Radhika Srinivasan

A sub‐hepatic nodule in a young female: Chase the case

Sertoli-Leydig cell tumours (SLCTs) are rare, mixed sex-cord stromal tumours composed of varying proportions of both Sertoli and Leydig cells, which account for <0.5% of all ovarian tumours. The cytomorphologic features of SLCTs are not well described in literature. Herein, we describe the cytomorphologic features of an SLCT at an uncommon metastatic site in a young female. Sertoli-Leydig cell tumours (SLCTs) are rare, mixed sex-cord stromal tumours composed of varying proportions of both Sertoli and Leydig cells, which account for <0.5% of all ovarian tumours. The cytomorphologic features of SLCTs are not well described in literature. Herein, we describe the cytomorphologic features of an SLCT at an uncommon metastatic site in a young female.

Tall‐columnar glandular cells in SurePath™ liquid‐based cytology Pap sample: Learning from mimics/pitfalls

We offer a comprehensive depiction of the cytomorphological characteristics of lobular endocervical glandular hyperplasia (LEGH) as observed in SurePath™ liquid-based cytology (LBC), subsequently confirmed on cone biopsy. Lobular endocervical glandular hyperplasia (LEGH), a precursor to gastric-type adenocarcinoma (GAE) of the endocervix, is rare and reports of it in cervical cytology are scarce. We provide a thorough description of the cytomorphological features of LEGH observed in SurePath™ liquid-based cytology (LBC), later confirmed by cone biopsy. To the best of our knowledge, this is the first report documenting cytology of LEGH in LBC of a Pap sample.

Small Cell Carcinoma of the Ovary: Clinicopathologic and Immunohistochemical Analysis of 7 New Cases of a Rare Malignancy

Background Small cell carcinoma of ovary (SCCO) is extremely rare. Two types of SCCO are recognized, the pulmonary type (SCCOPT) and the hypercalcemic type (SCCOHT). Establishing an accurate diagnosis is challenging, owing to its rarity and paucity of data describing the distinctive histopathologic and immunohistochemical (IHC) features. Methods This was a retrospective study conducted over a period of 4 years. All cases reported as SCCO on histopathology were retrieved. All the available clinical, histopathological, and IHC features were studied in detail. Results A total of 7 cases of SCCO were diagnosed during the study period. There were 4 cases of SCCOPT and 3 cases of SCCOHT and with mean age of 57.25 and 22 years, respectively. All the cases presented as stage IV disease. Among the SCCOPT cases, 3 showed bilateral involvement with 1 showing concurrent uterine endometrioid adenocarcinoma. Microscopy revealed small hyperchromatic cells with brisk mitosis and multifocal necrosis. On IHC, these were consistently positive for chromogranin, CD56, and synaptophysin. All the SCCOHT cases showed unilateral involvement. Microscopically, in addition to small hyperchromatic cells, larger “rhabdoid” tumor cells were also seen. On IHC, chromogranin was negative, with positivity for vimentin and epithelial membrane antigen. The expression of SMARCA4/BRG1 was lost while SMARCB1/INI1 was retained in all cases. All of these patients developed recurrence and died due to disease progression despite treatment. Conclusions SCCO is an extremely infrequent ovarian malignancy with poor prognosis. Knowledge about its characteristic features is important for accurate tissue diagnosis and appropriate management.

Morphologic and Immunocytochemical Features of High-Grade Serous Carcinoma of Ovary in Ascitic Fluid Effusion and Fine-Needle Aspiration Cytology

Abstract Objectives High-grade serous carcinoma (HGSC) is the most common ovarian malignancy. The role of cytopathology in obtaining tissue diagnosis before institution of neoadjuvant chemotherapy (NACT) was evaluated. Methods All histopathology-proven HGSC specimens between 2015 and 2018 with prior cytopathologic diagnosis by ascitic fluid evaluation or fine-needle aspiration (FNA) of ovarian mass were reviewed with cell block immunocytochemistry for CK7, CK20, PAX8, WT1, and p53. Results Of 288 cases of HGSC, pre-NACT cytology diagnosis was established in 32% (93/288), with specific HGSC diagnoses made on ascitic fluid in 88% (82/93) and by ovarian mass FNA in 12% (11/93). The ascitic fluid showed moderate/high cellularity with papillary clusters in 76% (71/93) cases. Cell block immunocytochemistry showed tumor cells positive for CK7, PAX8, and WT1. p53 showed mutant or null-type positivity in 65% (33/51) and 33% (17/51) of cases, respectively, with 100% concordance with subsequent histopathology specimens. Poor/intermediate response to chemotherapy was shown in 75% of cases. Conclusions Combined assessment of cytomorphology, cell block histomorphology, and ancillary immunohistochemical testing, including PAX8, WT1, and p53, allows for specific pre-NACT diagnoses of HGSC in ascitic fluid and ovarian FNA cytology. This practice allows for initiation of chemotherapy and diminution of disease burden prior to definitive surgical therapy.

Ultrasound‐guided fine needle aspiration of ovarian masses: Assessment of diagnostic accuracy and risk stratification using a categorical reporting system

AbstractIntroductionThe present study was undertaken to assess the accuracy of fine needle aspiration cytology (FNAC) and cell‐block immunocytochemistry, and to estimate the risk of malignancy, using a categorical reporting system, in the diagnosis of ovarian masses.MethodsThis was a 5‐year retrospective study of FNAs of ovarian masses. The cytological diagnoses were categorised as inadequate, non‐neoplastic, benign neoplasms, indeterminate for malignancy, suspicious for malignancy and malignant neoplasms. The cytology was correlated with the corresponding histopathology to assess the diagnostic accuracy and risk of malignancy associated with each diagnostic category.ResultsOf a total of 66 703 FNAs performed during the study period, 580 (0.9%) were performed on ovarian masses. Of these, 40 (6.9%) were reported as non‐neoplastic; 76 (13.1%) as benign neoplasms; 14 (2.4%) as indeterminate for malignancy, 48 (8.3%) as suspicious for malignancy, 337 (58.1%) as malignant neoplasms and 65 (11.2%) as inadequate for interpretation. Immunocytochemistry (ICC) was performed on 99 (17%) aspirates. Subsequent histopathology was available in 208 (35.8%) cases. On cyto‐histopathological correlation, 183 (88%) were concordant and 25 (12%) were discordant. The overall sensitivity, specificity, positive and negative predictive values and diagnostic accuracy for diagnosing ovarian malignancy were 88.4%, 85.7%, 96.8%, 60.0% and 88% respectively. Risk of malignancy for each category was 80%, 0%, 4.5%, 66.7%, 88.5% and 98.5% respectively.ConclusionsUltrasound‐guided FNAC has high specificity and diagnostic accuracy for preoperative diagnosis of ovarian malignancies and hence is a valid diagnostic procedure in certain clinical situations. Reporting using a categorical system imparts uniformity and also provides the clinicians with an associated risk of malignancy to guide further management.

Health-related quality of life among cervical cancer patients in India

Estimation of health-related quality of life of cervical cancer patients in India is important in assessing the well-being of patients, monitor treatment outcomes, and conduct health technology assessments. However, health-related quality of life estimates for different stages of cervical cancer are not available for the Indian population. This study aims to generate stage-specific quality of life scores for cervical cancer patients in India. A cross-sectional study using the EQ-5D (EuroQol 5-dimensions) instrument, that consists of the EQ-5D-5L descriptive system and the EuroQol Visual Analog Scale (EQ-VAS) was conducted. A total of 159 cervical cancer patients were interviewed. Mean EQ-5D-5L quality of life scores (utility scores) were calculated using the EQ-5D-5L index value calculator across different stages of cervical cancer. The proportion of patients reporting problems in different attributes of EQ-5D-5L was assessed. The impact of socio-economic determinants on health-related quality of life was evaluated using multiple linear regression. The mean EQ-5D-5L and EQ-VAS utility scores among patients of cervical cancer were 0.64 [95% CI=0.61-0.67] and 67.6 [95% CI=65.17-70.03], respectively. The most frequently reported problem among cervical cancer patients was pain/discomfort (61.88%), followed by difficulty in performing usual activities (53.81%), and anxiety/depression (41.26%). Cervical cancer significantly impacts the health-related quality of life of the patients in India. Clinical interventions should focus on the control of pain and relief of anxiety. The measurement of health-related quality of life should be an integral component of the effectiveness of interventions as well as health technology assessment.

Insulin growth factor-1 pathway in cervical carcinoma cancer stem cells

Cancer stem cells (CSC) drive tumour progression and are implicated in relapse and resistance to conventional cancer therapies. Identification of differentially expressed genes by gene expression (GEP) profiling may help identify the differentially activated signalling pathways in cancer stem cells as opposed to bulk tumour cells which will provide new insights into cancer stem cell biology and aid in identification of novel therapeutic targets. Our study focused on the inhibition of CSC from cervical cancer cell lines by targeting insulin-like growth factor (IGF), which was identified by differential GEP. Targeted inhibition of IGF-1 by JB-1 trifluoroacetate (inhibitor of IGF) was carried out in SiHa, RSBS-14 and RSBS-43 cervical cancer derived cell lines. Effect of cisplatin was also evaluated. Inhibition of IGF-1 signalling was confirmed by demonstration of reduction in p-Akt levels. The cell biological effects of IGF-1 inhibition included an increase in G2M/S fraction, increased apoptosis and decreased invasive ability. JB-1 and cisplatin showed synergism. However, transcript levels of stemness and EMT markers showed variable levels following IGF inhibition. Overall, this proof-of-concept study has shown that IGF-1 is an attractive target for inhibition of CSC in invasive cervical cancer.

Use of p53 immunohistochemistry can improve diagnostic agreement for differentiated vulvar intraepithelial neoplasia ( dVIN ): an international reproducibility study

Aims Differentiated or HPV‐independent vulvar intraepithelial neoplasia (dVIN) can progress rapidly to invasive cancer and accurate pathological diagnosis is essential to facilitate appropriate interventions. Histological similarities of dVIN with non‐neoplastic lesions, however, often make the diagnosis less reproducible. We investigated among a diverse group of pathologists whether the diagnostic agreement improves with the use of p53 immunohistochemistry (IHC) interpreted using the pattern‐based schema. Methods and results Fifty haematoxylin–eosin (HE) stained archival slides (30 dVIN and 20 non‐dysplastic vulvar lesions) were selected and p53‐IHC was performed. Twenty‐four board‐certified pathologists from eight countries first assessed the HE slides alone, and after a washout period, re‐evaluated them alongside the p53‐IHC slides. During both rounds, slides were diagnosed as dVIN, favour dVIN, favour no‐VIN or no‐VIN. p53‐IHC was scored as wild‐type or mutant (diffuse, basal, cytoplasmic or null). Kappa ( κ ) statistics and McNemar's test were used for statistical analyses. Overall diagnostic agreement for dVIN saw a significant increase in the Kappa value ( κ  = 0.6 vs. κ  = 0.4, P  = 0.002) when HE and p53‐IHC slides were assessed together compared with histology assessment alone, although the level of agreement remained moderate. For p53‐IHC assessment, overall agreement was substantial ( κ  = 0.7). Diagnoses changing from no‐VIN/favour no‐VIN to dVIN correlated significantly with the identification of a p53‐mutant pattern ( P  &lt; 0.001). Conclusions Our findings indicate that p53‐IHC is a robust ancillary tool that can be reproducibly interpreted by pathologists with varying experience levels and supports the routine use of p53‐IHC in cases where dVIN is considered in the differential diagnosis.