Contiguous Lumbar Vertebral Involvement with Vertebral Collapse in Giant Cell Tumor: A Usual Tumor with an Unusual Presentation.

Giant cell tumor (GCT) is a primary bone tumor of long bones, which can rarely involve the vertebrae. Contiguous vertebral involvement by GCT is a rare presentation and poses a diagnostic dilemma on imaging. We report a case of GCT involving three contiguous lumbar vertebrae causing vertebral collapse along with a large soft tissue component. Considering the site and clinical presentation, possibilities of a round cell tumor with large extraosseous soft tissue component and malignant neurogenic tumor were suggested on initial radiological examination but histopathology confirmed the diagnosis of GCT. It is important to diagnose this entity correctly because of totally different lines of management. In our case, initial surgical management was excluded in view of high surgical morbidity and, thereby, adjuvant therapy with denosumab was planned.

Prevalence of Molecular Subtypes in Operated Cases of Breast Cancer and Its Clinicopathological Correlation: A Single Institute Study from a Tertiary Cancer Centre in North India.

Breast cancer has emerged as a major health problem among women in India. There are few Indian studies which have looked at prevalence of molecular subtypes of breast cancer in Indian population. The primary objective of our study was to find out the prevalence of various molecular subtypes in operated cases of breast cancer patients presenting to us. Three hundred sixty patients who were operated in our department were analysed. Clinicopathological features of all cases were recorded. Classification into various molecular subtypes was done using St. Gallen 2013 criteria. Luminal B HER2 negative was the predominant molecular subtype in our study population constituting 30.3% of patients. The percentage of aggressive subtypes, viz. triple negative breast cancer and HER2 enriched, were 21.7% and 11.4% respectively. Only 19.4% of patients in our study population had tumour size ≤ 2 cm with nodes being positive in 56.9% of our patients at presentation. Data from our study and other studies published from India show that the two most aggressive subtypes of, viz. triple negative breast cancer and HER2 enriched, may be more prevalent in our population as compared to western population.

Diagnostic utility of multiple site duodenal biopsies in celiac disease.

BACKGROUND: Celiac Disease involves the small intestine patchily affecting more frequently the proximal small bowel but the histological changes have been observed till terminal ileum. Of late in addition to D2, the duodenal bulb (D1 region) biopsies have been found helpful in identifying a small group of patients with CD. Therefore, multiple site biopsies are recommended as histological changes are not uniform throughout small intestine. METHODS: During this present 1.5 years prospective study, we evaluated 84 cases of suspected celiac disease with respect to the light microscopy (D1, D2, and D3 biopsy) and serology (anti tTg and or EMA). Histological examination was done according to Modified Marsh grading system. RESULTS: Out of 84 cases with raised anti tTg, the segmental biopsies significantly increased the diagnostic accuracy from 39/44 cases (88.6%) to 43/44 cases (97.7%) and 44/44 cases (100%) when D2 alone, D1 + D2 and D1 + D2 + D3 biopsies were evaluated, respectively. Of the suspected cases of celiac disease patients (tTg > 10 ULN and associated weight loss, diarrhea), additional D3 biopsy increased the diagnostic yield by 2.1%, compared to D1, D2 region biopsy and 6.38% compared to standard D2 biopsy alone. Of the 28 cases (tTg > 10 times ULN + EMA positive and associated weight loss, diarrhea), the potential celiac disease (histologically Type 1/Normal) cases reduced from 28.5% (standard D2 region alone) to 21.4% and 17.8% when additional biopsies were taken from D1 region and D3 region, respectively, and additional D3 biopsy increased the diagnostic yield by 10.8% (compared to standard D2 biopsy alone) and 3.7% (compared to D1 and D2 biopsy). CONCLUSION: We believe multiple sites duodenal biopsies including D3 region biopsies might increase the diagnostic accuracy of adult celiac disease in addition to sensitive and specific serologic tests.

Clinical and Molecular Attributes of Patients With BCR/ABL1-negative Myeloproliferative Neoplasms in India: Real-world Data and Challenges.

INTRODUCTION: Classic BCR/ABL1-negative myeloproliferative neoplasms (MPNs) are characterized by clinical and genetic heterogeneity and include 4 distinct constituents. Very little data on clinical presentation and epidemiology of the same is available from the Indian setting. PATIENTS AND METHODS: Patients referred to Hematology-Oncology from January 2018 to August 2020 with suspected MPNs were included in the analysis and prospectively followed-up. All patients were initially screened, and only those meeting the updated World Health Organization 2016 criteria were included in the analysis. Epidemiologic, clinical, and molecular characteristics were documented, and patients were followed-up prospectively. RESULTS: A total of 233 patients were referred for evaluation of MPN, of which 63 were included in the analysis, including 39 males and 24 females. The median age at diagnosis was 57 years (range, 28-82 years), and 38% patients were younger than 50 years of age. The most common presentations were incidental detection in 35 (55.5%), abdominal symptoms in 13 (20%), fatiguability in 7 (11%), and recent vascular events in 6 (9.5%) patients. Final diagnosis was polycythemia vera in 27, essential thrombocytosis (ET) in 21, prefibrotic myelofibrosis in 9, and myelofibrosis in 6 patients. The frequency of driver mutations in polycythemia vera included JAK2 in 75%; in ET, JAK2 in 33%, CALR in 33%, and MPL in 4%; and in prefibrotic myelofibrosis, JAK2 in 66% and CALR in 33%. Aspirin was used for all patients along with risk-adapted cytoreduction with hydroxyurea. Ruxolitinib was reserved for symptoms refractory to hydroxyurea. After a median follow-up of 15 months (interquartile range, 10-28 months) from diagnosis, disease progression was noted in 4 patients. Two patients died at the end of the follow-up period, including 1 with secondary acute myeloid leukemia post myelofibrosis and one with ET and coexistent oral malignancy. The remaining 61 patients are alive and on regular treatment. RESULTS: This is one of the first systematic descriptions and prospective follow-up of patients with BCR/ABL-negative MPNs from India. Our study indicates a younger median age of presentation and higher proportion of JAK2-unmutated disease across all subtypes. The primary role of bone marrow morphology and supportive role of somatic mutations in differentiating MPN subtypes is indicated. CONCLUSIONS: This study sets the stage for a collaborative registry for defining epidemiologic data and long-term outcomes with MPN in India.

A Clinicopathological Study of Skin Tumors from a Tertiary Care Centre in North India.

BACKGROUND: There is a huge spectrum of skin tumors which can be confused clinically with malignancies, particularly when they are pigmented or inflamed, and histopathological examination of a biopsy specimen is required to establish a definitive diagnosis and to facilitate appropriate intervention and follow up. AIM: To evaluate all skin tumors and categorize them according to their origin. METHODS: The present study was conducted over a period of 4 years (July 1, 2013 to June 31, 2017) comprising of 1.5 years prospective and 2.5 years retrospective analysis in the departments of Dermatology and Pathology, at a tertiary hospital in North India. All specimens of skin tumors were analyzed grossly and microscopically. Immunohistochemistry was done wherever possible. RESULTS: A total of 232 skin tumors were seen; of which 123 cases were benign (53.0%) and 109 cases were malignant (47.0%). The mean age of patients with benign and malignant skin tumors was 40.3 ± 19.9 and 60.8 ± 14.8 years, respectively. The most common site was face (n = 106; 45.7%) followed by limbs (n = 44; 19.0%). The male:female ratio of benign and malignant tumors was 1.01:1 and 1.31:1, respectively. Among the benign tumors, keratinocytic tumors were the commonest (n = 57; 46.3%) followed by the melanocytic tumors (n = 37; 30.1%) and appendageal tumors (n = 29; 23.6%). The most common malignant skin tumors were the keratinocytic tumors (n = 87; 79.8%) followed by 12 cases (11%) of hematolymphoid tumors and five cases (4.6%) each of melanocytic and appendageal tumors. LIMITATIONS: The lack of clinical and dermatoscopic correlation and inclusion of retrospective data are the limitations of this study. CONCLUSIONS: Skin tumors affect people of all ages. The benign tumors are seen in the younger age group as compared to malignant tumors. Face is the most common site and keratinocytic tumors are the most common skin tumors in both benign and malignant categories.

An open-label randomised pilot trial on safety of wheat variety C273 in patients with adult celiac disease.

BACKGROUND: The only effective treatment for celiac disease (CeD) is gluten free diet (GFD). However, GFD is restrictive and efforts are being made to explore alternative therapies including safer wheat varieties. Wheat variety C273 has been previously identified to have reduced load of intact T-cell stimulatory epitopes via in silico and in vitro analysis. METHODS: Adult patients diagnosed with CeD and recovered on GFD were included in the study. Patients were randomised into two groups in a 2:1 ratio. Patients in group I had graded introduction of C273 wheat in diet, maintained for 24 weeks; in Group II, wheat was restricted with continuation of GFD. Clinical symptoms, serology [anti-tissue transglutaminase (anti-tTG), anti-endomysial antibody (anti-EMA)], circulating inflammatory biomarkers [intestinal fatty-acid binding protein (I-FABP), plasma citrulline, interferon-γ (IFN-γ)] and histology were evaluated periodically. Final evaluation was performed at week 28. RESULTS: A total of 15 patients were enrolled (Group I: n = 10, Group II: n = 5). All patients except two in Group I remained compliant. None of the remaining eight patients in group I developed symptoms. No significant changes in serology (anti-tTG, anti-EMA) and histology were observed between the two groups at 28 weeks (p > 0.05). Significant changes in plasma citrulline(29.87 ± 8.98 versus 36.58 ± 3.09, p = 0.049) and IFN-γ (44.56 ± 9.74 versus 33.50 ± 3.68; p = 0.031) were observed in Group I. CONCLUSION: Consumption of C273 wheat did not result in development of symptoms or evident changes in serology and histology at 28 weeks. However, variations in circulating inflammatory markers were noted. Larger randomised trials are needed to corroborate these findings. CLINICAL TRIALS REGISTRY-INDIA: CTRI/2018/06/014521.

Diagnostic role of fine needle aspiration cytology (FNAC) in the evaluation of gall bladder lesions: an institutional experience.

BACKGROUND: Carcinoma of the gall bladder is the most common malignancy of the biliary tract. Ultrasonography guided Fine Needle Aspiration Cytology (FNAC) plays a crucial role in early detection of gall bladder (GB) lesions. Early diagnosis of GB lesions is a necessity in view of rising trend in GB carcinoma related mortality in India. The aim of this study is to determine the diagnostic accuracy of pre-operative ultrasonography guided FNAC in the diagnosis of GB masses. METHODS: This was a retrospective observational study performed at a tertiary care university hospital over a period of one and a half years. A total of 47 patients with clinico-radiological suspicion of GB malignancy were subjected to USG guided FNA. 20 of these patients underwent diagnostic Trucut biopsy in addition to FNA. RESULTS: Forty-one out of 47 patients analyzed were positive for malignancy with female preponderance; MF ratio of 0.6:1. There were 29 females (61.8%) and 18 males (38.2%) in the range of 34 to 85 years. Cytomorphology was inconclusive for malignancy in two patients and unsatisfactory in one case. Two were labeled as chronic cholecystitis and one as acute cholecystitis. Adenocarcinoma was the most common malignancy found in 36 patients (76.6%). CONCLUSION: USG guided FNAC is a rapid, safe and successful diagnostic procedure with high sensitivity for diagnosis of GB lesions. In the present scenario of increasing incidence of GB malignancy, FNAC has proved to be a useful first choice of investigation in the detection of GB lesions.

Synchronous high-grade bladder carcinoma associated with chronic lymphocytic leukemia: A rare entity in Indian literature.

B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is one of the common lymphoproliferative disorders with an increased risk of developing subsequent neoplasms of epithelial and mesenchymal origin. The decreased immunity and B-cell dysfunction in CLL probably accounts for this emergence of secondary malignancy. Breast, brain, skin and prostate tumors have been reported as usual coincident malignancies of CLL, while in occasional cases CLL may occur with malignancies of other solid organs, such as skin, lung, heart, and prostate. Synchronous CLL with urothelial carcinoma (UC) is an infrequent occurrence. We report this case because of its rarity in Indian literature and interesting hematological, immunophenotypic, histopathological, and cytopathological features of metastatic high-grade UC in a 61-year-old male with CLL.

Primary Extranodal Non-Hodgkin Lymphomas: A First Tertiary Care Experience from Punjab, North India.

Background Primary extranodal lymphomas are less frequently encountered and difficult to diagnose in routine practice. The histopathological and immunohistochemical studies are essential in addition to clinical details to diagnose. The incidence is varied in different parts of India along with variation in histopathological spectrum. Methodology The clinical features and histopathological findings of patients diagnosed with primary extranodal lymphoma over 3-year period were retrieved from archives of pathology department and analyzed. Results During the 3-year study period, a total of 135 cases of non-Hodgkin lymphomas were evaluated, and of these, 41.4% (56/135) of cases presented with primary extranodal involvement. The mean age of primary extranodal lymphoma presentation was 61.3 ± 17.5 with M:F ratio of 1:1.1 Most common extranodal site involved was gastrointestinal tract 32.1%, 18/56 (small intestine [17.8%, 10 cases] and large intestine [8.9%, 5 cases]). Non-Hodgkin lymphomas of B cell type were the predominant subtype (48/56, 85.7%), while 8/56 (14.2%) cases were of T cell lineage. Of the B cell non-Hodgkin lymphoma diffuse, large B cell lymphoma was the predominant subtype constituting ~83.3% (40/48). Conclusion Primary extranodal lymphomas exhibit varied histomorphological and clinical presentation. The present study is first such analysis from Punjab that intends to compare with studies from other parts of India.

Comparative Analysis of Erythrocyte Sedimentation Rate Measured by Automated and Manual Methods in Anaemic Patients.

Purpose Erythrocyte sedimentation rate (ESR) is a widely used indicator of inflammation and a routinely done hematology investigation to monitor patients of autoimmune and infectious diseases. We aimed to compare the ESR results obtained by Roller 20LC automated instrument and standard reference Westergren method and analyzed the effect of anemia (hematocrit) on ESR measurements through the automated method. Methods We analyzed 1377 random anemic OPD patients (hematocrit [HCT] < 35%) for ESR levels measured by Roller 20LC using EDTA blood and Westergren method using citrated blood for a one and half year period from January 1, 2018 to June 30, 2019. Fabry's formula was used to correct the Westergren ESR. Results The total number of samples after evaluation were divided into low ( n = 232), intermediate ( n = 417), high ( n = 406), and very high range of ESR (≥100 mm/hr; n = 422). Mean difference between values of corrected and automated ESR for the low, intermediate, high and very high ESR range was 2.33 ± 5.03, 10.95 ± 8.04, 28.22 ± 19.11 and 43.3 ± 19.22 mm/hr, respectively. The 95% limit of agreement calculated by the Bland-Altmann analysis between the two methods for low-ESR range was -7.53 to 12.2 (highest correlation coefficient -0.65), while for very high ESR, range was -5.1 to 81.5 (least coefficient of 0.18) ( p < 0.001). Conclusion In laboratories with high-sample load and where manual measurement may be tedious, the automated method of ESR measurement can safely replace the Westergren method for low-ESR values in patients with low hematocrit. While for high-ESR values, validation by the standard Westergren method may be needed.

Cerebrospinal fluid pleocytosis in immunocompromised patients: Can it be Cryptococcus.

Cryptococcal meningitis commonly affects immunocompromised cases and can have varied presentation. In some instances, the presence of a plethora of inflammatory cells on cerebrospinal fluid (CSF) in an immunosuppressed patient can lead to further investigations, which unravel the presence of cryptococcal meningitis. The aim of this retrospective study was to analyze the spectrum of CSF findings of immunosuppressed patients who were diagnosed to have cryptococcal meningitis. Retrospective analysis of CSF cytospin slides exhibiting pleocytosis and belonging to immunocompromised patients was performed, and these cases were found to have cryptococcal meningitis. Out of 932 cases of CSF (January 2016-July 2017), 10 had pleocytosis and 5 of these 10 cases demonstrated spores of Cryptococcus. Male-to-female ratio was 1:1.5. All the patients were immunocompromised and had CSF leukocytosis. Lymphocytes and monocytes were present in all samples while only one case showed plasma cells. Spores of Cryptococcus were also noted in all the cases and highlighted on India Ink Preparation and Gomori Methenamine Silver stain. All the cases were positive for agglutination-based cryptococcal antigen assay, except one where the test was not done. All immunosuppressed patients having pleocytosis in CSF were found to have cryptococcal infection. Therefore, pleocytosis in CSF in any immunosuppressed patient should raise the suspicion of cryptococcal meningitis. The pathologist and the clinician need to be vigilant in such scenarios to rule out any opportunistic infection and investigate the patient thoroughly for any underlying immunosuppression.

Jejunal stricture due to mucormycosis.

Mucormycosis is generally considered to be an acute, rapidly progressing, opportunistic fungal infection. Chronic manifestations are extremely rare. Mucormycosis affecting the jejunum is very rare and few cases have been reported. We report a case of mucormycosis causing jejunal stricture in an infant aged six months.

Feasibility of Masood's cytological index for screening breast lesions in low resource setting.

Fine needle aspiration cytology has long been an accepted diagnostic modality in combination with physical examination and mammography to investigate breast lesions. In the present era, more proficient methods such as stereotactic mammographically guided breast biopsy is the preferred choice, however, in low resource setting, FNAC still remains the most cost effective and sampling modality to diagnose breast cancer. With the intention to evaluate the efficacy and limitations of FNAC in evaluation of breast lesions in low resource setting, we employed the Masood's cytological staging system to stratify the breast lesions and correlate them with histopathology wherever possible. All breast lesions aspirates were analyzed and classified according to the Masood's cytological scoring system and correlated with histopathological findings wherever adequate material was available. A total of 776 patients were studied of which 23 aspirates were unsatisfactory, 120 aspirates were categorized as inflammatory breast disease. Six hundred and thirty-three cases were classified according to Masood's cytological system. Nonproliferative breast diseases (Group I) encompassed maximum cases with 55% followed by carcinoma in situ and invasive cancers (Group IV) with 39% and proliferative breast disease without atypia (Group II) and with atypia (Group III) which had equal number of cases constituting 2.4% each. Cyto-histopathological correlation done in 102 cases revealed 100% concordance in group IV and 75% concordance in group III while it could not be performed in Group I and II as no histopathological specimen was available in those patients. Masood Cytological grading for breast aspirates is a reliable and an easily reproducible system which can be used to formulate appropriate treatment protocols in cases presenting with breast lesions.

Variable Immunogenic Potential of Wheat: Prospective for Selection of Innocuous Varieties for Celiac Disease Patients via in vitro Approach.

Celiac Disease (CD) is a multifactorial, autoimmune enteropathy activated by cereal proteins in genetically predisposed individuals carrying HLA DQ2/8 genes. A heterogenous gene combination of the cereal prolamins is documented in different wheat genotypes, which is suggestive of their variable immunogenic potential. In the current study, four wheat varieties (C591, C273, 9D, and K78) identified via in silico analysis were analyzed for immunogenicity by measuring T-cell proliferation rate and levels of inflammatory cytokines (Interferon-γ and Tumor Necrosis Factor-α). Peripheral Blood Mononuclear Cells and biopsy derived T-cell lines isolated from four CD patients in complete remission and two controls were stimulated and cultured in the presence of tissue transglutaminase activated pepsin-trypsin (PT) digest of total gliadin extract from test varieties. The immunogenicity was compared with PBW 621, one of the widely cultivated wheat varieties. Phytohaemagglutinin-p was taken as positive control, along with unstimulated cells as negative control. Rate of cell proliferation (0.318, 0.482; 0.369, 0.337), concentration of IFN- γ (107.4, 99.2; 117.9, 99.7 pg/ml), and TNF- α (453.8, 514.2; 463.8, 514.2 pg/ml) was minimum in cultures supplemented with wheat antigen from C273, when compared with other test varieties and unstimulated cells. Significant difference in toxicity levels among different wheat genotypes to stimulate celiac mucosal T-cells and PBMC's was observed; where C273 manifested least immunogenic response amongst the test varieties analyzed.

Pulmonary Hydatid Disease with Aspergillosis - An Unusual Association in an Immunocompetent Host.

Echinococcosis is a common cause of pulmonary cavities. Aspergillus fumigatus, a saprophytic fungus, can colonise pulmonary cavities caused by tuberculosis, sarcoidosis, echinococcosis, bronchiectasis and neoplasms. Infection by Aspergillus is often seen in immunosuppressed cases. However, co-infection of Aspergillus with pulmonary echinococcosis is unexpected and very unusual, especially in an immunocompetent patient. We present the case of a 45-year-old immunocompetent male who came with non-resolving pneumonia and fever for 8 months and dyspnoea since 15 days accompanied by recurrent episodes of hemoptysis since 5 days. Chest X Ray and Computed Tomography scan showed a cystic lesion in the middle lobe of the right lung. Middle lobectomy with video-assisted thoracoscopic surgery was performed and histopathology revealed ectocyst of Hydatid cyst which was also colonised by septate fungal hyphae exhibiting acute angled branching, morphologically consistent with Aspergillus. Gomori Methanamine Silver and Periodic Acid Schiff stains highlighted the hyphae of Aspergillus as well as the lamellated membranes of ectocyst and an occasional scolex of Echinococcus. Sections from surrounding lung parenchyma also showed these fungal hyphae within an occasional dilated bronchus. Thus a diagnosis of dual infection of Aspergillosis and Pulmonary Echinococcosis was established. The possibility of dual infection by a saprophytic fungus must be kept in mind while dealing with a case of a cavitary lesion in long-standing and non-resolving pneumonia, even in an immunocompetent patient. Establishing the correct diagnosis of Aspergillosis with Echinococcosis is essential for proper and complete management.

Student perception of peer teaching and learning in pathology: A qualitative analysis of modified seminars, fishbowls, and interactive classroom activities.

CONTEXT: Peer-assisted teaching and learning (PTL) is being experimented in different medical universities worldwide. It is a learner-centered approach involving students through active learning strategies. AIMS: To study the student perception of PTL in methods such as group-led seminars and fishbowls, in classroom through various interactive activities; compare and find out the student acceptability and efficacy of each of these methods in learning conceptual topics such as various types of anemia. SUBJECTS AND METHODS: Medical students of second-year professional course were subjected to PTL in classroom during allotted teaching hours for 10 successive sessions using group-led modified seminars, fishbowls, and different formality-level interactive activities such as street plays, prop sessions, quiz sessions, to make them understand the clinical features and presentation of different types of anemia through understanding of etio-pathogenesis. To ascertain the aspects that influenced learning, focus group discussions were conducted in small groups consisting of 14 students and one facilitator in each group. Qualitative thematic analysis was performed on transcripts of the audio recordings by authors. RESULTS: The emerging themes from qualitative analysis of transcripts were pertaining to teacher, student, and organization. We found motivation, interest, and involvement of peer teacher, student behavior and collaboration, contact time between students and facilitator, preparation time, coherence with other curricular activities, group size and composition, suitability of topic for the kind of activity, and availability of material for preparation as few sub-aspects affecting learning. CONCLUSION: For PTL to be effective, adequate transfer of knowledge through good peer teacher involvement, learner receptiveness, and adequate contact time is needed. Proper preparation with suitability of topics for the type of activity, alignment of seminars with other activities, and course coherence are prerequisites for the same.