A case of pediatric anaplastic large cell lymphoma with hemophagocytic lymphohistiocytosis mimicking juvenile myelomonocytic leukemia

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening inflammatory syndrome characterized by reactive proliferation of histiocytes in hematopoietic tissues, with accompanying hemophagocytosis. A number of primary and secondary triggers have been identified, including some hematolymphoid neoplasms. We submit the case of an 11-year-old female who presented with HLH and met diagnostic criteria for juvenile myelomonocytic leukemia, which included the apparently non-recurrent clonal cytogenetic abnormality t(5;12)(q35;q24.1). The diagnosis was eventually revised to systemic anaplastic large cell lymphoma with cryptic NPM-ALK fusion. We review the previously reported cases of pediatric HLH triggered by systemic ALCL and find that the marked neutrophilia, monocytosis, and circulating myeloid precursors seen in our case were unique. In addition, our review highlights the challenge of detecting ALCL in the context of HLH, and identifies features that may be of assistance. While the bone marrow is the most frequently examined tissue in HLH, its diagnostic yield is low. The suspicion for ALCL, and perhaps other neoplasia, should be higher when associated with pulmonary disease (especially if multi-nodular), skin lesions or lymphadenopathy. Under these circumstances, additional biopsies are recommended even when lymph node enlargement is minimal-a finding often attributed directly to HLH and ignored. Furthermore, it is important to assess for both CD30 and ALK expression, because malignant cells may be too sparse to be detectable with routine H&E or CD3 stains and may not consistently demonstrate both markers.