Dermatology: Practical and Conceptual DERMATOLOGY PRACTICAL & CONCEPTUAL www.derm101.com Observation | Dermatol Pract Concept 2013;3(3):3 7 Case presentation A 56-year-old man presented with a 12-month history of tingling ulcers on both feet (Figure1A). He was otherwise well. On examination there were ulcers on both feet, 1-1.5 cm in diameter with a macerated edge. Skin-colored to red- brown papules were noted on both knees (Figure 1B) as well as irregular red circles on both calves. Skin biopsies taken from knee papules and red circles on the lower leg showed extravascular eosinophilic deposits in the dermis (Figure 1C), which stained positive with PAS, IgM (Figure 1D) and kappa stains, but negative with Congo red. Investigations are summarised here: Serum kappa free chains, 85.9 mg/l (nor- mal 3.3-19.4 mg/l); serum lambda free chains, 17 mg/l (nor- mal 7.7-26.3 mg/l); serum free kappa chains /free-lambda chains ratio, 5.05 (normal 0.26-1.65); serum electrophoresis, elevated Ig M gradient; serum immunofixation, monoclonal Ig M/kappa-type immunoglobulin; urine immunofixation, monoclonal kappa-free chain; bone marrow microscopy, infiltrate of lymphoplasmocytic cells (15%) (most CD20 and CD138 positive) with preferential expression for IgM. Discussion The cutaneous manifestations of Waldenström macroglobu- linaemia have been classified as either infiltration by neo- plastic cells or those related to the paraproteinaemia, such as immunoglobulin deposition, cryoglobulinaemia or blood hyperviscosity. A number of other nonspecific cutaneous presentations have been reported. Approximately 5% of patients with Waldenström macroglobulinaemia develop cutaneous manifestations, with neoplastic infiltration being the least common. Skin signs may either precede or follow the diagnosis. Prognosis does not appear to be influenced by the presence or absence of cutaneous disease [1]. Waldenström macroglobulinaemia presenting as tingling ulcers on the feet Isabelle Fischer,1 Delwyn Dyall-Smith,1 Birgit Peters,1 Wilhelm Stolz,1 Brigitte Coras-Stepanek1 1 Department of Dermatology, Klinikum Schwabing, Munich, Germany Key words: peripheral neuropathy, storage papules, macroglobulinaemia cutis Citation: Fischer I, Dyall-Smith D, Peters B, Stolz W, Coras-Stepanek B. Waldenström macroglobulinaemia presenting as tingling ulcers on the feet. Dermatol Pract Conc. 2013;3(3):3 . http://dx.doi.org/10.5826/dpc.0303a03. Received: May 1, 2013; Accepted: June 1, 2013; Published: July 31, 2013 Copyright: ©2013 Fischer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: None. Competing interests: The authors have no conflicts of interest to disclose. All authors have contributed significantly to this publication. Corresponding author: B. Coras-Stepanek, M.D., Department of Dermatology, Klinikum Schwabing, Koelner Platz 1, 80804 Munich, Germany. Tel. 0049 89 3068; Fax . 0049 89 3068 3918. Email: brigitte.coras@klinikum-muenchen.de. A 56-year-old man presented with tingling ulcers on the feet. On further skin examination, papules on the knees were observed. Biopsies revealed extravascular eosinophilic deposits of IgM, and Walden- ström macroglobulinaemia was diagnosed. The skin manifestations have resolved with chemotherapy. Peripheral neuropathy and storage papules are rare manifestations of Waldenström’s macroglobu- linaemia. ABSTRACT 8 Observation | Dermatol Pract Concept 2013;3(3):3 showed a leukocytoclastic vasculitis with a neutrophilic infil- trate. Storage papules were present on the knees and perianal skin. Another report described IgM dermal deposits that pre- sented as painful hyperkeratotic papules on the soles of the feet that were not ulcerated [5]. On further examination, our patient had the papules of macroglobulinosis. Storage papules, also known as macro- globulinaemia cutis, are rare but well described and are usu- ally found on the knees or other extensor surfaces. They are usually skin-coloured, red-brown or translucent, and may be umbilicated, crusted or haemorrhagic. Biopsy shows dermal eosinophilic hyaline material, which is IgM. Our patient was treated with six cycles of bendamustine infusions. After five cycles the lower limb ulceration and neurological symptoms had resolved, although the blood IgM level did not change. Conclusion Waldenström macroglobulinaemia is a low-grade lympho- plasmacytoid lymphoma that usually presents with nonspe- cific systemic symptoms, but cutaneous changes may be the initial manifestation and hence may present first to a derma- tologist. Although our patient presented with tingling ulcers, the diagnosis was reached after skin biopsy from knee pap- ules demonstrated dermal immunoglobulin deposition. References 1. Libow LF, Mawhinney JP, Bessinger GT. Cutaneous Walden- ström’s macroglobulinemia: report of a case and overview of the spectrum of cutaneous disease. J Am Acad Dermatol. 2001; 45(6 Suppl): S202-6. 2. Abdallah-Lotf M, Bourgeois-Droin C, Perronne V, et al. Cutane- ous manifestations as initial presentation of Waldenstrom’s mac- roglobulinemia. Eur J Dermatol. 2003;13(1):90-2. 3. Silberman J, Lonial S. Review of peripheral neuropathy in plasma cell disorders. Hematol Oncol. 2008;26(2):55-65. 4. del Olmo J, España A, Idoate MA, Panizo C. Waldenström mac- roglobulinemia associated with cutaneous lesions and type I cryo- globulinemia. Actas Dermosifiliogr. 2008;99(2):138-44. 5. Harnalikar M, Pande S, Kharkar V, Khopkar U. Keratotic vascular papules over the feet: a case of Waldenström’s macroglobulinae- mia-associated cutaneous macroglobulinosis. Clin Exp Dermatol. 2010;35(3):278-81. Neoplastic cell infiltrates present as red or purple patches and plaques. In one case the patient presented with a burning red face which was initially diagnosed as rosacea but with time the more typical purple infiltration developed [2]. Peripheral neuropathy is a well recognised presentation of dysproteinaemias, particularly IgM [3]. In Waldenström macroglobulinaemia the neuropathy is typically sensorimo- tor, initially with paraesthesias and numbness in the feet and hands. Motor symptoms, such as weakness or foot drop, develop later. The possible mechanisms in Waldenström macroglobulinaemia include microangiopathy, direct infil- tration of nerves, endoneural deposition of IgM protein or amyloidosis, hyperviscosity or immunoglobulin deposit in blood vessels. The tingling ulcers in our patient are probably an example of this and, although biopsies were not taken from the ulcers, may have been due to IgM deposition given he also had macroglobulinaemia cutis. There has been only one other case reported, to our knowledge, of ulcers on the sides of the feet [4]. These devel- oped in areas of hyperkeratosis and were associated with dysaesthesia and a burning sensation. However, the biopsy Figure 1A. The patient presented with tingling ulcers on the feet. [Copyright: ©2013 Fischer et al.] Figure 1B. On further examination, papules were noted on the knees. [Copyright: ©2013 Fischer et al.] Figure1C. Biopsy from a knee papule showed homogeneous extra- vascular eosinophilic hyaline deposits throughout the papillary and reticular dermis (H&E 40x). [Copyright: ©2013 Fischer et al.] Figure 1D. IgM stain demonstrates the extravascular IgM deposits in the dermis (40x). [Copyright: ©2013 Fischer et al.]