Hypercalcemia and parathyroid hormone related protein expression in cutaneous T-cell lymphoma

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A 64-year-old white man presented to our clinic with a 2-year history of a leonine facies and extensive erythematous plaques over his trunk and extremities sparing the palmar and plantar surfaces. Further evaluation revealed profound peripheral and internal lymphadenopathy without visceral involvement on computed tomography (CT) scan. A diagnosis of cutaneous T-cell lymphoma (CTCL) was made based upon a skin biopsy (Fig. 1) and a cell phenotype analysis that revealed the predominance of helper T cells with a helper/suppressor cell ratio of greater than 10.The patient failed systemic psoralen plus UVA therapy and developed a 20 lb weight loss, circulating atypical lymphocytes, and hypercalcemia. He was asymptomatic from the hypercalcemia. He was started on 60 mg/day of prednisone. The patient's hypercalcemia resolved within 4 days of steroid therapy only to recur with attempts to taper the steroid dose.Laboratory studies (Table 1) were significant for negative human T-cell lymphotropic virus type 1 (HTLV-1) antibody, calcium = 14 mg/dL (normal, 8.5-10.5 mg/dL), plasma parathyroid hormone (PTH) = 9 pg/mL (normal, 10-65 pg/mL), and parathyroid hormone related peptide (PTH-rp) = 1.7 pmol/L (normal, <1.3 pmol/L).Immunohistochemistry staining with rabbit anti-PTH-rp1-34 polyclonal antibody (Peninsula Laboratory, Belmont, CA, USA) was performed to study the expression of PTH-rp in paraffin-embedded sections of skin from the patient, five patients with CTCL without hypercalcemia, two patients with squamous cell carcinoma, and one normal human skin control. The sections were deparaffinized, rehydrated gradually, quenched and treated with 1 mg/mL protease-1 for 10 min at room temperature, and used in the immunohistochemistry staining as described by Deng et al. (Deng JS, Brod BA, Saito R, Tharp MD. Immune-associated cells in basal cell carcinomas of skin. J Cutan Pathol 1996; 23: 140-146.) Peripheral blood leukocytes from the reported patient were also stained in this manner to assess PTH-rp expression of the atypical lymphocytes.There was minimal staining for PTH-rp in skin from the normal control as well as patients with mycosis fungoides without hypercalcemia (Fig. 2), and a slight increase in staining intensity for PTH-rp in specimens from squamous cell carcinoma. There was strong expression of PTH-rp in keratinocytes as well as the infiltrating cells in the skin from the reported patient (Fig. 3). The patient's peripheral blood leukocytes were negative for PTH-rp. This strongly indicates that the keratinocytes and abnormal lymphocytes in the involved skin of our patient synthesized and expressed PTH-rp, which was subsequently secreted or released, contributing to the elevated circulating PTH-rp level and hypercalcemia.

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