Epithelioid trophoblastic tumor: A case series

An epithelioid trophoblastic tumor (ETT) is an extremely rare gestational trophoblastic tumor. Cases of ETT present with abnormal vaginal bleeding in women of reproductive age group with marginally elevated beta human chorionic gonadotrophin (B-hCG) levels. Here, we describe a series of four patients (all were females) including histomorphology, immunoprofiles, and diagnostic difficulty of this rare entity. All cases were in their reproductive age group. The mean pre-treatment hCG level was 665.24 (mIU/mL). Microscopically, all cases had a tumor showing an epithelioid appearance arranged in large nests and sheets. Individual tumor cells were round to polygonal with abundant eosinophilic cytoplasm, with central vesicular nuclei and prominent nucleoli. Areas of hemorrhage, necrosis, and intercellular hyaline-like material deposition were identified in all cases (100%). Immunohistochemically, tumor cells in all cases showed diffuse positivity for AE1/AE3 and p63 (100%). GATA3 was available in one case (25%), which was positive in the tumor cells. In one case (25%), hPL was focally positive, and in one case (25%), it was negative. SALL4 was performed in two cases (50%) and was negative in tumor cells. The mean Ki67 labeling index was 19.2 (range 10–30%). All four patients underwent surgical intervention and were treated with hysterectomy. The mean follow-up in this series was 39.4 months (range 6–70), and all patients are alive to date with a mean survival of 32.8 months (range, 4–67).

Pulmonary inflammatory myofibroblastic tumor coexisting with lymphangitis carcinomatosis: Mimicking metastatic papillary thyroid carcinoma with nodular fasciitis-like stroma

Inflammatory myofibroblastic tumors (IMTs) are uncommon; intermediate grade soft tissue tumors occurring in young individuals with an uncertain behaviour. The incidence of pulmonary lymphangitis carcinomatosis (PLC) is around 6-8% of all pulmonary metastases. However, PLC due to papillary thyroid carcinoma (PTC) is very uncommon. We present a case of a 26-year-old male, who presented with a solitary left lung nodule on radiological scans. There was also a past history of thyroid surgery done two years back for PTC. Histology revealed a soft tissue tumor reminiscent of IMT. The periphery of the IMT nodule showed metastatic PTC in the form of extensive PLC. In view of this unusual histology, a diagnosis of PTC with nodular fasciitis-like stroma (PTC-NFS) was initially considered. However, molecular studies for anaplastic lymphoma kinase (ALK) gene rearrangement confirmed the diagnosis of IMT. This case highlights the unusual occurrence of tumor-to-tumor metastasis causing diagnostic challenges and also the importance of molecular testing.

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

Introduction: 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. Aim: Our aim was to study LEEP reports for its contents and to see their correlation with preprocudure histology and/or cytology report. Results: 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. Conclusion: Literature shows wide range of concordance due to variable definitions and variety of reasons; possible reasons are discussed.

Detection of MDM2 gene amplification on tissue microarray-based Fluorescence In-Situ Hybridization (FISH) in well-differentiated and dedifferentiated liposarcomas, displaying a wide morphological spectrum: A validation study at a tertiary cancer referral centre

Background: Liposarcomas including atypical lipomatous tumors (ALT)/well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPSs) display a histomorphological spectrum with their several diagnostic mimics. Murine double minute 2(MDM2) gene amplification characterizes ALT/WDLPS and DDLPS. Presently, there is no documented study from our subcontinent on the validation of MDM2 gene testing in these tumors. Material and Methods: Twenty-eight cases, diagnosed as ALT/WDLPS (n = 5) and DDLPSs (n = 23), along with 10 other tumors were tested for MDM2 gene amplification, using fluorescence in situ hybridization (FISH) on tissue microarrays (TMAs). Fourteen cases, diagnosed as ALT/WDLPS and DDLPS, along with 49 other tumors were tested for MDM2 immunostaining. Twenty tumors were tested for p16INK4a immunostaining. Results: FISH was interpretable in 25 (89.2%) cases. Among the 20 cases diagnosed as DDLPSs, 19 displayed MDM2 gene amplification. Among the 5 cases diagnosed as ALT/WDLPS, four showed MDM2 gene amplification. Finally, 19 cases were confirmed as DDLPS and 4 as ALT/WDLPS. Furthermore, 7/19 cases confirmed as DDLPS and all 4 cases as ALT/WDLPS tested for MDM2 immunostaining, displayed its diffuse immunoexpression, while a single case of DDLPS showed its focal immunostaining. None of the 49 control cases displayed diffuse MDM2 immunoexpression. ALL 16 DDLPSs and 4 cases of ALT/WDLPS displayed p16INK4a immunostaining. The sensitivity for diffuse MDM2 immunostaining was 87.5% in cases of DDLPS, 100% in ALT/WDLPS, and specificity was 100%. The sensitivity for MDM2 gene amplification was 94.7% in cases of DDLPS and 100% in cases of ALT/WDLPS. The sensitivity for p16INK4a was 100%. Conclusion: This constitutes the first sizable study on MDM2 testing in ALT/WDLPS and DDLPS from our subcontinent using TMAs. MDM2 gene amplification testing continues as the diagnostic gold standard for ALTs/WDLPSs and DDLPSs and is useful in cases of diagnostic dilemmas. Diffuse MDM2 (IF2 clone) and p16INK4a immunostaining, together seem useful for triaging cases for FISH.

Comparison between Fluorescence in-situ Hybridization (FISH), Reverse Transcriptase PCR (RT-PCR) and fragment analysis, for detection of t (X; 18) (p11; q11) translocation in synovial sarcomas

Background: Synovial sarcoma (SS) is an aggressive, but a relatively chemosensitive soft tissue sarcoma, characterized by a specific, t (X;18)(p11;q11) translocation, leading to formation of SS18–SSX chimeric transcript. This translocation can be detected by various techniques, such as fluorescence in-situ hybridization (FISH), reverse transcriptase PCR (RT-PCR) and fragment analysis. Objectives: To compare the results of detection of t (X;18)(p11;q11) translocation, across three different platforms, in order to determine the most optimal and sensitive technique. Methods: Formalin-fixed paraffin embedded (FFPE) tissue sections of 45 soft tissue sarcomas were analyzed, including 16 cases of SS confirmed by histopathology, immunohistochemistry and molecular technique (s)(Group 1); 13 cases, wherein SS was one of the differential diagnosis, preceding molecular testing (Group 2) and 16 cases of various other sarcomas (Group 3). Various immunohistochemical (IHC) markers studied, including INI1/SMARCB1. All cases were tested for t (X;18) translocation, by fragment Analysis, FISH and RT-PCR. Results: There were 23 cases of SS, including 16 of group 1 and 7 of group 2. By fragment analysis, t (X;18)(p11;q11) translocation was detected in 22/23 cases (95.6%). By FISH, SS18 gene rearrangement was detected in 18/22 cases (78.2%), whereas by RT-PCR, SS18-SSX transcripts were detected in 15/23 cases (65.2%). Immunohistochemically, a unique “weak to absent”/reduced INI1 immunostaining pattern was exclusively observed in 12/13 cases of SS (92.3%). Fragment analysis and FISH were relatively more sensitive techniques. Unique “weak to absent”INI1 immunoexpression significantly correlated with positive t (X;18) translocation results (P = 0.0001). Conclusion: The present study constitutes first such study from our subcontinent. Fragment analysis is a promising technique for detection of t (X;18)(p11;q11) translocation. FISH and INI1 immunostaining pattern were also relatively more sensitive, over RT-PCR.

Role of immunohistochemistry in gynec oncopathology including specific diagnostic scenarios with associated treatment implications

Over the years, immunohistochemistry has emerged as a powerful tool for a more precise diagnosis of certain tumors in gynecologic oncopathology and resolving certain diagnostic dilemmas with significant treatment implications. Certain specific immunohistochemical (IHC) markers have been useful in the more correct identification of rare tumors, characterized by specific molecular signatures. Immunohistochemistry has also been useful in the identification of underlying genetic events, characterizing various tumors, as well as precancerous lesions. This review will focus upon the judicious application of various IHC antibody markers in gynec oncopathology, including authors' experience during “sign-outs” and especially during interaction with other oncology colleagues within the institutional disease management group. The updated references were retrieved from PubMed.

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.

Clinicopathologic features of undifferentiated round cell sarcomas of bone & soft tissues: An attempt to unravel the BCOR-CCNB3- & CIC-DUX4-positive sarcomas

Background & objectives: Certain genetically defined undifferentiated round cell sarcomas, namely BCOR-CCNB3 and CIC-DUX4 positive, have been described. Here we present detailed clinicopathologic features and molecular results in such cases. Methods: Fifty one cases of undifferentiated round cell sarcomas, including 32 cases, tested for BCOR-CCNB3 and CIC-DUX4 fusions, by reverse transcription polymerase chain reaction technique and 44 tumours, for CCNB3 immunostaining, were analyzed. Results: Twenty seven (52.9%) tumours occurred in males and 24 (47%) in females; in soft tissues (38; 74.5%), commonly, trunk and extremities and bones (13; 25.4%), frequently, femur and tibia. Five of 32 (15.6%) tested cases were positive for BCOR-CCNB3 fusion and seven (21.8%) for CIC-DUX4 fusions. Histopathologically, CIC-DUX4-positive sarcomas comprised nodular aggregates of round to polygonal cells, containing hyperchromatic nuclei, prominent nucleoli and moderate cytoplasm, with focal myxoid stroma and variable necrosis, in certain cases. BCOR-CCNB3- positive sarcomas mostly comprised diffusely arranged, round to oval to short spindly cells with angulated nuclei, vesicular chromatin, inconspicuous nucleoli and interspersed vessels. Immunohistochemically, tumour cells were positive for MIC2 in 24 of 49 (48.9%) and CCNB3 in 12 of 44 (27.2%) cases. Four of five BCOR-CCNB3-positive sarcomas showed CCNB3 immunostaining and 6 of 7 CIC-DUX4-positive sarcomas displayed WT1 immunostaining. Most patients (27/37) (72.9%) underwent surgical resection and chemotherapy. Median overall survival was 12 months, and disease-free survival was seven months. Interpretation & conclusions: Undifferentiated round cell sarcomas are rare; mostly occur in soft tissues of extremities, with CIC-DUX4 positive, as these are relatively more frequent than BCOR-CCNB3 positive sarcomas. CCNB3 and WT1 are useful immunostains for triaging such cases for BCOR-CCNB3 and CIC-DUX4 fusion testing, respectively. Overall, these are relatively aggressive tumours, especially CIC-DUX4-positive sarcomas.

Small round cell lesions of the bone: Diagnostic approach, differential diagnoses and impact on treatment

Small round cell lesions of the bone encompass a heterogeneous group of tumors and tumor-like lesions, including Ewing sarcoma, small cell osteosarcoma, mesenchymal chondrosarcoma, neuroblastoma, non-Hodgkin's lymphoma (NHL), “Ewing-like” undifferentiated round cell sarcomas, metastasizing small cell carcinoma, along with plasma cell dyscrasia and Langerhan's cell histiocytosis. At the same time, there are tumor mimics, for example, chronic osteomyelitis, which has overlapping radiologic features with Ewing sarcoma and a primary intraosseous NHL. An exact diagnosis necessitates integration of clinical, radiologic, pathologic, and ancillary test results, including immunohistochemical and molecular results. Currently, there are several immunohistochemical markers and specific molecular signatures, driving most of these tumors, available, for an exact diagnosis. This review focuses on a pragmatic approach towards uncovering specific small round cell lesions of the bone, emphasizing upon integration of traditional morphology with ancillary techniques, including immunohistochemical markers and molecular techniques, the latter, especially in cases of Ewing sarcoma, Ewing-like undifferentiated round cell sarcoma, mesenchymal chondrosarcoma, and neuroblastoma. Subsequent to the diagnostic approach, including an impact on treatment, individual intraosseous round cell lesions have been described in detail. The references include updated articles from PUBMED.

Superficial CD34-positive fibroblastic tumor in the forearm of a middle-aged patient: A newly described, rare soft-tissue tumor

Superficial CD34-positive fibroblastic tumor is a recently described soft-tissue tumor entity. A 48 year-old-male presented with a gradually increasing soft-tissue mass in his right forearm of 2 years' duration, along with multiple subcutaneous soft-tissue nodular lesions, and reminiscent of lipomas over his body. He underwent a wide excision of his forearm mass. Microscopic sections showed a circumscribed tumor in the dermis and subcutaneous fat, composed of spindle cells, inflammatory cells, including lymphocytes, plasma cells, and eosinophils, along with interspersed markedly pleomorphic giant cells containing moderate-to-abundant “glassy” cytoplasm, vesicular nuclei, exhibiting prominent nucleoli, and intranuclear pseudoinclusions. There were no significant mitotic figures, areas of hemorrhage, necrosis, or pigment histiocytes. By immunohistochemistry, the tumor cells were diffusely positive for CD34 while negative for cytokeratin (CK), pan CK (AE1/AE3), S100 protein, CD30, and CD31. MIB1/Ki-67 was low and highlighted 4%–5% tumor nuclei. Diagnosis of superficial CD34-positive fibroblastic tumor was offered. Sections from the various resection margins were free of tumor. Postresection, the patient is alive with no evidence of disease for the past 8 months. This constitutes as one of the first case reports of this rare tumor entity from our country. Its diagnostic and treatment implications are discussed herewith.

Polymorphisms in cytotoxic T-lymphocyte associated antigen 4 gene does not affect scytotoxic T-lymphocyte associated antigen 4 levels in human papillomavirus-infected women with or without cervical cancer

Background: Cervical cancer (CaCx) is the second most common cancer in Indian women. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) + 49 AA polymorphism is known to be associated with CaCx. Current attempt is to use immunotherapy for the treatment of metastatic melanoma and metastatic castration-resistant prostate cancer, i.e., blocking of CTLA-4 using a fully human monoclonal CTLA-4 antibody to disrupt its inhibitory signal. This allows the CTLs to destroy the cancer cells. There is no information available on the soluble level of CTLA-4 on which the immunotherapy is targeted. This is specifically in Indian population including cases with CaCx. Objective: The aim of this study is to evaluate the levels of soluble CTLA-4 (sCTLA-4) in human papillomavirus (HPV)-infected women with or without CaCx and their association with the polymorphism at CTLA-4 + 49 A/G and CTLA-4 ?318 C/T genotypes. Materials and Methods: This is an exploratory case–control study involving two groups of HPV-infected women, the cases were with invasive CaCx and the control group was women with the healthy cervix. sCTLA-4 levels were measured using ELISA in 92 CaCx cases and 57 HPV-positive women with the healthy cervix. Results: Both cases and controls have similar sCTLA-4 levels. Comparison of CTLA-4 + 49A/G and ?318 C/T genotypes with sCTLA-4 levels among cases and control also did not show any statistically significant difference. Conclusion: The present study suggests sCTLA-4 levels are not affected by a polymorphism at + 49 A>G CTLA-4. Hence, levels of CTLA-4 are similar in both CaCx cases and control group.

A clinico-morphological study of 95 cases of sarcomas with metastases to the lungs.

Background: Metastasis of soft tissue sarcoma most commonly occurs to the lungs. There are very few studies on histology of pulmonary metastatectomy and hardly any wherein the histology of the primary tumor has been compared with the metastasis. Aims and Objectives: To review histologically all metastatic sarcomas to lung and compare with the primary where available. Materials and Methods: Ninety-five patients with pulmonary metastases from sarcoma were analyzed histologically for type of sarcoma, chemotherapy-related changes, and changes in adjacent lung. Various clinical parameters like laterality, multiplicity, and interval between primary and metastasis were also studied. Results: Osteosarcoma constituted half of the metastatic sarcomas (48 cases, 50.5%) followed by synovial sarcoma (16 cases, 16.8%) and high grade spindle cell sarcoma-NOS (10 cases, 10.5%). The histology of primary and the metastases was similar in 60% of cases of osteosarcoma. Conclusions: Osteosarcoma is the commonest metastatic sarcoma to the lung. There is often a change to fibroblastic histology in patients of conventional osteosarcoma treated with chemotherapy.

A t(X; 18) SYT-SSX2 positive synovial sarcoma in the pelvis of a young adult male: A rare case report with review of literature.

Synovial sarcoma is uncommonly documented in the pelvis. Rarely, such cases have dealt with molecular analysis. A 19-year-old boy presented with pain and swelling in his left lower limb of two months duration. He developed acute urinary retention four days prior to his hospital admission, wherein radiological examination unraveled a large soft tissue mass, displacing his pelvic muscles, along with a lytic lesion involving his right pubic bone. Biopsy showed a cellular spindle cell sarcoma, exhibiting hemangiopericytoma-like vascular pattern with focal necrosis. Immunohistochemistry (IHC) showed positivity for vimentin, BCL-2, calponin and MIC 2. Cytokeratin (CK) and epithelial membrane antigen (EMA) were negative. MIB 1 count was 70% (high). P53 was positive. Diagnosis of a poorly differentiated synovial sarcoma was offered and confirmed with a positive t(X; 18) SYT-SSX2 translocation. This case highlights the value of molecular analysis in diagnosis of a synovial sarcoma at rare sites, especially when IHC results are equivocal and the biopsy material is limited.

Premalignant lesions of prostate and their association with nodular hyperplasia and carcinoma prostate.

BACKGROUND: A relatively new development in the arena of prostatic histopathological study is the premalignant proliferative changes in the glandular epithelium, possibly relating to carcinoma. Two major categories have come up, namely prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia (AAH). AIMS: The aims of present study were to identify foci of the two putative premalignant conditions viz. PIN and AAH in ducto-acinar lining epithelia of 200 prostatectomy specimens and their association with nodular hyperplasia and adenocarcinoma prostate. MATERIAL AND METHODS: Micro sections from 200 prostatectomy specimens, received in the Department of Pathology, PGIMS, Rohtak, were extensively studied for the presence and association of premalignant conditions. Significant values were obtained by employing Chi-square (chi2) test, with P value < 0.05 as significant. RESULTS: Out of 177 cases of nodular hyperplasia, 53 (29.9%) showed PIN and 38 (20.3%) showed presence of AAH. All 6 cases (100%) of pure carcinoma revealed foci of PIN. Out of the remaining 23 cases of carcinoma with nodular hyperplasia, foci of PIN were observed in 16 cases (94.1%) and AAH in 2 cases (11.7%). High-grade PIN was observed in 20 cases (86.9%) of the total 23 cases of carcinoma, with/without nodular hyperplasia and 20 cases (11.2%) of nodular hyperplasia. Low-grade PIN was observed in 33 cases (18.6%) of nodular hyperplasia and in only 1 case (5.8%) of carcinoma prostate with nodular hyperplasia. CONCLUSION: PIN, especially high-grade type was the most commonly observed premalignant lesion, in cases of adenocarcinoma, thereby suggesting it to be the likely precursor of carcinoma prostate. AAH showed a weaker association with carcinoma.