Generalized crystal-storing histiocytosis with diffuse large B-cell lymphoma and monoclonal gammopathy in a Chinese elderly woman: a case report

A 74-year-old woman was admitted with the chief complaint of subcutaneous masses, abdominal pain, and fever. Six months before the admission, the patient developed thrombocytopenia while being treated with antibiotics for pneumonia. At the time of admission, physical examination revealed a firm non-tender subcutaneous mass on the left upper arm (Fig. 1a) and two at the waist. Her abdomen was soft, but light tenderness was present in the upper abdomen without rebound tenderness. The liver and the spleen were not palpable below the costal margin. The laboratory tests results were as follows. (1) A white blood cell count of 3.48 × 10⁹/L (reference range 3.5–9.5 × 10⁹/L), an extremely low platelet count of 7.0 × 10⁹/L (reference range 100–300 × 10⁹/L) and haemoglobin of 96 g/L (reference range 115–150 g/L) were noted. (2) Serum protein electrophoresis showed a monoclonal band, which was determined to be of the IgM κ type by immunofixation (Fig. 2a). Serum protein quantitative analysis revealed 10.30 g/L IgM, 20.10 g/L kappa light chain, 7.04 g/L lambda light chain and kappa/lambda = 2.86 (reference range 2.20,13.00 and 6.50 g/L and reference ratio of 2.56, respectively). All the other immunoglobin (Ig) levels were normal. (3) Urinalysis result was 1 + (0.5 g/L) (reference range negative, 0 g/L) for protein. (4) Bone marrow aspiration and flow cytometry (FCM) analysis were normocellular. Computed tomographic (CT) scan showed a 2.0 cmx1.6 cm subcutaneous mass on the left upper arm and several ill-defined soft tissue lesions at the waist along with intra-abdominal lymphadenopathy and moderate splenomegaly (Fig. 1b&c). Abdominopelvic contrast-enhanced CT displayed multiple low-density plaques in the spleen (Fig. 1d). The patient underwent a needle biopsy of the subcutaneous mass on the left arm in a local hospital. After her admission, the subcutaneous mass at the right waist was excised, and laparoscopic splenectomy was performed.

(1) Macroscopically, the resected lumbodorsal specimen was a firm grey-brown mass measuring 5.5 cm × 3.0 cm × 1.5 cm in volume. Microscopic examination revealed diffuse proliferation in the subcutaneous tissue, which was composed of large polygonal and spindle histiocytes with abundant eosinophilic cytoplasm, round to ovoid eccentric nuclei, reticulate chromatin and median nucleoli (Figs. 3a&b). Needle-shaped crystals were confined to the cytoplasm, some of which were in parallel arrays (Fig. 3c). These crystal-containing cells were located in and around an intact lymph node measuring 0.8 cm in maximal dimension. The paracortical area of the lymph node was expanded by extensive infiltration of the crystal-containing cells and mature plasma cells (Fig. 3a). These crystal-containing cells were strongly positive for CD68/PGM1 (Fig. 3d) and CD163 and negative for S-100, desmin, SMA, MSA, and myogenin. Immunostain for IgM heavy chain was strong and diffuse (Fig. 3e). Immunostain for the κ light chain was relatively weak. Immunostains for the IgG heavy chain and λ light chain were negative (Fig. 3f). The plasma cells were characterized by CD38+, MUM1+, and kappa > lambda. Congo red staining was negative. BIOMED-2 multiplex PCR analysis showed diversity-joining gene segments of immunoglobin heavy chain (IgH-DH-JH) gene rearrangement (the monoclonal peak was at approximately 400 bp) and Igκ gene rearrangement. The MYD88 L265p mutation was not detected. The diagnosis of “CSH associated with IgH and Igκ rearrangements” was made with a comment that an underlying lymphoproliferative disorder should be suspected.

(2) Review of the needle biopsy of the mass on the left upper arm identified a similar cell population as the one at the waist, which was characterized by sheets of large rhabdoid cells with abundant deeply eosinophilic cytoplasm containing massive crystalline materials, eccentric irregular nuclei, and inconspicuous nucleoli.

(3) The spleen was enlarged to 15 cm × 10 cm × 8 cm and weighed 198 g with a smooth surface. Serial sectioning showed a grey irregular solid tumour measuring 3 cm × 1.5 cm × 1.3 cm at the splenic hilum mixed with adipose tissue and focal necrotic areas. Microscopic examination revealed diffuse infiltration of large cells with a round, oval or irregular nuclei, distinct nucleoli and scant cytoplasm, centroblast like (Fig. 4a-b). Frequent mitoses were observed (Fig. 4b). Immunohistochemically, the neoplastic cells were CD20+, Bcl6+, MUM1+, CD3p-, CD10-, CyclinD1- and CD43- (Fig. 4c-d). IgM was strongly positive in the cytoplasm of some neoplastic cells, while IgG, CD38, and CD138 were negative (Fig. 4e-g). The Ki-67 index was 80% (Fig. 4h). Fluorescence in situ hybridization (FISH) suggested BCL-6 rearrangements but the absence of dysregulations of BCL2 and MYC. In situ hybridization for Epstein-Barr virus-encoded RNA (EBER-ISH) was negative. A monoclonal peak of the IgH gene was detected at approximately 420 bp by commercial BIOMED-2 multiplex PCR system. These findings conformed to a diagnosis of DLBCL, non-GCB subtype (Hans algorithm). The pancreas was involved, while the liver was not. CSH lesions were not found in the spleen and the regional lymph nodes.

After splenectomy, the platelet count increased to 128 × 10⁹/L. The patient was administered eight courses of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and was in partial remission (PR) 9 months after diagnosis. Positron emission tomography-computed tomography (PET-CT) scan showed resolution of the mass at the left arm, smaller lumbar subcutaneous masses and intraperitoneal lymphadenopathy (Fig. 1e-f). However, serum paraprotein levels remained elevated (IgM 4.01 g/L). Thus, the patient received four cycles of rituximab (600 mg/m² day 1) plus lenalidomide (25 mg/m² days 1–14 q28), and the MG was not visible (Fig. 2b) at a one-year follow-up.