Gaucher-like crystal-storing histiocytosis associated with kappa chain myeloma: A case report with next generation sequencing study

Crystal-storing histiocytosis is a rare entity due to tumorous deposits of histiocytes containing crystalline inclusions, which in a majority of cases are made of immunoglobulins associated with lymphoproliferative disorders, although association with non-neoplastic disorders has also been reported. The histiocytes may be so abundant to obscure the underlying lymphoplasmacytic neoplasm. On the other hand, the Gaucher-like histiocytes might lead to a misinterpretation of granulomatous inflammation or storage disease. Herein, this case study reported clinical, pathological and next generation sequencing (NGS) features of a case of kappa chain myeloma with Gaucher-like crystal-storing histiocytosis in the bone marrow (BM). The methodology included BM aspiration and biopsy, immunohistochemistry, electron microscopy and NGS study by TruSight Oncology 500. Morphologically, the BM smear showed dense infiltration of sea blue histiocytes and atypical plasma cells with rhomboid crystals in cytoplasm. The BM biopsy showed excessive plasmacytic aggregates and dense histiocytic infiltrates with wrinkled paper-like or needle shaped cytoplasm. These plasma cells were positive for CD138 and showed lambda chain restriction. Electron microscopy highlighted the long rhomboid crystals with distinct periodicity consistent with crystalline immunoglobulins in the histiocytes. In addition, the NGS study from the BM aspiration specimen revealed PARP1, MSH6, KDR, CCND3 and STK11 mutations, which might be associated with inferior survival of myeloma patients. Accordingly, this case died of pneumonia with septic shock during treatment. Our findings suggest that the presence of rhomboid crystals in bone marrow smears may alert pathologists to look for the possibility of crystal-storing histiocytosis and the prognosis of patients with multiple myeloma may depend on the genetic features of tumor cells rather than the association with crystal-storing histiocytosis.