Sign of Leser-Trélat Associated with Waldenström's Macroglobulinemia.

Sir,

Waldenström's macroglobulinemia (WM) is a rare, incurable, low-grade lymphoplasmacytic lymphoma characterized by the presence of immunoglobulin-M (IgM)-secreting clonal cells in the bone marrow. Here, we report a patient exhibiting the sign of Leser-Trélat with WM.

A 54-year-old Japanese man noticed an increase of brown papules and nodules on his trunk and easy fatigability. These eruptions spread over his body within one month. Physical examination revealed multiple pruritic brown papules and nodules of 3–20 mm in diameter [Figure 1a and b]. The results of laboratory investigations were as follows: white blood cell count of 7640/mm3(normal range: 4700–8700/mm3) and a hemoglobin level of 8.9 mg/dL (normal range: 13.0–17.0 mg/dL). Immediately after hospitalization, his blood results were: C-reactive protein: 2.88 mg/dL (normal range: 0–0.3 mg/dL); total protein: 8.7 g/dL (normal range: 6.5–8.3 g/dL); albumin: 2.2 g/dL (normal range: 3.8–5.2 g/dL); IgG: 2739 mg/dL (normal range: 870–1700 mg/dL); IgM: 2774 mg/dL (normal range: 33–190 mg/dL). A bone-marrow aspiration sample showed the infiltration of lymphoplasmacytoid cells. Serum immunoelectrophoresis revealed an IgM-k monoclonal protein. Histopathological examination of a skin papule showed massive hyperkeratosis and papillomatosis. It had a verrucous appearance with the proliferation of basaloid and squamoid cells. Pseudohorn cysts were also present. This histopathology was consistent with seborrheic keratosis [Figure 1c and d]. On the basis of clinical and histological findings, a diagnosis of the sign of Leser-Trélat associated with WM was made. The patient has been followed-up at the outpatient clinic of the Hematology Department. There has been no change in the number or volume of seborrheic keratoses.

Figure 1

Clinical and histological features. (a and b) Multiple pruritic brown papules and nodules of 3–20 mm in diameter. (c and d) Hematoxylin and eosin staining of papules showed extensive hyperkeratosis and papillomatosis. There was a verrucous appearance with proliferation of basaloid and squamoid cells. Pseudohorn cysts were also present. (c) ×4, Scale bar: 4 mm; (d) ×10, Scale bar: 1.6 mm

Only 103 patients of the sign of Leser-Trélat had been reported in the literatures until 2010.[1] Several theories have been postulated to explain the concurrence of malignancy and skin manifestations of the sign of Leser-Trélat. Wagner and Wagner speculated that malignant carcinoma cells may contain cells that secrete polypeptides or hormones that induce the paraneoplastic skin changes seen in the Leser-Trélat sign.[2] Curry and King reported a case of the sign of Leser-Trélat associated with adenocarcinoma of the duodenum.[3] In that case, they confirmed the lack of increased epidermal growth factor (EGF) production. In contrast, Ellis et al. reported a melanoma patient who had acanthosis nigricans, the sign of Leser-Trélat, and multiple acrochordons.[4] Increased epidermal staining for the EGF receptor was noted in specimens of acanthosis nigricans. The patient's preoperative urinary fraction showed an increase of a-tumor growth factor (TGF). In contrast, postoperatively, the a-TGF level progressively decreased to that in subjects without cancer. Inamadar and Palit reported the sign of Leser-Trélat associated with human immunodeficiency virus (HIV) infection.[5] This phenomenon indicates that immunological impairment due to HIV infection is related to the sudden appearance of multiple seborrheic keratoses.

To the best of our knowledge, our patient is the first reported case of the sign of Leser-Trélat associated with WM. The accumulation of similar cases will be helpful to understand the pathomechanism for the sudden appearance of many seborrheic keratoses in patients with visceral malignancy.

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