Autopsy and Case Reports
https://www.autopsyandcasereports.org/article/doi/10.4322/acr.2019.101
Autopsy and Case Reports
Article / Autopsy Case Report

Fatal familial hemophagocytic lymphohistiocytosis with perforin gene (PRF1) mutation and EBV-associated T-cell lymphoproliferative disorder of the thyroid

Agrima Mian; Kalpana Kumari; Seema Kaushal; Farhan Fazal; Parul Kodan; Atul Batra; Prabhat Kumar; Upendra Baitha; Pankaj Jorwal; Manish Soneja; Mehar Chand Sharma; Ashutosh Biswas

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Abstract

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare fatal autosomal recessive disorder of immune dysregulation. The disease presents most commonly in the first year of life; however, symptomatic presentation throughout childhood and adulthood has also been identified. Biallelic mutation in the perforin gene is present in 20%–50% of all cases of FHL. Secondary hemophagocytic lymphohistiocytosis (HLH) in association with hematological malignancies is known; however, whether mutations in HLH-associated genes can be associated with FHL and hematolymphoid neoplasms is not well documented. Also, Epstein–Barr-virus- (EBV) positive systemic T-cell lymphoproliferative disease (SE-LPD) in the setting of FHL is not clearly understood. Here, we present the case of a young boy who presented with typical features of childhood FHL harboring the perforin gene (PRF1) mutation, and had SE-LPD diagnosed on autopsy, along with evidence of recent EBV infection. The patient expired due to progressive disease. Five siblings died in the second or third decade of life with undiagnosed disease. Genetic counseling was provided to the two surviving siblings and parents, but they could not afford genetic testing. One surviving sibling has intermittent fever and is on close follow-up for possible bone marrow transplantation.

Keywords

Epstein–Barr Virus Nuclear Antigens, Familial Hemophagocytic Lymphohistiocytosis, Lymphoma, Perforin Gene Mutation

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Publication date:
07/19/2019

5d31fde00e88258e78e91f55 autopsy Articles
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