ALK-positive Large B-cell Lymphoma: A Clinicopathologic Retrospective Descriptive Study from a Tertiary Care Cancer Centre in India

Introduction: Anaplastic Lymphoma Kinase (ALK) positive Large B-Cell Lymphoma (ALK+ LBCL) is a very rare aggressive B-cell lymphoma presenting significant diagnostic challenges due to their rarity and unique immunophenotypic features. ALK is a tyrosine kinase receptor and is expressed by ALK+ LBCL due to ALK rearrangement.

Aim: To analyse the histopathological features including morphology and immunophenotype, clinical details, pattern of care, progression-free survival (PFS) and overall survival of cases diagnosed as ALK+ LBCL.

Materials and Methods: This clinicopathological retrospective descriptive study was conducted in the Department of Pathology at a Tertiary Care Cancer Centre, Thiruvananthapuram, Kerala, India. The duration of the study was six months, from January 2022 to June 2022. All the cases of ALK+ LBCL were diagnosed over a period of 10 years, from January 1st 2010 to December 31st 2020. The cases of LBCL diagnosed during the 10 year period were reviewed. Clinical details were obtained from the case sheets of the cases diagnosed as ALK+ LBCL and summarised. Data collection variables included age, sex, stage, nodal and extranodal status, bone marrow, Central Nervous System (CNS) involvement, haemoglobin, Total Leukocyte Count (TLC) and platelet count, Lactate Dehydrogenase (LDH) value, performance status, date of diagnosis, date of treatment started, date of progression, date of last follow-up, date of death (if dead). Review of Haematoxylin & Eosin (H&E) sections and immunohistochemical slides were done and observations were recorded. Descriptive statistics was used to summarise the basic features of the dataset and Kaplan-Meier method was used for calculation of survival.

Results: The age of study participants was ranged from 16-56 years. During the 10 year period, LBCL accounted for 2415 cases. Among these, ALK+ LBCL constituted 6 (0.25%) cases. There was a male predilection (n=5). Blood counts were normal except for anaemia in three patients. LDH was raised in all the patients. Advanced stage disease was present in two patients. Histopathologically, tumour cells in all the cases showed plasmablastic morphology. Immunohistochemistry (IHC) revealed plasma cell immunophenotype and positivity for ALK in all the cases. Cytokeratin (CK) and Epithelial Membrane Antigen (EMA) were positive in three cases simulating carcinomas. Six year overall survival and progression free survival in the present study was 50% and 33.3%, respectively.

Conclusion: Careful interpretation of the morphology and immunophenotype is essential for diagnosis of ALK+ LBCL, as it can be easily misdiagnosed as a non haematological malignancy thus, affecting the treatment and prognosis in these patients.