ALK-positive large B-cell lymphomas: A clinicopathologic study

Background and Aim: Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphomas (ALK+-LBCLs) are aggressive CD20-negative lymphomas, accounting for <1% of diffuse LBCLs. Being rare and with peculiar immunophenotypic characteristics, these can be easily misdiagnosed. We present 11 cases of ALK+-LBCLs diagnosed over a period of 11 years at a tertiary care hospital in South India to analyze the clinical, morphological, and immunophenotypic profile of these tumors. Subjects and Methods: ALK+-LBCL cases diagnosed from September 2009 to August 2020 were included. Clinical details were obtained from stored electronic records and summarized. Available hematoxylin and eosin (H and E) stained slides and immunohistochemistry slides were reviewed and observations tabulated. Results: Eleven patients (nine males and two females) were diagnosed with ALK+-LBCLs in the study period with seven presenting primarily with extranodal disease manifestations. Tumors in the lymph nodes showed diffuse architecture effacement and variable sinusoidal invasion. All tumors showed immunoblastic and plasmablastic-type large lymphoid cells with scattered anaplastic/multinucleate large cells, including rare Reed–Sternberg-like cells. Cytoplasmic granular ALK-1 staining, CD20 negativity, and immunohistochemical features of plasmablastic differentiation were noted in all. Of eight patients treated, only one achieved remission with multi-agent chemotherapy but relapsed after 6 months. Two patients died of disease and five others had progressive/persistent disease and were lost to follow-up. Conclusion: Although rare, these tumors should always be in the differential diagnoses of tumors with plasmablastic and immunoblastic morphology, especially in extranodal sites to avoid diagnostic delay/misdiagnosis.

Comparison of primary follicular lymphoma of gastrointestinal tract and secondary involvement: A study from South India

Primary follicular lymphoma of the gut (PFL-GI) is a rare entity. This study aims to compare the clinicopathologic features of PFL-GI with cases of gastrointestinal involvement by disseminated nodal follicular lymphoma. This is a retrospective study with 6 cases of primary follicular lymphoma and 8 cases of secondary involvement of the gut, over a period of 9 years. The slides and blocks were retrieved and reviewed. Clinical data was obtained from hospital records. Clinicopathologic features were compared. PFL-GI cases had a slightly higher median age group (p value 0.23) and no gender predilection when compared to cases with secondary involvement which showed a female preponderance. Para-aortic lymphadenopathy was seen in all secondary cases whereas none of the primary cases showed significant lymphadenopathy. The only microscopic feature that was different was the presence of hollowed out pattern of immunostaining for follicular dendritic cells seen in all cases of PFL-GI but in none of the secondary cases

Peripheral T cell lymphoma: Clinico-pathological characteristics & outcome from a tertiary care centre in south India

Background & objectives: Peripheral T cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin's lymphomas (NHLs), with universally poor outcome. This study was undertaken to provide data on demographics and outcomes of patients with PTCL who underwent treatment in a single tertiary care centre in southern India. Methods: Retrospective study was done on all patients (age ?18 yr) diagnosed with PTCL from January 2007 to December 2012. The diagnosis of PTCL was made according to the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. Results: A total of 244 adult patients were diagnosed with PTCL (non-cutaneous). The most common subtype was PTCL-not otherwise specified (35.7%), followed by anaplastic large cell lymphoma (ALCL), ALK negative (21.3%), natural killer/T cell lymphoma, angioimmunoblastic T-cell lymphoma (AITL), ALCL, ALK positive, hepatosplenic T cell lymphoma (HSTCL) and adult T cell leukaemia/lymphoma followed in frequency with 13.1, 11.5, 8.6, 8.2 and 1.6 per cent cases, respectively. The three-year Kaplan-Meier overall survival (OS) and event-free survival (EFS) for the patients who received chemotherapy (n=122) were 33.8�0 and 29.3�7 per cent, respectively. Various prognostic indices developed for T cell lymphomas were found to be useful. Interpretation & conclusions: Except for ALCL, ALK positive, all other PTCLs showed poor long-term outcome with CHOP-based chemotherapy. Novel therapies are needed to improve the outcome.

Clinicopathologic features of non-small cell lung cancer in India and correlation with epidermal growth factor receptor mutational status.

INTRODUCTION: We performed retrospective analysis of 106 patients with lung cancer for which formalin‑fixed paraffin‑embedded tissues was available. Their epidermal growth factor receptor (EGFR) mutation status and treatment outcomes are described. MATERIALS AND METHODS: All patients with confirmed non–small cell lung cancer (NSCLC) during Jan 2008 to Dec 2010 were included. EGFR sequencing was performed with ABI PRISM 310 genetic analyzer. RESULTS: Forty‑two (39.6%) patients had mutation in one of the four exons characterized. Patients whose EGFR mutational status was not available at presentation before the start of treatment were started on chemotherapy, n = 46 (43.39%). If EGFR mutational analysis was available and mutations were present, the patients were started on either upfront tyrosine kinase inhibitor (TKI), n = 15 (14.15%) or if on chemotherapy arm were allowed to finish six cycles and then start with maintenance TKIs, n = 26 (24.52%). The median progression free survival for patients with and without mutations was 11 months (95% CI,7-14) and 9 months (95% CI,7-10) respectively. A median PFS of 14 months (95%CI, 12-16) was seen in the mutation‑positive group that received both chemotherapy followed by switch maintenance with TKIs versus 8 months (95%CI, 7-8 months) in the group that received only TKI. CONCLUSION: The prevalence of EGFR mutations in this population of NSCLC patients was 39.6% with exon 19 mutation being the most common. The observed benefit of addition of chemotherapy over TKI in EGFR mutation‑positive group raises the question, can we offer the therapy of chemotherapy–TKI combination to EGFR mutation‑positive lung cancer patients as shown in the present study.

Outcomes of renal transplantation in patients with immunoglobulin A nephropathy in India.

BACKGROUND: There is a paucity of data on the course of renal transplant in patients with immunoglobulin A (IgA) nephropathy (IgAN) from India. While the natural history of IgAN in the Indian context is rapidly progressive, the post-transplant course remains speculative. AIM: To study the graft survival in renal transplant recipients whose native kidney disease was IgAN and the incidence and correlates of recurrent disease. SETTINGS AND DESIGNS: Retrospective case control study from a Nephrology unit of a large tertiary care center. MATERIALS AND METHODS: The outcomes of 56 transplant patients (58 grafts) with biopsy-proven IgAN and of 116 patients without IgAN or diabetic nephropathy, transplanted during the same period were analyzed. Correlates of biopsy-confirmed recurrent disease were determined. STATISTICAL ANALYSIS: Means were analyzed by Student's t test and Mann-Whitney test; proportions were determined by Chi-square analysis and graft survival curves were generated using the Kaplan-Meier. RESULTS: Five-year graft survival for IgA patients was not significantly different from that in the reference group (90% and 79%, P = 0.6). During a mean follow-up of 42 months (range, 1-144), 28 event graft biopsies were required in 20 grafts of IgAN. Histological recurrence was diagnosed in five of the 20 available biopsies (25%) after a mean duration of 28 months. Recurrence did not correlate with donor status, HLA B35 and A2, recipient age, gender or immunosuppression. CONCLUSIONS: Renal transplantation is an appropriate treatment modality for IgA nephropathy patients with end-stage renal disease in India, despite the potential for recurrent disease. The posttransplant course is an indolent one when compared to the malignant pretransplant phase.

Spectrum of severe chronic kidney disease in India: a clinicopathological study.

BACKGROUND: The healthcare burden due to chronic kidney disease has increased worldwide in the past decade. Elucidating the aetiology of chronic kidney disease may help in identifying strategies for prevention, both in the population and the Individual patient. Only a clinicopathological study can define the exact spectrum of chronic kidney disease since epidemiological studies have not shown a consistent aetiological profile. The histological evidence used to support the diagnosis varies with the degree to which renal biopsy is done. Renal biopsy is the gold standard in making an aetiological diagnosis in renal failure, but as a diagnostic tool in chronic kidney disease it is underutilized. METHODS: This prospective study done at Christian Medical College, Vellore in southern India from 1998 to 2003 aimed to determine the aetiological profile of severe chronic kidney disease by analysing renal biopsies. The value of pre-renal biopsy clinical Judgement in predicting the histological diagnosis was also assessed. Patients with diabetic nephropathy were excluded from the study. RESULTS: Four hundred and fifty-seven patients had evidence of chronic kidney disease as evidenced on biopsy as well as on clinical parameters. Three hundred and twenty-two of these patients (70.5%) had glomerulonephritis as the histological diagnosis. Fifty-five (12%) had Interstitial nephritis, 30 (6.6%) had hypertensive arteriosclerosis and 28 (6.1%) had metabolic nephropathies. The positive predictive value of a pre-biopsy clinical diagnosis in predicting interstitial nephritis was very low (33%). A large number of patients clinically diagnosed to have chronic interstitial nephritis had other aetiologies of chronic kidney disease. CONCLUSION: Glomerulonephritis was the most common cause of chronic kidney disease, not including diabetic nephropathy, followed by interstitial disease and benign arterionephrosclerosis. In patients with unidentified severe chronic kidney disease, renal biopsy provided an aetiological diagnosis.

Prognostic factors in diffuse proliferative lupus nephritis.

BACKGROUND: Patients with diffuse proliferative lupus nephritis (DPLN) can have variable clinical course. Identification of the predictors of outcome would help to improve the management. We have studied the prognostic significance of clinical, laboratory and histological parameters in patients with DPLN. METHODS: Twenty nine patients diagnosed to be having DPLN seen between 1987 and 1991 were followed up for over 57 months. Parameters assessed for prognostic significance included serum creatinine, urine protein at the time of biopsy, blood pressure, type of immunosuppression, composite scores and individual components of activity index (AI) and chronicity index (CI). Kaplan-Meier survival curves were plotted and the results were compared using log rank test. Fishers' exact test was used to study the risk factors. RESULTS: End stage renal failure developed in 7/29 (24.1%) patients; 7/19 (36.8%) who had hypertension and 7/16 (43.8%) who had nephrotic proteinuria developed renal failure, while none who had normal blood pressure or nonnephrotic proteinuria, developed renal failure (p < 0.01). Three patients had high activity index (> 12) and all three developed renal failure. Other parameters such as age, gender, serum creatinine, type of immunosuppression, CI and individual components of AI failed to predict the outcome (p > 0.05). CONCLUSION: Hypertension, nephrotic proteinuria and high AI were predictive of progression to end stage renal failure in patients with diffuse proliferative lupus nephritis.

Treatment of diffuse proliferative lupus nephritis: an Indian experience.

BACKGROUND: Immunosuppressive therapy has improved the prognosis in lupus nephritis. However, infectious complications may contribute to morbidity. There is also debate on the best form of therapy. We, therefore, compared the results of two different forms of therapy. METHOD: Twenty-nine patients diagnosed to have diffuse proliferative lupus nephritis were followed up over 54 months. The treatment consisted of azathioprine (1.5 mg/kg/day) or pulse intravenous cyclophosphamide (500 mg/m2 body surface area monthly) along with prednisolone (2 mg/kg on alternate days). RESULTS: Seventeen patients received azathioprine (group A) and 12 received cyclophosphamide (group B). The mean (SD) follow up in groups A and B were 54.35 (33.6) and 52 (35.8) months, respectively. Apart from the higher number of males in group B, both groups were comparable for age, presence of hypertension, renal function, 24-hour urinary protein excretion and composite scores for histological activity and chronicity indices (p > 0.05). The renal survival estimated by the Kaplan-Meier method was similar in both groups (p > 0.05). Four patients had renal failure requiring replacement therapy in group A and 3 in group B. Major infective episodes were more common in group B than in group A (p = 0.03). CONCLUSION: Azathioprine was as effective as pulse intravenous cyclophosphamide in preserving renal functions up to 54 months. Major infective episodes were more common with pulse intravenous cyclophosphamide.