Haemophagocytic lymphohistiocytosis in association with granular lymphocyte proliferative disorders in early childhood: characteristic bone marrow morphology

Abstract

Summary. Five paediatric cases of haemophagocytic lymphohistiocytosis (HLH) which showed proliferation of granular atypical lymphocytoid cells in bone marrow are reported. All cases were girls aged 8 months to 4 years who had marked hepatosplenomegaly. Marker analysis on peripheral blood mononuclear cells revealed an increase in the CD3 þ HLADR þ subset in three cases and the CD3 ¹ CD56 þ subset in one case. An Epstein-Barr virus genome was detected in three cases, and monoclonality was confirmed in two cases. A characteristic morphology of large granular lymphocytes (LGL) was identified, with elongated bizarre features that resembled horsetail-, tadpole-, cucumber-or shooting star-type configurations on the bone marrow smear. Serum concentrations of soluble interleukin-2 receptor and interferon-gamma were elevated in all cases. All five cases required multi-agent chemotherapy which resulted in two complete remissions, two partial remissions and one no response. Refinement of treatment is required for these paediatric GLPD cases which probably comprise a specific high-risk subgroup among secondary HLH patients which had previously escaped notice.

Splenectomy in haemophagocytic lymphohistiocytosis: report of histopathological changes with CD19+ B‐cell depletion and therapeutic results

“…T cells or NK cells (Chan & Ng, 1989;Oyama et al, 1989;Okuda et al, 1991;Imashuku et al, 1997). That is, the hyperstimulated granular lymphocytes could induce apoptosis of B cells through the Fas±FasL system (Tanaka et al, 1995(Tanaka et al, , 1997Elenitoba-Johnson et al, 1998;Hasegawa et al, 1998;Yamashita et al, 1998).…”

Large Granular Lymphocyte Leukemia

“…Viral infections (EBV, cytomegalovirus, hepatitis B virus, hepatitis C virus, and human immunodeficiency virus), connective tissue disease, idiopathic thrombocytopenia purpura, various skin disorders, and hemophagocytosis syndrome are the main nonmalignant disorders potentially associated with reactive LGL expansion. 2,5,58,59 Myelodysplasia, non-Hodgkin's lymphoma, and solid tumors are sometimes associated with increased NK cells in peripheral blood. 58…”

Pulmonary strongyloidiasis associated CD3+ large granular lymphocytosis

“…EBV, CMV, HBV, HCV, HIV, ITP, connective tissue disorders such as rheumatoid arthritis, skin disorders such as pyoderma gangrenosum and hemophagocytosis syndromes have been described as potential causes of reactive LGL. [81112] One previous case report[10] has described strongyloides as a potential cause of CD3-LGL.…”