Background: Tanycytic ependymoma (TE) (WHO grade II) is a rare and morphologically distinct variant of ependymoma with only 77 cases reported worldwide so far. Variable clinical and radio-pathological features lead to misdiagnosis as WHO grade 1 tumors. On imaging, differentials of either schwannoma, meningioma, low-grade glial (like angiocentric glioma), or myxopapillary ependymoma are considered. In this study, we aim to discuss clinical, radiological, and pathological features of TE from our archives. Method: We report clinicopathological aspects of six cases of TE from archives of tertiary care center between 2016 and 2018. Detailed histological assessment in terms of adequate tissue sampling and immunohistochemistry was done for each case. Result: The patient's age ranged between 10 and 53 years with a slight male predilection. Intraspinal location was seen in two cases (intramedullary and extramedullary), three cases were cervicomedullary (intramedullary), and one was intracranial. One case was associated with neurofibromatosis type 2. Four cases mimicked as either schwannoma or low-grade glial tumor on squash smears. On imaging, ependymoma as differential was kept in only two cases and misclassified remaining either as low-grade glial or schwannoma. Discussion: In initial published reports, the spine is the most common site (50.4%) followed by intracranial (36.4%) and cervicomedullary (3.9%). They have also highlighted the challenges in diagnosing them intraoperatively and radiologically. Treatment is similar to conventional ependymoma if diagnosed accurately. A multidisciplinary approach with the integration of neurosurgeon, neuroradiologist, and neuropathologist is required for accurate diagnosis and better treatment of patients.

Aims: Astrocytomas are common tumors and grade is an important parameter in determining the treatment modalities. Tumor proliferation activity should be determined for the differentiation of grades II and III tumors. In difficult cases, an auxiliary parameter is required. Nucleostemin (NS) is nucleolar Guanosine triphosphate (GTP)-binding protein 3. It has important roles in cell proliferation, cell cycle regulation, self-renewal, and apoptosis. In this study, we investigated whether the level of NS expression is different in grades II and III astrocytomas. Settings and Design: Adults diagnosed with grades II and III astrocytomas were included in the study. Material and Methods: Paraffin blocks that best reflected tumor morphology were studied via immunohistochemical staining for NS. Only nuclear staining was evaluated; cytoplasmic staining was not considered. Statistical Analysis Used: Fisher's exact test, continuity corrections, and Pearson's Chi-square tests were used in the crosstabs. The survival analysis was based on the Kaplan-Meier method. Results: Only 20% (6/30) of grade II tumors had high intensity staining, while 54,2% (13/24) of grade III tumors had high staining intensity. NS was significantly more intense in grade III tumors than grade II tumors. In cases with high NS expression, survival was significantly shorter than the cases with low expression. Conclusion: NS is significantly higher expressed in grade III tumors than grade II tumors. In difficult cases, it can be used as a useful proliferation marker in the differentiation of grades II and III astrocytomas.

Background: Silicosis is a public health issue in developing countries for long and cannot be completely cured. Objective: To study the changes of ion content with TNF-α and TGF-β expression in alveolar lavage fluid (BALF) at different time points in rats exposed to silica and to investigate their correlation with pulmonary fibrosis. Methods: 42 rats were randomly divided into control group (n = 12) and exposure group (n = 30). Tissues of right lower lungs were collected and fixed for further Hematoxylin-eosin (HE) and Masson staining. We collected the BALF to examine the inflammatory cytokines of TNF-α and TGF-β and measured the ion contents in BALF. Results: The increase of TNF-α level was earlier than TGF-β. The content of silica in BALF was significantly increased after exposure and reached the maximum at 7^th day, similar to the curve of cytokine TGF-β level. However, phosphorus ions increased quickly after gradual decline of silicon ion and roughly proportional to the curve of degree of fibrosis. Conclusions: Crystalline silica exposure can cause changes in TGF-β and TNF-α in BALF and accompanied with fibrosis and ions content variation. The abnormal expression of phosphorus ion may have significance in the occurrence and development of silicosis.

Background: Acute rheumatic fever (ARF) and its post-inflammatory sequel chronic rheumatic heart disease (RHD) are endemic in the Indian setting. Despite the updated Jones criteria, many cases of ARF remain undiagnosed or are missed. Aims: This study aims to analyze pathological profiles of such cases and their importance in context of clinical presentation and Jones criteria. Materials and Methods: A 22-year retrospective observational study of ARF was conducted in the Department of Pathology in a tertiary care institute. The cases were categorized as 1. Those fulfilling and 2. those partially or not fulfilling the Jones Criteria. Based on the autopsy findings, the lesions were classified as categorized mitral stenosis and/or regurgitation (MS ± MR) and pure mitral regurgitation (MR). Statistical Analysis: Nil. Results: In 22 years, among 697 cases of autopsied cases of RHD, there were 59 cases (8.5%) of ARF. Among them, seven cases fulfilled the Jones criteria; five of them were clinically diagnosed. The remaining 52 cases (88.1%, 34 with MS ± MR and 18 with MR) did not fulfill or partially fulfilled the Jones criteria and were not diagnosed. A total of 18 patients (30.5%) had the first attack of ARF, whereas recurrences were noted in the remaining patients (69.5%). Conclusions: The study indicates that the typical manifestations of ARF under Jones criteria may not be present, especially in cases with recurrence. Hence, a presumptive or possible diagnosis of ARF can be made with presence of minor criteria or strong clinical suspicion in such cases.

Introduction: Malignant mesothelioma is an aggressive neoplasm arising from serosal lining and has a poor prognosis. Definite diagnosis requires confirmation through a biopsy; however, it is sometimes difficult on microscopic evaluation alone and requires the use of a wide panel of immunohistochemical markers. So, immunohistochemistry (IHC) is of paramount importance and must be routinely used for a definite diagnosis. Till date, very few studies on morphology and detailed IHC markers of mesothelioma have been reported from India. Aims: To analyze the histomorphological findings of malignant mesothelioma, study the utility and role of the various immunohistochemical markers. Material and Methods: A total of 76 cases of mesotheliomas diagnosed at a tertiary cancer center in Udaipur were analyzed retrospectively from January 2015 to January 2020. Comprehensive data were analyzed including demographic, clinical, radiological, histopathological features along with a wide panel of IHC markers. Results: Mesothelioma occurs over a wide age range from 40 to 70 years. It most commonly involved pleura in 68 cases (89.47%) with very few cases from the peritoneum. On computed tomography (CT) scan, nodular pleural or peritoneal thickening was present. On microscopy, the most common histopathological type was epithelioid mesothelioma (58 cases, 74.3%) followed by sarcomatous (9 cases, 12.8%), deciduoid (6 cases, 8.6%), and 3 cases of biphasic (4.3%). On IHC, WT1, mesothelin, and calretinin markers were positive in 85.91%, 80%, and 93.33% cases of mesothelioma, respectively. Other markers were helpful to rule out differential diagnosis in difficult scenarios. Conclusion: Therefore, the correlation of histopathology with clinico-radiological findings and judicious use of a panel of IHC markers is required for routine evaluation and definite diagnosis. IHC is also useful in situations with similar morphological spectrum in specific locations.

Background: The programmed cell death protein – 1 (PD-1) – programmed cell death ligand – 1 (PD-L1) axis is emerging as a promising target for immunotherapy in triple-negative breast cancers (TNBC). Aims: We analyzed the expression of PD-L1 in TNBC cases, with special emphasis on lymphocyte-predominant tumors along with correlation of the same with clinicopathological features and outcome. Settings and Design: Tissue microarrays (TMA) were prepared from resection specimens of TNBC cases diagnosed from 2004 to 2008. Subjects and Methods: Immunohistochemical staining was performed on the TMA using the ventana PD-L1 antibody (Clone SP 263). Statistical Analysis: Chi-square test was used for correlation of PD-L1 positivity in tumor and immune cells with clinicopathological features. Univariate and multivariate survival analyses were carried out using the Kaplan Meir and Cox Regression methods, respectively. Results: Overall, PD-L1 staining was seen in 35.9% (66 out of 184) tumors. PD-L1 positivity of tumor cells was seen in 14.7% (27 out of 184 cases), whereas stromal immune cell expression was observed in 21.2% (39 out of 184) cases. Lymphocyte-predominant tumors showed statistically significant expression of PD-L1 in both tumor (P < 0.0001) and immune cells (P 0.036). On univariate analysis, PD-L1 in immune cells was associated with good overall survival (P 0.05) as well as disease-free survival (P 0.013). On multivariate analysis, the same was associated with a significantly decreased risk for recurrence (P 0.018). Conclusion: PD-L1 expression in stromal immune cells proved to be a significant prognostic factor for TNBC. This data can serve as a baseline to plan clinical trials with anti-PD-L1 drugs for TNBC in the Indian setting.

Aim: We aimed to determine the hormone receptor status in breast cancers and to investigate the relationship between single hormone receptor-positive, double hormone receptor-positive, double hormone receptor negativity, and human epidermal growth factor receptor 2 (HER2) status and some clinicopathological features. Materials and Methods: The study includes 85 patients who were diagnosed in our center between 2018 and 2019 and having surgical specimens were included in the study. Data of the cases, such as estrogen receptor (ER), progesterone receptor (PR), HER2 status, silver in situ hybridization (SISH) evaluation results, age distribution, histopathological findings were recorded. Results and Conclusions: We investigated the relationship between age, grade, tumor size, lymph node metastases and ER, PR, and HER2. However, there was not a significant association between ER, PR, and HER2 and age, tumor size, lymph node metastases (P > 0.05). On the other hand, we found a significant association between grades and ER (P = 0.02) and PR (P = 0.004), but not between grades and HER2 (P > 0.05). High-grade tumors were tumors with the lowest ER, PR positivity rate. Considering the four subtypes, cases aged above 45 years were at most double hormone receptor-positive (75%) and ER-positive/PR-negative (56%), respectively (P < 0.001). High-grade tumors were mostly double hormone receptor-negative and at least double hormone receptor positive. The ER-positive/PR-negative subtype was between these two groups (P < 0.001). The increased tumor size (T3) and increased metastatic lymph node number (N2 and N3) were observed at least in the ER-positive/PR-negative subtype. The majority of cases are in the older age group and invasive ductal carcinoma (IDC) is the most common tumor type. Older cases are most frequently double hormone receptor-positive and ER-positive/PR-negative, respectively. The ER, PR positivity rate is low in high-grade tumors. ER-positive/PR-negative tumors are of a higher grade than double hormone receptor-positive tumors, but they are of a lower grade than double hormone receptor-negative tumors. The increased tumor size and increased lymph node metastasis number are at most in the double hormone negative subtype and at least in the ER-positive/PR-negative subtype. The ER-negative/PR-positive subtype is observed very rarely, which raises the question of whether ER-negative/PR-positive tumors really exist. Further studies are needed to investigate this subtype and its properties.

Background: Human epidermal growth factor receptor 2 (HER2) over-expression in breast cancer is associated with aggressive tumor behavior and predicts response to targeted therapy. Accurate HER2 result is paramount for optimal patient management. However, routine HER2 immunohistochemistry (IHC) testing are subjected to intra- and inter-laboratory variability. Objective: This study aims to determine inter-laboratory variation in HER2 IHC testing through a slide-exchange program between five main reference laboratories. Method: A total of 20 breast carcinoma cases with different known HER2 expression and gene status were selected by the central laboratory in five testing rounds. Three unstained tissue sections from each case were sent to participating laboratories, which immunostained and interpreted the HER2 immunohistochemistry result. One of the stained slides was sent to one designated participating laboratory for evaluation. Results were analyzed by the central laboratory. Results: A complete concordance was achieved in six IHC-positive and six IHC-negative cases, its gene status of which was confirmed by in-situ-hybridization (ISH) study. The discordant results were observed in six equivocal cases, one negative case and one positive case with a concordance rate of 50–88.3%. Interestingly, the negative discordant case actually displays tumor heterogeneity. Good inter-observer agreement was achieved for all participating laboratories (k = 0.713-1.0). Conclusion: Standardization of HER2 testing method is important to achieve optimum inter-laboratory concordance. Discordant results were seen mainly in equivocal cases. Intra-tumoral heterogeneity may impact the final HER2 IHC scoring. The continuous quality evaluation is therefore paramount to achieve reliable HER2 results.

Background: The “Ring-and-Sling” complex (RSC) comprises congenital tracheal stenosis and an abnormal origin/course of the left pulmonary artery. Based on clinical and imaging studies, the luminal narrowing is assumed to be as a result of rings cartilage (forming an “O”). Aims: This is a postmortem based study of tracheal histology in infants after an autopsy encounter of a case of RSC. Subject and Methods: RSC was identified in an infant at autopsy. The tracheal histomorphology revealed the presence of cartilaginous plates (instead of rings) and fibro-elastotic proliferation at the site of trachealis muscle. These changes prompted a study on variations in the histology of the trachea (with no known anomaly) in 35 autopsied neonates and infants. The transverse sections of the trachea were taken at one or more levels (Level 1 – at the level of the thyroid, Level 2 – midway between the thyroid and the carina, and Level 3 – just above the carina. Statistical Analysis: Epi-info software (v1.4.3, CD, US). Results: On histology, 83 sections showed the trachealis muscle on the posterior aspect. A single semicircular cartilage was identified in only 17 of the 83 sections studied (20.5%, 6 in level 1, 9 in level 2 and 2 in level 3). In the remaining 66 sections (79.5%), the cartilage was disposed as multiple plates, ranging in number from 2 to 10. No significant association was found between semicircular cartilage rings and age, sex, gestational age, and level of section (P < 0.05). However, 14 cases with sectioning at all three levels were taken into account; all levels showed more cartilaginous plates compared to single rings, which were more common at level 1 (P > 0.05). Conclusions: The “ring” in RSC and normal infantile tracheas show cartilage plates with intermittent semicircular cartilage rings. These findings may have surgical implications for tracheal anomalies and bode favorable surgical outcomes.

Background: Gall bladder carcinoma (GBC) is a multi-factorial disease, involving multiple genetic alterations. The present pilot study aims to explore some of the molecular pathways, by studying immunohistochemical (IHC) expression of biomarkers (HER2/neu, KRAS, and VEGF) in GBC with their correlation with various clinicopathological parameters. Aim of the Study: To study the expression of prognostic biomarkers (HER2/neu, KRAS and VEGF-A) in GBC and their correlation with clinico-morphological parameters. Materials and Methods: This prospective study was conducted over a period of 2 years. The study group included tissue of GBC (29) reported as malignant on histopathology and cholecystitis as a control group (29) for histopathological evaluation and IHC expression of above markers. Results: HER2/neu was expressed in 27.5% cases, and KRAS in 51.6%; however, both showed no association with tumor type, stage and grade. No association was found in KRAS expression and dysplasia. Vascular Endothelial Growth Factor - A (VEGF-A) was expressed in 86.1% cases, of which strong positivity was seen in 48.27%; it showed significant association with tumor stage (P value-0.027, Fishers' exact test), hence possibly suggesting its role in tumor progression; though no association was found in VEGF expression with tumor type and grade. No significant association was seen with vascular and tumor invasion also. Conclusion: The results suggest that the VEGF-A expression may be used as a potential prognostic biomarker in GBC.

Introduction: Pancreaticobiliary subtype of Periampullary carcinoma (PAC) has a poor prognosis in comparison to the intestinal subtype. We assessed the potential of cytokeratins and mucin markers to classify the sub-types of periampullary tumors and compared them with the survival data to identify markers that may predict prognosis. Methodology: PAC tumor tissues were obtained from 94 patients undergoing Whipples Pancreaticoduodenectomy. Paraffin-embedded tissues were immunostained with cytokeratins CK7, CK20), mucins (MUC1, MUC2, MUC5Ac), and CDX2 antibodies. The survival status of patients was obtained as follow-up up to 5-years of surgery. The Receiver Operating Character Curve (ROC) analysis was used for detecting sensitivity and specificity. The survival data were analyzed using the Kaplan-Meier survival curve. Results: Tumors were initially categorized on the basis of histological classification as pancreaticobiliary (n = 46), intestinal (n = 35) and indeterminate (n = 13). Further, using immunohistochemical markers (MUC1, CK20, and CDX2), we gave systematic classification of IHC-PB (n = 51), IHC-Int (n = 30) and IHC-Mixed (n = 13). The interobserver analysis showed good agreement between histologic and IHC type with a kappa value of 0.554. Combined expression of CK20, MUC1 and CDX2 accurately classify the mixed type of tumor. Overall survival rate and duration were 74.4% and 44.95 ± 2.29 months. Survival analysis for subtypes reveal, pancreaticobiliary tumors have low survival (27.9 ± 1.63 months) than mixed type (35.5 ± 0.45 months) and intestinal-type (52.92 ± 2.18 months). Among these, intestinal-type have better survival. Only TNM Stage III (tumor staging as per American Joint Committee on Cancer classification) and perineural invasion have been associated with predicting poor survival in PAC patients. Conclusion: Our results suggest that the combined expression of MUC1, CK20 and CDX2 could serve as markers to diagnose histological inconclusive specimens as mixed subtype tumors.

Introduction: Synovium has been documented as a primary site of inflammation and a major effector organ in a variety of joint diseases. Study of simple technique like synovial biopsy can help in early diagnosis and treatment of diseases significantly improving outcome of patient in cases of rheumatoid arthritis, osteoarthritis, etc., Only limited data exist on utility of synovial biopsies. Aim and Objectives: To analyze the pattern of synovial lesions to differentiate between different kinds of arthritis. Also, to identify early stages of arthritis so as to prevent unnecessary invasive surgical procedure. Materials and Methods: It's a retrospective study to analyze 103 cases of synovial lesions diagnosed in last five years at a tertiary care orthopedic center. All synovial biopsies obtained mainly by open method and few by arthroscopic method, that came to the Dept of Pathology were included. Lesions were classified into four categories that is, inflammatory joint diseases, degenerative joint diseases, tumor-like conditions and tumors. Results: Age group most affected was between 61 and 70 years, with male predominance. Osteoarthritis (OA) was the most common histopathological diagnosis. Early OA tissues showed greater lining layer thickness, vessel proliferation, and inflammation, while surface fibrin deposition along with fibrosis was noted in later stages. Conclusion: The histo-morphological observations made in this study may have important therapeutic implications for some patients during the early evolution of arthritis and could prevent unnecessary operative intervention of later stages.

Background and Objectives: Synovial sarcomas (SS) are enigmatic soft tissue tumors, which are yet to have a defined cell of origin. SS have a variety of differential diagnosis depending upon the age of the patient and the site of presentation. This makes diagnosis cumbersome unless the specific fusion SS18:SSX is identified by reverse transcription-polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH). Immunohistochemistry is a useful tool in resource-poor settings in helping to narrow the differentials and help diagnose this tumor. This study set about assessing possible candidate immunohistochemical markers in their utility to recognize SS. Methods: Forty cases of SS, proven by FISH were included. A tissue microarray (TMA) was constructed, and immunohistochemistry was done using antibodies – TLE1 (OTI1F5), β-catenin (14), INI1 (MRQ-27), CK7 (OV-TL), CK19 (polyclonal), SS18 (polyclonal), calponin (CALP), and claudin1 (Polyclonal). The expression was analyzed to arrive at sensitivity and specificity. Results: TLE1 had a sensitivity of 92.5% and a specificity of 100%; β-Catenin had a sensitivity of 17.5% and specificity of 100%; Calponin had a sensitivity of 97.5% and a specificity of 81.25%; SS18 had a sensitivity of 95% and specificity of 100%; INI1 had a sensitivity of 95% and specificity of 100%; CK7 had a sensitivity of 90% and specificity of 87.5%; CK19 had a sensitivity of 90% and a specificity of 59.38%; and Claudin had a sensitivity of 85% and a specificity of 78.12%. Interpretation and Conclusions: The study showed both TLE1 and SS18 are robust diagnostic markers of synovial sarcoma with a sensitivity of 92% and 95%, respectively. INI1 can be used to discriminate SS from nonepithelioid and nonrhabdoid differentials. Calponin expression is helpful to differentiate poorly differentiated SS from its mimics. CK7 is a better marker than CK19 and can be used as a replacement for EMA in the initial screening panel. The use of claudin1 was restricted to delineating the epithelial component. β-Catenin had poor sensitivity, restricting its utility in SS.

Objective: To analyze the clinicopathological features of metastatic bone tumors over a period of two decades and identify the primary site of malignancy in metastasis of unknown origin. Materials and Methods: A total number of 365 cases were included in the study. The clinical features and location of the tumors were noted. The histopathological features of all the cases were studied. Immunohistochemistry (IHC) was done either to categorize or confirm the primary diagnosis using organ specific/organ restricted markers. Results: A total 712 bony sites were involved by metastasis in 365 patients, of which spine was the most commonly affected. Metastasis was the initial presentation in 69.5% patients. The primary site was known in 220 patients and almost half of them were detected after the diagnosis of metastasis. IHC was used as adjunct to suggest the possible origin in cases with unknown primary in 27.4%. Among the metastatic carcinoma, adenocarcinoma was the most common histological subtype with thyroid being the most frequent primary site of origin followed by lung and breast. Conclusion: More than two-third of cases in surgical pathology practice present as initial manifestations. Detection rate of primary depends on extent of metastatic work-up and IHC with organ specific/organ restricted markers to facilitate treatment with bone targeting agents.

Background: Multiple primary malignancy (MPM) is defined as occurrence of two or more synchronous or metachronous primary malignancies. With the rise in cancer burden and meticulous screening of index primary malignancy (IPM) during treatment, increased incidence of second primary malignancy (SPM) is expected. This study was undertaken with an attempt to analyze the incidence, commonest associations, management strategies, and clinical outcomes of MPM. Materials and Methods: This is an observational retrospective study carried out in a single institute with patients registered between 1^st January 2015 and 31^st August 2019. The International Association of Cancer Registries and International Agency for Research on Cancer (IACR/IARC) definition was used for identification of IPM and SPM. Synchronous SPM was defined as malignancy occurring within 6 months from the diagnosis of IPM. Results: Out of 16,461 registered patients during the study interval, 44 (0.26%) cases were found to have MPM. A total of 31 (70.5%) cases were women and 13 (29.5%) cases were men. Median age at presentation of IPM was 48 years and of SPM was 56 years, with median duration between two primaries being 38 months. Seven patients (15.9%) had synchronous malignancies. Gynecological tumors were the most common site of IPM presentation (n = 14, 31.8%) followed by breast (n = 09, 20.5%) and head and neck tumors (n = 07, 15.9%), respectively. The most common SPM was gynecological tumors (n = 12, 27.3%) followed by gastrointestinal malignancies (n = 10, 23.3%). Curative treatment was offered to 88% of patients with IPM and 70% patients with SPM. At a median follow-up of 365 days, 21 (47.72%) patients were disease free, six (13.6%) died of disease and nine (20.5%) were lost to follow-up. Conclusion: The study emphasizes the importance of detecting SPM as a result of improved diagnostic and screening procedures. Clinicians should be aware of it and offer multidisciplinary management.

Invasive pulmonary aspergillosis (IPA) is mainly caused by Aspergillus fumigatus and other Aspergillus species. Galactomannan (GM) is a polysaccharide antigen that exists primarily in the cell walls of Aspergillus species. GM may be released into the blood and other body fluids even in the early stages of Aspergillus invasion; therefore, detection of the GM antigen level can be useful in making an early diagnosis of IPA.

Background: COVID-19 is a pandemic viral disease that has affected the Indian population very badly with more than 8.46 million cases and > 0.125 million deaths. Aim: Primary objective of the study is to establish the role of hematological, coagulation and inflammatory biomarkers in early identification of clinically severe covid-19 cases. Materials and Methods: This study was conducted from July 2020 to August 2020 at a dedicated COVID-19 referral hospital in central India. Only RT-PCR confirmed COVID-19 positive 300 cases admitted in the hospital were included in this study. Based on the clinical assessment, patients were categorised as mild, moderate, and severe groups as per ICMR guidelines. Blood samples of all cases were tested for haematological, coagulation and inflammatory biomarkers and mean values were compared among the three groups of patients. Results: 46% patients belonged to >60 years of age group. Hematological parameters like total leukocyte count, absolute neutrophil count, Neutrophil: Lymphocyte ratio, Platelet: Lymphocyte ratio significantly increased with lymphocytopenia (P=0.001). Coagulation profile(D-dimer and PT) and inflammatory biomarkers like CRP, LDH, ferritin, procalcitonin and NT- Pro BNP, all were significantly increased with severity of patients(p=0.001). ROC plotted for all the parameters between severe v/s non-severe cases showed that CRP, LDH and D-dimer had a good discriminative precision with AUC >0.8. Conclusion: We suggest that biochemical markers like CRP, LDH and D-dimer can be used as a screening tool to differentiate severe patients from non-severe patients of Covid-19 disease in order to identify severe disease at early stage for optimal utilization of resources & reducing further morbidity & mortality.

Objectives: The spectrum of thrombophilia in women with recurrent pregnancy loss (RPL) is different in Indian ethnicity as reported by few studies. We aimed to study the prevalence of thrombophilia in RPL patients referred to hematology department of a tertiary centre. Material and Methods: This is an observational study of 112 RPL patients with no apparent cause after extensive workup for non-hematological causes. The investigations performed were routine coagulogram, APLA workup, plasma homocysteine, MTHFRC677T polymorphisms, Protein C, free Protein S, Anti-thrombin III levels, test for Activated Protein C resistance (APC-R) ,Factor V Leiden and Prothrombin gene G20210A mutation. Results: Of 112 patients, at least one thrombophilia was identified in 70.5% and combined thrombophilia in 12.5% patients. Hyperhomocysteinemia (30.4%) and APLA (25.9%) were the commonest thrombophilia whereas anticoagulant defects were seen in 12.5% of the population. Protein C deficiency (5.35%) was the commonest anticoagulant defect followed by APCR (3.6%). Mutational analysis revealed MTHFRC677T polymorphism in 20.5% whereas Factor V Leiden heterozygous in 1.8% patients. None of the patients had homozygous Factor V Leiden or Prothrombin gene G20210A mutation. Hyperhomocysteinemia, MTHFRC677T and Protein C deficiency were more associated with early pregnancy losses whereas Protein S deficiency, Factor V Leiden and APLA caused both early and late losses. Patients with greater number of losses were positive for homozygous MTHFRC677T, factor V Leiden and APLA. Conclusion: The approach to investigating Indian women with RPL should be based on the prevalence of thrombophilia which is unique to Indian ethnicity.

Context: Teaching methods in pathology for undergraduate medical students are not effective. Aims: To document measures that can be adopted by individual teachers that can excite the interest, participation of the students and help them learn pathology in a clinical reasoning context. Settings and Design: Medical students in a large international medical school with class sizes of 700–900 were taught the pathology course in a period of sixteen weeks for two cohorts of students each year over a period of twenty years. Subjects and Methods: Specific learning objectives were devised to achieve higher levels of cognitive domain including interpretation, analysis and problem solving of clinical data of patients related to the objectives. The teaching sessions were modified to provide for maximum active participation by students with effective feedback at multiple points. Additional learning tools like concept maps, clickers, modified essay questions, flipped classrooms, clinicopathological conferences, directed self-learning activities were included. Learning objectives and assessment tools for professional behavior and communication skills were included. Results: The students actively participated in all the learning activities with enthusiasm and achieved the objectives as reflected in the performance in the in-house examinations and the USMLE step one examination which tests clinical vignette-based problem-solving principles of which around 70% are related to pathology. Conclusions: The teaching sessions in pathology were useful and effective with adaptation to interactive, clinical reasoning platforms for teaching and assessment.

We present a case of acute myeloid leukemia developing acute graft-versus-host-disease (GVHD) in the post transplant phase. The patient had GVHD of skin, liver and gastro-intestinal tract (resolved) with polymicrobial sepsis. The clinical course, treatment and pathological findings on autopsy including the cause of death have been discussed.

Background: Follicular dendritic cell sarcoma (FDCS) is a rare tumor derived from follicular dendritic cells (FDC) occurring in lymph nodes and extranodal sites. It is usually regarded as an indolent tumor with a tendency of local recurrence but a low risk of metastasis. Common extranodal sites are liver, lung, tonsil, spleen, soft tissue, and mediastinum. Extranodal FDCS of gastrointestinal tract (GIT) is exceedingly rare, with just 36 cases reported in the literature. Methods: We report an unusual case of FDCS of caecum in a 13-year-old boy who presented as intussuception. On histology, it posed a diagnostic challenge for us. An inconclusive initial immunohistochemistry (IHC) lead us to suspect FDCS which was confirmed by FDC markers. Conclusions: The diagnosis of FDCS at extranodal site like GIT is all the more challenging because of its rarity, morphologic heterogeneity, and lack of awareness.

Pediatric colorectal carcinomas are extremely rare with an incidence of nearly 1.3 per million. Diagnosis is usually delayed following a lack of suspicion at this age. Increasing incidence as well as awareness provides an insight into the disease entity. Two cases of childhood colorectal carcinoma, one in an 11 and another in a 19-year-old boy are presented. However, they have been reparted to carry a forarable outcome. Both the cases showed mucin and signet ring cells which indicates an aggressive behavior. The presentation highlights the clinical characteristics and genetic implications in most of the patients. However, both our cases did not show any predisposing or genetic predisposition. These cases are presented to make aware the readers as to how the common dictum can be reversed and adolescents can also be affected by cancer, a disease of the elderly. Early diagnosis can provide a better management and prognosis.

Alveolar soft part sarcoma (ASPS) and certain perivascular epithelioid cell neoplasms (PEComas) exhibit overlapping histopathological features, including immunohistochemical expression of TFE3, as well as TFE3 gene rearrangement. PEComas with an epithelioid morphology are known to exhibit variable immunoexpression of muscle markers. At the same time, aberrant immunoreactivity of HMB45 immunostain, which is invariably, used to substantiate a diagnosis of a PEComa, has been reported in various other tumors. Herein, we discuss two rare cases of soft tissue tumors with overlapping morphological and immunohistochemical features. Case1: A 34-year-old male underwent a biopsy for a recurrent, right-sided nasal polyp. Biopsy showed polygonal tumor cells, containing prominent nucleoli, arranged in a “nesting-type”/alveolar growth pattern. Immunohistochemically, tumor cells displayed TFE3 positivity and an aberrant positivity for HMB45. Special stain (PAS-diastase) highlighted intracytoplasmic granules and crystals. Diagnosis of ASPS was offered. Furthermore, the tumor cells displayed TFE3 gene rearrangement. Case 2: A 29-year-old female underwent an aural polypectomy. Microscopic examination revealed a tumor with a “nesting-type”/alveolar arrangement of tumor cells with vacuolated cytoplasm, arranged around thin-walled blood vessels. Immunohistochemically, tumor cells were diffusely positive for HMB45 and TFE3 and focally for SMA. A diagnosis of a PEComa was offered. This report constitutes the first documentation of aberrant HMB45 immunoreactivity in case of ASPS, and one of the first reported cases of a PEComa in the ear. It emphasizes the value of integrating clinicopathological features with immunohistochemical and molecular results in differentiating two rare, but distinct soft tissue tumors with overlapping features. An exact diagnosis of both these tumor entities has therapeutic implications.

Context: The rapid outbreak of SARS-CoV-2 has become a significant global health concern, highlighting the dire need for antiviral therapeutic agents. RNA-dependent RNA polymerase (RdRp) of coronavirus plays crucial roles in RNA synthesis, and hence remains the druggable target for the treatment of this disease. The most potent broad-spectrum inhibitors of viral RdRp are members of nucleoside analogs (NAs). However, SARS-CoV-2 proved to be a challenging one for the novel NA drug designing strategy because coronavirus possesses an exonuclease (ExoN) domain that is capable of excising NAs, thus showing resistance to existing antiviral drugs. Aim: The objective of our study was to compare the SARS-CoV-2 exonuclease (nsp14) protein sequence of Wuhan-type virus with those of Indian SARS-Cov-2 isolates and to study the effect of multiple mutations on the secondary structure alterations of proteins. Subjects and Methods: Multiple-sequence alignment of exonuclease amino-acid sequences followed by phylogenetic analysis and prediction of its secondary structure of the protein was performed. Results: Altogether, seven mutations were detected in the nsp14 of Indian SARS-CoV-2 isolates. Subsequently, prediction of their secondary structures revealed that mutations altered the structural stability of exonuclease proteins. Conclusions: Present findings, therefore, further suggest that evolvability of SARS-CoV-2 is primarily associated with the onset of multiple novel mutations that rapidly spread at several new locations of the viral genome and also provides important insight to develop specific control strategies to fight against COVID-19 infections.

Thanatophoric dysplasia type 1 (TD1) is a lethal form of osteochondral dysplasia due to mutation of FGFR3 gene. In addition to severe shortening of the limbs there is temporo-occipital lobe dysplasia along with a range of other CNS anomalies. In this report we describe the radiological and anatomical features at autopsy in neonate with TD1 along with the CNS anomalies. We have also summarized the key distinguishing features of TD1 from other common types of osteochondral dysplasia. An accurate diagnosis is important for genetic counseling and impact on future pregnancies.

Benign ectopic thyroid tissue within the parotid gland is very rare with only one case reported till date in the world literature. We report a case of ectopic thyroid in the left parotid gland with an orthotopic thyroid in an elderly female, who was presented to us with the simultaneous onset of right-sided thyroid swelling and left parotid swelling for 6 months. Fine-needle aspiration cytology (FNAC) was done from both the swellings and a diagnosis of Hurthle cell neoplasm metastasizing to the left parotid gland was initially made. However, histopathological examination along with the immunohistochemistry (IHC) panel proved it to be an ectopic thyroid in the parotid. The case is being documented here for its rarity as well as an unusual presentation so that the readers are aware of this entity and the complete workup required to prevent diagnostic pitfalls.

Mammary analog secretory carcinoma (MASC) of salivary gland is a recently described entity. Due to its rarity and cytomorphological overlap with other salivary gland tumors, it is often difficult to recognize on cytology. Here we describe three such cases with their histopathological correlation. All the three tumors arose in the parotid gland. They were misdiagnosed as mucoepidermoid carcinoma, acinic cell carcinoma and salivary duct adenocarcinoma, respectively. Final diagnosis of MASC was established on their follow-up histopathology and immunochemistry evaluation. Cytosmears of these tumors showed high cellularity with papillary architecture lying within fluid background rich in foamy macrophages. Nuclear atypia varied from minimal to marked with frequent mitosis and presence of necrosis. Cytoplasmic vacuolation was a consistent finding. Although the cytomorphological features of MASC are not specific, a diagnosis of MASC should be strongly considered in the presence of papillary architecture, prominent cytoplasmic vacuolations of the tumor cells and a background of cyst fluid. Immunohistochemistry on cell block may be done to confirm the diagnosis.

Whipple's disease is a multisystem disorder and responds well to antibiotic therapy if treated timely. It is seen in the fourth to fifth decades of life with a male to female ratio of 10:1. It mainly affects the intestine, the central nervous system, and joints. To the best of our knowledge, we present the first case of duodenal Whipple's disease in an Indian female, who presented with hyperpigmentation and chronic diarrhea with malabsorption. Whipple's disease was diagnosed based on specific upper GI endoscopic and histopathology findings.

Amyloidosis is caused by an extracellular accumulation of insoluble fibrillary protein predominantly in the kidneys, spleen, and heart. The deposition of amyloid into the joints, synovia, and osseous tissues (amyloid arthropathy) is an uncommon condition with only a few case reports in the English literature. Similarly, amyloid deposition predominantly limited to the vascular wall is rarely described. In this report, we describe an additional case of amyloidosis of the hip joint along with amyloidosis of intramural coronaries leading to sudden death in a middle-aged male.

The glomus tumor of stomach is an unusual submucosal mesenchymal tumor of the gastrointestinal tract. We describe a 42-year-old female who presented with chronic anemia and an episode of painless hematemesis. A preoperative diagnosis of the probable gastric gastrointestinal stromal tumor was made. Post-surgical histopathological examination of the specimen demonstrated a glomus tumor of the stomach confirmed on immunohistochemistry. The present case highlights the importance of morphology and immunohistochemistry in differentiating the subepithelial tumors of the stomach and one must consider glomus tumor in differential diagnosis of these gastric lesions.

Eosinophilic solid and cystic renal cell carcinoma (ESCRCC) is an under-recognized, emerging new entity of sporadic renal neoplasms, with an approximate incidence of 0.2% of renal tumors. A total of 60 cases have been reported in the literature till date. ESCRCC are usually seen in adult females, with a low stage and indolent behavior, and rare incidence of recurrence or metastasis. They are solid and cystic tumors with variably sized cysts resembling eosinophilic RCC, showing a characteristic positive immune-expression for PAX-8, CK20 (in ~80% cases) and/or Melan–A (in ~6.7%), with negative CK7 and CA-IX expression. They consistently harbor TSC1 or TSC2 mutations in all tumors, which is a proposed molecular marker for this entity. We here present the first reported case of this rare tumor from India. The tumor was positive for PAX-8, and showed diffuse strong positivity for Melan-A, while was negative for CK7 and CK20. It was an early-stage tumor (T1), managed with partial nephrectomy, with no evidence of any recurrence/metastasis after 1 year of follow-up.

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.

Mesonephric adenocarcinoma (MNA) is a rare malignancy arising from the mesonephric remnant of the female reproductive tract, typically found in the cervix. MNA is uncommon in the uterine corpus, only 33 cases have been described in the literature. A 55-year-old postmenopausal woman presented with pink vaginal discharge and bilateral hip pain for 2 months, with the help of histopathologic observation and immunohistochemical staining, a diagnosis of “MNA” was made. The tumor invaded the whole layer of myometrium without endometrium involvement, mesonephric remnants and hyperplasia of the mesonephric duct were also found at the periphery of the neoplasm. After the operation, the patient was treated with 3 cycles of chemotherapy. The patient was followed for 6 months with disease. Further experience to diagnose and cure this rare tumor is warranted.

Amyloidosis is a heterogeneous group of diseases with the most common form being systemic distribution. The least common type of the disease is tumor formation due to deposition which is called “amyloid tumor (amyloidoma)”. Although such tumors can occur in any region of the body, extremity localization is fairly seldom. Here, we report the clinical and histopathological features of amyloidoma in an 81-year-old female patient who presented with a large rapidly growing mass in the left lower extremity.

Extranodal follicular dendritic cell sarcoma (ENFDCS) is a rare hematolymphoid tumor, masquerading as soft tissue sarcoma on initial histological examination. So, for its confirmation, the application of immunohistochemistry (IHC) is of paramount importance. Over the years there has been a major shift in the demography of follicular dendritic cell sarcoma (FDCS), with a rise in the number of extranodal cases. Herein we report a case of ENFDCS presenting as a rectal polyp, who had a history of intermittent bleeding per rectum and passage of fleshy mass while defecation. As these tumors share an overlapping morphology with other spindle cell tumors and can occur at unpredictable locations, they pose a diagnostic challenge, especially for young pathologists.

We report a 52-year-old man who presented with erythroderma and nodular lesions on face manifesting as “Leonine facies”. He had impaired sensation over the face and was initially diagnosed to have lepromatous leprosy and was treated with antileprosy drugs. Investigations showed a total Leukocyte count of 550 X 10⁹/l with 90% atypical lymphoid cells with prominent central nucleolus suggestive of prolymphocytes. On flow cytometry, these cells were positive for cytoplasmic CD3, CD2, CD5, CD7, CD4, and CD38 (dim) and were negative for CD1a and TdT and diagnosis of T-prolymphocytic leukemia was made.

Chronic Myeloid Leukemia, BCR-ABL1 positive (CML) is distinct from other myeloproliferative neoplasms (MPNs) as it is positive for the Philadelphia chromosome (Ph) with presence of BCR-ABL1 translocation that makes it responsive to targeted therapy with tyrosine kinase inhibitors (TKI). Distinctly there is another group of Ph-negative myeloproliferative neoplasms as polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET) and others that harbor an activating mutation in the Janus Kinase 2 gene (JAK2), i.e., JAK2 V617F mutation. BCR-ABL1 translocation and the JAK2 V617F mutation are generally considered disease defining and mutually exclusive due to diagnostic and therapeutic implications. We hereby present a rare case of MPN with coexistent expression of BCR-ABL1 translocation and JAK2 V617F mutation thus posing a challenge in diagnosis, treatment, and follow-up.

Brucellosis remains a major public health problem worldwide. It is commonly found in most developed and developing countries, such as the Mediterranean region, the Middle East, and Latin America. In China, brucellosis is mainly distributed in some of the northern provinces and is relatively rare in Shandong province. Brucellosis has a variety of clinical manifestations, with fever, sweating, fatigue, and migratory joint pain being the most common. Because of the non-specific clinical symptoms, brucellosis is often misdiagnosed as other diseases. Here, we report a rare case of brucellosis of thoracic vertebrae misdiagnosed as thoracic malignant tumor and present a review of related literature.

Gastrointestinal (GI) histoplasmosis usually occurs as a part of disseminated histoplasmosis in immunocompromised or elderly subjects. Isolated histoplasmosis involving the GI tract in an immunocompetent host is very rare. It is also not considered as an etiology for chronic abdominal pain in children. Here we present an 8-year-old boy with abdominal pain and weight loss who underwent treatment for tuberculosis but on reinvestigation was diagnosed as GI histoplasmosis. He responded well to treatment and achieved good catch up growth.

Infection with Strongyloides stercoralis, a human pathogenic roundworm, is common in tropical countries like India. Owing to its variable clinical presentation and irregular larval output in stool, it often remains neglected and underdiagnosed. Signs and symptoms are largely dependent on the immune status of the infected individual. Alteration in the host immunity due to chronic use of steroids can surge the number of parasites and cause hyperinfection syndrome. This can be catastrophic with a fatal outcome. Focus on early detection and treatment of the parasite in at-risk patients is imperative to reduce mortality. We summarize here an interesting case of hyper infection syndrome of strongyloidiasis with gangrenous bowel changes later progressing to burst abdomen.

Soft tissue tumors are a highly heterogeneous group of lesions with varied clinical presentation. The majority is primary tumors and metastatic tumors are very rare. Malignant pleural mesothelioma presenting as a soft tissue mass at a distant site is even rarer and can cause diagnostic challenges both clinically and pathologically. We report a case of malignant pleural mesothelioma presenting as a soft tissue mass in the left thigh. A 59-year-old man, non-smoker, working in a cement factory since 30 years presented with complains of difficulty in walking since 1½ months. Review of his previous medical records revealed malignant pleural mesothelioma, which was diagnosed 9 months before. He had denied chemotherapy and was on Ayurvedic medication. The lesion involved the adjacent intercostal muscles. Few enlarged lymph nodes were noted in mediastinal and cervical regions. Biopsy of left supraclavicular and right cervical lymph nodes showed metastases. Metastasis from malignant pleural mesothelioma to the thigh was confirmed by immunohistochemistry. The tumor was positive for CK5/6, CK7, Calretinin and vimentin and immunonegative for CEA, Napsin A and TTF 1.

Leiomyoma is a benign smooth muscle cell tumor commonly occurring in the uterine myometrium. Extra-uterine tumors are infrequent and those occurring in an intracranial location are extremely rare. We report a primary intracranial leiomyoma as an incidental autopsy finding in a 60-year-old woman, who died of acute myocardial infarction.