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Coexpression of S-100 and Smooth Muscle Actin in Nodular Hidradenoma

Vodovnik, Aleksandar MD

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The American Journal of Dermatopathology: August 2003 - Volume 25 - Issue 4 - p 361-362

An unusual case of nodular hidradenoma (NH) is reported. A 41-year-old, previously healthy female sought medical help for an oval, bluish, and painless protrusion on her stomach, lasting for 6 months. A cyst-like lesion, measuring 13 mm in diameter, was palpated and excised in toto.

Few fragments of brown-white, soft tissue were received. A histologic evaluation revealed tumor tissue composed of lobulated, focally encapsulated masses located in the dermis (Fig. 1). Within the lobulated masses, tubular lumina of various sizes were noticed. There also were cystic spaces containing a faintly eosinophilic, homogeneous material. Both cuboidal ductal and columnar secretory cells lined the tubular lumina. Tumor cells mostly bordered the wide cystic spaces; only focally a single row of luminal cells was seen. In solid parts of the tumor, 2 types of cells were recognized. One type of cell was polyhedral with rounded nucleus and slightly basophilic cytoplasm. Some of these cells appeared fusiform and showed an elongated nucleus. The second type of cell was round and contained very clear cytoplasm with distinctly visible cell membrane. There also were cells transitional between these 2 types showing rather light eosinophilic cytoplasm. A high mitotic rate was found in tumor cells (12 mitoses per 10 HPF) without pathologic mitotic figures. The nuclear texture was mostly uniform. There was rather focal, minimal variation in size of the tumor cells. The tumor nodules were only focally associated with a characteristic eosinophilic hyalinized stroma. At the tumor periphery, the stroma was highly vascularized. Focal areas of tissue necrosis were found, mostly in the central parts of the tumor.

Solid and tubular tumor tissue showing lack of cellular pleomorphism but several mitotic figures (H&E, ×100).

Tumor cells revealed diffusely positive immunohistochemical reaction for smooth muscle actin (SMA), pancytokeratin (CK), and EMA as well as patchy reaction for S-100 (Figs. 2 and 3). Expression of Ki-67 was found in approximately 10% of tumor cell nuclei. Immunohistochemical reaction for vimentin was negative.

Expression of S-100 in tumor cells (LSAB, ×100).
Expression of SMA in tumor cells (LSAB, ×100).

Of 10 additionally immunostained unequivocal nodular hidradenomas from our archive, none has revealed both S-100 and SMA positivity.

Three months after the surgery, the patient is doing well. No clinical signs of recidivism have been observed.

Morphologic criteria alone may not always accurately differentiate between NH and glomus tumor (GT) and in equivocal cases immunohistochemistry may be useful. 1 GT has been considered in differential diagnosis even in this case. Most of the NH are EMA-, CK-, and vimentin-positive as well as S-100- and SMA-negative. On the contrary, GT are usually CK-negative as well as vimentin- and SMA-positive. 1–4 A phenotypic heterogeneity of NH has been established and S-100- or SMA-positive cases have been described. 1,4 Nevertheless, coexpression of S-100 and SMA in NH has not been previously reported.

An immunohistochemical coexpression of antibodies in general is a confusing feature subsequent to disturbing cellular differentiation of the originating cell population. However, its myoepithelial origin in NH has been questioned. It seems that high mitotic rate and tumor necrosis, as a part of suspected malignant transformation, could explain coexpression of SMA and S-100 in this case. These findings also might confirm a role for myoepithelial cells in the histogenesis of NH.

Despite morphological similarities, a careful examination of HE slides still has a crucial importance distinguishing between GT and NH, especially due to occasionally divergent immunohistochemical patterns.

Aleksandar Vodovnik, MD


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2. Eckert F, Betke M, Schmoeckel C, et al. Myoepithelial differentiation in benign sweat gland tumors. Demonstrated by a monoclonal antibody to alpha-smooth muscle actin. J Cutan Pathol. 1992; 19:294–301.
3. Liapi-Avgeri G, Karabela-Bouropoulou V, Agnanti N. Glomus tumor. A histological, histochemical and immunohistochemical study of the various types. Pathol Res Pract. 1994; 190:2–10.
4. Biernat W, Kordek R, Wozniak L. Phenotypic heterogeneity of nodular hidradenoma. Immunohistochemical analysis with emphasis on cytokeratin expression. Am J Dermatopathol. 1996; 18:592–6.
© 2003 Lippincott Williams & Wilkins, Inc.