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

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.

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

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 serous carcinoma: A retrospective review of histological features & their clinicopathological association with disease-free survival & overall survival.

Background & objectives: Endometrial serous carcinoma (ESC) is a high-grade epithelial neoplasm with increased risk for metastasis and recurrence. This study was aimed to assess various histomorphological features of ESC and their clinicopathological association with disease-free survival (DFS) and overall survival (OS). Methods: A total of 205 slides (belonging to 120 patients) diagnosed as ESC from January 2009 to December 2015 were reviewed. Receiver operating characteristics (ROC) curves were established for the diagnostic performance of depth of invasion (DOI), tumour-free distance (TFD) to serosa and percentage myometrial invasion (MI%). OS and DFS were generated by Kaplan-Meier curves and prognostic significance by Cox regression analysis. Results: The mean age at diagnosis was 61.8 yr and the mean tumour size was 4.01 cm. Majority of the females were multiparous (84%; n=94) and postmenopausal (89.2%; n=107). On histopathology, <50 per cent of MI was identified in 37 of the 104 (35%), while 62/104 (59.61%) patients had ≥50 per cent MI. Seven (6.7%) patients had full-thickness invasion with serosal involvement, while five (4.8%) patients had no microscopic MI (minimal uterine serous carcinoma). Information about MI was not available in 16 patients. TFD ≥7.0 mm, DOI ≥6.0 mm and MI% ≥40 were significant variables in univariate analyses for OS; however, on multivariate analysis; none of these turned out to be an independent predictor in terms of OS. For DFS, DOI (≥6.0 mm) and MI% (≥40%) showed a significant association, in univariate as well as multivariate analysis; however, TFD (≤7.0 mm) did not show any significant association with DFS. Follow up data were available in 111 of the 120 (92.5%) patients with a five-year OS and DFS of 22.2 and 17.2 per cent, respectively. Interpretation & conclusions: Conventionally calculated DOI (less than or more than half thickness) did not show significance in the present study. Thus, calculating the actual myometrial DOI, MI% and TFD to serosa have the potential for contributing meaningfully to prognostication of ESC.

Histopathological and immunohistochemical features of 14 peritoneal mesotheliomas with clinical outcomes and recent updates.

Background: Malignant peritoneal mesotheliomas (MPMs) are rare tumors with overlapping clinical and histopathological features, especially with epithelial ovarian carcinomas (EOCs). There is no substantial documentation on these rare tumors from our country. Objective: To study the clinicopathological features including immunohistochemical (IHC) profile and clinical outcomes of 14 MPMs, diagnosed at our institution. Materials and Methods: This was a retrospective study, wherein 14 cases of MPM, occurring in female patients, diagnosed at our institution, between January 2008 and May 2019 were included, after a critical review. Results: Median age was 54.5 years. Most patients presented with ascites, omental nodularity, and fat stranding. Microscopically, most cases (11, 78.6%) displayed epithelioid morphology, followed by biphasic pattern (2, 14.3%) and a single case of well-differentiated MPM. IHC, diagnostic sensitivity and specificity of calretinin were 100% (13/13) and 85.7%; of HBME1 were 100% (5/5) and 100%; and of podoplanin (D2-40) were 60% (2/5) and 100%. Other positively expressed immunomarkers were epithelial membrane antigen (n = 2/5, 40%), cytokeratin 5/6 (n = 4/4, 100%), and WT1 (n = 9/10, 90%). Most patients (5/12, 41.7%) were treated with chemotherapy. The 3-year disease-free and overall survival rates were 25.7% and 54%, respectively, including improved survival trend in patients with epithelioid type of MPMs. Conclusion: MPMs are diagnosed with a combination of clinicopathological features and optimal IHC markers. Their differentiation from EOCs and other metastatic carcinomas is imperative in view of significant treatment implications.

An audit of frozen sections for suspected gastrointestinal malignancies in a tertiary referral hospital in India.

Background: Frozen Sections (FS) are used to assess margins, for staging, and primary diagnosis. FS guide intraoperative treatment decisions in oncological gastro-intestinal tract surgeries and further management of the patients. Aim: To analyze the distribution, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of frozen sections in gastrointestinal pathology in our institution during the period of 3 years (2016-2018). Material and Methods: This study was an audit to determine the accuracy of FS reports by comparing them with the paraffin section (PS) reports. The FS diagnoses and their PS diagnoses were noted in 1704 gastrointestinal surgeries during the period from 2016 to 2018. Discrepancies were noted and slides of discrepant cases were reviewed to determine the cause. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated using the standard formulae. Results: Out of 1704 cases, correct diagnosis on frozen section was made in 1649 cases (96.77%), 20 (1.17%) were deferred cases, and 35 (2.05%) were discrepant cases. The commonest discrepancies were seen in the primary diagnosis of the gall bladder and gastrectomy margins. The commonest causes for discrepancies were interpretation errors and technical errors. Sensitivity was 91.71%, specificity was 99.69%, positive predictive value was 98.84%, negative predictive value was 97.68%, and accuracy was 97.92%. Conclusion: FS diagnosis is a reliable guide to surgeons for intraoperative management. Studying deep cuts and careful sampling at frozen sections will help reduce discrepancies.

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.

Assessing the histopathology reports of colorectal carcinoma surgery: An audit of three years with emphasis on lymph node yield.

Background: A comprehensive histopathology report of colorectal carcinoma surgery is important in cancer staging and planning adjuvant treatment. Our aim was to review histopathology reports of operated specimens of colorectal carcinoma in our institution between 2013 and 2015 to assess different histological parameters, including lymph node yield, and to evaluate compliance to minimum data sets. Methods: After approval by the institutional review board (IRB), we analyzed 1230 histopathology reports of colorectal carcinoma between 2013 and 2015. Various gross and microscopic findings (along with age, sex) were noted, for example, specimen type, tumor site, resection margins including circumferential resection margin (CRM), lymphovascular invasion, perineural invasion, pTNM stage, lymph node yield, etc. Results: Out of 1230 patients, 826 (67.15%) were men and 404 (32.85%) were women. The overall mean age was 52 (range: 18 - 90) years. There were 787 surgeries for rectal cancers. All reports commented on the type of specimen, tumor size (mean = 4.38 cm), proximal, and distal margins. Lymphovascular invasion (LVI) and the pT stage were mentioned in 98.06% and 99.84%, respectively. The overall mean lymph node yield was 18.38 (median = 15, range = 0-130 lymph nodes). A statistically significant difference in lymph node yield was detected between rectal and colonic cancer patients (14.79 and 27.26); post neoadjuvant therapy (NACT) cases, and NACT naive cases (13.51 and 25.11); and high tumor stage and low tumor stage disease (20.60 and 15.22). Not commenting on extramural vascular emboli, tumor budding, and CRM in non-rectal cancer cases were the lacunae. Conclusion: Our compliance with minimal data sets is satisfactory. The overall mean lymph node yield was 18.38 (median = 15). Extramural vascular emboli, tumor budding need to be captured.

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.