Crystal-storing histiocytosis: a clinicopathological study of 13 cases

Abstract

Aims: Crystal-storing histiocytosis (CSH) is a rare lesion composed of histiocytes with abnormal intralysosomal accumulation of immunoglobulin (Ig) as crystals, reported in patients with plasmacytic/lymphoplasmacytic neoplasms. The aims of this study were to report the clinicopathological features of 13 patients with CSH, and to describe the proteomic composition of the crystals in three cases analysed by mass spectrometry (MS).

Methods and results: There were seven men and six women, with a median age of 60 years (range, 33-79 years). CSH was generalized in one patient (8%) and localized in 12 (92%) patients, involving various sites. CSH was associated with a low-grade B-cell lymphoma with plasmacytoid differentiation or a plasma cell neoplasm in all cases. In 10 (77%) cases, CSH represented >50% of the neoplastic infiltrate. According to immunohistochemical studies, histiocytes were positive for monotypic kappa in 5 (50%) cases, and for monotypic lambda in 4 (40%) cases; in 1 (10%) case, the results were equivocal. MS analysis of the histiocyte contents in all three tested cases showed a predominance of variable-region fragments of Ig light and/or heavy chains.

Conclusions: CSH is frequently associated with an underlying lymphoplasmacytic neoplasm. MS findings suggest that Ig alterations and/or possibly defects in the ability of histiocytes to process Ig play a role in pathogenesis.

Keywords: crystal-storing histiocytosis; immunoglobulin; lymphoplasmacytic neoplasm; mass spectrometry; proteomic analysis.

Figure 1

Case 1 (A-F): A, bone marrow touch imprint showing histiocytes with numerous crystalline inclusions within the cytoplasm, Giemsa-Wright stain, x1000; B-C, low and high power magnifications of bone marrow biopsy; marrow space demonstrates extensive spindle cell proliferation composed of polygonal-shaped histiocytes with crystalline cytoplasmic inclusions, H & E stain, x100 and x400; D, By immunohistochemistry, these histiocytes were positive for CD163 (x100, shown); CD68 (KP-1), SMA (focal) and IgG and negative for desmin, myogenin, EBER, melanoma cocktail, S-100, IgM, IgA (not shown); E and F, Staining for kappa and lambda immunoglobulin light chains highlight sparse plasma cells that show bright monotypic lambda staining; the spindle cells show weak blush of lambda and kappa (equivocal)

Figure 2

Case 4 (A-C): A 74 year old man with a history of perinephric non-Hodgkin lymphoma with lymphadenopathy and IgM gammopathy. A, Lymph node biopsy showing complete replacement of architecture by a combination of abnormal histiocytic proliferation (90%) as sheets of large bland histiocytes with pink granular crystalline cytoplasm and a lymphoplasmacytic proliferation (10%) as scattered islands with numerous Russell bodies and rare Dutcher bodies. B, PAS stain highlighting plasma cells and immunoglobulin-laden histiocytes; C, IgM positive in histiocytes and plasma cells; Case 7 (D): A 43 year old man with waxing and waning abdominal cramping. Endoscopy showed multiple, submucosal, firm, umbillicated nodules in the proximal stomach. D, Oxyntic type gastric mucosa showing crystal-storing histiocytosis associated with lymphoplasmacytic infiltrate (H & E stain, x400); Immunohistochemistry showed monotypic IgA kappa staining in CSH and lymphoplasmacytic infiltrate. PCR studies showed clonal immunoglobulin heavy chain gene rearrangement.

Figure 3

Case 5 (A, B): A, lymph node biopsy showing CSH associated with lymphoplasmacytic lymphoma (H&E, x100, H&E, x1000); Case 11 (C, D): C, Duodenal biopsy in a 73 year old woman showing CSH; D, Crystal-laden histiocytes positive for kappa

Figure 4

Scaffold analysis on cases 1 and 4 listing the proteins identified by mass spectrometry within the crystals based on detected peptide spectra. Columns 1 and 2 represent two different areas of microdissection. The numbers listed within each box is the number of unique peptide spectra detected of a given protein. Inset represents areas selected for analysis by laser capture microdissection.

Figure 5

Scaffold analysis of case 7 showing the proteome components. Inset represents areas selected for analysis by laser capture microdissection.