High (Nuclear) Grade Adnexal Carcinoma With Microcystic Adnexal Carcinoma-Like Structural Features Marı´a-Teresa Ferna ´ndez-Figueras, MD,* Maria-Angeles Montero, MD,* Joaquim Admella, MD,w Noelia de la Torre, MD,* Ariadna Quer, MD,* and Aurelio Ariza, MD* Abstract: Microcystic adnexal carcinoma (MAC) is a slow growing, locally aggressive sweat gland tumor. It predominantly affects the face and tends to recur despite local excision. Microscopically, MAC is characterized by a stratified prolifera- tion of microcysts, cords, and ducts of cells that show squamous or adnexal differentiation. Atypia and mitoses are almost completely absent and metastatic deposits are rare and mostly limited to the regional lymph nodes; rather than real metastases, they might be the result of local extension of the tumor through perineurial spaces. We report a case of adnexal carcinoma with architectural features of MAC that displayed also marked nuclear pleomorphism and hyperchromasia with squamous pearl formation and a widespread strong p53 immunoreaction. The lesion behaved as a high-grade neoplasm with rapid growth, carcinosarcomatous metaplastic transformation in a relapse, and what were clinically suspected to be metastases. The literature contains several other examples reported as metastatic high-grade MAC, one of them with widespread distant metastases. We therefore want to sound an alert about the possible existence of tumors displaying microscopic findings characteristic of the aggressive forms of sweat gland carcinoma (nuclear pleomorphism and hyperchromasia, vascular invasion, and necrosis) in addition to architectural features of MAC. Whether these tumors should be called high-grade MACs or belong to a separate category remains an open issue until more cases are reported and bridge cases are eventually documented. Key Words: sweat gland carcinoma, microcystic adnexal carcinoma, high grade (Am J Dermatopathol 2006;28:346–351) M icrocystic adnexal carcinoma (MAC) was first reported in 1982 by Goldstein et al 1 who described 6 cases of a neoplasm with a deceptively bland histopathologic appearance, probably originating from a pluripotent adnexal keratinocyte capable of both follicu- lar and sweat gland differentiation. Soon afterwards, as additional cases were described, 2–16 the marked tendency of these tumors to spread through perineurial spaces and relapse locally, and the discovery of a range of appearances beyond the initial report prompted the development of locally aggressive adnexal carcinomas (LAACs) as a concept to include these findings. Currently, MAC is considered by some authors to belong in the group of apocrine neoplasms due to its capacity to combine sudoriparous, follicular, and sebaceous differentiation. 4 The microscopic appearance of MAC is characteristic, its most distinctive trait being the stratified disposition of its various components: superficial micro- cysts, solid cords in the midportion, and syringoid ductal formations containing PAS-positive material in the deepest area. Although most cases are located on the face, especially around nasolabial folds and periorbital skin, many other sites such as the axilla 9 and the breast have been described. 10,16 In the breast, MAC is also known as syringomatous tumor of the nipple. Several cases of MAC have developed within sites of previous irradiation after a long latency period; in many of these instances radiation therapy was administered because of acne. 4,7 CASE REPORT A 76-year-old man was admitted to our hospital because of lower lip indurations. There was no previous history of irradiation. A wide triangular excision of the lower lip including grossly free margins was performed. Microscopically, these focally showed perineurial tumor invasion, but the patient refused further surgery and only received local radiation therapy. The tumor recurred shortly afterward and, 1 year later, had caused extensive lower lip induration and massive involvement of the mandible and the perimandibular soft tissues. The patient died 6 months later, with radiologic findings highly suggestive of metastatic lung disease. MATERIALS AND METHODS The 2 biopsies were formalin fixed and paraffin embedded. Immunohistochemical studies were performed using NCL-Ki67-MM1 mouse monoclonal antibody [Novocastra, Newcastle, UK, diluted 1:50 with phosphate- buffered saline (PBS)], anti-p53 protein mouse monoclonal antibody, clone DO7 (Novocastra, diluted 1:500 with citrate buffer), anti-p27 protein mouse monoclonal anti- body, clone 1B4, (Novocastra, diluted 1:30 with PBS), anti c-ERB-2 mouse monoclonal antibody, clone CB11 (Novocastra, diluted 1:150 with PBS), anti bcl-2 mouse Copyright r 2006 by Lippincott Williams & Wilkins From the Departments of *Pathology and wMaxillofacial Surgery, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain. Reprints: Dr Ferna´ ndez-Figueras, Hospital Universitari Germans Trias i Pujol, Carretera Canyet, s/n, 08916 Badalona, Barcelona, Spain (e-mail: mtfernandez.germanstrias@gencat.net) EXTRAORDINARY CASE REPORT 346 Am J Dermatopathol  Volume 28, Number 4, August 2006