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 extrem
ities sparing the palmar and plantar surfaces. Further evaluation revealed
profound peripheral and internal lymphadenopathy without visceral involveme
nt on computed tomography (CT) scan. A diagnosis of cutaneous T-cell lympho
ma (CTCL) was made based upon a skin biopsy (Fig. 1) and a cell phenotype a
nalysis that revealed the predominance of helper T cells with a helper/supp
ressor 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 a
symptomatic from the hypercalcemia. He was started on 60 mg/day of predniso
ne. The patient's hypercalcemia resolved within 4 days of steroid therapy o
nly to recur with attempts to taper the steroid dose.
Laboratory studies (Table 1) were significant for negative human T-cell lym
photropic virus type 1 (HTLV-1) antibody, calcium = 14 mg/dL (normal, 8.5-1
0.5 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 antibo
dy (Peninsula Laboratory, Belmont, CA, USA) was performed to study the expr
ession of PTH-rp in paraffin-embedded sections of skin from the patient, fi
ve patients with CTCL without hypercalcemia, two patients with squamous cel
l carcinoma, and one normal human skin control. The sections were deparaffi
nized, rehydrated gradually, quenched and treated with 1 mg/mL protease-1 f
or 10 min at room temperature, and used in the immunohistochemistry stainin
g 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 lymphocy
tes.
There was minimal staining for PTH-rp in skin from the normal control as we
ll as patients with mycosis fungoides without hypercalcemia (Fig. 2), and a
slight increase in staining intensity for PTH-rp in specimens from squamou
s 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. Th
is strongly indicates that the keratinocytes and abnormal lymphocytes in th
e 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.