M protein deposition in the skin: a rare manifestation of Waldenström macroglobulinemia

Waldenstrom macroglobulinemia (WM) is defined by diffuse and nodular bone marrow infiltration of lymphoplasmacytic lymphoma as defined by the World Health Organization (WHO), and by a monoclonal IgM serum paraprotein (macroglobulin) [1]. Clinical symptoms at presentation are frequently unspecific, including fatigue, weakness, and weight loss. Clinical symptoms such as hyperviscosity syndrome, peripheral neuropathy, and glomerular disease are often related to the IgM paraprotein, both in form of circulating IgM and IgM deposition in tissue. The skin constitutes an unusual site of manifestation of WM, both for tumor infiltrates and IgM paraprotein deposition. A 70-year-old male patient was hospitalized in April 2009 with progressive peripheral neuropathy and poor general condition. Further examination revealed small, non-pruritic, soft indolent wart-like papules on both knees. As noted by the patient, the lesions were easily scratched off, bled slightly, leaving scabs and causing additional papules to appear during healing. Laboratory findings included slight anemia with a hemoglobin level of 8.2 mmol/l (normal 8.4–10.9 mmol/l) and a hematocrit reading of 0.379 l/l (normal 0.400–0.530 l/l). The RBC count was 4.22 9 10/l (normal 4.50–5.90 9 10/l) with 3% reticulocytes (normal 6–18%). The thrombocyte count and the differential white blood count were within the normal range. Renal, hepatic and cardial functions were also normal, and there was no splenomegaly or lymphadenopathy. The total protein level was 94.8 g/l (normal 66.0–87.0 g/l), and quantitative immunoglobulin findings were as follows: IgM 23.70 g/l (normal 0.40–2.80 g/l), j-light chains 5.63 g/l (normal 1.50–3.90 g/l), free j-light chains 284.00 mg/l (normal 3.30–19.40 mg/l), free k-light chains 13.90 mg/l (normal 5.71–26.30 mg/l) and a free j-light chains/k-light chains ratio of 20.43 (normal 0.26–1.65). Serum electrophoresis presented an elevated IgM gradient. Serum immunofixation provided a clear precipitation pattern of monoclonal IgM j-type immunoglobulin. The b2 microglobulin level was 1.7 mg/l (normal \2.0 mg/l). Bone marrow microscopy revealed atypical lymphoplasmocytic cells. Immunohistochemistry demonstrated low proliferation and B cell nature of the lymphocytes (25% of all hematopoietic cells) beside a mature CD138 positive plasma cell population (15%) with monotypic restriction for j-light chain and IgM heavy chain (Fig. 1). Given these findings, the diagnosis of Waldenstrom’s macroglobulinemia was established. Skin sections displayed multifocal nodular strongly eosinophilic, PASpositive and Elastica van Gieson, Congo red, and Alcian blue-negative homogeneous deposits in the upper portion of the dermis. Immunohistochemistry presented a faint monotypic staining for IgM and j-light chains, manifesting as multifocal nodular depositions of monoclonal immunoglobulin (Fig. 1). A diagnosis of macroglobulinemia cutis presenting as IgM storage papules was therefore established. To suppress disease activity, the patient received four cycles of Rituximab-CHOP, during which the cutaneous lesions disappeared. B. Oberschmid U. Siebolts (&) A. Beller C. Wickenhauser Institute of Pathology, University of Leipzig, Leipzig, Germany e-mail: udo.siebolts@medizin.uni-leipzig.de