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Sebaceous carcinoma is the rarest type of oral malignancies. We report a case of primary sebaceous carcinoma of the tongue. Systemic imaging studies revealed that the patient had a T2N2cM0 (International Union Against Cancer guidelines) primary lingual tumor. Histopathological examination revealed neoplastic sebocytic and basaloid cells, and Sudan III staining and electron microscopy revealed intracytoplasmic lipid droplets. The neoplastic cells stained positive for adipophilin; epithelial membrane antigen; epithelial antigen; and cytokeratins 7, 8, and 15, but negative for cytokeratins 5/6, 18, 19, and 20; the androgen receptor; and carcinoembryonic antigen. Superselective intraarterial chemotherapy was administered via the superficial temporal artery concurrent with daily radiotherapy. Multiple biopsies confirmed a complete response of the primary lesion. The patient then underwent neck dissection followed by pathological examination, which revealed lymph nodes metastases. After postoperative radiotherapy to the neck, distant metastases were identified in the mediastinal lymph nodes and the lung. The patient died 17 months after completing the initial course of chemoradiotherapy. Our case demonstrates that superselective intraarterial chemotherapy combined with concurrent radiotherapy can be effective in treating the primary lesion of patients with a sebaceous carcinoma of the tongue. However, an effective strategy to eradicate metastases has yet to be established.

Sebaceous carcinoma (SEB) is the most important malignant tumor of the eyelid. Early diagnosis and proper treatment significantly improve the outcome. SEB should be differentiated histopathologically from basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). In this study, the expression of androgen receptor (AR) in SEB, SCC, and BCC was evaluated. AR was positive in all 19 SEB cases. Of 18 BCCs, 6 (33%) showed focal nuclear immunoreactivity. The 18 SCCs showed no nuclear immunoreactivity. AR is a sensitive marker for SEB, especially in less differentiated tumors. Along with other markers and morphologic features, AR can be helpful in the diagnosis of SEB and its differentiation from SCC and BCC.

Sebaceous carcinoma has a predominant periocular origin but can also be extraocular. These two groups have distinct clinical courses. Insight into the molecular determinants of tumorigenesis and metastasis is limited. There is no effective treatment for metastatic sebaceous carcinoma. Epidermal growth factor receptor (EGFR) is implicated in tumorigenesis and can be a therapeutic target in certain settings. We evaluated EGFR levels by immunohistochemistry (IHC), comparing its expression between periocular and extraocular tumors and assessed EGFR mutation status. IHC was performed in 36 cases: 19 periocular and 17 extraocular (10 associated with Muir-Torre syndrome-MTS). EGFR IHC was scored for percentage of positive cells (< 5%, 5-25%, 26-50%, > 50%) and intensity (+1 = low , +2 = moderate , +3 = high ). Extraocular carcinomas showed markedly increased levels of EGFR when compared to periocular carcinoma cases, both in terms of distribution (88% were > 25% of tumor cells vs. 16%) and intensity (77% were 2+ or 3+ vs. 21%) (p < 0.001). Among extraocular cases, there was significantly lower EGFR expression in MTS-related cases (p < 0.05). No EGFR mutations were identified. Our results underscore the divergent mechanisms underlying the tumorigenesis of periocular and extraocular sebaceous carcinoma and suggest an association between aggressive behavior and increased EGFR expression in extraocular sebaceous carcinoma.

Purpose: The purpose of this study was to detect mutation of the p53 gene, to assess its relationship with p53 or p21(WAF1/CIP1) expression, and to evaluate the correlation between p53 mutation or p21(WAF1/CIP1) expression and clinicopathologic findings in sebaceous carcinoma of the eyelid., Methods: Fifteen conventional paraffin-embedded samples of sebaceous carcinoma of the eyelid were analyzed. Using the single-strand conformation polymorphism technique, the authors sequenced coding exons 5-8 of the p53 gene. The expression of p53 and p21(WAF1/CIP1) protein was analyzed by immunohistochemistry., Results: In 10 of the 15 cases (66.7%), point mutations were detected in the p53 gene. CC to TT double-base changes (tandem mutations), which are known to be induced only by UV, were not detected in any of the mutations. Correlations between p53 mutation and expression were found to be statistically significant (P = 0.007). There was no significant correlation between p53 mutation and clinicopathologic findings or p21(WAF1/CIP1) expression. However, there was a significant inverse correlation between p21(WAF1/CIP1) expression and presence of lymph node metastasis (P = 0.007)., Conclusions: Among human cancers, sebaceous carcinoma of the eyelid may be one of those showing most frequent mutation of the p53 gene, which may not be caused by exposure to UV. p21(WAF1/CIP1) downregulation may be associated with lymph node metastasis.

Merkel cell carcinoma is occasionally associated with other types of cutaneous malignancies including squamous cell carcinoma, basal cell carcinoma and lentigo maligna. We report a case of Merkel cell carcinoma co-existent with sebaceous carcinoma in the right upper eyelid of a 61-year-old Japanese man. Histopathologically, the resected tumor consisted of three nodules located in the tarsal plate, showing two distinct histopathological types. Two nodules were Merkel cell carcinoma and located in the proximal part of the palpebral conjunctiva. The third was sebaceous carcinoma located in the distal transitional zone between the epidermis and the conjunctiva. No features of transition between these two components were noted. Metastatic deposits were identified in the regional lymph nodes, which solely consisted of Merkel cell carcinoma without sebaceous carcinoma. This is the first report of such co-existent lesions.

Purpose: Crystallins are molecular chaperones that protect various cells from apoptosis. This study used immunohistochemistry to examine the expression of alphaA-crystallin and alphaB-crystallin in human sebaceous carcinoma tissues., Methods: Nine patients with sebaceous carcinoma of the eyelid underwent excision of the eyelid or orbital exenteration. Formalin-fixed, paraffin-embedded tissue sections were submitted for hematoxylin-eosin staining and immunohistochemistry with anti-alphaA- and alphaB-crystallin antibodies., Results: In the noncancerous eyelid, crystallins were weakly and homogeneously expressed in the Meibomian gland lobules. In eyelids with sebaceous carcinoma, alphaA-crystallin and alphaB-crystallin were highly expressed in 4 cases, where the cytoplasmic immunoreactivity was heterogeneously detected in the tumor cells. Three and 2 cases were shown to express low levels of alphaA-crystallin and alphaB-crystallin, respectively. A statistically significant correlation was observed between expression levels of alphaA-crystallin and alphaB-crystallin in sebaceous carcinomas (p=0.012). All sebaceous carcinoma tissues contained mitotic tumor cells, which showed predominantly perinuclear immunoreactivity of alphaB-crystallin. The mitotic rate of tumor cells was 5.85+/-1.76 and 10.72+/-1.64 in high and moderate/low alphaB-crystallin-expressing cases, respectively. The number of mitotic cells was significantly higher in moderate/low alphaB-crystallin-positive than in high-positive cases (p<0.01)., Conclusions: Crystallins are expressed in human sebaceous carcinomas including mitotic cells. Expression of alphaB-crystallin correlated with low number of mitotic tumor cells, suggesting that alphaB-crystallin may play a potential role in the regulation of tumor cell proliferation.

Although the significance of immunohistochemical detection of DNA mismatch repair proteins and/or microsatellite instability testing in identifying patients at risk for germline deficiency in DNA mismatch repair genes is well established in colorectal carcinomas, the proper use of such techniques in sebaceous neoplasms, another tumor type that has been implicated in patients with hereditary DNA mismatch repair deficiency, has not been clearly defined. In this study, we stratified a series of 27 patients with 1 or more sebaceous neoplasms based on the pattern of immunohistochemical expression of MLH1, MSH2, MSH6, and PMS2, and comparatively analyzed their clinical and pathologic characteristics, including tumor-infiltrating lymphocytes and peritumoral lymphocytic response as determined by immunohistochemical staining for CD3. The study tissue samples included 30 sebaceous carcinomas, 14 sebaceous adenomas, and 7 sebaceous hyperplasias, along with 8 concurrent nonsebaceous lesions from 6 patients. Overall, 12 of the 27 (44%) patients showed abnormal IHC staining with mismatch repair proteins in their sebaceous tumors, the most commonly seen abnormality being concurrent loss of MSH2 and MSH6 (8/12, 67%). Sebaceous adenomas and carcinomas occurring in the same patients showed an identical staining pattern, as did hereditary nonpolyposis colorectal cancer-related nonsebaceous tumors in the same patients. When compared with cases that had normal expression of the mismatch repair proteins, cases with abnormal expression tended to be younger (median age, 56.5 y vs. 68 y), more likely to involve sites outside the head and neck (9/12 vs. 0/15), and more likely to have synchronous or metachronous visceral malignancies (8/12 vs. 3/15) and a positive family history. Furthermore, sebaceous tumors with abnormal expression had significantly higher CD3-positive tumor-infiltrating lymphocytes and peritumoral lymphocytic response. Thus, all these factors (age less than 60 y, involvement of nonhead and neck sites, visceral malignancy, family history fulfilling at least Bethesda guidelines, and lymphocytic infiltration) bore informative value in predicting abnormal expression of DNA mismatch repair proteins. However, their sensitivity was only modest, being 58%, 75%, 67%, 78%, and 75%, respectively. On such a premise, given that sebaceous neoplasms are only infrequently encountered, and that immunohistochemistry is easily available and reasonably reliable, we recommend that, when there exists a desire to identify hereditary DNA mismatch repair deficiency, routine immunohistochemical detection of DNA mismatch repair proteins be performed in all sebaceous neoplasms regardless of patient's age or other clinical characteristics.

Sebaceous carcinoma (SC) of the breast is a rare malignant tumor and only nine cases, including the present one, have been reported in the English-language literature. The present report describes a case of mammary SC in a 50-year-old Japanese woman. The tumor was gray-white on cut surface and separate from the skin and the nipple. Microscopically, lobules encircled by a fibrous envelope and cords or small cell nests in the stroma were noted. These two types of structures were composed of dark cells and clear foamy cells. The dark cells had large nuclei and amphophilic cytoplasm. The clear foamy cells had numerous lipid vacuoles, confirmed on immunostaining with anti-adipophilin antibody and electron microscopy. In the lobules the gradual transitions from basal dark cells to central clear foamy cells and comedo-like necrosis were observed. The tumor cells were positive on immunohistochemistry for cytokeratins (CAM5.2, AE1/AE3), Her2/neu and androgen receptor but negative for estrogen and progesterone receptors. This is the first case of an androgen receptor-positive mammary SC to be reported, and therefore contributes to the understanding of the clinicopathological features of SC of the breast.

We present herein the case of an 80-year-old woman with a keratotic plaque measuring 1.4x1.3 cm on the left popliteal fossa. The plaque was resected and diagnosed on microscopic examination as low-grade sebaceous carcinoma. Sebaceous carcinoma on the leg seems extremely rare.

The diagnosis of sebaceous carcinoma presents an important challenge to both clinicians and pathologists, as many cases are initially misdiagnosed both clinically and histopathologically, potentially leading to adverse medical and legal outcomes. The distinction of sebaceous carcinoma from benign sebaceous proliferations and other tumors is therefore of utmost importance, and immunohistochemistry may be useful in this differential. We studied the expression of D2-40 (podoplanin) by immunohistochemistry to determine if it can aid in this differential diagnosis and to evaluate the possibility of lymphangiogenesis in sebaceous carcinoma. A total of 36 cases of sebaceous lesions, including 16 sebaceous carcinomas, 7 sebaceous adenomas, 6 sebaceomas, and 7 cases of normal glands and sebaceous hyperplasia, and 17 cases of basal cell carcinoma and 10 cases of squamous cell carcinoma, were also examined. We found no significant increase in tumor lymphangiogenesis by semiquantitative scoring of lymphovascular density per square millimeter of tumoral/peritumoral stroma in sebaceous carcinoma versus benign sebaceous proliferations. However, D2-40 staining showed a different pattern in the benign tumors, which were positive only in the basaloid cells (most pronounced in sebaceoma), versus sebaceous carcinoma, which was either negative or focally positive in a haphazard pattern in most cases, although some cases of basaloid sebaceous carcinomas showed strong positivity. We also found D2-40 to be only weakly and focally positive in basal cell carcinoma and weakly to moderately positive in squamous cell carcinoma, which showed increased staining with decreased differentiation. Therefore, overall, D2-40 is, of limited diagnostic utility in sebaceous lesions but may be useful in distinguishing sebaceoma and basaloid sebaceous carcinoma from basal cell carcinoma.

Background: Survivin is a member of the inhibitor of apoptosis family of proteins implicated in the inhibition of apoptosis and cell cycle control, both crucial in the progression to malignancy. Survivin overexpression has been demonstrated in numerous malignancies including cutaneous squamous cell carcinoma and melanoma. To date, there are no studies evaluating the expression of survivin in sebaceous neoplasms., Methods: Immunohistochemical expression of survivin was evaluated in a total of 20 extraocular sebaceous neoplasms: sebaceous hyperplasia (SH, 8), sebaceous adenoma (SA, 8), and sebaceous carcinoma (SC, 4). All the results were independently evaluated by a single dermatopathologist., Results: Nuclear expression of survivin was present in 1.4% of lesional SH cells, 8.2% of SA cells, and 12.5% of SC cells. A significant difference in survivin expression with the Student t test was noted between SH and SA (P=0.01), SA and SC (P=0.05), and SH and SC (P=0.001)., Conclusions: There is a statistically significant difference in survivin expression among SH, SA, and SC. These findings demonstrate the potential diagnostic utility of survivin, further assisting in the microscopic differentiation of benign and malignant sebaceous neoplasms. However, larger studies are needed to determine the significance of survivin expression as it relates to recurrence, metastatic potential, and outcome.

Background: The distinction between ocular sebaceous carcinoma, poorly differentiated ocular squamous cell carcinoma and ocular basal cell carcinoma can be challenging. An appropriate immunohistochemical panel may help to differentiate these lesions., Methods: To determine the distribution and use of several immunostains in these specimens, formalin-fixed, paraffin-embedded tissue from several of each was studied using an immunohistochemical technique., Results: Positive staining for cytokeratin (CK)7 was seen in 100% of sebaceous carcinomas, 77.8% of basal cell carcinomas and 67.7% of squamous cell carcinomas. One hundred percent of sebaceous and basal cell carcinomas were positive for cytokeratin CAM 5.2, while only 83.3% of squamous cell carcinomas were positive. Using epithelial membrane antigen (EMA), 100% of squamous cell carcinomas and 80% of sebaceous carcinomas were positive, while basal cell carcinomas were uniformly negative. One hundred percent of basal cell carcinomas and 80% of sebaceous carcinomas were positive for Ber-EP4, while all squamous cell carcinomas were negative. Finally, 77.8%, 20% and 16.7% of basal cell carcinomas, sebaceous carcinomas and squamous cell carcinomas showed immunoreactivity for the androgen receptor., Conclusion: An EMA positive, Ber-EP4 positive immunophenotype supports sebaceous carcinoma, EMA positive, Ber-EP4 negative result supports squamous cell carcinoma and an EMA negative, Ber-EP4 positive result supports basal cell carcinoma.

We describe a 54-year-old man with a pedicled tumour on the neck. The surgical specimen revealed a sebaceous carcinoma. He belonged to a cancer-prone family susceptible to gastrointestinal cancer. Systemic evaluation for latent malignancies revealed early-stage colonic adenocarcinoma. These findings were compatible with Muir-Torre syndrome (MTS). Microsatellite instability was detected in the sebaceous carcinoma, suggesting a DNA mismatch repair gene mutation. Moreover, duplication of exon 7 generated a nonsense codon at codon 427 of the MSH2 gene causing truncation of MSH2 protein. Immunohistochemical analysis showed diminished MSH2 protein levels in the sebaceous carcinoma and colonic adenocarcinoma. To date, there have been no reports showing duplication of exon 7 of the MSH2 gene in MTS or hereditary nonpolyposis colorectal cancer kindreds. Furthermore, the present case indicates that the dermatologist plays an important role in the diagnosis of MTS and evaluation for latent malignancies.

Background: Recent studies have demonstrated that the cytokeratin 15 (CK15)-positive stem cells located in the hair follicle bulge are also involved in sebaceous gland renewal. No previous studies have dealt with the CK15 expression in sebaceous neoplasms., Methods: We studied the CK15 expression in 30 sebaceous neoplasms including 10 sebaceomas (sebaceoma defined as a distinct benign neoplasm with sebaceous differentiation), 10 sebaceous neoplasms of Muir-Torre syndrome, and 10 sebaceous carcinomas, in addition to that in the mantles of normal hair follicles., Results: CK15 was positive in the undifferentiated sebocytes of the mantles. All 10 sebaceomas showed CK15 expression in the basaloid, germinative cells. Both sebaceous neoplasms in Muir-Torre syndrome and sebaceous carcinomas demonstrated negative or only a focal positive reaction, including the occasional aberrant expression in matured sebocytes, to CK15., Conclusions: CK15 may be a useful marker for stem cells with a sebaceous fate, and a constant CK15 expression in sebaceomas supported the hypothesis that sebaceoma is a benign neoplasm of sebaceous germinative cells in the mantles. The similar staining pattern of CK15 between sebaceous neoplasms in Muir-Torre syndrome and sebaceous carcinomas may be one piece of evidence supporting the hypothesis that most sebaceous neoplasms in Muir-Torre syndrome are low-grade sebaceous carcinomas., (Copyright Blackwell Munksgaard 2006.)

Background: Muir-Torre syndrome (MTS) is an autosomal dominant genodermatosis characterized by the association of at least 1 cutaneous sebaceous tumor and 1 internal malignancy, often arising in the gastrointestinal tract. It is secondary to germline mutations in DNA mismatch repair genes, mainly MLH-1 and MSH-2., Observations: We report the case of a 54-year-old man with a 2-year history of skin-colored papules clinically reminiscent of large sebaceous hyperplasias on the nose and back, but histologically diagnosed as sebaceous adenomas and epitheliomas. His family history was positive for colon cancer in the mother and 2 brothers. A colonoscopy done during the hospitalization revealed 2 sessile polyps in the left colon, both showing a low-grade dysplasia on the biopsy specimen. Immunohistochemical staining performed on the cutaneous and colic biopsy specimens revealed a lack of expression of MSH-2 and MSH-6. Genetic testing revealed microsatellite instability in the colon and cutaneous tumors., Conclusion: The immunohistochemical testing for MSH-2, MSH-6, and MLH-1 is useful for rapid identification of an underlying mismatch repair defect and early diagnosis of MTS.

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.

Aims: To investigate the expression of human telomerase gene RNA (hTR) and human telomerase reverse transcriptase (hTRT) in eyelid sebaceous gland carcinoma and to evaluate risk factors for sebaceous carcinoma recurrence., Methods: The expression patterns of hTR and hTRT were detected by in situ hybridization (ISH) in paraffin-embedded samples of 55 eyelid sebaceous gland carcinoma, 12 chalazia, and four sebaceous adenoma. The proliferation index (PI) of sebaceous gland carcinoma was determined by Ki-67 immunolabeling and the results were compared with the expression of hTR and hTRT. Several factors for recurrence of sebaceous gland carcinoma were evaluated by statistical analysis., Results: Expression of hTR and hTRT was present mainly in the sebaceous gland carcinoma tissues and not in adjacent tissues of carcinoma, chalazia, and sebaceous adenoma. The prevalence of hTR, hTRT, and Ki-67 expression in 55 sebaceous carcinoma samples were 84.45%, 58.1%, and 78.18%, respectively. hTR expression was highly associated with the degree of carcinoma differentiation (P<0.001) and hTRT expression was correlated with the proliferation index as determined by Ki-67 staining (P<0.005). There was a correlation between the recurrence of sebaceous gland carcinoma and the patient's onset age (OR=0.914, P<0.05), as well as the time to first treatment (OR=1.163, P<0.01)., Conclusions: Telomerase may play an important role in the carcinogenesis of sebaceous gland carcinoma, and expression of hTR and hTRT combined with other features of sebaceous gland carcinoma may be helpful for the diagnosis and evaluation of clinical prognosis. Risk factors for recurrence of sebaceous gland carcinoma are patients' onset age and the time to first treatment.

Purpose: The aim of this study is to investigate whether there are any abnormalities in the in vivo expression of retinoid acid receptors (RAR-alpha, RAR-beta and RAR-gamma) and retinoid X receptors (RXR-alpha, RXR-beta and RXR-gamma) in sebaceous cell carcinoma., Methods: Expression of retinoid receptors in paired specimens of cancerous tissues (n = 10) and adjacent normal tissues (n = 10) from 10 patients with sebaceous cell carcinoma was studied immunohistochemically by using anti-retinoid receptor antibodies., Results: In eight of the 10 normal tissue samples, all six receptors were expressed. In the other two samples, all receptors were expressed except RAR-gamma (one sample) or RXR-gamma (two samples). Five tumours (50%) lacked RAR-alpha; RAR-alpha expression was lower in tumours than in normal tissues in eight of 10 cases. RAR-beta was expressed in the cytoplasm of nine of 10 tumours; RAR-beta expression was at least as high in tumours as in normal tissue in eight of 10 cases. Two tumours lacked RAR-gamma; three tumours had lower RAR-gamma expression than paired normal epithelium; four had the same RAR-gamma expression, and one had higher RAR-gamma expression. RXR-alpha expression was strong in all normal tissues and tumour samples. Ten tumours lacked RXR-beta and all 10 tumours lacked RXR-gamma expression., Conclusions: Diminished RXR-beta and RXR-gamma expression might be related to the development of sebaceous cell carcinoma. Additional studies are required to establish whether the defects in RAR expression in sebaceous cell carcinoma might affect the potential response of this tumour to treatment with retinoids.

Purpose: To study retinoid receptor expression in sebaceous cell carcinoma of the eyelid., Methods: Expression of retinoid receptors (RAR alpha, beta, and gamma and RXR alpha, beta, and gamma) in tumor specimens from 10 patients with sebaceous cell carcinoma of the eyelid and in 3 normal incidental tarsus specimens from healthy adults without cancer was studied immunohistochemically by using antiretinoid receptor antibodies., Results: In all 3 specimens of normal tarsus, all 6 retinoid receptors were expressed. RARalpha expression was absent in 3 tumors and was decreased in 3 tumors compared with expression in the control tissues. RARbeta expression in carcinomas was primarily perinuclear; 6 tumors showed increased RARbeta expression compared with controls. RARgamma expression was absent in 4 tumors and was decreased in 2 tumors compared with controls. RXRalpha nuclear expression was decreased compared with controls in 5 tumors. RXRbeta expression was low in 7 tumors. RXRgamma expression was absent in 6 tumors., Conclusions: Aberrant expression of retinoid receptors in sebaceous cell carcinoma of the eyelid might play a role in the pathogenesis and progression of this carcinoma.

This report emphasizes a carcinoid-like pattern, a previously unrecognized feature in cutaneous sebaceous neoplasms. We report 7 patients with sebaceous tumors in which neoplastic cells were arranged in a trabecular and ribbon-like pattern or formed rosettes/pseudorosettes. The cases included 6 men and 1 woman, with their ages at the diagnosis ranging from 43 to 87 years (median age, 59). All patients presented with a solitary lesion. Locations were the scalp (n = 6) and forearm (n = 1). The carcinoid-like arrangement of neoplastic cells was the sole pattern in 4 cases, and in 3 cases the so-called labyrinthine/sinusoidal and/or rippled patterns were seen in addition. Sebaceous differentiation in the form of mature sebocytes varied from almost none to approximately 10%. Although the neoplasm appeared benign architecturally, the presence of cytologic atypia qualified 2 tumors as low-grade carcinomas. Four lesions represented sebaceomas, and in 1 case microscopic delineation between a carcinoma and sebaceoma was difficult. No neuroendocrine differentiation was demonstrated immunohistochemically, histochemically, and ultrastructurally. Electron microscopic examination performed in 1 case of carcinoma revealed lipid vacuoles in a minority of cells. There were no membrane-bound neuroendocrine granules. Rare cells contained peculiar large helioid inclusions. We conclude that the carcinoid-like pattern is another distinctive pattern indicative of sebaceous neoplasms. This pattern seems to be closely related to the rippled and labyrinthine/sinusoidal patterns, as exemplified by our cases, in which these arrangements sometimes occurred simultaneously.

Purpose: To evaluate the relationships among histopathological type, clinical malignant grade, and Ki-67 labeling index (LI) in sebaceous gland carcinoma (SGC), conjunctival squamous cell carcinoma (SCC), and conjunctival intraepithelial neoplasia (CIN), with pterygium and normal conjunctiva as controls., Methods: This retrospective study was conducted at the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan. We used tissue specimens obtained from 20 patients (four SGC, four SCC, four CIN, four pterygium, and four normal conjunctiva). Ki-67 immunohistochemical analysis was performed in all 20 cases., Results: The Ki-67 labeling index (LI) was 46.1 +/- 3.0% (average +/- SD) in SGC, 28.4 +/- 4.5% in SCC, 20.0 +/- 7.2% in CIN, 9.0 +/- 2.2% in pterygium, and 6.8 +/- 2.3% in normal conjunctiva. Ki-67 LI was significantly (Mann-Whitney U test, P < 0.05) higher in SGC than in SCC, and higher, but not significantly, in SCC than in CIN. Ki-67 LI was significantly (P < 0.05) higher in SCC and CIN than in pterygium., Conclusions: These results suggest that Ki-67 LI may be a sensitive marker for ocular malignant tumor grading.

Some authors have used sebaceous epithelioma as a synonym for basal cell carcinoma (BCC) with sebaceous differentiation. However, our review of the literature revealed that definite cases of BCC with sebaceous differentiation that provide adequate clinical and histopathologic information are scarce. We present the case of a 72-year-old woman with a pigmented nodular lesion on her right ala nasi region, clinically diagnosed as pigmented BCC. Histopathologically, this nodular lesion, which was completely excised, showed typical features of BCC. It was noteworthy that within one aggregation of the presented BCC, tiny and small duct-like structures lined by cornified layers with a crenulated inner surface were seen. Vacuolated cells were scattered within a few aggregations, and they had foamy, bubbly cytoplasm and starry nuclei. The vacuolated cells were immunohistochemically positive for epithelial membrane antigen (EMA). These histopathologic findings demonstrated unquestionable sebaceous differentiation in this BCC, namely BCC with sebaceous differentiation, which should be distinguishable from both sebaceoma and sebaceous carcinoma. The small duct-like structures lined by eosinophilic cuticle, indicating apocrine differentiation, were also observed in this BCC.

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.

Sebaceous neoplasms, including carcinomas, are tumors most often seen around the eye and eyelid. Cases of extraorbital sebaceous tumors associated with skin adnexa are less common. The parotid gland may also be a source for sebaceous neoplasms, and cases associated with minor salivary gland tissue have also been reported. Once beyond the oropharynx, individual cases of pharyngeal and laryngeal sebaceous tumors are reported. The case of a patient with primary sebaceous carcinoma of the bronchus is presented. Our case is that of an endobronchial mass that has histopathologic features of a sebaceous carcinoma, with predominance of areas with morphologically classic sebaceous differentiation, confirmed by oil red O stain for lipid, analyzed by immunohistochemistry and evaluated ultrastructurally. This unique tumor extends the spectrum of extraocular, extracutaneous neoplasms with sebaceous differentiation from existing single reports in the hypopharyx and larynx to now include bronchus.

Purpose: To elucidate the relation between infiltrating cytotoxic T lymphocytes and the expression of MUC1 and sialoglycans in malignant eyelid tumors., Methods: The distribution of MUC1, Maackia amurensis lectin-II (MAL-II)-recognized sialoglycan, and CD8-positive T lymphocytes was examined histochemically in 14 patients with malignant eyelid tumors: three squamous cell carcinomas, six sebaceous gland carcinomas, and five basal cell carcinomas. The density of CD8-positive cells was examined and correlated with MUC1 and sialoglycan expression., Results: MUC1 was identified in squamous cell carcinoma and sebaceous gland carcinoma, but not in basal cell carcinoma. CD8-positive cells were more densely distributed in those squamous cell and sebaceous gland carcinoma cases that were more intense in MUC1 expression and weaker in MAL-II binding. Tumors with a strong expression of both MUC1 and MAL-II-bound sialoglycans showed few CD8-positive cells., Conclusions: MUC1 with few sialoglycans is likely to induce an intense infiltration of CD8-positive cytotoxic T lymphocytes in eyelid cancers.

The type and distribution of keratins (K) in malignant tumors of eyelids were examined immunohistochemically to understand the pathomechanism of intercellular interactions. All of the tumor cells in the basal cell carcinoma were positive for K14, which is specific for basal cells, whereas all of them were negative for K10, which is specific for suprabasal layers in stratified squamous epithelia. These findings suggest that basal cell carcinoma may consist of uniform, basal cell-like tumor cells. On the other hand, the squamous cell carcinoma and sebaceous carcinoma, which were positive for either K14 or K10 to varying extent, may consist of various tumor cells with different types and degrees of differentiation. In these tumors, K14 was frequently detected throughout the border cells of the tumor mass. Apoptotic bodies were detected at the region where this continuous distribution of K14 was interrupted. These findings may help to clarify the pathomechanism of the interactions between the tumor cells and stromal cells.

Background: Since sebaceous carcinomas with a poor prognosis arising from the cutaneous adnexae of the eyelid are sometimes difficult to differentiate from squamous cell carcinoma or basal cell carcinoma on clinical and histopathological findings, definite differentiation between these tumors by additional methods is necessary., Objective and Methods: To clarify the usefulness of histochemical and immunohistochemical examinations in diagnosing ocular sebaceous carcinoma, histochemical and immunohistochemical studies were carried out on the 2 patients with unusual ocular sebaceous carcinoma., Results: The findings of ocular sebaceous carcinoma, at least in our 2 cases, were almost identical to those of extraocular sebaceous carcinoma., Conclusion: Immunohistochemical detection of human milk fat globules subclass 1, human milk fat globules subclass 2, and breast carcinoma-associated antigen 225 was useful for diagnosing ocular sebaceous carcinomas as well as extraocular ones.