Loss of p21(WAF1) compartmentalisation in sebaceous carcinoma compared with sebaceous hyperplasia and sebaceous adenoma.
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AIMS: Regulation of cell cycle progression is a fundamental control process, linked to cellular differentiation and apoptosis in normal tissues. p21(WAF1) is a nuclear protein that regulates cell cycle progression. p21(WAF1) can be transcriptionally upregulated by p53, but may be activated independently of p53-for example, during terminal differentiation. Loss of topological control of p21(WAF1) expression is an early feature of malignancy in the colorectal system. Similar to the colonic mucosa, sebaceous glands contain cells that are constantly going through a process of cell division, differentiation, and cell death. This study investigated the expression of p53, p21(WAF1), and the proliferation marker Ki67 in normal sebaceous glands, sebaceous adenoma, sebaceoma, and sebaceous carcinoma. METHODS: Serial sections were stained with monoclonal antibodies to p21(WAF1), p53, and Ki67 (MIB1) using standard immunohistochemical techniques. RESULTS: In normal sebaceous glands, p21(WAF1) positive cells were only seen within the differentiating compartment, which was spatially distinct from the cycling peripheral Ki67 positive cells. In sebaceous adenoma and sebaceoma, topological control was maintained, with the distribution of markers being similar to that seen in normal sebaceous glands. Loss of topological control of markers of cellular control was seen in sebaceous carcinoma only. This contrasts with colonic tumours, in which loss of p21 compartmentalisation is seen in adenomas at an early stage of tumour progression. CONCLUSION: This work confirms the hypothesis that the dysregulation of cell cycle progression is an important process in the development of malignancy within sebaceous glands, although loss of topological control was seen only in sebaceous carcinoma. (+info)
Immunohistochemical staining for adipophilin, perilipin and TIP47.
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BACKGROUND: The presence of lipid in the cell cytoplasm is useful for supporting the diagnosis of sebaceous gland carcinoma (SGC). Currently this requires histochemical stains that are carried out on frozen sections of unprocessed tissue. Recently, several anti-adipocytic antibodies that recognise proteins associated with lipid vesicles have been described. These antibodies can be applied to paraffin-wax sections. AIM: To assess the ability of anti-adipocytic antibodies to identify intracytoplasmic lipid in SGC. METHODS: Immunohistochemistry with a monoclonal antibody to adipophilin and polyclonal antibodies to perilipin and TIP47/PP17 was carried out on archival, formalin-fixed, paraffin-wax-embedded sections of 26 samples of SGC. The immunostaining was compared with 22 other eyelid tumours (11 basal cell carcinomas (BCC), 10 squamous cell carcinomas (SCC) and 1 Merkel cell tumour). RESULTS: Immunohistochemical staining was positive in 23, 10 and 2 cases of 26 SGC with adipophilin, perilipin and TIP47, respectively. The positive staining identified cytoplasmic lipid vesicles. Anti-adipophilin was positive in five other eyelid tumours (4 BCC and 1 SCC) staining small cytoplasmic granules that can be easily distinguished from the staining in SGC. CONCLUSIONS: Immunohistochemical staining for adipophilin and perilipin is a useful ancillary technique for the demonstration of lipid in SGC that may be applied to paraffin-wax sections. (+info)
Complications of mitomycin C therapy in 100 eyes with ocular surface neoplasia.
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AIM: To determine the complications associated with mitomycin C (MMC) in the treatment of ocular surface neoplasia. METHODS: A retrospective and consecutive study of 100 eyes in 91 patients with ocular surface neoplasia treated with MMC in a single centre between November 1998 and January 2005. Outcome measures included complications of MMC and the treatment required for these complications. RESULTS: One to three 7 day cycles of topical MMC 0.04% four times a day were given to 59 eyes with localised corneal-conjunctival intraepithelial neoplasia (CIN), 19 eyes with diffuse CIN, six eyes with recurrent CIN, one eye with ocular surface squamous cell carcinoma, three eyes with primary acquired melanosis (PAM) with atypia, nine eyes with conjunctival malignant melanoma (MM), two eyes with sebaceous carcinoma with pagetoid spread, and one eye with recurrent atypical fibroxanthoma. Nine patients had bilateral CIN. 31 (34%) cases developed an allergic reaction to MMC and 14 (14%) eyes had epiphora secondary to punctal stenosis at a mean follow up period of 26.5 months. CONCLUSION: In the largest study looking at complications of topical MMC in the treatment of ocular surface neoplasia, allergic reaction and punctal stenosis are relatively common. Serious complications were not observed suggesting the safe use of MMC in mid-term follow up. (+info)
To examine the consequences of inhibiting activator protein-1 (AP-1) transcription factors in skin, transgenic mice were generated, which use the tetracycline system to conditionally express A-FOS, a dominant negative that inhibits AP-1 DNA binding. Older mice develop mild alopecia and hyperplasia of sebaceous glands, particularly around the eyes. When A-FOS was expressed during chemical-induced skin carcinogenesis, mice do not develop characteristic benign and malignant squamous lesions but instead develop benign sebaceous adenomas containing a signature mutation in the H-ras proto-oncogene. Inhibiting AP-1 activity after tumor formation caused squamous tumors to transdifferentiate into sebaceous tumors. Furthermore, reactivating AP-1 in sebaceous tumors results in a reciprocal transdifferentiation into squamous tumors. In both cases of transdifferentiation, individual cells express molecular markers for both cell types, indicating individual tumor cells have the capacity to express multiple lineages. Molecular characterization of cultured keratinocytes and tumor material indicates that AP-1 regulates the balance between the wnt/beta-catenin and hedgehog signaling pathways that determine squamous and sebaceous lineages, respectively. Chromatin immunoprecipitation analysis indicates that c-Jun binds several wnt promoters, which are misregulated by A-FOS expression, suggesting that members of the wnt pathway can be a primary targets of AP-1 transcriptional regulation. Thus, AP-1 activity regulates tumor cell lineage and is essential to maintain the squamous tumor cell identity. (+info)
A clinicopathological study of eyelid malignancies from central India.
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BACKGROUND: Eyelid malignancies are completely treatable if detected early. The treatment depends on the invasiveness of the cancer which in turn depends on the type of malignancy. AIM: The aim of the study was to characterize the distribution of the types of eyelid malignancies in central India. SETTINGS AND DESIGN: The study was conducted in the Department of Plastic and Maxillofacial Surgery at a tertiary care hospital. MATERIALS AND METHODS: We report a series of 27 cases of eyelid malignancies. In the same case series, we also include a case of malignant hemangiopericytoma which is an extremely rare form of eyelid malignancy worldwide. STATISTICAL ANALYSIS: Depending on the underlying statistical distribution, either analysis of variance (ANOVA) or the Kruskal-Wallis (K-W) test was used to assess the differential distribution of these variables across the types of eyelid malignancies observed in this study. RESULTS: We observed that sebaceous cell carcinoma (approximately 37%) was almost as prevalent as basal cell carcinoma (approximately 44%) in the study subjects and had an earlier age of occurrence and a more rapid clinical course. CONCLUSIONS: Sebaceous cell carcinoma of the eyelid is almost as common as basal cell carcinoma in a large tertiary care centre in central India. (+info)
Dual role of inactivating Lef1 mutations in epidermis: tumor promotion and specification of tumor type.
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The NH(2) terminus of LEF1 is frequently mutated in human sebaceous tumors. To investigate how this contributes to cancer, we did two-stage chemical carcinogenesis on K14DeltaNLef1 transgenic mice, which express NH(2)-terminally truncated Lef1 in the epidermal basal layer. Transgenic mice developed more tumors, more rapidly than littermate controls, even without exposure to tumor promoter. They developed sebaceous tumors, whereas controls developed squamous cell carcinomas. K14DeltaNLef1 epidermis failed to up-regulate p53 and p21 proteins during tumorigenesis or in response to UV irradiation, and this correlated with impaired p14ARF induction. We propose that LEF1 NH(2)-terminal mutations play a dual role in skin cancer, specifying tumor type by inhibiting Wnt signaling and acting as a tumor promoter by preventing induction of p53. (+info)
Role of fine needle aspiration cytology in diagnosis of eyelid sebaceous carcinoma.
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Sebaceous carcinoma of the ocular adnexa is a malignant neoplasm which can exhibit aggressive local behavior and can metastasize to regional lymph nodes and distant organs. The neoplasm is known to masquerade as other benign and less malignant lesions, resulting in delay in diagnosis and relative high morbidity and mortality. Fine needle aspiration cytology (FNAC) of recurrent upper eyelid nodules treated elsewhere as chalazion was done. Cytological smears were suggestive of malignancy. Subsequently histopathology confirmed the diagnosis of sebaceous gland carcinoma. Eyelid reconstruction was done after histopathologically confirmed tumor-free margins. The article highlights the role of FNAC in early diagnosis and subsequent appropriate surgical management of eyelid sebaceous gland carcinoma to prevent recurrence and metastasis. (+info)
Adnexal skin tumors in Zaria, Nigeria.
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BACKGROUND: Adnexal skin tumors share many features in common and differentiate along one line. Their detailed morphological classification is difficult because of the variety of tissue elements and patterns seen. They may be clinically confused with other cutaneous tumors. The aim of this report is to review and classify all adnexal tumors seen in a pathology department over a 16-year period. METHOD: A 16-year retrospective analysis of all adnexal skin tumors seen in a large University Teaching Hospital in Nigeria from January 1991- December 2006. All tissue specimens were fixed in 10% formalin, processed in paraffin wax and stained with Haematoxylin and Eosin. Histology slides were retrieved, studied and lesions characterized. RESULTS: Fifty-two adnexal tumors were seen, accounting for 0.9% of all cutaneous tumors seen within the same period. The median age was 33 years (range: 4 days-70 years). Clinical presentations varied from discreet swellings and nodules to ulcerated masses. Five patients presented with recurrent lesions. Only two cases had a clinical diagnosis of adnexal tumor. Twenty-four (46%) of the lesions were distributed in the head and neck region. Duration of symptoms was 2 months to 15 years (median: 12 months). Tumours of the sweat gland were the commonest--41 (78.8%); they comprised predominantly eccrine acrospiroma (17), characterized histologically by solid nests of round to polygonal cells with clear to eosinophilic cytoplasm, forming tubules in areas. Tumours of sebaceous gland were 7 (13.5%); they comprised mainly Nevus sebaceous of Jadassohn (6), composed of immature sebaceous glands and pilar structures microscopically and a solitary sebaceous adenoma. Tumours of hair follicle were 4 (7.7%) and included trichoepithelioma, characterized microscopically by multiple horn cysts and epithelial tracts connecting abortive pilar structures and a trichofolliculoma. Forty-six lesions (88.5%) were benign and six (11.5%) malignant. CONCLUSION: Adnexal skin tumors have distinct histological patterns which differentiates them from other cutaneous tumors. They are commonly distributed in the head, neck and trunk. The commonest variants are those of eccrine sweat gland origin. Malignant adnexal tumors are uncommon in our setting. (+info)