Annika Windon MD, Yusong Yang MD PhD, Leonas Bekeris MD, Adam Bagg MD Crystal-storing histiocytosis: definite diagnostic difficulties associated with this marvelous masquerader masking malignant myeloma Case #: EAHP16-BMWS-224 Annika Windon MD, Yusong Yang MD PhD, Leonas Bekeris MD, Adam Bagg MD

Clinical History 57-year-old male Presented with a creatinine of 14 mg/dL in acute renal failure during an episode of severe diarrhea secondary to Clostridium difficile Bone marrow showed peculiar inclusions in macrophages that were interpreted to be concerning for leishmaniasis  slides submitted in consultation

Bone marrow aspirate smear, modified Wright-Giemsa (20x): Expanded macrophage population with intracytoplasmic inclusions

Bone marrow aspirate smear, modified Wright-Giemsa (40x): Macrophages contain abundant irregular purple intracytoplasmic inclusions

Bone marrow aspirate smear, modified Wright-Giemsa (100x): Plasma cells contain similar irregular pinkish-purple intracytoplasmic inclusions

Aspirate clot, H&E (20x): Cluster of macrophages with eosinophilic intracytoplasmic inclusions

Aspirate clot, H&E (50x): Clusters of macrophages with intracytoplasmic crystals

Aspirate clot, H&E (100x): Macrophages and plasma cells with intracytoplasmic crystals

Immunohistochemistry summary Plasma cell expansion (20-30%) CD79a+ CD138+ MUM1+ kappa-restricted CD20- CD45- CD56- PAX5- Macrophages CD68+ CD163+ lysozyme+ Crystalline material within macrophages Kappa+ CD138+

Aspirate clot, immunohistochemistry, lighter image (50x): CD138 highlights plasma cells and inclusions in macrophages Plasma cells: Macrophages:

Aspirate clot, immunohistochemistry, darker image (40x): CD138 highlights plasma cells and inclusions in macrophages Plasma cells: Macrophages:

Aspirate clot, immunohistochemistry (50x): Plasma cells (brighter) and intracellular inclusions (dimmer) are kappa restricted Kappa Lambda

Additional Workup Laboratory Studies Radiology SPEP Hypogammaglobulinemia, no monoclonal spike Urine immunofixation Free kappa light chains Creatinine 2.3 mg/dL (Max:14 mg/ dL) Radiology X-ray Focal lytic lesion of the distal shaft of the left humerus measuring 1.7 x 1.2 cm Just need to add imaging

Cytogenetics Conventional cytogenetics FISH Normal male karyotype Positive for t(11;14)/CCND1-IGH

Diagnosis Crystal-storing histiocytosis

Interesting Features Diagnostic challenges Crystals are CD138+ Macrophages harboring crystalline material often mistaken for Gaucher cells or pseudo-Gaucher cells of CML This case was thought to reflect leishmaniasis The macrophages masked the underlying plasma cell neoplasm Crystals are CD138+ Raises the possibility that the macrophages may be ingesting plasma cell fragments rather the protein Prognosis Typically poor, but this patient remains alive and well 4 years after presentation