Tenascin is a significant extracellular matrix glycoprotein, which is upreg
ulated in various neoplasias and pathologic processes. Pheochromocytomas ar
e rare tumors of the sympathoadrenal system, whose malignancy is almost imp
ossible to predict. There are no histologic or chemical markers available t
hat would define the malignant behavior of these tumors, except the discove
ry of metastases. In our search for new markers, we investigated the immuno
histochemical expression of tenascin in a lar-e number of pheochromocytomas
and paragangliomas. Seven tumors were metastasized and were thus considere
d malignant. Normal adrenal medulla was tenascin negative. A striking diffe
rence was seen between malignant and benign pheochromocytomas. All malignan
t pheochrornocytomas expressed stromal tenascin strongly or moderately, whe
reas most benign pheochromocytomas (28 of 37, 70%) showed no or only weak i
mmunopositivity. The staining was strong or moderate also in 13 of 28 (46%)
of the tumors that showed histologically suspicious features, here called
borderline tumors. Paragangliomas showed a more heterogeneous staining patt
ern, and no significant difference was found between benign and malignant p
aragangliomas. To our knowledge, this is the first study to demonstrate the
expression of tenascin in pheochromocytomas and particularly the enhanced
expression in malignant pheochromocytomas. We therefore suggest that tenasc
in may be associated with the malignant transformation and metastasis of ph
eochromocytomas. It is also a potential marker predicting more aggressive b
ehavior in pheochromocytomas.