Parathyroid-hormone-related protein (PTHrP) is the main mediator of th
e humoral hypercalcemia of malignancy. It is also detected in many nor
mal adult and fetal tissues. Altered calcium metabolism occurs in sarc
oidosis, and two cases of sarcoidosis with hypercalcemia and elevated
plasma PTHrP are described. An archival study of 20 lymph node biopsie
s with the pathological diagnosis of sarcoidosis was performed. Immuno
histochemistry using a polyclonal antiserum to human PTHrP and in situ
hybridization using a riboprobe to human PTHrP were performed on the
lymph node biopsies. Immunohistochemistry for PTHrP was also performed
on the biopsies from the two cases with elevated plasma levels. Immun
ohistochemical analysis detected PTHrP in macrophages within granuloma
ta in 17 of the 20 (85%) biopsies. In situ hybridization detected a po
sitive signal for messenger RNA in the granulomata of 11 of 19 (58%) b
iopsies. PTHrP immunoreactivity and PTHrP gene expression are present
in sarcoid granulomata. PTHrP may contribute to the hypercalcemia of s
arcoidosis.