br Discussion Clinically extraocular SC often appears as
Discussion Clinically, extraocular SC often appears as a pink to red-yellow nodule, but can exhibit diverse clinical presentations and is commonly confused with other lesions, especially basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The tumor may appear on top of pre-existing dermatoses, like nevus sebaceous, actinic keratosis, and Bowen\'s disease. SC arising in the nipple is much rarer than other types of nipple tumors, such as Paget\'s disease and nipple duct adenoma, which may appear similar in clinical images. On pathological examination, IHC stains are often less necessary for distinguishing SC from most cutaneous tumors. Identification of the characteristic histologic feature—the multivesicular appearance of tumor cells—is beneficial to differentiating SC from the more common tumors of other lineages with simple cytoplasmic clarity, such as BCC, pagetoid variant of Bowen\'s disease, SCC, poroma/porocarcinoma, trichilemmal tumor, and Paget\'s disease. However, the following facts may render the differential diagnosis difficult: (1) sebaceous differentiation may be rarely found in the less/poorly differentiated cases; (2) sebaceous differentiation can be focally encountered in other types of cutaneous tumors, like SCC, BCC, and trichoblastoma; (3) there are some cases/variants of SC (e.g., the basaloid) with other feature(s) similar to that of the other cutaneous tumors, e.g., superficial epithelioma with sebaceous differentiation, sebaceous adenoma, sebaceoma, and BCC with sebaceous differentiation; (4) similar foamy fccp can be seen in the rare signet-ring cell variant of melanoma. The key points for making a differential diagnosis have been well described in the textbooks and literature. We will focus on those encountered in diagnosing the case displaying, as ours, predominance in intraepidermal proliferation with blunt bulbous downward extensions and superficial dermal invasion. The frequent classical multivesicular cytoplasm/sebaceous differentiation, occasional holocrine secretion, the absence of dysplastic keratinocytes in the overlying epidermis, the absence of pagetoid growth of tumor cells in the whole thickness of epidermis, and frequent staining with CK7 and androgen receptor in the tumor cells of our case are helpful in making a diagnosis of SC rather than SCC and invasive carcinoma arising in Bowen\'s disease with sebaceous differentiation. (CK7 has been reported in pagetoid Bowen\'s disease but not in the other types of SCC.) Sebaceoma is well circumscribed: it has bland basaloid cells with some bland mature sebocytes, it stains in a similar way to sebaceous adenoma and hyperplasia, and it has statistically significant lower expression levels of p53 compared to SC (11% versus 50%, respectively) and Ki-67 (10% versus 30%, respectively). The prominent blunt bulbous downward growth pattern, apparent nuclear atypia of neoplastic sebocytes and germinative/immature cells, disordered arrangement of kinds of tumor cells without peripheral palisading, high p53 level, and frequent mitoses in our case all render the diagnosis of malignancy and help to distinguish it from superficial epithelioma with sebaceous differentiation and BCC with sebaceous differentiation. Paget\'s disease and some melanomas tend to have marked intraepithelial spread and pale to sometimes vacuolated cytoplasm. However, they express clinical features, histologic findings, and immunophenotypes much different from those of SC. The IHC stain for adipophilin, another sensitive and fairly specific marker said to be useful especially in diagnosing poorly differentiated SC, is not yet available in our laboratory and seems not indispensable to our case, which reveals apparent sebaceous differentiation. Finally, another important differential diagnosis—cutaneous spreading from an underlying sebaceous carcinoma of the breast parenchyma/duct can be ruled out due to lack of tumor in the underlying breast tissue and the excised lactiferous ducts in our case.