Histotyping of Indian thymomas: A clinicopathologic study from north India.

Background & objectives: Thymomas are rare, but most common anterior mediastinal lesions. The histomorphologic spectrum of thymic epithelial tumours (TETs) in Indian population has not been explored in depth. This study was aimed to assess the histomorphology of TETs in the Indian patients and correlate clinical parameters with pathological features. Methods: It was a retrospective study conducted in a tertiary referral hospital in north India. All morphologically confirmed cases of TETs since 2009 were included. Clinical details and histology slides were reviewed using the Modified Masaoka-Koga staging system and WHO 2015 classification. Clinicopathological correlation and survival analysis were done. A comparative review from other published Indian studies was performed. Results: A total of 219 cases of TETs (138 resections and 81 biopsies) were identified. The most common histomorphologic type was B2, and the most frequent stage was I. Types A/AB were common in older age (P<0.01). Clinically, higher stage tumours were found mostly in men (P<0.01), and these were Type B thymomas (P<0.01). Myasthenia gravis was more common in women (P<0.02) and in lower stages (P<0.05). Survival analysis revealed significant association between recurrence and tumour stage. Although thymic carcinoma was diagnosed on biopsy, no resectable case was identified. Interpretation & conclusions: Our findings showed that the thymomas in Indian patients were most commonly Stage I tumours of B2 and AB histotypes. Resected thymic carcinomas were conspicuously absent in our study. More studies need to be done to establish the frequency and biology of TETs from India.

Cytological diagnosis of Langerhans cell histiocytosis: A series of 47 cases.

OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare disease affecting predominantly children and young adults but can be found in any age group. Diagnosis of LCH is often difficult and can be delayed because of its rarity. The present study highlights the cytomorphological features in a large cohort of cases. An accurate cytological diagnosis may avoid unnecessary biopsy and guide appropriate management. METHOD: Fourty seven (47) cases of LCH diagnosed on cytological material & fine-needle aspiration (FNA) over a period of 14 years (2003-2016) were retrieved from the archives. The cytological smears were evaluated and microscopic findings collected by semi-quantitative assessment done by two different pathologists RESULT: The age at the diagnosis of the patients ranged from 9 months to 28 years. The majority of cases were in the age group of 0-5 years. The most common site was head and neck region, which included cervical lymphadenopathy and scalp swelling. Two cases were diagnosed each from inguinal lymph node and bronchio-alveolar lavage (BAL). Cytological smears in the majority of the cases were moderate to highly cellular (58%) and showing abundant Langerhans cell in (72%) of cases. Areas of necrosis were seen in 38%, while 78% of cases showed giant cells. The majority of cases showed mild eosinophilia (61%), sparse lymphocytosis (83%) and mild neutrophilic infiltration (64%). There were 1-2 mitoses per 10 high power field in 12 cases (25.5%). No abnormal mitoses were identified. CONCLUSION: The presence of cells with features of Langerhans cells associated with the expression of selected immunohistochemical markers allow the diagnosis of LCH on cytological samples, sparing more invasive procedure as a biopsy.

PD-L1 immuno-expression assay in thymomas: Study of 84 cases and review of literature.

BACKGROUND AND AIMS: Programmed death ligand 1 (PD-L1), an immune check point inhibitor, is known to be expressed in several malignancies and is being considered as a prognostic factor and a potential immunotherapeutic target. The aim of this study was to characterize PD-L1 expression in thymomas and to determine correlation with clinicopathological features and previously published studies in the literature. METHODS: Tissue microarrays were prepared from selected blocks of thymomas and immunohistochemistry (IHC) for PD-L1 was performed. Cases were considered as PD-L1 positive or negative depending on whether the percentage of stained thymic epithelial cells were <25 or >25%. Results were compared clinically and with previously published studies using Google and Pubmed search engines. RESULTS: Of 84 cases of thymoma, 69 (82.1%) revealed PD-L1 positivity in >25% cells. 94.23% of type B thymoma subtypes (B1/B2/B3) were PD-L1 positive (P < 0.001). There was no correlation of PD-L1 with age, gender, myasthenia gravis, the tumor size or stage of disease. Nine studies were available in the literature; most of which showed PD-L1 expression in higher stage and B subtype however percentage positivity varied from 53.7% to over 90%. CONCLUSIONS: PD-L1 expression is frequent in type B (B1/B2/B3) thymomas. It can be easily evaluated by IHC even on small biopsies in unresectable cases, thereby enabling improved clinical evaluation as well as prognostic stratification of patients. It will serve as a potential indicator for benefit from anti-PD-L1 antibody immunotherapy in thymomas.

Epithelioid angiosarcoma of the pericardium: Case report of the challenges in the management of a rare malignancy with poor prognosis.

ABSTRACT: A primary epithelioid angiosarcoma of the pericardium is a rare soft tissue malignancy. This report describes a young adult woman who presented with progressive dyspnea and pericardial effusion. She was found to have pericardial mass on imaging along with extensive myocardial infiltration. The biopsy of the mass revealed epithelioid angiosarcoma, which was CD34 and CD31-immuno-positive. Due to unresectable disease, she was given a trial of immunotherapy followed by conventional chemotherapy. She showed partial response on interim assessment, but progressed soon after the completion of six cycles and succumbed to her rapidly progressive illness within nine months of diagnosis. This report discusses the diagnostic and therapeutic challenges faced while managing this disease of aggressive tumor biology.

18-F FDG PET/CT in a Case of Recurrent Pericardial Effusion Diagnosed as Cardiac Sarcoma.

Recurrent pericardial effusion poses a diagnostic challenge, especially in young patients. We present a case of a 22-year-old female who experienced recurrent pericardial effusion and cardiac tamponade. Despite initial treatment with anti-tubercular drugs and prednisolone, the patient had a relapse of symptoms, necessitating further investigation. Imaging studies revealed massive pericardial effusion with septations, suggestive of constrictive pericarditis with impending cardiac tamponade. To establish a definitive diagnosis, the patient underwent an FDG PET-CT scan after adhering to a specific dietary regimen. The scan revealed an ill-defined mediastinal mass with high metabolic activity, along with a gross pericardial effusion showing metabolic activity in the periphery and septations. Subsequent biopsy of the mediastinal mass confirmed a diagnosis of high-grade sarcoma.Primary malignant cardiac tumors are rare, and their prognosis is generally poor due to limited treatment options. While echocardiography and MRI are commonly used imaging techniques, FDG PET-CT is not routinely employed for evaluating cardiac tumors. However, in this case, FDG PET-CT played a crucial role in identifying the mediastinal mass and confirming the diagnosis.Early detection and accurate diagnosis of cardiac tumors are vital for initiating appropriate treatment strategies. Further studies are needed to explore the utility of FDG PET-CT in the evaluation of cardiac tumors, especially in cases of recurrent pericardial effusion.

Primary adenocarcinoma with yolk sac differentiation in the transplant ureter and salvage of the transplant kidney: a rare case report.

Renal transplant recipients are prone to a high risk of subsequent upper tract urothelial carcinoma, occurring in both native and transplant ureters. We report a rare case of adenocarcinoma with yolk sac differentiation of the transplant ureter, which was managed successfully with transplant ureterectomy and pyelovesicostomy, thereby salvaging the functioning transplant kidney.

Molecular Landscape of Pediatric Thyroid Cancer: A Review.

Thyroid carcinomas (TC) are rare in the pediatric population; however, they constitute the most common endocrine malignancy. Despite some similarities with adult carcinomas, they have distinct clinical behavior and responses to therapy due to their unique pathology and molecular characteristics. The age cut-off used for defining the pediatric age group has been variable across different studies, and the universally accepted recommendations influence accurate interpretation of the available data. Moreover, factors such as radiation exposure and germline mutations have greater impact in children than in adults. Papillary TC is the most common and the most evaluated pediatric TC. Others, including follicular, poorly differentiated and medullary carcinomas, are rarer and have limited available literature. Most studies are from the West. Asian studies are primarily from Japan, with few from China, India, Saudi Arabia and Republic of Korea. This review provides a comprehensive account of the well-established and novel biomarkers in the field, including point mutations, fusions, miRNA, and thyroid differentiation genes. Familial and syndromic associations are also discussed. Current management guidelines for pediatric patients are largely derived from those for adults. An awareness of the molecular landscape is essential to acknowledge the uniqueness of these tumors and establish specific diagnostic and therapeutic guidelines.

Solid papillary carcinoma of the breast.

Solid Papillary Carcinoma (SPC) of the breast is a rare tumor with an incidence of less than 1%, mainly affecting elderly females. It is morphologically characterized by well-defined nodules with low-grade nuclear features associated with fibrovascular cores and shows neuroendocrine differentiation. SPC can be in-situ or invasive but has a favorable prognosis. It is a morphological mimicker of some pre-malignant conditions leading to its frequent misdiagnosis. An appropriate immunohistochemical (IHC) panel workup helps in distinguishing this tumor from its various morphological mimics. In this report, we present one such case of SPC with a small focus of invasion, reviewing the literature.

Cancer in the Adolescent and Young Adults (AYA) and Children: A Comprehensive Analysis of the Epidemiology and Psychosocial Morbidity in the Indian Population.

Bhupesh GuleriaAims Adolescent and young adults (AYAs), children with cancer, and their guardians have unique psychosocial morbidities adversely effecting quality of life (QOL). This is measurable using patented tools. We analyzed epidemiological and clinicopathological patterns of solid organ cancers in this subgroup. We also assessed psychosocial morbidity and changes in QOL faced by them. Methods All patients aged 2 to 39 years, newly diagnosed with cancer from April 2017 to March 2019 were included. Clinical history, diagnosis, staging, treatment, outcomes, and follow-up were recorded. The National Comprehensive Cancer Network (NCCN) distress thermometer and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C-30) were used to assess psychosocial morbidity of AYAs, children ≥ 12 years, and parents of children < 12 years. Pediatric Quality of Life Inventory (Peds QL) version 3.0 was used for children < 12 years. Data was analyzed using descriptive statistics. Results A total of 571 patients (512 AYAs, 59 children) were enrolled. Median age was 30 years with male predominance (58.1%). Most cases (98.6%) were absent from school or work. Carcinoma breast was the most common in females (29.3%) and non-Hodgkin lymphoma in males (12.6%). 91.06% had overall NCCN distress score ≥ 4. Also, 73.81 and 79.49% had "quite a bit" or "very much" responses on functional and symptom scales, respectively, in EORTC QLQ C-30 questionnaire. Peds QL version 3.0 revealed total score ranging from 276 to 523 for each patient. Conclusion AYAs and children with cancer are extremely vulnerable to psychological stress and morbidity. Use of well-established tools help in assessing their mental status and timely psychiatric referral can be initiated.

Pituicytoma: Case report of a rare suprasellar tumor.

Pituicytoma is a distinct sellar or supracellar tumor which originates from specialized glial cells of neurohypophyses and infundibulum known as pituicytes. Because of its sellar location patients present with headache, visual disturbance, and endocrine abnormalities. Pituicytoma is difficult to diagnose on neuroimaging as radiological features overlap with other more common tumors of this region. Thus, diagnosis is established by histopathology and immunohistochemistry of resected tumor only. Pituicytomas are composed of bipolar spindle cells arranged as fascicles and are immunoreactive for TTF-1, S100p, and vimentin. These tumors are extremely rare and only around 70 published cases are known in literature. We report a case of suprasellar SOL in a 58-year-old male who presented with headache and gradual visual deterioration in both eyes. He was diagnosed as a case of pituicytoma based on light microscopy findings and immunohistochemical expression of TTF-1, vimentin, S100p, and bcl-2.

"Single-cell pattern" of adenocarcinoma cells in effusion cytology: Morphologic challenges of lung cancer.

BACKGROUND: Lung adenocarcinomas present as tight clusters and three-dimensional balls in effusion specimens. Unlike carcinomas of breast and stomach where singly lying malignant cells are seen in effusion samples, lung adenocarcinomas usually show cohesive morphology. This single-cell pattern may also be confused with reactive mesothelial cells. We studied the frequency of pulmonary adenocarcinoma with single-cell pattern cytomorphology in pleural effusion specimens. MATERIALS AND METHODS: All cases reported as either suspicious or positive for malignancy on pleural effusion cytology (PFC) over the past 1 year were retrieved. The clinical details were obtained from requisition forms. Cases with predominant single-cell pattern, clinically suspicious of carcinoma lung were segregated. These were de-stained and immunocytochemistry (ICC) for TTF-1 was performed. RESULTS: Of 103 cases reported as either suspicious or positive for malignancy on PFC, 29 had a predominant single-cell pattern. Of these, 13 (44.8%) were primary lung carcinoma. The rest were metastasis from ovary (5; 17.2%), breast (2; 6.9%), stomach (2; 6.9%), lymphoma (1; 3.5%), and Ewing's sarcoma (1; 3.5%). Five (17.2%) were those with unknown primary. All cases of lung carcinoma were positive for TTF-1 ICC. CONCLUSION: Single-cell pattern of pulmonary adenocarcinoma is commoner than popularly believed. This pattern may be difficult to differentiate from carcinoma cells of other sites as well as from reactive mesothelial cells. A high degree of suspicion is therefore needed to perform relevant ICC to clinch the correct diagnosis.

GTF2I Mutation in Thymomas: Independence From Racial-Ethnic Backgrounds. An Indian/German Comparative Study.

Thymomas are the most frequent adult mediastinal cancers. Their etiology is unknown and their pathogenesis poorly understood. Racial, ethnic and environmental factors influence tumorigenesis in many cancers, but their role in thymomas remains unclear to date. In this study that included pretreatment thymoma cases from India and Germany (n = 37 and n = 77, respectively) we compared i) the prevalence of the thymoma-specific chromosome 7 c.74146970T > A mutation of the GTF2I gene in type A and AB thymomas; ii) epidemiological features; and iii) the frequency of myasthenia gravis (MG). Due to a known predominance of GTF2I mutation in A and AB histotypes, we included only a marginal number of type B thymomas as a control group in both cohorts. While the distribution of histological types between the cohorts was similar (p = 0.1622), Indian patients were strikingly younger (p < 0.0001; median age 50 vs. 65 years) and showed significantly lower tumour stage (Masaoka-Koga stage I) at primary diagnosis (p = 0.0005) than the German patients. In patients with known MG status (n = 17 in Indian and n = 25 in German cohort), a clear trend towards more frequent MG was observed in the Indian group (p = 0.0504; 48 vs. 82%). The prevalence of the GTF2I mutation (analysed in n = 34 Indian and n = 77 German patients) was identical in the two cohorts. We conclude that racial-ethnic and environmental factors do not significantly influence the most common molecular feature of thymomas but may have an impact on the timing of clinical presentation.

The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group.

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

Paediatric mesenchymal tumors of the mediastinum.

Paediatric mesenchymal tumors of the mediastinum are extremely rare tumors forming approximately 2% of all mediastinal neoplasms. There are subtle differences in the clinical and histomorphological profile of these tumors from their adult counterparts. The management of these tumors in the children is primarily surgical. This review was done to perform a comprehensive analysis of these mesenchymal tumors in the paediatric age group.

Indian experience of AUS/FLUS diagnosis: is it different from rest of Asia and the West?-A systematic review and meta-analysis.

BACKGROUND: Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is the most heterogeneous subcategory of the Bethesda system for thyroid cytopathology with laid down permissible limits of frequency and risk of malignancy (ROM). Due to differences in thyroid clinical practice worldwide, variations have been found in frequency, resection rates (RR) and ROM. Therefore, this systematic review and meta-analysis of AUS/FLUS across different regions was conducted and comparison of data from India was done with the rest of Asia and the West. METHODS: We searched PubMed and Google search engines from January 2009-Dec 2019 using terms "AUS Thyroid" and "FLUS Thyroid". Meta-analysis was performed using DerSimonian-Laird method and 95% confidence intervals were calculated using random effects model. Independent samples t-test was used to compare frequency, RR, and ROM of AUS/FLUS between India, rest of Asia and the West. RESULTS: Out of 15,000 studies on internet, 60 (18 Indian, 12 Asian and 30 Western) were included. Total aspirates were 201,657; 14,279 Indian, 62,448 Asian, 124,930 Western. Pooled estimates were: frequency 7.3% (6.3-8.3%), RR 41.9% (37.4-46.6%), ROM 33.3% (26.8-39.9%). Pooled prevalence of rate did not vary significantly across the three regions. Pooled prevalence of RR was highest in India (52.9%) and lowest in rest of Asia (26.5%); of ROM was highest in Asia (45.9%), lowest in the West (26.3%) (P<0.01). Statistical analysis demonstrated publication bias, limited to Indian and Western studies. Papillary thyroid carcinoma was the most common surgical diagnosis (87.9%; 1,082/1,231). CONCLUSIONS: This meta-analysis showed differences in thyroid clinical practice followed in India, rest of Asia and the West. Although pooled prevalence of rate of AUS/FLUS was similar across the three, pooled RR and ROM varied. AUS/FLUS nodules were more frequently resected in Indian and Western studies than in rest of Asia. ROM was higher than recommended values in all three areas, being intermediate for India.

PD-L1 Expression in Small Cell and Large Cell Neuroendocrine Carcinomas of Lung: an Immunohistochemical Study with Review of Literature.

High-grade neuroendocrine tumors (HGNET) have distinctive tumor biology/behaviour. Newer modalities of treatment (immunotherapy) for them have been included in recent NCCN guidelines. Detection of programmed death receptor-ligand 1 (PD-L1) expression by immunohistochemistry have made easy identification of patients eligible for immunotherapy. We aimed to ascertain expression of PD-L1 on small cell and large cell neuroendocrine carcinomas of lung and review existing literature. Eighty-five cases of HGNET lung (primary/metastatic), were retrieved and reviewed. Immunostaining for PD-L1 using clone SP263 was done. Any amount/intensity of membranous staining of > = 1% tumor cells was cut-off for positivity. Previously published studies using Google and/Pubmed search engines were reviewed. Of 85 cases, 70 were small-cell lung cancer (SCLC), 11 large-cell neuroendocrine carcinoma (LCNEC) and 4 combined SCLC. Median age was 46.5 years with male preponderance. No PD-L1 expression was seen in 91.6% cases. The 7 positive cases were 4 LCNEC, 2 SCLC and 1 combined SCLC. The percentage positivity varied from 1-100%; lower percentage positivity was seen in SCLC. PD-L1 expression on immune cells was seen in 31.3% cases. Sixteen studies evaluating 1992 NET were found; E1L3N PD-L1 clone was commonly used clone. PD-L1 positivity was associated with better prognosis in most studies. There are only a few studies available in literature related to PDL1 expression in high grade neuroendocrine carcinomas of lung. In general, PD-L1 positivity is highly variable and seen in lower percentage of these tumors. With the recent approval of immunotherapy, biomarkers other than PD-L1 should also be investigated in these tumors.

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

OBJECTIVE: 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. MATERIALS AND METHODS: 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; <10 mitosis/10 High power field (HPF) or >=11 mitoses/10 HPF and Ki-67 index; <10% Ki-67 and >=11% Ki-67. RESULTS: 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). CONCLUSION: 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.

Thymic lesions of the paediatric age group: a comprehensive review of non-neoplastic and neoplastic etiologies.

Thymus is an important part of the immune system of the paediatric age group. Thymic lesions are rare causes of anterior mediastinal pathology. Their occurrence in children is rarer, nevertheless, knowledge about their pathologies help in clinching the correct diagnosis. All lesions both non-neoplastic as well as neoplastic are found in children, however, they differ from adults not only in the clinical presentation but also in the pathogenesis and natural history of the disease. Thymic hyperplasia may not actually be true if age is taken into consideration. Similarly, a type B thymoma may be mistakenly diagnosed as a lymphoblastic lymphoma especially on small biopsies. This review has been carried out after extensive search of literature using the Google and Pubmed search engines. An attempt has been made to comprehensively cover all aspects of thymic pathology of the paediatric age group having historical significance as well as the recent updates.

Immunohistochemical Assessment of BAP1 Protein in Mucoepidermoid Carcinomas.

Mucoepidermoid carcinomas are common malignant salivary gland tumors. Despite recent advances in diagnosis and treatment, there has not been much improvement in outcome of these patients, necessitating identification of novel targeted therapeutic agents. Genomic profiling of mucoepidermoid carcinomas has recently revealed aberrations in BAP1 gene. Therefore, we conducted this study to identify BAP1 loss by immunohistochemistry in these tumors. Mucoepidermoid carcinoma cases were retrieved; hematoxylin-and-eosin stained sections were reviewed. Immunohistochemistry for BAP1 was performed. Forty cases were assessed, including 25 salivary gland and 15 pulmonary mucoepidermoid carcinomas. There were 19 cases in the parotid (76%), two in submandibular gland (8%), and remaining 16% from minor salivary gland locations. Ten (40%) were low grade, nine (36%) were intermediate grade, and six (24%) were high grade mucoepidermoid carcinomas. Thirteen (86.7%) pulmonary mucoepidermoid carcinomas were tracheobronchial, while two (13.3%) were intraparenchymal; all were low grade mucoepidermoid carcinomas. On immunohistochemistry, BAP1 nuclear staining was retained in all cases (100%), irrespective of tumor location or grade. Therapeutic connotations necessitate the identification of readily applicable techniques to detect BAP1 loss in mucoepidermoid carcinomas. Using immunohistochemistry, loss of BAP1 staining was not seen in any of our cases, suggesting insensitivity of BAP1 IHC to detect aberrations at genomic level in these tumors. Analysis of BAP1 alterations by targeted sequencing may therefore be performed prior to excluding the possibility of response to BAP1-targeted therapeutics based on immunohistochemistry alone.