across the span. This study has expanded knowledge of patients with removal of Essure coil devices.

Two types of ovarian cortical inclusion cysts: proposed origin and possible role in ovarian serous carcinogenesis.

Ovarian cortical inclusion cysts (CICs) have been long regarded as a possible site of origin of epithelial ovarian carcinoma. It has been proposed that they develop from invagination of ovarian surface epithelium (OSE) which then undergoes metaplasia to form mullerian-type tissue and then undergoes neoplastic transformation. Recent studies have challenged this view, at least for high-grade serous carcinoma, proposing that the latter arise from occult carcinomas in the fallopian tube. Although there is compelling evidence supporting this view, it does not account for the origin of all high-grade serous carcinomas. We have postulated that a subset of high-grade serous carcinoma may develop from CICs, but that they are derived from implantation of tubal epithelium when the OSE is disrupted at ovulation. If true, it would be expected that the number of CICs would increase with age and that CICs would not be present before menarche. To test this hypothesis we examined ovaries removed at autopsy for the presence of CICs and correlated their presence with age. In addition, we used immunohistochemistry for PAX8 (mullerian marker) and calretinin (mesothelial marker). CICs were defined as either ciliated (tubal-type, PAX8-positive) or flat (OSE-type, calretinin-positive). As it has been argued that steroid hormones convert mesothelial-derived OSE to mullerian-type tissue, we performed immunohistochemistry for estrogen and progesterone receptors. CICs lined by tubal-type epithelium were found only in postmenarchial women and 20/21 (95%) were PAX8-positive; none of the 5 flat cysts expressed PAX8 but 4/5 (80%) expressed calretinin. Estrogen receptor was expressed in 1 of 21 (5%) ciliated CICs, whereas it was negative in all 5 flat CICs. Progesterone receptor was expressed in 14 of 21 (66%) ciliated CICs, and in none of the 5 flat cysts. The findings suggest that there are 2 types of CICs, 1 from OSE and 1 from tubal epithelium that probably develop at the time of ovulation.

Inflammatory Myofibroblastic Tumor of the Placenta: A Report of a Novel Lesion in 2 Patients.

Inflammatory myofibroblastic tumor has been described in a wide variety of anatomic sites, although in the gynecologic tract, it has mostly been documented in the uterus, and has never been described in the placenta. Two patients presented with well-circumscribed placental masses that showed classic histologic features of inflammatory myofibroblastic tumor including a proliferation of myofibroblastic cells, a mixed inflammatory infiltrate, and a myxoid background. One case was positive by immunohistochemistry for anaplastic lymphoma kinase (ALK-1), whereas the other was negative by immunohistochemistry and fluorescent in situ hybridization. Inflammatory myofibroblastic tumors should be differentiated from other more aggressive uterine tumors that may involve the placenta by direct extension/metastasis because they can be managed conservatively, and in these 2 cases, did not seem to affect the course of the patient's pregnancies.

Does the uterine cervix become abnormally reinnervated after subtotal hysterectomy and what is the association with future trachelectomy?

STUDY OBJECTIVE: To compare nerve fiber density in the cervices removed by trachelectomy from women with pelvic pain with those cervices removed for nonpain indications. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Two university hospitals. PATIENTS: Subjects who underwent trachelectomy during a 10-year time frame were identified. INTERVENTIONS: Two tissue sections were obtained from each preserved cervix specimen and stained for S100 antibody. The numbers of S100-immunoreactive peripheral nerve fibers were assessed in 6 high-powered fields (HPFs) per tissue section (12 total HPFs per patient). Information collected included patient characteristics and surgical findings. We excluded any patients with dysplasia/cancer and those without an available adequate specimen. MEASUREMENTS AND MAIN RESULTS: We evaluated the cervix specimens from 35 patients who underwent trachelectomy for pain (n = 25, group 1) and nonpain (n = 10, group 2) indications in addition to control cervices (n = 15, group 3) from benign hysterectomies performed for nonpain indications. There were increased numbers of nerve fibers in trachelectomy patients with pain versus those without pain (group 1 vs group 2, p = .02). There were also increased numbers of nerve fibers in both trachelectomy groups compared with the control group (group 1 vs group 3, p < .01; group 2 vs group 3, p = .04). Adjusted average cervical nerve counts/HPF were 17.8 (95% confidence interval [CI], 13.2-22.3) for pain-indicated trachelectomies, 11.5 (95% CI, 4.8-18.2) for nonpain, and 6.3 (95% CI, 0.8-11.8) for controls. Regardless of trachelectomy indication, adjusted average nerve counts/HPF were 17.7 (95% CI, 13.4-22.0) for patients with endometriosis and 14.6 (95% CI, 12.2-17.1) for patients without endometriosis. CONCLUSION: Nerve fibers in the cervical stump after supracervical hysterectomy are significantly increased in women undergoing trachelectomy for pain indications compared with those who underwent trachelectomy for nonpain indications and controls. Although not statistically significant, endometriosis may be an independent risk factor for increased nerve fibers. These histopathologic observations may support the idea that the cervix should be removed in women undergoing hysterectomy for chronic pelvic pain or endometriosis.

Characteristics of hydatidiform moles: analysis of a prospective series with p57 immunohistochemistry and molecular genotyping.

Immunohistochemical analysis of cyclin-dependent kinase inhibitor 1C (CDKN1C, p57, Kip2) expression and molecular genotyping accurately classify hydatidiform moles into complete and partial types and distinguish these from non-molar specimens. Characteristics of a prospective series of all potentially molar specimens encountered in a large gynecologic pathology practice are summarized. Initially, all specimens were subjected to both analyses; this was later modified to triage cases for genotyping based on p57 results: p57-negative cases diagnosed as complete hydatidiform moles without genotyping; all p57-positive cases genotyped. Of the 678 cases, 645 were definitively classified as complete hydatidiform mole (201), partial hydatidiform mole (158), non-molar (272), and androgenetic/biparental mosaic (14); 33 were unsatisfactory, complex, or problematic. Of the 201 complete hydatidiform moles, 104 were p57-negative androgenetic and an additional 95 were p57-negative (no genotyping), 1 was p57-positive (retained maternal chromosome 11) androgenetic, and 1 was p57-non-reactive androgenetic; 90 (85%) of the 106 genotyped complete hydatidiform moles were monospermic and 16 were dispermic. Of the 158 partial hydatidiform moles, 155 were diandric triploid, with 154 p57-positive, 1 p57-negative (loss of maternal chromosome 11), and 1 p57-non-reactive; 3 were triandric tetraploid, with 2 p57-positive and 1 p57-negative (loss of maternal chromosome 11). Of 155 diandric triploid partial hydatidiform moles, 153 (99%) were dispermic and 2 were monospermic. Of the 272 non-molar specimens, 259 were p57-positive biparental diploid, 5 were p57-positive digynic triploid, 2 were p57-negative biparental diploid (no morphological features of biparental hydatidiform mole), and 6 were p57-non-reactive biparental diploid. Of the 14 androgenetic/biparental mosaics with discordant p57 expression, 6 were uniformly mosaic and 8 had a p57-negative androgenetic molar component. p57 expression is highly correlated with genotyping, serves as a reliable marker for diagnosis of complete hydatidiform moles, and identifies androgenetic cell lines in mosaic conceptions. Cases with aberrant and discordant p57 expression can be correctly classified by genotyping.

Science, Medicine, and Cytology: an educational program of the Diversity, Equity, and Inclusion Committee of the American Society of Cytopathology.

INTRODUCTION: As our field of pathology continues to grow, our trainee numbers are on the decline. To combat this trend, the ASC Diversity, Equity, and Inclusion Committee established the Science, Medicine, and Cytology SumMer Certificate program to improve exposure to pathology/cytopathology with a focus on diversity, equity, and inclusion. Herein, we report our findings of the first 2 years of the program. MATERIALS AND METHODS: An online course was developed targeting students who are underrepresented in medicine at the high school and college level. It consisted of several didactic sessions, presenting the common procedures involving cytopathologists and cytologists. Interviews with cytopathologists were also included. Participants were surveyed for demographic information and provided course evaluations. RESULTS: In the first year of the program (2021), 34 participants completed the program, which increased to 103 in 2022. In both years there was a diversity in participant demographic backgrounds; however, only a minority of participants self-identified as being underrepresented in medicine. A vast majority (>85%) of participants in both years were high school or college students. In 2021, 100% of participants stated that the program format was effective and 94% thought the content was appropriate for their level of education; in 2022 the results were similar. In 2021, 66% considered health care as a potential career; this value increased in 2022 to 83%. In 2021 and 2022, 31% and 38%, respectively, considered cytology as a career. CONCLUSIONS: Evaluations were excellent, generating interest in cytopathology. Barriers in reaching underrepresented minorities exist and additional work is needed. Expansion to a wider audience may increase outreach.

Comparison of Human Papillomavirus RNA In Situ Hybridization and p16 Immunostaining in Diagnostically Challenging High-Grade Squamous Intraepithelial Lesions in the Background of Atrophy.

CONTEXT.­: Human papillomavirus (HPV) in the postmenopausal age group is complex, with infected patients in this age group at increased risk of progressing to invasive disease and showing decreased clearance of the virus. Additionally, atrophic changes of the cervix can make histologic distinction of high-grade squamous intraepithelial lesions (HSILs) difficult. OBJECTIVE.­: To determine morphologic and ancillary testing characteristics of atrophy and HSIL in postmenopausal patients. DESIGN.­: Files of patients at least 65 years of age were examined, with 81 patients (109 cases [53 benign, 56 HSIL]) included in the study. Results of morphology, immunostaining (p16 and Ki-67), and HPV RNA in situ hybridization (ISH) were noted on all cases with available material. RESULTS.­: Atrophy was present in 96 of 109 cases (88%) overall. Coarse nuclear chromatin was noted in none of the benign cases, in 19 of 30 HSIL biopsies (63%), and in 24 of 26 HSIL excisions (92%). All benign cases were negative for p16 and ISH. In the HSIL cases, 45 of 53 (89%) were positive for p16, and of cases with sufficient tissue for ISH, 44 of 45 (98%) were positive. Of the ISH/p16 discordant cases (n = 7), most were p16 negative/ISH positive (6 of 7; 86%), whereas 1 of 7 (14%) was p16 positive and ISH negative. A majority of HSIL cases showed near-full-thickness elevation of Ki-67 (45 of 54; 83%), whereas mitotic figures were less elevated. CONCLUSIONS.­: In postmenopausal patients with HSIL, mitotic activity is not reliably elevated, but Ki-67 is consistently high. ISH is a more direct method of HPV detection and should be considered in cases where morphology and immunolabeling show discordance.

The role of HER2 as a therapeutic biomarker in gynaecological malignancy: potential for use beyond uterine serous carcinoma.

Human epidermal growth factor receptor 2 (HER2) is a prognostic biomarker and therapeutic target in carcinomas of the breast, stomach and colon. In 2018, clinical trial data confirmed the prognostic and predictive role of HER2 in uterine serous carcinoma, with a demonstrated survival benefit from combined chemotherapy and anti-HER2 targeted therapy in patients with advanced or recurrent disease. Approximately one-third of uterine serous carcinomas demonstrate HER2 protein overexpression and/or gene amplification and HER2 immunohistochemistry, supplemented by in situ hybridisation in equivocal cases, is fast becoming a reflex ancillary test at time of diagnosis. The potential role of HER2 in gynaecological tumours other than uterine serous carcinoma is yet to be firmly established. With the advent of personalised medicine, routine tumour sequencing and pursuit of targeted therapies, this is a field currently under active investigation. Emerging data suggest triaging endometrial carcinomas for HER2 analysis based on molecular classification may be superior to histotype-based testing, with copy-number high/p53 mutant tumours enriched for HER2 overexpression or amplification. Accordingly, many carcinosarcomas and a subset of clear cell and high-grade endometrioid carcinomas may be eligible for HER2 targeted therapy, although any clinical benefit in this context is currently undefined. For ovarian carcinomas, combined data support the role of HER2 as a prognostic biomarker, however its use as a therapeutic target is yet to be elucidated through clinical trials. In the cervix, reported rates of HER2 overexpression vary and are generally low, and currently there is insufficient evidence to justify routine HER2 testing in this context. Limited data suggest HER2 holds promise as a prognostic and predictive biomarker in vulvar Paget disease. Future clinical trials, with pathologist input to develop and refine site-specific scoring criteria, are required to establish what role HER2 might play more broadly in gynaecological cancer care.

Interobserver Agreement on the Interpretation of Programmed Death-ligand 1 (PD-L1) Combined Positive Score (CPS) Among Gynecologic Pathologists.

The anti-programmed cell death (PD-1) checkpoint inhibitor pembrolizumab is approved for the treatment of cervical carcinoma with a programmed cell death-ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1. We assessed interobserver agreement in cervical carcinoma PD-L1 CPS to identify whether it may affect patient selection for immunotherapeutic candidacy. Twenty-nine cervical carcinomas were stained for PD-L1 (Dako 22C3), and slides were interpreted by 5 subspecialty-trained gynecologic pathologists with experience reading PD-L1 immunohistochemistry. Expression was scored using CPS and read out as positive (≥1) or negative (<1); in positive cases, a final score was assigned (1 to 100). There was consensus agreement across all 5 pathologists for 90% (26/29) (Fleiss Kappa value for interobserver agreement: 0.799). The 3 cases with disagreement were composed of 2 squamous cell carcinomas and 1 small cell carcinoma. Of the 26 with unanimous agreement, 88% (23/26) were positive and 12% (3/26) were negative. All (16/16) pure squamous cell carcinomas with full consensus were interpreted as positive, whereas tumors with glandular components were commonly consensus negative (33%, 3/9); this difference was significant ( P =0.037). Disagreements were attributable to low CPS versus negative reads (2 cases) and difficulty discerning glandular involvement from pushing invasion (1 case). In summary, experienced gynecologic pathologists showed substantial interobserver agreement in the interpretation of PD-L1 CPS at the Food and Drug Administration-approved treatment threshold, with the majority of tumors being classified as positive. Pure squamous histology was strongly associated with a consensus-positive read, whereas a subset of tumors with glandular differentiation was negative by all readers. Disagreements occurred in tumors with low versus negative CPS values and in the setting of limited invasion.

Characteristics of Pelvic Cytology in Patients with Gynecologic Malignancies: Comparison of Pre and Post-Neoadjuvant Specimens.

INTRODUCTION: The presence of tumor cells in pelvic cytology (PC) specimens can portend a worse outcome for patients undergoing gynecologic surgery. Primary debulking surgery (PDS) was a mainstay for most of these tumors; however, recent advances have triaged selected patients to neoadjuvant chemotherapy (NACT) with interval debulking surgery (IDS). Reduction in tumor cellularity and histologic alterations has been noted in these cases; however, similar cytologic characterization has not been performed. MATERIALS AND METHODS: PC was searched to find those in NACT patients. Additional PDS were included as controls. Cases were scored for cellularity of malignant cells and background components were described, and when available, pretreatment and posttreatment specimens from the same patients were compared. RESULTS: In all, 19 specimens from 16 patients were found, 6 (32%) of which were paired PTS and IDS from the same patient. Only 6/19 (32%) were from IDS, the remainder PTS. A majority (15/19; 79%) of specimens were malignant; all negative cases were PTS. Few (4/16; 24%) were endometrial primaries; the remainder were pelvic high-grade serous carcinoma. No difference in tumor cell morphology or inflammatory component was noted between the 2 groups, though in 3/3 paired specimens from PDS and IDS, the cellularity of malignant cells decreased in the IDS specimens. DISCUSSION/CONCLUSION: No identifiable trend was noted regarding cellularity of specimens in the pre compared to the post-neoadjuvant setting. A trend toward reduced cellularity was noted in individual patients, but no alteration in background cells or tumor morphology was noted.

Variants of in situ carcinoma of the endometrium: Clear cell and gastrointestinal types, with a review of the literature.

Two precursor lesions are commonly associated with endometrial carcinoma. Atypical endometrial hyperplasia/endometrial intraepithelial neoplasia is a known precursor lesion of endometrial endometrioid carcinoma, while endometrial intraepithelial carcinoma, is a recognized precursor lesion of endometrial high-grade serous carcinoma. Other than these two recognized entities, other rare precursor lesions for endometrial carcinoma do exist, although reported cases are relatively few and not universally recognized. This therefore poses diagnostic challenges in clinical practice. Here, we describe a series of rare precursor lesions of the endometrium identified at our institution, including clear cell and gastrointestinal variants, their morphologic and immunohistochemical characteristics, and review current literature regarding these variants. The information provided may guide the proper diagnosis and ultimately lead to effective clinical management in every-day practice.