Indian Journal of Pathology and Microbiology

Massive edema of ovary masquerading as neoplasm in a preteen girl

ABSTRACT Massive ovarian oedema, though rare, frequently mimics an ovarian neoplasm, both clinically and radiologically. Here, we discuss the case of a 12-year-old girl who presented with intermittent pain in the lower abdomen for last one month associated with vomiting. A suspicion of germ cell neoplasm was raised on ultrasound despite mildly raised serum markers. Microscopy from left salpingo-ophrectomy specimen revealed marked oedema of ovarian stroma with preserved primordial follicles at the periphery only. This case highlights the importance of a high index of suspicion, clinically, radiologically and pathologically, especially in cases with only mildly raised serum markers to avoid unwarranted surgery and preserve hormonal function as well as fertility in some cases.

Ovarian-dedifferentiated endometrioid adenocarcinoma: A rare case report

ABSTRACT We reported a case of dedifferentiated ovarian carcinoma in a 51-year-old woman. The microscopic tumor consisted of well-differentiated endometrioid carcinoma and undifferentiated carcinoma. Undifferentiated carcinoma was characterized by high-grade nuclear features, mainly solid growth, vacuolar nuclei, frequent nuclear division, and necrosis. Undifferentiated carcinoma did not express epithelial immune markers; p53 was completely deficient in both components; the expression of MMR proteins was only deficient in low-grade endometrioid carcinoma, while it was preserved in undifferentiated carcinoma; SMARCB1/INI1 was diffused expression in both components; SOX2 was diffusely expressed in undifferentiated carcinoma, but not in well-differentiated components; SMARCA4/BRG1 was inactivated in undifferentiated components. These resulted in a poor prognosis.

Synchronous uterine serous carcinoma and ovarian sex cord stromal tumor (thecoma)–A rare first case report

Synchronous endometrial and ovarian carcinoma is a rare instance and it accounts for 50 to 70% of all synchronous female genital tract tumors. However, it is very rare to find synchronous endometrial carcinoma and ovarian sex cord-stromal tumor (thecoma). The present case is a 75-year-old woman with a complaint of post-menopausal vaginal bleeding. Radiologically, the magnetic resonance imaging (MRI) pelvis revealed altered signal intensity mass in the uterus. Frozen section and routine histopathological examination were done on radical hysterectomy. Microscopically, serous carcinoma involving uterine corpus and left Fallopian tube was identified along with the unusual finding of contralateral ovarian sex cord-stromal tumor (thecoma), which was confirmed on immunohistochemical examination. It is a very rare association and is first reported in the present study after a thorough search of the published literature. Their relationship based on a high level of estrogen produced by the hyperactive ovary is controversial as serous carcinomas are less hormone-dependent.

Clinicopathological observation of mature teratoma with malignant transformation, a single center retrospective study

To investigate the clinicopathological features of mature teratoma with malignant transformation. Retrospectively analysis of 1179 cases mature teratoma was done from August 1999 to December 2019 in Institution. 14 cases of mature teratoma with malignant transformation were discussed mainly for the pathological characteristics and clinical manifestations. 4 of them were less than 40 years old. All but one occurred in the ovaries, and the one was in the left anterior mediastinum which was the only male. The clinical manifestations of the patients were atypical. Imaging showed cystic solid mass. Surgery was performed. Polypoid mass, solid nodule and thickened area of cyst wall can be seen on the section of tumor. Pathological results show that there were 5 cases of squamous cell carcinoma, 3 cases of carcinoid, 2 cases of serous carcinoma and 2 cases of thyroid papillary carcinoma, 1 case of carcinosarcoma and 1 case of strumal carcinoid. Two cases of squamous cell carcinoma had pelvic and abdominal metastasis. Immunohistochemistry of case 14 showed that AE1/AE3, CD56, SYN, NSE, PSAP, CDX2 were positive in carcinoid. EMA and CK20 were positive in mucinous glands around carcinoid. Calretinin and inhibin were positive in the mesenchyme adjacent to intestinal mucinous gland. Teratoma with malignant transformation is a rare malignancy, although teratoma is a common germ cell tumor. And it's more common in patients over 40 years, especially those patients who were in menopause. Squamous cell carcinoma is the most common type and prone to metastasis. Strumal carcinoid was well-defined, but as an endocrine tumor, it may cause a series of digestive, respiratory or hormonal disorders. Therefore, the mature teratomas should be removed in time after detection.

Cholesterolosis of ovary associated with benign serous cystadenoma

Melanosis tubae et ovarii

Melanosis is a rare benign entity defined by the deposition of brownish-black pigment in a wide variety of organs especially the gastrointestinal tract, peritoneum, fallopian tubes and ovaries. Melanosis of the fallopian tube is widely known as pigmentosis tubae. Literature has mentioned ovarian teratomas and serous cystadenomas to be associated with the ovarian and peritoneal melanosis. We report five such cases of tubo-ovarian melanosis. The cases include mature teratoma and serous cystadenoma as well as melanosis of the fallopian tubes with otherwise normal ovarian histology. The importance of recognising this entity lies in its differential diagnosis.

Inverted condyloma of the cervix: A rare mimicker of a high-grade cervical lesion

Cervical rhabdomyoma a rare entity: Case report with review of literature

Genital rhabdomyomas are extremely rare benign tumors of skeletal muscle origin, majority of them being reported in vaginal location. Extensive literature search revealed only three such cases reported in cervix. We hereby report fourth such case of cervical rhabdomyoma in a 35-years-old female patient. The diagnosis was confirmed by histomorphology with desmin and myoD1 positivity on immunohistochemistry. Due to paucity of cases no definite treatment guidelines are available. Differentiation from identical and more common malignant counterpart which is rhabdomyosarcoma is essential to avoid unnecessary aggressive therapy.

Expression of alpha-methylacyl-CoA racemase in vaginal gastric-type adenocarcinoma and uterine clear cell carcinoma

Alpha-methylacyl-coenzyme A racemase (AMACR, P504S) is a commonly used marker in immunohistochemical diagnosis of prostate cancer. Recent studies identified P504S markers of the clear cell histotype in the ovary and/or endometrium. Gastric-type adenocarcinoma (GAS) is difficult to diagnose histologically, particularly when there is crossover with clear cell carcinoma (CCC). However, the significance of P504S for differentially diagnosing GAS and CCC is unclear. To evaluate P504S as a potential diagnostic marker of GAS and CCC. We analyzed P504S expression in 48 cervical carcinomas (32 GAS and 16 CCC), as well as the expression of other markers including hepatocyte nuclear factor-1 beta (HNF-1β) and NapsinA. The expression differences of HNF-1β, NapsinA, and P504S in GAS and CCC were detected by immunohistochemistry. Immunohistochemical histoscores based on the intensity and extent of staining were calculated. The positive rates of HNF-1β in GAS and CCC were 90.32% and 75%, respectively. (χ2 = 2.251, P = 0.663). The positive rates of NapsinA in GAS and CCC were 19.36% and 81.25%, respectively. (χ2 = 47.332, P < 0.01). The positive rates of P504S in GAS and CCC were 16.13% and 81.25%, respectively. (χ2 = 41.420, P < 0.01). HNF-1β was frequently expressed in GAS and CCC, while NapsinA and P504S were frequently expressed in CCC, and reduced or lost in GAS. NapsinA and P504S can be used to differentiate between GAS and CCC.

A giant vulval fibroepithelial polyp: A case report and literature review

ABSTRACT Fibroepithelial polyps typically present as small and limited growths. Accordingly, giant fibroepithelial polyps arising from the female genital tract are extremely rare, and only a few cases have been reported. This report describes a case of a 54-year-old woman with a slowly growing right vulval mass presenting as a polyp. The patient underwent surgical excision, and histopathological examination revealed the diagnosis of a giant fibroepithelial polyp. Through an exhaustive review of the literature published over the past 10 years, we learn that fibroepithelial polyps arising from the female genital tract are rarely seen but only recently have been characterized. Due to its clinical and histologic overlapping characteristics with other external genital tumors, the differential diagnosis and correct management of fibroepithelial polyp become particularly important.

Vulvar dermatofibrosarcoma protuberans masquerading as angiomyxoma: A case report and review of 85 cases

ABSTRACT Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous mesenchymal locally aggressive sarcoma with high recurrence. We report a case of recurrent vulvar DFSP, and a literature review was performed with a PubMed search using the terms “Dermatofibrosarcoma protuberans” and “vulva.” Total 85 cases with vulvar DFSP were analyzed for their clinicopathological features among fibrosarcomatous DFSP (FS-DFSP) and non-FS-DFSP. Listless asymptomatic growth had resulted in delay in presentation of 2.3 years. Tumor size was significantly more in FS-DFSP ( P 0.005). Higher mitotic rate is found to have strong association with FS-DFSP ( P 0.0001). FS-DFSP has more recurrences compared with non-FS-DFSP ( P 0.0001). DFSP with FS transformation was more aggressive as there was significant difference in metastasis ( P 0.073, OR 0.18) and mortality ( P 0.210, OR 0.19). To investigate the risk of outcome, 59 cases were included following the exclusion of &lt;6 months follow-up. Age (&gt;50 years) was found to be a risk for metastasis and death from the disease. Tumor size (&gt;5 cm) and mitosis (≥5/10-HPF among non-FS-DFSP) were found to be the risk for the LR. Different histological diagnosis was made initially in 32%, and local excision was performed without margins in 65% of vulvar DFSP because of initial incorrect diagnosis. Therefore, pre-treatment biopsy or re-biopsy should be performed with immunohistochemistry for definitive diagnosis to exclude histologic mimics. The optimal treatment is wide local excision with 3-cm margin or with margin assessment for both primary and recurrent DFSP. As most recurrences occur within the first three years of wide excision in DFSP, regular follow-up visits are advocated.

Benign phyllodes tumor of the vulva

An unreported case of intraoperative frozen section diagnosis of a sclerosing stromal tumor of the ovary- A report with a review

ABSTRACT Sclerosing stromal tumor is a benign sex cord-stromal tumor, that commonly occurs in the second and third decades of age. Intraoperative diagnosis of this entity poses a great challenge because of the rare occurrence and can mimic malignant lesions. A 15-year-old female presented with a right ovarian mass. Serum markers were within normal limits. The radiological evaluation showed a large heterogeneously enhancing solid cystic abdominopelvic mass of size 16 × 14 × 9 cm with non-visualization of both ovaries separately and a few areas of calcification with mild ascites. An open cystectomy was performed. A part of the cyst wall was sent for an intraoperative frozen section. It was reported as sclerosing stromal tumor, and the post-operative specimen also confirmed the same. Areas of calcification and ossification were also identified as additional findings. We reported this case because of the uncommon occurrence, highlighting additional histological features, and also did a literature review, especially focussing on the intra-operative diagnosis.

To study the expression of estrogen, progesterone receptor and p53 immunohistochemistry markers in subtyping endometrial carcinoma

ABSTRACT Background: Endometrial cancer is one of the most commonly diagnosed cancers in women worldwide. Aim and Objectives: To study the expression of estrogen receptor (ER), progesterone receptor (PR) and p53 immunohistochemistry (IHC) markers in subtyping endometrial carcinoma. Materials and Methods: A total of 100 cases of carcinoma endometrium submitted during January 2016 to October 2018 were included in our study. The ER, PR and p53 expressions were scored as per the adopted scoring system. Agreement between ER, PR and p53 IHC expression and the consensus HE diagnosis, FIGO grading and tumour staging were assessed using Chi square tests. Results: There was a statistical association between ER, PR and p53 status and tumour histologic type with a P value &lt; 0.01. There was no statistical significance observed between ER and PR expressions and different FIGO grades. Statistical significance (P = 0.036) between p53 and different FIGO grades seen. No statistical significance was observed between ER, PR and p53 expressions and different tumour stages and tumour invasiveness. There was a statistical association between ER and PR status and lymph node metastasis. p53 did not show a statistical significance. Conclusion: Combination of ER, PR and p53 IHC markers can be used to distinguish type 1 and type 2 endometrial cancers. PR expression is more specific than ER in endometrioid carcinomas. p53 expression is more specific in serous carcinoma, however, p53 IHC alone cannot be used to distinguish different grades of endometrioid carcinomas as there is variability of staining in endometrioid carcinomas.

Assessment of endometrial carcinoma on biopsy as a predictor of final surgical pathology: Are we doing it right? A completed audit cycle and recommendations

ABSTRACT Background: Typing and grading of endometrial carcinomas (ECs) on small biopsy specimens is crucial to determine the need for full surgical staging. Histological subtype and grade are key factors available for risk stratification before surgery. However, this can be diagnostically challenging on small biopsy specimens, especially when morphologic features are subtle or overlapping. Aims: The aims of this audit were to assess concordance of endometrial carcinomas on biopsy specimens with hysterectomy specimens and to determine if the immunohistochemistry (IHC) panel being used in our practice was adequately subtyping ECs. Settings and Design: The audit was approved by the Clinical Effectiveness Team of the Royal College of Pathologists (UK) as meeting all the criteria and standards set out by the College. Materials and Methods: Biopsies from 67 cases of EC were compared for histological subtype and grade of endometrioid carcinoma with resection specimens. A re-audit was carried out on 59 cases after implementation of changes recommended by the initial audit. Results: Two of 35 (6%) tumours defined as G1 on biopsy were upgraded (to G2) on final pathology, as was one of 7 (14%) G2 tumours (to G3). One of these cases had solid areas just amounting to more than 6% on resection. In the second case, a comment was made that assessment had been difficult as the specimen was suboptimally fixed, but nuclei appeared atypical. Of seven G2 biopsies, one case was upgraded to grade 3 on final pathology based on proportion of solid areas. Our data show lower rates of discordance as compared to previous studies and on re-audit, the concordance between endometrioid and nonendometrioid serous carcinoma improved with the addition of immunohistochemistry (IHC) for Phosphatase and tensin homolog (PTEN) to biopsies. Conclusions: PTEN IHC can complement other stains and aid in the distinction of grade 3 endometrioid carcinoma from serous carcinoma on endometrial biopsies.

CK7+/CK20+/CDX2+ mucinous carcinoma, arising in a mature cystic teratoma of ovary, presenting with disseminated metastasis and pseudomyxoma peritonei

ABSTRACT Mucinous carcinomas arising within an ovarian dermoid tumor are rare. Most of the cases reported in the literature show morphological features resembling an appendiceal mucinous neoplasm. They exhibit CK7-/CK20+ immunophenotype similar to carcinomas of the lower gastrointestinal tract. In this report, we have described a case of a well-differentiated mucinous carcinoma arising within a mature cystic teratoma. The mucinous carcinoma showed a spectrum of morphological patterns, including cystadenoma-like areas, proliferative/borderline areas, villous adenoma-like areas, and areas of invasive carcinoma. In addition, our case showed some unusual findings, namely, diffuse CK7 positivity, associated pseudomyxoma peritonei, and metastasis to lungs. These features were not demonstrated in any of the previously reported cases. Our case shows that the teratomatous mucinous neoplasm of the ovary may show CK7+/CK20+/CDX2 + immunoprofile making it immunohistochemically indistinguishable from a primary ovarian mucinous neoplasm or a metastatic mucinous carcinoma of the lower gastrointestinal tract.

Invasive micropapillary carcinoma of the breast and bilateral ovarian mature cystic teratoma with benign Brenner tumor in a postmenopausal woman – An uncommon occurrence

ABSTRACT The synchronous occurrence of bilateral ovarian tumors and breast malignancy often raise the suspicion of a Krukenberg tumor or a hereditary breast and ovarian cancer syndrome, both of which are uncommon in clinical practice. A 58-years-old postmenopausal woman had a right breast lump and was diagnosed as infiltrating duct carcinoma, no special type, and incidentally detected bilateral adnexal mass with the clinical suspicion of Krukenberg tumor. However, following the radical surgical excision of the right breast and bilateral ovaries, the right breast showed invasive micropapillary carcinoma (IMPC) while the ovaries showed mature cystic teratoma (MCT) with benign Brenner tumor. IMPC of the breast along with bilateral ovarian MCT with benign Brenner tumor is an unusual clinical occurrence in a postmenopausal female and thus worthy of documentation. It should be categorized as a non-hereditary synchronous tumor. The histomorphology augmented by immunohistochemistry and appropriate clinical context is pivotal in rendering a correct diagnosis.

Therapy-related acute myeloid leukemia with CBFB/MYH11 in a patient with ovarian cancer after exposure to chemotherapy

ABSTRACT In patients with acute myeloid leukemia (AML), about 25%–35% of patients have a history of other hematological diseases, 10% of patients have a history of malignant tumors in other systems and have received cytotoxic treatment including chemotherapy and/or radiation, and the disease is categorized as therapy-related acute myeloid leukemia (t-AML) according to the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues. Two subsets of t-AML are generally recognized based on the nature of prior treatments and the characteristics of the disease. The most common type occurs after exposure to alkylating agents and/or radiation, with a latent period of 5 to 10 years. The less common type occurs after treatment with agents targeting topoisomerase II and has a shorter latent period of 1 to 5 years. The majority of these cases are associated with balanced recurrent chromosomal translocations frequently involving MLL at 11q23, RUNX1 at 21q22, or CBFB at 16q22 and morphologically resemble the features of de novo AML associated with these translocations. Here, we describe a rare case of a 48-year-old female with ovarian cancer who developed AML with CBFB/MYH11 fusion, less than two years after exposure to paclitaxel and carboplatin chemotherapy.

Neuroendocrine carcinoma of ovary: Hitherto rare entity in primary ovarian tumors

ABSTRACT Neuroendocrine neoplasms (NEN) of the female genital tract are extremely uncommon. These tumors can be broadly divided into well differentiated (carcinoid) and poorly differentiated NEN (small cell and large cell carcinomas). Occurrence of neuroendocrine carcinomas (NECs) in ovary has rarely been reported. These high-grade malignant tumors have a fulminant clinical course with a short period of survival, even when diagnosed at an early stage. We hereby report two cases of primary neuroendocrine carcinoma of the ovary.

Immature duodenal teratoma: Problems with occurrence of a common tumor at a rare site

Diagnostic, prognostic, and predictive importance of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and CA125 in endometrial hyperplasia and carcinoma

ABSTRACT Background: Inflammation has an important role in the progression of endometrial carcinoma. Aims: The aim of this study is to find the association between neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and CA125 in endometrial hyperplasia and endometrial carcinoma. The study also focuses on the association of CA125, NLR, and PLR with histopathological parameters in endometrial carcinoma that are of prognostic importance. Materials and Methods: This is a prospective cross-sectional study on 57 biopsy-proven cases of endometrial hyperplasia and carcinoma conducted over a period of two years. The NLR, PLR, and CA125 were calculated and recorded in all the 57 cases. Results: The 57 cases were divided into three groups: endometrial hyperplasia without atypia group which included 36 cases, endometrial atypical hyperplasia group which included 10 cases, and the endometrial carcinoma group which included 11 cases. Comparison was done between the groups, and parity, NLR, PLR, and CA125 were found to be significant, but patient age and postmenopausal status were not significant. NLR, PLR, and CA125 were found to increase with higher grade, pT-stage, and nodal stage for the endometrial carcinoma cases. Conclusion: NLR, PLR, and CA125 were marginally increased or normal in the case of endometrial hyperplasia without atypia and endometrial atypical hyperplasia, while they were significantly increased in endometrial carcinoma, and also correlated with an increase in grade, pT-stage, and nodal stage. Hence, these can be considered for additional screening as diagnostic, prognostic, and predictive markers in case of abnormal uterine bleeding with endometrial pathology.

Uterine collision tumor of endometrial stromal sarcoma and endometrioid adenocarcinoma

Collision tumors are characterized by occurrence of two or more histologically distinct tumor types at the same anatomic site. Collision tumors have been reported in various organs, such as esophagus, stomach, colon, kidney, lung, skin, thyroid, breast, ovary and uterus. Uterine collision tumors of epithelial and mesenchymal origin are rare and often underrecognized. We report a rare concurrent occurrence of endometrial stromal sarcoma and endometrioid adenocarcinoma in a 65-year-old female. It is important to differentiate collision tumors from carcinosarcoma due to impact on clinical management and prognosis. Extensive gross sampling and careful morphological examination aided by immunohistochemical studies is necessary for the diagnosis of this rare entity. This case report aims to increase the awareness of this rare pathological entity with discussion on the management issue based on review of literature. This is the first case in Indian literature to the best of our knowledge.

Angioleiomyoma of the uterus presenting as an endometrial polyp: An uncommon occurrence of two cases with a literature review

ABSTRACT Angioleiomyoma is a benign neoplasm that arises from vascular smooth muscle cells. Angioleiomyoma of the endometrium is very uncommon. The differential diagnoses of this entity are myopericytoma, angiomyofibroblastoma, endometrial stromal tumor, and perivascular epithelioid cell tumor. 31-year-old and 45-year-old patients presented with heavy menstrual bleeding, lower abdomen pain, and dysmenorrhea. Perspeculum and radiological investigations showed an endometrial polyp. They underwent diagnostic hysteroscopy, polypectomy, and endometrial biopsy. Polypectomy specimens of both cases revealed polypoidal lesions lined by the endometrium. The core of the polyp was arranged in long intersecting bundles of spindle cells and interconnecting anastomotic patterns with many intervening thick-walled blood vessels. These spindle cells have oval and cigar-shaped nuclei, fine chromatin, and a moderate amount of eosinophilic cytoplasm, resembling smooth muscle cells. These smooth muscle cells of the vessel wall were merging with the adjacent walls of the blood vessel. There was no nuclear atypia or necrosis. The mitotic rate was 0–1/10 HPF. Focal areas of hyalinization and adipocytic components were noted in one case. The endometrial glands did not show intraepithelial or invasive neoplasia. On immunohistochemistry (IHC), these spindle cells were diffuse and strongly immunopositive for SMA and Desmin. CD34 highlighted the endothelial lining of the prominent thick-walled blood vessels. By correlating with histomorphology and IHC positivity, a diagnosis of angioleiomyomatous polyp of endometrium was rendered. We report two uncommon cases of angioleiomyoma of the endometrium and discuss the differential diagnosis and literature review.

High-grade endometrial stromal sarcoma displaying immunohistochemical expression of BCOR—A report of two cases of a novel tumor entity

ABSTRACT Several defining molecular alterations have recently been identified underlying high-grade endometrial stromal sarcomas, such as YWHAE: NUTM2A/B fusions, ZC3H7B: BCOR fusions, and BCOR internal tandem duplication (ITD). BCOR is a useful immunohistochemical marker for identifying these tumors. A 37-year-old lady was presented with a 10-cm-sized tumor in the pouch of Douglas, involving the vaginal vault, bilateral adnexa, and peritoneum. A 53-year-old lady with a prior hysterectomy was presented with a 12-cm-sized tumor in the vault with abdominal deposits. Histopathological examination of both tumors revealed atypical cells comprising oval to spindle-shaped nuclei, a variable amount of myxoid stroma, and mitotic figures exceeding 10/10 high power fields. Immunohistochemically, the former tumor was diffusely positive for CD10, and the second tumor displayed patchy staining. Both tumors were positive for BCOR. Estrogen receptor (ER) showed variable staining in both tumors. By fluorescence in-situ hybridization (FISH), both tumors lacked YWHAE gene rearrangement. Both tumors had an aggressive clinical course, including extensive involvement This constitutes the first report of BCOR-positive high-grade sarcomas involving the female genital tract from our subcontinent. BCOR is a useful immunostain for identifying these relatively aggressive tumors. The differential diagnoses and the prognosis of these ultra-rare tumors are discussed herewith.

Endometrial blood vessel morphometry in patients presenting with abnormal uterine bleeding

Background: Abnormal uterine bleeding (AUB) is one of the most common problems encountered in gynecological practice. Various benign and malignant disorders of the endometrial tissue show vascular changes such as congestion, dilatation, and vessel wall irregularities. Aim: To evaluate the vascular morphometry of the endometrial tissue in AUB. Materials and Methods: A descriptive cross-sectional study of the endometrial tissue in patients presented with AUB was undertaken for vascular morphometric analysis. Histopathological processing of the endometrial tissue samples was done as per the standard format, and the slides were evaluated for vascular morphometry. Results: Out of 150 cases of endometrial tissue in patients presented with AUB, 80 cases were reported as proliferative phase, 41 as secretory phase, 15 as disordered proliferative endometrium, 6 as atrophic phase endometrium, and 4 each of endometrial hyperplasia without atypia and endometrial carcinoma. An average number of endometrial blood vessels and large-sized blood vessels were more in endometrial carcinoma and endometrial hyperplasia without atypia as compared to proliferative phase, secretory phase, atrophic endometrium, and disordered proliferative endometrium. Vessel shape irregularities and vascular congestion were observed in all the cases of atrophic endometrium, endometrial carcinoma, and endometrial hyperplasia without atypia. Endometrial carcinoma showed severe dilatation of the endometrial blood vessels. Conclusion: Vascular morphometry changes were noted in endometrial hyperplasia, endometrial carcinoma, disordered proliferative endometrium, and atrophic phase endometrium. These findings suggest that studies or trials related to anti-angiogenic therapy may help to plan anti-angiogenic therapy in patients with AUB.

Tumor budding is a valuable prognostic parameter in endometrial carcinomas

Background: Tumor budding (TB) is a morphological finding believed to play an important role in determining the prognosis in many cancers. Aim: Our aim is to evaluate the prognostic importance of TB in endometrial carcinomas. Settings and Design: Two-hundred-eleven endometrial cancers were obtained from 2008 to 2015 that were comprised of those having undergone surgical staging with a hysterectomy and at least 5 years followed up. Material and Methods: All hematoxylin and eosin stained slides were reevaluated for the status of TB. Statistical Analysis: Nonparametric tests, the Kaplan–Meier method, the Log-rank test, and Cox proportional hazard regression were used. Results and Conclusion: TB was found to correlated with larger diameter (P = 0.000), nonendometrioid (P = 0.038), mixed cell types (P = 0.005), higher grade (P = 0.000), deeper invasion of the myometrium (P = 0.000), cervical stromal invasion (P = 0.000), advanced pT (P = 0.011), lymph node involvement (P = 0.000), lymphovascular invasion (P = 0.000), and advanced stage (P = 0.000). The presence of TB worsens the 5-year overall survival (OS) (P = 0.0001). In cases such as grade 1, pT1, or stage 1 endometrial carcinomas, the presence of TB decreases the OS rate (P = 0.00017, P = 0.0016, P &lt; 0.0001). Our result suggested that the presence of TB adversely affects the prognosis. It was concluded that TB could be a valuable prognostic parameter.

Significance of CD47 expression in endometrial carcinoma

Objectives: CD47 is a membrane protein that belongs to the immunoglobulin superfamily and regulates macrophage phagocytosis negatively. As CD47 expression at the cancer cell membrane would inhibit the phagocytic activity of immune cells, it is connected to an unfavorable prognosis in leukemia and malignancies of various solid organs. Materials and Methods: In this study, retrospectively evaluated 72 patients who had been diagnosed with endometrial carcinoma at Pathology Department and had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH + BSO) and/or lymphadenectomy. CD47 expression was evaluated in tumorous and nontumor areas in all patients considering cytoplasmic and membranous brown staining in cells. The proportion of expression was evaluated as well as the intensity and an “h score” was obtained. This score was compared with known prognostic parameters. Results: CD47 expressions showed a statistically significant correlation with tumor grade (P &lt; 0.05); however, no significant relationship was observed with myometrial invasion depth and lymph vascular invasion status (P = 0.923 and P = 0.754, respectively). Conclusions: As with other tumors, anti-CD47 antibody may be an alternative treatment option in patients with high-grade endometrial carcinoma.

The extent of cyclin D1 expression in endometrial pathologies and relevance of cyclin D1 with the clinicopathological features of endometrioid endometrial carcinoma

Cyclin D1, a member of the cyclin protein family, is instrumental in the cell cycle due to its influence on the progression from G1 to the S phase. Its overexpression causes reduced doubling time and is also associated with clonogenic growth. The purpose of the present study was to assess cyclin D1 expression in patients with simple hyperplasia (SH), endometrial intraepithelial neoplasia (EIN) and endometrioid endometrial carcinoma, and to evaluate whether there was an association between cyclin D1 expression and the clinicopathological features of endometrioid endometrial carcinoma. Retrospective data were available for 193 patients (30 SH, 40 EIN, and 123 endometrioid endometrial carcinoma cases). To detect cyclin D1 expression, immunohistochemistry staining was performed with tissue microarrays. The percentage of cases with positive cyclin D1 staining were 30%, 60% and 78%, for SH, EIN and endometrioid endometrial carcinoma, respectively (P < 0.001). Carcinomas with higher nuclear grade, histological grade, and FIGO grade displayed higher mean cyclin D1 expression compared to lower grade carcinomas. In addition, patients with lymphovascular invasion (P = 0.006), myometrial invasion (P < 0.001) and lymph node invasion (P < 0.001) had higher mean cyclin D1 expression compared to those without invasion. There was a significant correlation between cyclin D1 expression and clinicopathological features of endometrioid endometrial carcinoma including tumor grade, FIGO grade, lymphovascular invasion, lymph node invasion and myometrial invasion (P < 0.05 for each). Cyclin D1 expression is significantly higher in patients with endometrioid endometrial carcinoma compared to that of the SH and EIN. The extent of cyclin D1 expression is strongly correlated with nuclear and histological grade, myometrial invasion, lymphovascular invasion and lymph node invasion in patients with endometrioid endometrial carcinoma. These findings contribute in several ways to our understanding of cyclin D1 expression and provide a basis for future research on this topic.

Can TROP2 be used as a prognostic marker in endometrioid endometrial carcinoma?

Endometrioid-type endometrial carcinoma is the most common malignancy of the female genital tract in developed countries. The prognosis greatly depends on the grade and stage of the disease. In some patients, the disease recurs in a short time after the surgical/medical therapy. Hence, it is important to predict the patients who will have worse prognosis at the beginning, to choose the appropriate treatment; resuming the search of new prognostic markers. Therefore, our study aimed to detect trophoblast cell surface antigen 2 (TROP2) as a new prognostic marker. The patients who underwent a hysterectomy and diagnosed with endometrioid-type endometrial carcinoma were evaluated retrospectively and TROP2 immunostain was performed to their tumoral slides. We evaluated TROP2 expressions in 102 patients immunohistochemically who underwent hysterectomy with the diagnosis of endometrioid-type endometrial carcinoma histopathologically and correlated them with the other generally accepted prognostic parameters. The Kolmogorov-Smirnov test and Q-Q plot test were used to verify the normality of the distribution of continuous variables. The Chi-square/Fisher's exact tests were used for categorical variables. Analyses were performed with SPSS Statistics for Windows, Version 20. High overexpression of TROP2 was seen in larger, higher-grade, deeper-invasive tumors, tumors with vascular invasion, and pelvic-lymph-node metastasis. These results were statistically significant (P ≤ 0.05). Overexpression of TROP2 in endometrioid-type endometrial carcinoma seems to be a poor prognostic factor; it may be useful in determining the biologically more aggressive tumors before the treatment. This early determination is very important to choose the appropriate surgery, adjuvant-treatments, and follow-up.

Endometrial glandular dysplasia: A finding not to be missed

Uterine tumor resembling ovarian sex cord tumor: A series of six cases displaying varied histopathological patterns and clinical profiles

Uterine tumors resembling ovarian sex cord tumor (UTROSCT) are a unique group of neoplasms with diverse morphology and immunophenotypic characteristics, coexpressing sex cord, epithelial, and smooth-muscle markers. To date, less than 100 cases have been reported and there is paucity of data concerning their clinical behavior. All cases of uterine body tumors diagnosed over a period of two and a half years (2016-2018) were retrieved. Histopathological features were reviewed and extended panel of immunohistochemistry was performed to identify cases of UTROSCTs. Six cases of UTROSCTs were identified with a median age of 46.5 years. Four of them presented with menorrhagia, while two with postmenopausal bleeding including one with a history of carcinoma breast. Three of these cases were initially misdiagnosed as endometrial stromal sarcoma and adenocarcinomas. They all underwent hysterectomy with bilateral salpingo-oophorectomy. It is considered a tumor with low malignant potential; however, one out of six cases (16.7%) in our study showed metastasis, within 1 year of diagnosis. It is important to recognize this entity as it mimics a wide range of both benign and malignant tumors. Molecular pathogenesis and exact management protocols remain elusive due to rarity,hence, multi-institutional studies are warranted.

A report of two cases of dedifferentiated endometrioid carcinoma: A newly described underrecognized tumor of poor prognosis

Dedifferentiated endometrioid carcinoma or dedifferentiated endometrioid adenocarcinoma (DEAC) is defined by the presence of undifferentiated carcinoma with endometrioid carcinoma. Undifferentiated component can be misinterpreted as solid component of high-grade endometrioid carcinoma or sarcomatous component of malignant mixed mullerian tumor. We present two cases of DEAC. Two postmenopausal women underwent hysterectomy for vaginal bleeding. Microscopically, sections from the endometrial tumors showed a biphasic growth consisting of an undifferentiated component and a glandular component with sharp transition between the two components. The undifferentiated component showed focal positivity for cytokeratin and vimentin, while glandular component was diffusely positive for cytokeratin and negative for vimentin expression.

Recent advances in gynecologic oncopathology

Fallopian tube papilloma

Invasive stratified mucin-producing carcinoma of the cervix: A case report and review of the literature

ABSTRACT Invasive stratified mucin-producing carcinoma (ISMC) is a rare, recently described subtype of HPV-associated cervical adenocarcinoma. It shows varied morphological patterns, making it difficult to diagnose, especially the mixed forms. A 57-year-old female, P7L7, presented with postmenopausal bleeding for the past five months. On per-vaginal examination, a friable cervical growth was noted. Microscopic examination of the cervical biopsy showed an invasive tumor composed of nests of stratified columnar cells with peripheral palisading and a variable amount of (alcian blue-positive) intracytoplasmic mucin. Another component of the tumor showed sheets and nests of undifferentiated tumor cells. IHC on both components showed diffuse positivity for P16, PAX8, and keratin 7. Based on these findings, a diagnosis of ISMC was made. Awareness of the morphological features and ancillary stain results of ISMC can aid in picking up the diagnosis in a small biopsy. These findings have prognostic value, as most cases of ISMC behave aggressively.

Carcinosarcoma of the cervix: Clinicopathological features of 17 tumors diagnosed at a Tertiary Cancer Referral Centre, India

ABSTRACT Background and Objectives: Carcinosarcoma of the uterine cervix is a rare entity. There are fewer reported series of this tumor. This study aims to evaluate clinico-pathological features of 17 carcinosarcomas primarily involving the cervix over a 14-year duration. Materials and Methods: This was a retrospective observational study conducted over the period of 14 years. Cases were critically evaluated and only tumors with the epicenter in the cervix were included. Results: Ten patients had cervical tumors; three had primary cervical masses, secondarily involving the lower uterine segment; 2 had cervicovaginal masses, and two patients had distinct tumors in the cervix and endometrium. Eight biopsies and 9 resections were evaluated. Patients with an age range of 44-68 years (median = 60), commonly presented with vaginal bleeding and whitish discharge and harbored a tumor with an average size ( n = 11) of 6.9 cm. The commonest gross appearance ( n = 9) was a polypoidal ulcerated tumor. Histopathologically, most common pattern included high-grade malignant glandular/epithelial and undifferentiated sarcomatous components. Two tumors morphologically revealed squamous differentiation; 4 exhibited chondromyxoid differentiation, while one each displayed rhabdomyoblastic, and osteosarcomatous differentiation. HPV-associated morphological features were seen in 13/17 tumors, in the carcinomatous components. Immunohistochemically, AE1/AE3 (12/12), EMA (7/7) and CK7 (3/3) highlighted epithelial components. Additionally, tumor cells expressed PAX8 (2/3), estrogen receptor (ER) (variable, 5/10), p53 (6/6, mutation-type), p16INK4a (diffuse, 4/5), SATB2 (1/1), GATA3 (1/1) and TTF1 (1/1) the latter 2 indicating mesonephric origin in one tumor. Desmin and myogenin positivity confirmed rhabdomyoblastic differentiation in one tumor. Therapeutically ( n = 14), 9 patients underwent surgery (TAH-BSO/radical hysterectomy, with adjuvant chemoradiotherapy (8/9) and 2 with neoadjuvant chemotherapy. Five (inoperable) underwent palliative chemoradiotherapy. During follow-up (7/17) (median = 8 months), one patient developed vault recurrence and two developed brain metastasis. Conclusions: All 7 patients in the study were alive with disease. Cervical carcinosarcoma is an uncommon tumor with a wide clinicopathological spectrum, invariably high-grade. Rare tumors exhibit a mesonephric type of differentiation. These tumors are associated with an aggressive clinical outcome.

Clinicopathological association of programmed death-ligand 1 (PD-L1) expression in uterine cervical carcinomas: A cross-sectional observational study

ABSTRACT Background: Programmed death ligand ( PD-L1 ) binds to its receptor PD-1 on T-cells and inhibits the immune response of T-lymphocytes. Cancer cells evade immune surveillance by upregulating PD-L1 expression, leading to tumor progression. Anti- PD-L1 immunotherapy has emerged as a new treatment modality in various solid carcinomas. Food and Drug Administration (FDA) has approved PD-1 / PD-L1 axis immunotherapy for immunohistochemically PD-L1 positive cervical cancer. In India, cervical cancer accounts for approximately 17% of all cancer deaths among women between 30 and 70 years. More than three-fourths of patients are diagnosed at an advanced stage. Materials and Methods: A hospital-based, cross-sectional prospective study was conducted over five years. 119 histologically proven cases of cervical carcinoma meeting the inclusion criteria were included in the study. Sections were stained with PD-L1 antibody clone SP263 as recommended on Ventana Benchmark XT. Results: Of 119 cases, PD-L1 expression was found in 42 cases (35%). Patients over 45 years (75.6%) had higher PD-L1 positivity compared to those under 45 years (24.4%). 31% of squamous cell carcinoma was PD-L1 positive compared to adenocarcinoma (29%). PD-L1 expression was more frequent in poorly differentiated carcinoma (37.5%). Conclusion: A significant proportion of cervical cancers expressed PD-L1 . Increased PD-L1 expression was seen with increasing age and poorly differentiated histological grade. Anti- PD-L1 immunotherapy can be an option in PD-L1 -positive cervical cancer. The findings of our study support the requirement for further investigation of anti- PD-L1 immunotherapy for the treatment of PD-L1 -positive cervical carcinomas.

An octad of fumarate hydratase-deficient uterine leiomyomas: Case series with review of literature from a single institution

ABSTRACT Background: Fumarate hydratase (FH)-deficient (FH-d) leiomyomas are included in the recent World Health Organization fascicle of the female genital tumors. These are known to be associated with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. The tumors can be diagnosed based on certain histopathological features, along with loss of immunohistochemical expression of FH immunostain in most tumors. Currently, there is no documentation on these tumors from our subcontinent. Aims: We analyzed eight FH-d leiomyomas diagnosed at our institute. Results: The most common presentation was vaginal bleeding (menorrhagia). Pelvic ultrasonogram revealed multiple fibroids in most patients except in two, who harbored a single fibroid. The size of these fibroids ranged from 3 to 19 cm. Five patients underwent myomectomies, while three underwent a total abdominal hysterectomy and bilateral salphino-ophorectomy. The most consistently observed histopathological features were hemangiopericytomatous vascular patterns, cytoplasmic globules, increased cellularity, distinct eosinophilic nucleoli, and cytological atypia (8/8, 100% tumors), followed by multinucleate giant cells and perivascular edema, seen in 62% and 50% tumors, respectively. Immunohistochemically, all tumors were positive for desmin, smooth muscle actin, and h-caldesmon and showed loss of FH immunostain, along with low Ki-67/MIB1. None of those patients had any renal or cutaneous manifestations. Conclusions: This constitutes the first such study from the Indian subcontinent and reinforces that although uterine leiomyomas constitute an integral component of the diagnosis of HLRCC syndrome, these occur in the absence of renal or cutaneous manifestations. FH-d uterine leiomyomas are more likely sporadic and could be a false alarm to raise the possibility of HLRCC with their exclusive presence.

Clear cell adenocarcinoma of the cervix and its mimickers - A series of 19 cases from a tertiary care referral centre in India

ABSTRACT Clear cell adenocarcinoma (CCAC) of cervix is a rare subtype of endocervical adenocarcinoma that accounts for 4% of all cervical adenocarcinoma with many morphological mimickers. Retrospectively study cases of cervical clear cell adenocarcinoma of the cervix. Clinical profile and pathological features of CCAC of the cervix diagnosed between 2018-2022 were retrospectively analyzed.The database of the Department of Pathology of our institute was systematically searched for patients diagnosed with clear cell adenocarcinoma of the cervix during 2018-2022.A total of 19 patients were studied with the mean age of patients being 53.72 years (range 25 -84 yrs,standard deviation-25.9) and median tumor size being 5.6cm. Lymph node metastasis was identified in 33.3% and distant metastasis were seen in 20% of the cases. Staging could not be done in 4 cases.FIGO staging of the cases included IB1(2 cases), IB2(2 cases), IIB (3 cases),IIIA (1 case)IIIB(4 cases),and IV(3 cases). On histopathological evaluation, heterogeneous architectural pattern comprising of tubulocystic, solid, and papillary patterns were seen in 13 cases (13/19,68.4%). Pure tubulocystic (3/19,15.7%), pure papillary (2/19,10.5%), and pure solid patterns (1/19,5.3%) were also identified. Tumor cells with clear cytoplasm ranged from 5% to 95%. Nuclear atypia was moderate to marked in all the cases (19/19,100%). Mitotic activity varied from 1/10hpf to 20-22/10hpf. By immunohistochemistry, tumor was positive for Napsin A in all the cases,p16INK4a was negative in majority of cases (15/19,78.9%) and ER was negative in 14 cases (14/19,73.7%) .p53 showed wild type staining except for one case . Clear cell adenocarcinoma being a rare subtype of cervical adenocarcinoma, needs to be differentiated from other Human Papilloma Virus(HPV) independent adenocarcinomas (gastric and mesonephric types) and benign entities such as endocervical glandular Arias-Stella reaction. Judicious use of a panel of immunostains is often helpful.

Breast mass - An uncommon clinical manifestation of ovarian carcinoma: A case report and brief literature review

Metastasis from non-mammary malignant neoplasms to the breast is rare and represents 0.2%-1.3% of all breast malignancies. Fine needle aspiration cytology (FNAC) is the first line of investigation for any breast lump and cyto-morphological appearance of primary breast malignancies is well documented. Occasionally metastasis to the breast may be the initial presentation and can masquerade clinically as primary breast malignancy. The present case describes the clinical and cytological challenges in an unusual case of ovarian carcinoma with initial presentation as breast mass, mimicking as inflammatory carcinoma. In cytology the breast lesion was initially misdiagnosed as primary breast carcinoma and subsequently diagnosed as metastatic ovarian carcinoma based on core needle biopsy findings, aberrant immuno-profile and clinical findings; thus making the complex case worthy of discussion.

Primary liposarcoma of the uterus with MDM2 negative

ABSTRACT Liposarcoma is one of the most common soft-tissue sarcomas that originates from adipose tissue. Primary uterine liposarcoma is extremely rare. With the MDM2, negative is even rarer. We report a 37-year-old woman presented with lower abdominal discomfort and increase in vaginal secretions for more than 2 months. The ultrasonography revealed a hypoechoic mass sized 81 × 73 × 67 mm in the right adnexal area. Histopathologically, the neoplasm was mainly composed of mature adipose tissue, a small number of scattered lipoblasts, and the spindle cell which with mild atypia. Immunohistochemistry showed that the tumor cells were positive for CDK4 but negative for MDM2, and FISH analysis showed no MDM2 amplification. The patient only underwent tumor excision and is currently doing well.

STRN-ALK rearranged malignant peritoneal mesothelioma—Presenting with bilateral extensive pelvic masses in a young woman

Malignant peritoneal mesothelioma (MPM) is an exceptionally rare tumor type. Although some somatic/germline genetic alterations including BAP1 loss have been identified in some cases, the molecular properties of MPMs are remained poorly understood. In recent years, anaplastic lymphoma kinase (ALK) gene rearrangement was revealed in a subset of (3.4%) MPMs. Low-grade serous carcinomas (LGSCs) are a rare subtype of ovarian carcinoma and have some morphologic and immunophenotypic overlapping features with MPMs and this may cause misdiagnosis in daily practice. Here, we report a case of 18-year-old women with STRN-ALK-rearranged MPM and no previous exposure to asbestos. This case was presented with bilateral pelvic masses and histologically was displaying pure papillary morphology with mild-to-moderate nuclear atypia, psammoma bodies, and diffuse PAX8 expression as LGSCs. With the detection of ALK alteration in some of the MPMs, a targeted treatment option has emerged for these unusual tumor types.

Hair within bony trabeculae in a mature cystic teratoma with mucinous adenocarcinoma of ovary

Neuroendocrine differentiation in a metachronous metastatic deposit in a case of mature growing ovarian teratoma: A rare occurrence

ABSTRACT Growing teratoma syndrome is a rare condition seen in non seminomatous germ cell tumor after completion of chemotherapy. Ectodermal, mesodermal and endodermal differentiation is commonly seen in mature teratoma. neuroendocrine differentiation in a metastatic deposit of mature teratoma is rarely reported. We are presenting a case of neuroendocrine differentiation in a long standing metastatic deposit of a mature teratoma.

Pediatric primary extra-ovarian Sertoli Leydig cell tumor of the retroperitoneum

Ovarian Sertoli Leydig cell tumors (SLCT) accounts for less than 0.5% of all ovarian malignancies. The incidence of primary extra-ovarian SLCT is extremely rare with reported cases occurring in young adult women till now. We report case of primary retroperitoneal extra-ovarian SLCT in a seven-year girl child without any hormonal manifestation. She presented with complaint of left side abdominal swelling associated with intermittent pain for a duration of six months. CT scan revealed a huge retroperitoneal space-occupying lesion abutting the dorsal vertebrae and present posterior to pancreas, spleen and left kidney. The tumor was diagnosed as extraovarian Sertoli Leydig cell tumor with intermediate differentiation on histopathology and immunohistochemistry.

Mature cystic teratoma of stomach in a 6-year-old child

Pregnancy luteoma associated with missed abortion clinically masquerading as ruptured ectopic pregnancy

Clear cell carcinoma arising in a seromucinous borderline tumor with co-existing endometriosis- Case report of a rare association

Florid histiocytic reaction to oxidized cellulose masquerading as ovarian malignancy: Report of two cases

Bioabsorbable hemostatic agents like oxidized regenerated cellulose (ORC) are widely used in surgical practice. Rarely, adverse events due to retained ORC may occur and can pose a diagnostic dilemma. The unique tissue response to ORC may be misdiagnosed as signet ring type of adenocarcinoma. This article aims to highlight this rare phenomenon. We report two such cases involving the ovaries. Both the patients presented with ovarian cysts and tubo-ovarian adhesions 1-2 years following surgery for benign ovarian pathology. The present biopsies were featured by sheets of large cells with abundant vacuolated cytoplasm and often small peripherally displaced nuclei having "signet ring" appearance. These cells were negative for pan-cytokeratin and strongly positive for CD68, indicating the histiocytic nature of the cells. It was confirmed that in both the patients, at the time of the initial surgeries, hemostasis was ensured by packing with ORC.

Malignant granulosa cell tumor of testis with metastasis to liver: Case report and review of literature

We report a case of testicular granulosa cell tumor of adult type in a 65-year-old male patient who has presented with hepatic metastasis. Although, this type of sex cord stromal tumor is relatively common in the ovaries, it is extremely unusual in the testis, and it probably represents the rarest type of testicular sex cord stromal tumor.

Evaluation of cell blocks from effusion specimens in Gynecologic Oncopathology: An experience of 220 cases, diagnosed at a Tertiary Cancer Referral Center

One of the common indications of ascitic fluid examination in gynecological oncopathology is the detection and classification of malignant cells, especially in cases of clinically suspicious tubo-ovarian masses. The present study was undertaken to assess and validate the diagnostic utility of cell blocks (CBs) and compare its results with the corresponding conventional smears, prepared from effusion samples. CBs were prepared by thromboplastin technique in 220 cases. In 208 cases, diagnostic concordance between results obtained from smears and corresponding CBs was evaluated. Various antibody markers were tested, as per individual case. The average age of patients was 52.2 years. Positive immunohistochemical (IHC) staining for various markers was observed in 182 cases (82.7%) The most frequently positive antibody marker was PAX8 (101/134), followed by p53 (85/92) [mutation type (either diffusely positive or completely negative)], WT1 (tumor cells) (80/112), calretinin (2/87) (diffuse), BerEP4 (21/49), CA125 (21/24), CK7 (31/39) and CK20 and CDX2, together (5/16). Various other IHC markers utilized, including their positive expression, were TTF1 (1/10), p40 (3/3), p63 (2/4), ER (21/29), HBME1 (1/7), GATA3 (1/4), and MIC2 (1/1). Complete diagnostic concordance between CBs and smears was observed in 170/208 cases (81.7%). There were 20 major discordances, 10 minor and 8 cases with sampling errors. IHC was useful in classifying 158/182 (86.8%) cases, including serous or Müllerian adenocarcinoma (n = 123), mostly high-grade (121); metastatic squamous carcinoma (3); gastrointestinal-type adenocarcinoma (8); pulmonary adenocarcinoma (1); breast adenocarcinoma (1); Ewing sarcoma (1); and mesothelioma (2). CBs are complementary to smears in the detection of gynecological malignancies, mostly high-grade serous adenocarcinomas. These provide an opportunity for testing several IHC markers, for a precise diagnosis, including in various uncommon case scenarios, associated with significant therapeutic implications.

Expression of p53 in epithelial ovarian tumors

Ovarian cancers remain the most lethal of all gynecological malignancies despite major developments in their treatment. To study the rate of expression and staining patterns of p53 in various histological types and grades of epithelial ovarian tumors (EOT). Sixty EOTs received in a tertiary care center were studied for gross, microscopy, and p53 immunohistochemistry (IHC) expression patterns. Parameters such as age, laterality of tumor, ascites, capsule rupture, tumor size, stage at presentation, metastasis, tumor grade, and number of mitosis were correlated. Of the sixty cases studied, 23 (38.3%) were malignant. Serous carcinomas were the largest group with 17 cases (74%) followed by mucinous with 4 cases (17%) and 2 clear cell carcinomas (9%). All benign and borderline EOT were p53 negative. 65.2% of the malignancies were p53 positive and all of them were serous malignancies. 15 out of 16 high-grade serous carcinomas were p53 positive (94%), while one case was negative (6%). 10 cases (63%) showed intense diffuse positivity of more than 60% of the nucleus, while 5 cases (31%) showed aberrant null staining <5% staining of the nucleus. All mucinous, clear cell carcinomas, and the only low-grade serous carcinoma in the study were p53 negative. P53 staining had positive correlations with variables like capsule rupture, ascites, laterality, and CA 125. The study highlights the different rates of expression and staining patterns of p53 and the need for correct interpretation of p53 IHC for the diagnosis of various EOT.

A rare case of therapy-associated acute megakaryoblastic leukemia

Subtype specific biomarkers associated with chemoresistance in epithelial ovarian cancer

In spite of the advent of many high throughput technologies, tumor tissue biomarkers are still the gold standard for diagnosis and prognosis of different malignancies including epithelial ovarian cancer (EOC). EOC is a heterogeneous disease comprised of five major subtypes which show distinct clinicopathological features and therapy response. Acquirement of chemoresistance toward therapy is a major challenge for successful treatment outcome in EOC patients. Several markers have been tested by immunohistochemical method to evaluate their prognostic merit to predict clinical outcome. However, a vast majority of such markers have been assessed for high-grade serous and clear cell ovarian cancer, among all subtypes of EOC. The current review elaborates upon those biomarkers that can potentially predict chemoresistance with subtype specificity.

High-grade glioma arising in immature ovarian teratoma

A clinicopathological study of granulosa cell tumors of the ovary: Can morphology predict prognosis?

Granulosa cell tumors (GCT) are low-grade malignant sex cord-stromal tumors (SCST) with late metastasis/recurrences and long disease-free periods. We performed a clinicopathological evaluation of GCT to ascertain features having prognostic impact. All cases of GCT of ovary from January 2006 to December 2018 were assessed for architectural patterns, nuclear grooves, and Call-Exner bodies. Each feature was graded on frequency of occurrence: not present (0)-very frequent (3). Anisonucleosis, necrosis, and inflammation were noted. Cases were grouped on mitotic count; =11 mitoses/10 HPF and Ki-67 index; =11% Ki-67. GCT formed 60.1% of SCST. Sixty cases' ages were in the range of 15-78 years (median 45). Clinical details were available in 37. Commonest presentation was abnormal uterine bleeding. Serum CA125 was raised in 16.1% and Inhibin in 58.8%. Seventy percent were in stage I. Disease recurrence was associated with higher stage (P = 0.007). The most frequent pattern was diffuse sheets (47%). Call-Exner bodies were absent in 22.2%. Grooves with score 1, 2, and 3 were seen in 35.8%, 23.5%, and 13.6%, respectively. Anisonucleosis was present in 26.7%, necrosis in 11.1%, and lympho-plasmacytic infiltrate in 43%. Out of total, 93.3% had <10 mitosis/10 HPF and 43.2% had recurrence, most with high Ki-67 (P = 0.064). Our study outlines histomorphological spectrum of GCT and emphasizes its frequent occurrence in lower stages with late recurrences. The presence of grooves may indicate granulosa-cell origin. Call-Exner bodies are not a necessity. Histomorphological features are not prognostically important. However, prognostic value of Ki-67 cannot be excluded. Limitation of the study was a small number of cases with follow-up.

From Editor's desk

Study of histopathology reports of loop electrosurgical excision procedure of cervical transformation zone and their correlation with preprocedural cervical biopsy and/or cytology: An audit

Loop electrosurgical procedure of the transformation zone of the cervix (LEEP) is the preferred method for many investigators for early detection and treatment of high grade intraepithelial neoplasia(HGCIN). Histopathology reports of LEEP should contain information about the diagnosis, presence or absence of neoplasia ( with its grade) and comment on excison margins. Our aim was to study LEEP reports for its contents and to see their correlation with preprocudure histology and/or cytology report. Between 2011 and 2017, 44 LEEP reports were archived and studied for their contents from our records. Slides were not reviewed. Mean age was 47.66 years (median 47 years). Forty two (( 95.45%) reports mentioned that all the tissue was examined. Deep cut examination was mentioned in 17/44 cases (38.64%). The concordance rate between LEEP and preprocudure histology and /or cytology for CIN II plus diagnosis is 65.9%. A strict definition is used. If, however, diagnoses between inflammation and CIN I, ASC-H and inflammation, and ASC-H and CIN I are considered non discordant, then the concordance rate rises to 72.7 %. The breakup of discordant cases is given. Literature shows wide range of concordance due to variable definitions and variety of reasons; possible reasons are discussed.

Diffuse peritoneal keratinization in endometrioid adenocarcinoma of ovary masquerading as metastatic deposit

ABSTRACT Diffuse keratinization of peritoneum can be seen in various neoplastic and non-neoplastic diseases. This exuberant keratinization exhorts a granulomatous response with multinucleated giant cell reaction. In malignancy of ovary or endometrium they mimic tumor deposits, sometimes leading to erroneous upstaging. We report one such case of ovarian endometroid adenocarcinoma in 42-year multigravida with multiple nodules over peritoneum and pelvic tissue. The case was intraoperatively staged as FIGO stage III due to nodularity over momentum and pelvic areas. Hematoxylin and eosin-stained section from the ovary revealed endometroid adenocarcinoma (FIGO grade 1) with extensive squamous morales. Sections from the omentum showed diffuse keratinization with granulomatous response against keratin. There were no viable tumor cells in the multiple sections examined. The peritoneal fluid for cytology was negative for malignancy. Final stage was given as FIGO stage IB. This case highlights this rare presentation in Ovarian endometroid adenocarcinoma posing diagnostic dilemma to clinician and pathologist and emphasizes upon the importance of clinicopathological discussion, fluid cytology and extensive sampling for accurate staging.

Sertoli-Leydig cell tumor of ovary in children

Sertoli-Leydig cell tumors (SLCTs) are rare and heterogeneous group of ovarian neoplasms which belong to the sex cord-stromal category of tumors. SLCTs are classified into well, intermediate, and poorly differentiated types. Retiform growth pattern and heterologous elements are commonly found in moderately and poorly differentiated tumors. SLCTs are usually encountered in the third decade of life and patients most often present with virilization. Here, we report two cases of SLCTs of the ovary, both in 2-year-old girls without any hormonal symptoms. The first case was a retiform variant of Sertoli-Leydig cell tumor and the second was a well-differentiated SLCT. Because of its wide spectrum of morphology, several tumors enter in the differential diagnosis and the presence of heterologous elements further complicates the diagnosis. Here, we have described the morphological characteristics of these tumors and discussed their differential diagnoses. SF-1, WT1, and α-inhibin are useful immunostains in establishing the diagnosis and differentiating these from the more the common ovarian germ cell tumors in children.

Pure primary ovarian carcinoid tumor with carcinoid syndrome and cervical carcinoma

Carcinoid tumors are defined as rare slow-growing neuroendocrine tumors. A majority of primary ovarian carcinoids occur in association with mature cystic teratoma or are metastatic to the ovary. A 48-year-old post-menopausal woman presented with progressive facial puffiness, and intractable diarrhea. Radiological imaging suggested a 10 × 9 × 9.2 cm right ovarian mass. She underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histopathological examination revealed primary pure carcinoid tumor of the ovary with the synchronous presence of early invasive squamous cell carcinoma of the cervix, along with the icthyosis uteri. The patient is doing well on 5 years of follow-up post-surgery without any recurrence or metastasis. In this report, we intend to highlight the rare association of cervical carcinoma and ichthyosis uteri with this tumor. In addition, we present a short review of the literature, over a decade of ovarian carcinoids associated with carcinoid heart disease.

Moderately differentiated Sertoli-Leydig cell tumor of ovary with associated mucinous carcinoma and carcinoid—A case report and review of literature

Sertoli-Leydig Cell Tumors (SLCT) are very rare neoplasms of the ovary (0.2%) and they belong to the group of sex cord-stromal tumors. Of these, 20% of the cases show heterologous elements. We report a case of a 22-year-old woman who presented with complaints of lower abdominal pain and secondary amenorrhea for 10 months. Physical examination revealed right lower abdominal tenderness and fullness. Imaging showed a right ovarian mass. She underwent right salpingo-oophorectomy with bilateral pelvic lymphadenectomy and omentectomy. Microscopic examination revealed a neoplasm with varied histomorphological patterns. The predominant pattern was an atypical proliferative mucinous tumor with foci of microinvasion. The other component was that of moderately differentiated Sertoli-Leydig Cell Tumor. Focal areas resembling carcinoid were also noted. Immunohistochemistry was performed and the Sertoli-Leydig Cells were positive for CD56, calretinin, inhibin, vimentin, and ER. The glandular component was positive for CK20, EMA, CEA, and CDX2. Synaptophysin and chromogranin were positive within nests resembling carcinoid. With the given histomorphological features and immunohistochemistry findings, a diagnosis of moderately differentiated Sertoli-Leydig Cell Tumor of the ovary with associated mucinous carcinoma and carcinoid was rendered. The presence of heterologous elements in SLCTs has been reported to be associated with poor prognosis.

Synchronous colonic adenocarcinoma and well-differentiated neuroendocrine tumor arising in a mature cystic teratoma of ovary — rare presentation in a postmenopausal woman with literature review

Mature cystic teratoma of the ovary (MCT) is rare in pre and postmenopausal age patients. Among various types of malignant transformation in MCT, adenocarcinoma is a rare subtype. Dual type tumors arising from ovarian MCT have been described in the literature very rarely. A 47-year-old postmenopausal female patient presented with abdominal mass for ten years. The radiological opinion was a dermoid cyst. Grossly, a 22 × 20 × 10 cm, unilocular cystic left ovarian mass with intact capsular surface and focal thickened wall measured 3.0 cm. Microscopically, it showed components of all three germ cell layers. In addition, features of colonic type adenocarcinoma and well-differentiated neuroendocrine tumor (carcinoid) were noted and confirmed by immunohistochemistry (IHC). We report this rare case of synchronous malignancy arising from an ovarian MCT with a clinicopathological review.

Collision tumor of the ovary

Collision tumor consists of two tumors occurring in the same organ without intermixture of the two cell types. The most common type of collision tumor in ovary is between teratoma and surface epithelial tumor. A 38-year-old woman presented with complained of lower abdominal pain and tightness, and a solid partially cystic left ovarian mass with minimal ascites was detected. Left salpingo-oophorectomy was performed. The ovarian mass measured 15 × 12 × 7 cm with a pedunculated mass on its surface which measured 6 × 2.5 × 2.5 cm. Histologically, it was a collision tumor of fibroma and mature cystic teratoma. Fibroma becomes more edematous as their size increases, which is frequently accompanied by the escape of increasing quantities of fluid from the tumor surfaces. Ascites is often detected when the fibroma is more than a diameter of 10 cm. It is important to identify the different components of a collision tumor for proper management.

Desmoplastic small round cell tumor of the ovary

Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive neoplasm of uncertain histogenesis that preferentially involves the abdominal and pelvic cavities. DSRCT mainly develops in adolescent and young adults with a strong male predominance; the male to female ratio is 4:1. Ovarian location is exceptional. DSRCT generally develops in the abdomen and have a tendency towards peritoneal spread, with subsequent metastasis to distant lymph nodes, liver and lungs. It is a poorly understood malignancy with a very characteristic morphology, immunophenotype, cytogenetic features, and poor prognosis. This tumor can co-express epithelial, neuronal, and mesenchymal markers. Despite intensive therapy, including surgery, radiotherapy and chemotherapy, and immunotherapy; the 5-year survival is less than 15%.

Primary leiomyosarcoma of ovary

Primary leiomyosarcoma (PLMS) of the ovary is extremely rare tumors comprising 1% of ovarian tumors. About 3% of all ovarian malignancies are primary ovarian sarcomas. Only 72 cases have been reported till date. A 57-year-old postmenopausal female presented with abdominal pain for the last 6 months. Ultrasonography and MRI revealed a heterogeneously enhancing solid lobulated mass in the left adnexa abutting the fundus of the uterus and bowel loops. The endometrial cavity was normal. Ovarian markers CA 125, CEA, CA 19.9, and all hematological parameters were within normal limits. LDH was near normal (284 IU/ml). The specimen was sent for frozen section and a diagnosis of malignant spindle cell lesion of ovary was rendered. Histopathology of the ovarian mass revealed intersecting fascicles of tumor cells consisting of ovoid to spindle-shaped cells having a moderate amount of cytoplasm. Bizarre and atypical cells were seen singly dispersed and in small aggregates along with the brisk mitotic activity. Focal areas of necrosis and hemorrhage were also noted. Immunohistochemistry showed strong positivity for smooth muscle actin and Caldesmon while focal positivity for Desmin and Epithelial Membrane Antigen (EMA) was noted. The lesion was negative for Inhibin, Calretinin, and CD 117 and S100. The final diagnosis of primary ovarian Leiomyosarcoma was given based on histopathology and Immunohistochemistry. PLMS of the ovary are rare incidental findings in postmenopausal women. These are highly malignant tumors and carry a poor prognosis. Hence, early diagnosis and surgical treatment with cytoreduction improve patient survival.

Mixed endocervical adenocarcinoma and high-grade neuroendocrine carcinoma of the cervix

Adenocarcinoma admixed with neuroendocrine carcinoma of the uterine cervix is a rare malignancy with a poor prognosis. In the literature, there are few reported cases. Herein, we report a case of a 56-year-old Turkish woman with cervical adenocarcinoma admixed with small cell neuroendocrine carcinoma. Histological examination of endocervical curettage specimens revealed a tumor composed of almost equal areas of small cell neuroendocrine carcinoma and adenocarcinoma. Neuroendocrine differentiation was confirmed by immunohistochemistry for chromogranin-A, synaptophysin, and CD 56. After the adenocarcinoma and small cell neuroendocrine carcinoma association was detected in the curettage material, both cervicovaginal smear and then total abdominal hysterectomy and bilateral salpingo-oophorectomy resection material of the patient were submitted to our pathology department. Histological features of both curettage and resection material were determined by immunohistochemical studies.

Metastatic micropapillary adenocarcinoma in cervix revealing an occult primary in breast

Intestinal metastasis from carcinoma cervix: An (un) common occurrence in a common cancer. A series of five cases from a single institution

Carcinoma cervix usually spreads directly to contiguous structures, such as the vagina, urinary bladder, ureter, and rectum. Intestinal metastasis from cervical cancer is very uncommon and accounts for less than 4% of cases and to date, 24 cases have been reported in Medical literature. These may be asymptomatic or present with features of intestinal obstruction, bowel wall perforation, and mimic acute abdomen. Intestinal metastasis is a late occurrence and carries a poor prognosis, hence a high index of suspicion with prompt diagnosis and management is essential. We report a series of five patients with squamous cell carcinoma (SCC) of the cervix with intestinal metastasis diagnosed in our hospital.

Merits and pitfalls of normal saline rehydrated air-dried cervical smears over conventional wet.fixed PAP smears

Background: Cervical Papanicolaou (PAP) smear is the simplest, minimal invasive, and excellent screening method to reduce the female morbidity and mortality due to cervical carcinoma. Immediate alcohol fixation of the cervical smears is required to preserve nuclear details, delay in alcohol fixation leads to air drying artifacts. Rehydrating of the air-dried cervical pap smear with normal saline can help to overcome these artifacts and also have its own advantages. Aims: This study was design to evaluate the effects, merits and pitfalls of normal saline Rehydrated Air-Dried Cervical PAP Smears (RADPS) compared with the Conventional Papanicolaou Smear (C-PAPS). Settings and Design: Comparative study. Methods and Material: Prospectively paired cervical smears of 100 women, who presented to the outpatient department of gynecology of our institute, were prepared. Alcohol fixed smears were labelled as conventional Papanicolaou smear (C-PAPS) and air-dried smears labelled as rehydrated air-dried PAP smears (RADPS). Eight cytomorphological parameters were considered for comparison and analyzed. Statistical analysis used: Chisquare (χ2)/Fisher exact test. Results: Clear background with red blood cells (RBC) lysis was noted in 93% of RADPS and 54% of C-PAPS. Cytolysis was observed more in C-PAPS (18%) than in RADPS (08%). Air-drying artifacts observed in 30% of C-PAPS and 08% of RADPS. Cytoplasmic staining (92% of RADPS and 85% of C-PAPS) was superior in RADPS. Cell border, nuclear chromatin, and border were also better appreciated on RADPS as compared to C-PAPS. Statistically significant difference was observed with 3 parameters, i.e., air-drying artifacts, RBC background, and distinct cell borders. Conclusion: Rehydration of air-dried smears can be adopted in regular practice, as an alternative or coupled with conventional wet fixation method to overcome the commonly faced problems of air-drying artifacts, especially in rural screening programs.

Unraveling SET: Exploring ovarian high-grade serous carcinoma and its BRCA1/2 immunoexpression

ABSTRACT Introduction: BRCA1 and BRCA2 (breast cancer type 1 and 2 susceptibility protein antibody) dysfunction, frequently seen in ovarian high-grade serous carcinomas (HGSC), often results from germline mutations, somatic mutations, and promoter methylation. Identification of tumors with BRCA defects has therapeutic and prognostic implications. Materials and Methods: Our goal was to assess the clinicopathological characteristics and significance of solid, pseudoendometrioid, and transitional (SET) ovarian HGSC and to correlate these with BRCA1 and 2 immunoexpression. Result: Of the total 45 HGSC cases assessed, SET growth pattern was seen in 64.4% (29/45) cases. Furthermore, 35.5% (16/45) of the total cases showed BRCA1 loss, and 17.7% (8/45) cases showed BRCA2 loss. Tumor-infiltrating lymphocytes (TILs), necrosis, lymphovascular invasion, and BRCA1 loss positively correlated with SET pattern morphology. Conclusion: Immunohistochemical analysis for BRCA1 is an effective and alternative method for the detection of BRCA1 dysfunction and can be correlated with the histomorphological pattern of HGSC.

Prevalence of precursor lesions (P53 signature, SCOUT, STIL, STIC) in fallopian tubes resected for non-neoplastic causes

High-grade pelvic serous carcinoma is a common cause of death in women worldwide and India. Recent evidence has clearly implicated the changes in the mucosa of the fimbrial end of the fallopian tube in its pathogenesis. 1) To study histopathology features of surgically resected specimens of fallopian tubes received with non-neoplastic lesions of the uterus and ovary for the presence of any precursor lesions [secretory cell outgrowth (SCOUT), serous tubal intraepithelial lesion (STIL), p53 signatures, and serous tubal intraepithelial carcinoma (STIC)]. 2) To confirm the findings with immunohistochemistry. 3) To correlate the prevalence of precursor lesions with clinical parameters and benign lesions of the uterus and ovaries. Assessment of histopathological changes in 100 specimens of distal fallopian tubes was done using the sectioning and extensive examination of the fimbrial end (SEE-FIM) protocol. H and E stain followed by immunohistochemistry for Bcl-2, p53, and Ki-67. The statistical significance of the difference in the mean values of precursor areas was evaluated by an unpaired t-test. Among 100 specimens taken on H and E, precursor lesions were suspected in 49% of the cases. SCOUT, suspicious for STIC, suspicious for STIC with areas of SCOUT, and unequivocal for STIC with areas of SCOUT were seen in 8%, 4%, 33%, and 4% of the cases, respectively. However, on IHC, SCOUTS were confirmed in 45% of the cases, p53 signature in 2%, STIL in 9%, and STIC in 4% of the cases. Sectioning and extensive examination of the fimbrial end (SEE-FIM) should be routinely done as it provides the opportunity to detect the early malignant changes. It may help in evolving the strategies for early detection, management, and reducing mortality.

Primary ovarian mucinous carcinoid arising in a mature cystic teratoma-A rare entity

Mature cystic teratomas are benign unilateral tumors often diagnosed in young females. Carcinoid tumors are slow-growing tumors originating from neuroendocrine cells. A thorough histopathological study of the tumor is mandatory and the surgical treatment is adapted according to the characteristics of the patient. The present case was considered as a primary mucinous carcinoid tumor of the ovary because it was confined to the ovary, had an intact capsule, no vascular invasion, or other suspicious lesions were noted in the abdominal cavity. This case is notable due to the rarity of its occurrence and the age of presentation.

Poorly differentiated biphasic synovial sarcoma of the vulva, displaying SS18::SSX1 fusion and weak to absent (mosaic) INI1/SMARCB1 immunostaining: A rare case with literature review

ABSTRACT Synovial sarcoma (SS) is rarely documented in the female genital tract, especially confirmed by molecular testing for SYT::SSX translocation and TLE1 immunostaining. A 62-year-old lady presented with a progressively increasing lump and pain over her right groin, for 6-month duration. Radiologically, a well-defined, solid-cystic mass was seen involving the right labia with necrotic areas, sparing the underlying muscles and the overlying skin. She underwent a biopsy followed by a surgical excision. Histopathologic examination revealed a spindle cell sarcoma, including tumor cells exhibiting a prominent hemangiopericytomatous pattern. There were focal areas of epithelial differentiation (pseudoglandular) along with areas of round cell morphology and increased mitoses (poor differentiation) in the resected specimen. Immunohistochemically, the tumor cells were diffusely positive for TLE1, patchily positive for pan keratin (AE1/AE3) and EMA, the latter more in the areas of epithelial differentiation, while negative for CD34, SMA, desmin, S100P, and SOX10. INI1/SMARCB1 showed a characteristic weak to absent (mosaic) staining pattern. Furthermore, the tumor displayed SS18::SSX1 fusion by RT-PCR. This constitutes one of the few reported cases of vulvar SS, confirmed by molecular testing and the first documented vulvar SS showing a mosaic pattern of INI1/SMARCB1 immunostaining. A review of the literature and diagnostic implications are presented herewith.

Adult extrarenal teratoid Wilms’ tumor: A case report and review of literature

ABSTRACT A 19-year-old woman presented with painless lower abdominal discomfort and a cystic-solid mass measuring 15.9 cm on the right ovary. She subsequently underwent laparoscopic right ovarian cystectomy. Microscopic examination of the mass showed the typical morphological features of Wilms’ tumor and the predominance of teratoid elements constituting more than 50% of the tumor. To date, few cases of extrarenal teratoid Wilms’ tumor (TWTs) in adults have been reported in the literature. The case presented in the present is the third reported case of adult extrarenal TWT occurring in ovary.