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A case of superficial epithelioma with sebaceous differentiation.

Superficial epithelioma with sebaceous differentiation (SESD) is a rare benign neoplasm with peculiar histopathologic characteristics, which occurs in aged skin. We report upon a case of SESD occurring on the left upper back, which histopathologically is a superficial, multilobular tumor with numerous basaloid cells mixed with sebaceous cells attached to the overlying epidermis. This case represents a solitary benign neoplasm without any associated malignancy.

Basal Cell Carcinoma↗

Muir-Torre syndrome.

A 65-year-old man with a history of multiple neoplastic and pre-neoplastic gastrointestinal lesions as well as urogenital carcinoma presented for evaluation of two asymptomatic skin-colored papules in the head and neck region. Biopsy revealed sebaceous neoplasms and immunohistochemical staining was negative for the presence of hMSH-2 protein in both specimens. These findings were consistent with a diagnosis of Muir-Torre syndrome in the setting of a prior history of visceral malignancies. Muir-Torre Syndrome is a rare autosomal dominant genodermatosis associated with mutations in mismatch repair proteins, hMSH-2 and hMLH-1, which predispose affected patients to visceral malignancies as well as sebaceous gland neoplasms.

Adaptor Proteins, Signal Transducing↗

Masquerade syndrome.

A 52-year-old man experienced chronic blepharoconjunctivitis of the right eye of the three years' duration that was unresponsive to medications. Conjunctival cytologic examinations suggested carcinoma and this was confirmed. However, only a full-thickness eyelid biopsy established that the tumor was a sebaceous carcinoma. We discuss the importance of considering this condition in all cases of unilateral, persistent, or recurrent eyelid inflammation resistant to the usual therapy; the diagnostic value of conjunctival scrapings and full-thickness lid biopsy; and the necessity of interpretation of the biopsy material by a pathologist experienced with, and alerted to look for, this neoplasm. Early recognition of sebaceous carcinoma followed by prompt adequate therapy should improve the survival of patients with this rare but malignant tumor.

Blepharitis↗

Sebaceous skin lesions as clues to hereditary non-polyposis colorectal cancer.

Cutaneous lesions consonant with Muir-Torre syndrome strongly suggest hereditary non-polyposis colorectal cancer (HNPCC). Ponti et al. discuss the importance of combining molecular genetic features of the sebaceous neoplasms, including microsatellite instability and immunohistochemistry, with family history, to determine the likelihood of HNPCC. Proof of diagnosis is identification of one of the mismatch repair germline mutations.

Colorectal Neoplasms, Hereditary Nonpolyposis↗

Assessment of cellular proliferation of sebaceous neoplasms by AgNOR counts and immunohistochemical demonstrations of PCNA and Ki-67.

We assessed cellular proliferation of sebaceous neoplasms by AgNOR counts and the immunohistochemical demonstration of proliferating cell nuclear antigen (PCNA) and Ki-67, using formalin-fixed and paraffin-embedded tissue specimens. We used three categories of sebaceous neoplasms: four cases of sebaceoma, three cases of basal cell carcinoma with sebaceous differentiation (BCSD), and seven cases of sebaceous carcinoma (SC). Significant differences were noted between SC and non-SC tumors (sebaceoma and BCSD) in AgNOR counts and semi-quantitative grading of PCNA and Ki-67 labelling indices (P < 0.01). When a cut-off value of 6 was chosen, the AgNOR value discriminated SC from non-SC tumors with high specificity and sensitivity. When a cut-off value of 25% was chosen, PCNA and Ki-67 labelling indices also discriminated between these tumors. Significant differences were not observed between sebaceoma and BCSD with PCNA and Ki-67 labelling indices. AgNOR counts of BCSD were a little higher than those of sebaceoma, but the number of cases was too small to perform statistical assessment. We consider AgNOR counts and semi-quantitative grading of PCNA and Ki-67 labelling indices to be useful in differentiating SC from BCSD and sebaceoma.

Cell Division↗

Sebaceous adenoma in the retromolar region: report of a case with a review of the English literature.

This paper reports a rare case of sebaceous adenoma on the right mandibular retromolar mucosa in a 73-year-old Japanese man, with a review of the English literature of sebaceous adenomas of salivary gland origin. A painless and yellowish polypoid lesion in the retromolar mucosa was histologically a relatively well-circumscribed neoplastic mass composed of well-differentiated sebaceous cells with cystic and duct-like structures, and was considered to be a true sebaceous gland neoplasm arising from the minor salivary gland tissue.

Adenoma↗

Loss of mismatch repair proteins in sebaceous gland tumors.

BACKGROUND: Sebaceous gland neoplasms are rare tumors that are associated with visceral malignancies in patients with Muir-Torre syndrome (MTS). The majority of the MTS-associated tumors reveal mutations in DNA mismatch repair (MMR) genes (most often hMSH-2 and hMLH-1) and microsatellite instability. The sebaceous gland lesions in patients with MTS can often precede or occur concurrently with the visceral neoplasms. The early recognition of those lesions and their differentiation from sporadic sebaceous gland tumors are critical for proper patient management. Here we investigate the MMR gene expression in a variety of sebaceous gland tumors, with or without associated visceral malignancy. METHODS: We studied the expressions of hMLH-1 and hMSH-2 in 10 consecutive sebaceous hyperplasias, 10 sebaceus nevi, 12 sebaceous adenomas, seven sebaceous carcinomas and the adjacent normal sebaceous glands using immunohistochemistry and paraffin-embedded sections. RESULTS: The normal sebaceous glands and the glands of all the sebaceus nevi were positive for hMLH-1 and hMSH-2. Loss of hMSH-2 expression was found in 1/10 (10%) sebaceous hyperplasias, 3/12 (25.0%) sebaceous adenomas, and 2/7 (28.6%) sebaceous carcinomas. Loss of hMLH-1 expression was seen in 1/10 (10%) hyperplasias, 3/12 (25.0%) adenomas, and 1/7 (14.3%) carcinomas. No concurrent loss of both hMLH-1 and hMSH-2 was observed. Loss of MMR (either hMLH-1 or hMSH-2) was detected in 80% of the benign sebaceous lesions associated with malignancy. In comparison, only 23% of sebaceous lesions not associated with malignancy showed loss of MMR proteins. No loss of hMSH-2 protein was found in the visceral cancer in one patient with hMSH-2-negative sebaceous adenoma. CONCLUSIONS: Our results confirm the previous reports of alterations of mismatch repair genes in the sebaceous neoplasms of patients with MTS. However, we showed that those changes also occur early at the stage of sebaceous hyperplasia, even in the absence of a visceral malignancy. This indicates the importance of the abnormal DNA mismatch repair in the progression of this disease.

Adaptor Proteins, Signal Transducing↗

Distinction of benign sebaceous proliferations from sebaceous carcinomas by immunohistochemistry.

Sebaceous lesions, including sebaceous hyperplasia, sebaceomas, and sebaceous adenomas and carcinomas, are histologically distinctive adnexal proliferations with a spectrum of biological behavior ranging from benign to frankly malignant. The histologic distinction between sebaceous adenomas and carcinomas may be challenging, especially in cases showing atypical features and in small or partial biopsies. We studied multiple oncogenic and therapeutic related proteins by immunohistochemistry to identify differences in expression between benign and malignant sebaceous proliferations. A total of 27 cases, including 9 sebaceous adenomas, 4 sebaceomas, 8 sebaceous carcinomas, and 6 cases of sebaceous hyperplasia, were examined by immunohistochemistry, with antibodies directed against Ki-67 (MIB-1), bcl-2, p53, p21WAF1, p27Kip1, c-erbB-2 (Her-2/neu), CD117 (c-kit), cyclin D1, MDM2, CD99, MLH-1, and MSH-2. We found that sebaceous adenomas and sebaceomas stained like sebaceous hyperplasia did, whereas carcinomas had statistically significantly increased levels of p53 (50% versus 11%, respectively) and Ki-67 (30% versus 10%). The carcinomas also had significantly reduced levels of bcl-2 (7% versus 56%, respectively) and p21 (16% versus 34%) compared to the adenomas. Thus, a combination of several of these markers may be diagnostically useful in challenging cases. In addition, we found little or no Her-2/neu and CD117 staining, indicating that immunotherapy with Herceptin or Gleevac would likely not be useful for sebaceous carcinomas. Moreover, these results show that sebaceous adenomas and carcinomas are distinct neoplasms and provide no support for the theory that all sebaceous adenomas are truly malignant.

Adenocarcinoma, Sebaceous↗

Mantleoma. A benign neoplasm with mantle differentiation.

Four cases of neoplasms with mantle differentiation are presented. The mantle (sebaceous mantle) is a well-described but little known part of the sebaceous gland cycle. In the resting phase of that cycle, the mantle is seen as cords of undifferentiated cells that emanate from the infundibulum of a hair follicle and droop down aside the follicle in the form of a mantle or skirt. Cyclically, vacuolated sebocytes appear at the terminus of these cords, singly, then in groups, and finally as fully developed sebaceous lobules and glands. Presumably, sebaceous glands involute to become undifferentiated mantles. Clinically, neoplasms with mantle distribution occur on the face. Three of our cases were found fortuitously in sections of tissue removed because of basal-cell carcinoma. One was thought by the clinician to be a basal-cell carcinoma. Histopathologically, mantleomas vary in complexity. Presumably early neoplasms consist only of cords and columns of undifferentiated epithelial cells that radiate from an infundibulum. Later on, these cords interweave in a retiform pattern that contains sebocytes of varying degrees of vacuolization and sebaceous ductal structures. Mantleomas are benign because none in our series recurred after surgical removal and no atypical neoplastic cells were seen histopathologically.

Epithelium↗

Immunohistochemical demonstration of breast-derived and/or carcinoma-associated glycoproteins in normal skin appendages and their tumors.

Sixty-six benign and malignant skin appendage tumors were studied for the expression and localization of the glycoproteins identified by the monoclonal antibodies (MoAbs) GCDFP-15, CU18, B72.3, and VU-1D9. Formalin-fixed, paraffin-embedded tissue was processed by the avidin-biotin complex method. In normal eccrine and apocrine sweat glands, GCDFP-15, CU18, B72.3, and VU-1D9 staining was localized differently (intracellular, membranous, or intraluminal), whereas eccrine glands showed no B72.3 staining. There were various patterns of positive staining of tumors arising from sweat glands, but no immunoreactivity for B72.3 was found in eccrine-derived tumors. CU18 and VU-1D9 labeled mature sebocytes in a vacuolar fashion and stained sebaceous carcinomas. VU-1D9 labeled membranes of the secondary germ cells in early anagen of a hair follicle bulb as well as the basaloid cells of trichoepitheliomas and basal cell carcinomas. These MoAbs appear to be valuable markers for the study of normal skin appendages and their tumors.

Antibodies, Monoclonal↗