CAR T-cell toxicities resembling hemophagocytic lymphohistiocytosis (HLH) occur in a subset of patients with cytokine release syndrome (CRS). As a variant of conventional CRS, a comprehensive characterization of CAR T-cell associated HLH (carHLH) and investigations into associated risk factors are lacking. In the context of 59 patients infused with CD22 CAR T-cells where a substantial proportion developed carHLH, we comprehensively describe the manifestations and timing of carHLH as a CRS variant and explore factors associated with this clinical profile. Amongst 52 subjects with CRS, 21 (40.4%) developed carHLH. Clinical features of carHLH included hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, coagulopathy, hepatic transaminitis, hyperbilirubinemia, severe neutropenia, elevated lactate dehydrogenase and occasionally hemophagocytosis. Development of carHLH was associated with pre-infusion NK-cell lymphopenia and higher bone marrow T/NK-cell ratio, which was further amplified with CAR T-cell expansion. Following CRS, more robust CAR T-cell and CD8 T-cell expansion in concert with pronounced NK-cell lymphopenia amplified pre-infusion differences in those with carHLH without evidence for defects in NK-cell mediated cytotoxicity. CarHLH was further characterized by persistent elevation of HLH-associated inflammatory cytokines, which contrasted with declining levels in those without carHLH. In the setting of CAR T-cell mediated expansion, clinical manifestations and immunophenotypic profiling in those with carHLH overlap with features of secondary HLH, prompting consideration of an alternative framework for identification and management of this toxicity profile to optimize outcomes following CAR T-cell infusion.

A microscopic examination of an appropriately prepared and well-stained blood smear by a knowledgeable laboratory professional is necessary and clinically useful in a number of circumstances and for a variety of reasons. In this article, an attempt is made to delineate the purpose and criteria for blood smear examination in a variety of circumstances that are encountered in everyday laboratory hematology practice. A blood smear scan serves to at least (a) verify the flagged automated hematology results and (b) determine if a manual differential leukocyte count needs to be performed. Blood smear examination/manual differential leukocyte count with complete blood count (CBC) provides the complete hematologic picture of the case, at least from the morphologic standpoint. Blood smear review with or without interpretation serves to ensure that no clinically significant finding is missed, besides providing diagnosis or diagnostic clue(s), particularly if and when interpreted by a physician.

Synucleins are small soluble proteins found in normal brain that facilitate rapid release of neurotransmitters. α-synuclein is a major component of the Lewy body of neurodegenerative diseases and γ-synuclein is a marker of aggressive carcinomas. As the role of γ-synuclein has not yet been investigated in the lymphoid system, we immunohistochemically stained normal lymphoid organs, lymph nodes with reactive lymphoid hyperplasia, and malignant lymphomas. The anti-γ-synuclein antibody strongly stained the follicular dendritic cell (FDC) meshworks and vascular and lymphatic endothelial cells in reactive lymphoid tissues, in B-cell lymphomas with a nodular pattern, and in angioimmunoblastic T-cell lymphomas. There were no γ-synuclein-positive FDC meshworks in B-cell or T-cell lymphomas with a diffuse pattern. This is in contrast to CD21, which only stained the arms of the FDCs; γ-synuclein highlighted both the long slender cellular processes and the cell body, thereby clearly demonstrating the number of individual FDCs. In addition, γ-synuclein was strongly expressed by the neoplastic counterpart of reactive FDCs (FDC sarcoma) and by the neoplastic counterparts of normal lymphatic and vascular endothelial cells (Kaposi sarcoma, hemangioma, and angiosarcoma). Only a few spindle cell neoplasms (SSNs) derived from smooth muscle, peripheral nerve, or gastrointestinal stroma expressed γ-synuclein; however, γ-synuclein was not expressed by 11 other types of SSNs tested. These results suggest that γ-synuclein is a promising new adjunct marker for identifying reactive FDCs and for diagnosing FDC sarcoma and benign and malignant vascular tumors.

The sensitivity of the DM96 for detecting PLT clumps can be maximized to 82.8% by reviewing the entire white blood cell screen and the entire PLT screen. Microscopic review of the blood smears yielded a PLT-clump detection rate of 99.0% when we examined the feather edge and the readable area of the smear.

A case of multicentric Castleman's disease in an HIV− human herpesvirus 8+ patient who was successfully managed with concurrent bortezomib and ganciclovir is presented.