A sarcoid-like reaction (SLR) has been found occasionally in association with malignant tumors, such as Hodgkin's and non-Hodgkin's lymphomas, and carcinomas at different sites, and can occur in the context of the tumor itself, in metastatic lesions, or in lymph nodes draining the neoplasm. This reaction is a foreign-body inflammatory response to necrotic materials or an immunological reaction, the granulomatous response within draining lymph nodes representing a response to soluble tumor-related antigens or a stromal reaction representing a T cell-mediated immunological response to cell surface antigens [1
]. However, only a few benign tumors with SLR similar to that in the present case of angioleiomyoma have been reported.
Two causes can be suggested for the pathogenesis of the granulomatous change in the present case: either a sarcoid reaction or generalized sarcoidosis. Our patient had associated uveitis and bilateral hilar lymphadenopathy, and the tuberculin test gave a negative result. Therefore it was suspected that the granuloma in the thigh tumor had arisen as part of a series of changes related to generalized sarcoidosis. To our knowledge, only three cases of benign tumors accompanied by epithelioid granuloma have been reported. Generalized sarcoidosis was present in all three cases (table
Benign tumors exhibiting epithelioid cell granuloma
Sarcoidosis is a chronic granulomatous disease of unknown etiology characterized by the development of sarcoid granulomas in several organs. Histopathologically, these granulomas are composed of accumulations of tightly packed macrophages and macrophage-derived giant cells. It has also been demonstrated that differentiation of cells induced by various cytokines can lead to the formation of sarcoid granuloma [4
]. Prior et al. [4
] cultured bronchoalveolar and peripheral blood mononuclear cells in serum-free medium, and analyzed the supernatants for the concentrations of interleukin-1 beta (IL-1β), IL-2, IL-6, tumor necrosis factor-alpha (TNF-a), granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-?). Peripheral blood mononuclear cells from sarcoid patients were shown to release higher amounts of IL-1β, TNF-a, IL-6 and GM-CSF than those from normal controls [4
]. Sarcoid inflammation was found to be associated with an increased and concerted release of monocyte/macrophage-derived cytokines, not only in the lung, but also in the peripheral blood [4
]. Although we are unable to draw a definite conclusion with regard to the present case, these cytokines likely play an important role in the etiology of sarcoidosis.
On the other hand, leiomyomas are common dermal tumors arising from smooth muscle cells, and can develop in the erector pili muscle, vascular smooth muscle, scrotum, vulva, or mammilla [5
]. Angioleiomyoma is a neoplasm of exclusively vascular smooth muscle (VSM) origin. VSM can release monocyte/macrophage-derived cytokines such as IL-1 and TNF-a [6
]. Accordingly, we considered that the VSM constituting angioleiomyoma might have produced immunostimulatory cytokines, which induced the formation of epithelioid cell granuloma. We conclude that epithelioid cell granuloma may transform to angioleiomyoma under the influence of IL-1, TNF-a and IL-6 released from VSM cells. In order to test this hypothesis, further investigation will be needed.