EXTRAORDINARY CASE REPORT Primary Cutaneous Malignant Granular Cell Tumor: An Immunohistochemical Study and Review of the Literature Yosmar C. Pérez-González, MD,* Liliana Pagura, MD,† Mar Llamas-Velasco, MD,‡ Luis Cortes-Lambea, MD,* Heinz Kutzner, MD,§ and Luis Requena, MD¶ Abstract: Granular cell tumors (GCTs) are uncommon soft tissue tumors characterized by cytoplasmic granular appearance of the neoplastic cells. Malignant granular cell tumors (MGCTs) comprise less than 2% of GCTs and are mostly found in the subcutaneous soft tissues of the lower extremities, especially the thighs. Very few cases have been reported in the skin. The uncommon occurrence of cutaneous MGCTs and their histopathologic similarities with their benign counterpart make difficult the diagnosis of this particular malignancy. We describe a primary cutaneous MGCT that presented as a left posterior chest wall mass in a 51-year-old woman. Local excision was performed for the primary tumor, which was first interpreted as an atypical GCT, but 3 months later a left axillary mass appeared, and subsequent axillary lymph node dissection demon- strated metastatic disease in 4 of 12 excised lymph nodes. We report the immunophenotype of this primary cutaneous MGCT, which was studied with an ample panel of antibodies and compare our results with those of the few previously reported cases in the skin and subcutaneous soft tissues. Key Words: granular cells, malignant granular cell tumor, immuno- histochemistry (Am J Dermatopathol 2015;37:334–340) INTRODUCTION Granular cell tumor (GCT), originally designated as myoblastoma, was first described by Abrikossof 1 in 1926. In 1945, Ravich et al 2 reported the first example of a malignant granular cell tumor (MGCT) involving the urinary bladder. Abrikossof 1 originally described GCT as a “granular cell my- oblastoma” because he thought that the histopathologic appearance of neoplastic cells was similar to that of skeletal muscle cells. In 1962, Fisher and Wechsler 3 using electron microscopy postulated that neoplastic cells of GCT showed differentiation toward Schwann cells. This is the currently accepted histogenetic interpretation for GCT, 4,5 although in recent years descriptions of nonneural granular cell tumors have also appeared in the literature. 6–9 Although GCTs are not uncommon, the malignant counterpart of this neoplasm represents only 1%–2% of all GCTs, accounting for less than 100 reported cases and very few cases have been reported in the skin 10–68 (Table 1). Recently, there have been reports of GCTs with involvement of the dermoepidermal junction, mimicking a melanocytic neoplasm, and this finding may further complicate the histopathologic differential diagnosis with granular cell melanoma. 69 Therefore, immunohistochem- ical studies may play a very important role for this histopath- ologic differential diagnosis. Benign and malignant GCTs share several characteristics, including their higher incidence in women and their similar histopathologic features. The uncommon occurrence of MGCTs and the shared features with its benign counterpart make the diagnosis of MGCTs challenging. We describe a MGCT that presented as a left posterior chest wall mass in a 51-year-old woman. Local excision was performed for the primary tumor, which was initially diagnosed as an atypical GCT. However, 3 months later, a left axillary mass appeared and subsequent axillary lymph node dissection demonstrated metastatic disease in 4 of the 12 excised lymph nodes. We describe the immunophenotype of this cutaneous MGCT, which was studied with a large panel of antibodies and compare our results with those of the previously reported cutaneous and subcutaneous cases. CASE REPORT A 51-year-old woman presented with a rapidly growing cutaneous mass on her left scapular area. On physical examination, the lesion was painless, but it showed hard consistency and was adhered to deeper soft tissues. No erythema or any other color change was noted on the skin covering the mass. A computed tomography scan showed a large mass of 11 cm in diameter, involving the full thickness of the skin and subcutaneous tissues of the left posterior chest wall. It was solid, heterogeneous and extended deeply to the dorsal muscle. The tumor showed intense and diffuse enhancement after contrast administration, with 2 nonenhanced areas suggestive of necrosis. The patient underwent surgical excision of the tumor and had an unremarkable post- operative recovery. Histopathologic study demonstrated a well circumscribed but nonencapsulated neoplasm composed of large round and polygonal cells with granular cytoplasm. Neoplastic cells exhibited round pleomorphic nuclei located in their center and numerous mitotic figures (5 mitoses/10 high-power field) and large areas of necrosis en masse as well necrosis of isolated cells were also found (Fig. 1). No epidermal hyperplasia was seen in the overlying epidermis, and the From the *Department of Pathology, Hospital Infanta Cristina, Madrid, Spain; †Department of Pathology, Hospital Universitario de Móstoles, Madrid, Spain; ‡Department of Dermatology, Hospital Infanta Cristina, Parla, Madrid, Spain; §Dermatopathologie Bodensee, Friedrichshafen, Germany; and ¶Department of Dermatology, Fundación Jiménez Diaz, Madrid, Spain. Y. C. Pérez-González and L. Pagura contributed equally to this work. The authors declare no conflicts of interest. Reprints: Luis Requena, MD, Department of Dermatology, Fundación Jiménez Diaz, Avda Reyes Católicos 2, Madrid 28040, Spain (e-mail: lrequena@fjd.es). Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved. 334 | www.amjdermatopathology.com Am J Dermatopathol  Volume 37, Number 4, April 2015 Copyright © 201 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. 5