Painful plantar nodules: A specific manifestation of cutaneous macroglobulinosis
Authors: Carmine D'Acunto, Evandro Nigrisoli, Eliana Valentina Liardo, Davide Melandri
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: In December 2013, a 70-year-old man came to our service for nodules covered by a thick hyperkeratotic layer on the soles of his feet. The lesions were extremely painful to pressure, to the extent of limiting his daily activities (Fig 1). They had appeared about 2 years earlier and were treated as viral warts with keratolytic agents, without success. The patient's history showed that he had been followed by the hematology service for 15 years with periodic clinical evaluations and no therapy for a diagnosis of Waldenström macroglobulinemia (WM). The most recent laboratory studies were unremarkable with no detectable anti-myelin-associated glycoprotein (anti-MAG) or cryoglobulin. Serum immunofixation studies revealed the presence of an IgM-kappa monoclonal protein of 22.9 g/L (0.4-2.5 g/L); urine analysis identified Bence-Jones (IgM-kappa type) proteinuria. The patient was otherwise in good health. On the basis of clinical and laboratory findings, hematologists recommended no therapy. A biopsy of 1 of the plantar nodules showed hyperplastic and hyperkeratotic epidermis, and moderate perivascular lymphohistiocytic inflammation with rare plasma cells. In the dermis and in the intravascular space there was deposition of an amorphous, homogeneous, intensely periodic acid-Schiff−positive and Congo red−negative material. The biopsy specimen was IgM positive when immunohistochemical stains were used (Fig 2). Based on the clinical course, histology, and anamnestic data, we considered a diagnosis of cutaneous macroglobulinosis (CM) in the course of WM. WM is a lymphoplasmacytic lymphoma with a monoclonal IgM paraprotein; it represents about 2% of all hematologic malignancies and its incidence is 3.8 per million persons per year.1Gertz M.A. Waldenström macroglobulinemia: 2013 update on diagnosis, risk stratification, and management.Am J Hematol. 2013; 88: 703-711Crossref PubMed Scopus (35) Google Scholar WM cases usually have an indolent disease course for many years preceding clinical presentation related to tumor infiltration and deposition of monoclonal IgM paraprotein in tissues.2Dimopoulos M.A. Alexanian R. Waldenstrom's macroglobulinemia.Blood. 1994; 83: 1452-1459PubMed Google Scholar The symptoms of neoplastic infiltration may be due to the replacement of bone marrow, splenomegaly, and/or lymphadenopathy. Paraprotein can also lead to hyperviscosity syndrome, peripheral neuropathy, and immune complex vasculitis.1Gertz M.A. Waldenström macroglobulinemia: 2013 update on diagnosis, risk stratification, and management.Am J Hematol. 2013; 88: 703-711Crossref PubMed Scopus (35) Google Scholar Cutaneous manifestations of WM are distinguished as specific and nonspecific.3Gressier L. Hotz C. Lelièvre J.D. Carlotti A. Buffet M. Wolkenstein P. et al.Cutaneous macroglobulinosis: a report of 2 cases.Arch Dermatol. 2010; 146: 165-169Crossref PubMed Scopus (23) Google Scholar Specific manifestations, sporadically reported, are related to lymphoplasmacytic cell infiltrates or deposits of monoclonal component in the cutis. Nonspecific manifestations are the consequence of hyperviscosity or cryoglobulinemia such as purpura, livedo reticularis, mucosal bleeding, and Raynaud phenomenon.4Camp B.J. Magro C.M. Cutaneous macroglobulinosis: a case series.J Cutan Pathol. 2012; 39: 962-970Crossref PubMed Scopus (27) Google Scholar The accumulation of monoclonal IgM in the basement membrane zone (BMZ) may present with pruritic papules or bullous dermatosis when IgM antibodies are directed to antigens of BMZ.5Whittaker S.J. Bhogal B.S. Black M.M. Acquired immunobullous disease: a cutaneous manifestation of IgM macroglobulinaemia.Br J Dermatol. 1996; 135: 283-286Crossref PubMed Scopus (50) Google Scholar The isolated storage of IgM components in the dermis is known as CM; it is a very rare condition and clinically presents translucent erythematous papules that are located on the limbs, buttocks, and back.4Camp B.J. Magro C.M. Cutaneous macroglobulinosis: a case series.J Cutan Pathol. 2012; 39: 962-970Crossref PubMed Scopus (27) Google Scholar In our case, the skin lesions were exclusively localized on the soles and were characterized by intense pain on pressure. It seems appropriate to stress the importance of seeking these localized plantar lesions in CM associated with pain, which require a specific treatment for WM.