Sebaceous Carcinoma in Situ Masquerading Clinically and Histologically as Paget Disease of the Breast.

Sebaceous carcinoma in situ is a poorly understood and ill-defined entity. In situ sebaceous carcinoma exhibits a similar location pattern to its invasive counterpart in that most commonly has a periorbital distribution. Review of the literature found only seven cases of extraocular sebaceous carcinoma in situ. We present a unique and challenging case of sebaceous carcinoma in situ masquerading both clinically and histologically as Paget's disease of the breast. A 61-year-old female presented to her dermatologist complaining of a 6 mm erythematous waxy papule on her medial right breast. The patient's past medical history was significant for Muir-Torre syndrome. Clinically, the differential diagnosis included Paget disease of the breast, squamous cell carcinoma, and sebaceous carcinoma. A shave biopsy revealed an atypical proliferation of large single cells limited to the epidermis infiltrating in a pagetoid pattern, as well as cohesive nests of round neoplastic cells with mild nuclear atypia, prominent nucleoli, and vacuolated cytoplasm. Histologically, the differential diagnosis included Paget's disease of the breast, squamous cell carcinoma in situ, melanoma in situ, and sebaceous carcinoma in situ. A battery of immunohistochemical stains was performed including CK7, EMA, CAM5.2, CK20, and MART-1. The lesional cells were positive for adipophilin, factor XIIIa, CK7, and EMA and were negative for CAM5.2, CK20, and MART-1 supporting a diagnosis of sebaceous carcinoma in situ. Multiple deeper sections were examined and invasion beyond the epidermis was not identified. This case adds to the paucity of information available regarding extraocular sebaceous carcinoma in situ and warns clinicians of this potential diagnostic pitfall especially in patients with Muir-Torre syndrome.

Sebaceous carcinoma in association with actinic keratosis: A report of two cases with an immunohistochemical study.

We report two cases of sebaceous carcinoma associated with actinic keratosis (AK) with an immunohistochemical study, which suggests the possibility that sebaceous carcinoma really does develop within AK. Case 1 had sebaceous carcinoma arising within the atrophic type AK and case 2 had sebaceous carcinoma associated with bowenoid AK in the periphery and some parts of the overlying epidermis of the lesion.

Sebaceous carcinoma: clinicopathologic features and diagnostic role of immunohistochemistry (including androgen receptor).

OBJECTIVE: To explicate the clinicopathologic features of periocular sebaceous carcinoma (SC) and emphasize the importance of immunohistochemical staining that includes androgen receptor (AR) in their diagnosis. DESIGN: Retrospective study. METHODS: Clinical and histopathologic features in 56 patients with periocular SC were analyzed. Immunohistochemical staining for pan-cytokeratin (CK), epithelial membrane antigen (EMA), Ber-EP4, adipophilin (ADP), and AR was performed on all cases. Immunostaining in SC was compared with that of squamous cell carcinoma (SCC; n = 25) and basal cell carcinoma (BCC; n = 18) for all antibodies. RESULTS: SGC was more frequent in females, most commonly presenting as a discrete and nodular mass. Four patients had regional lymph node metastases, whereas in 2, the tumour metastasized to the liver. Eight patients had a locoregional recurrence between the 3rd and 45th months of follow-up. Fifty patients had a moderately differentiated tumour. In 3 patients, the resected margins displayed intraepithelial tumour spread, and 2 patients died of the disease. In general, the staining pattern in SGC was CK(+), EMA(+), BerEP4(-), ADP(+), and AR(+). SCCs were CK(+), EMA(+), Ber-EP4(-), ADP(-/+), and AR(-), whereas BCC were CK(+), EMA(-), Ber-EP4(+), ADP(-), and AR(-/+). p53 expression and Ki-67 index were higher in SC than SCC or BCC. CONCLUSIONS: Immunostaining using a panel of antibodies comprising BerEP4, ADP, EMA, and AR is useful in diagnosing sebaceous carcinoma and differentiating it from SCC and BCC, which are common to the periocular location and sometimes are morphologically identical to SC.

Diagnostic utility of adipophilin immunostain in periocular carcinomas.

PURPOSE: To determine the efficacy of adipophilin immunohistochemistry in the diagnosis of sebaceous carcinoma of the ocular adnexal region and to provide the guidelines for interpretation of this immunostain. DESIGN: Retrospective, histopathologic case series. PARTICIPANTS: A total of 25 patients with sebaceous carcinoma, 21 patients with basal cell carcinoma, 22 patients with conjunctival squamous cell carcinoma, 9 patients with cutaneous squamous cell carcinoma, and 5 patients with conjunctival mucoepidermoid carcinoma. METHODS: Immunohistochemical staining for adipophilin was performed on paraffin-embedded tissues and correlated with hematoxylin-eosin, periodic acid-Schiff (PAS), and mucicarmine-stained preparations. Immunostaining was quantified by light microscopy and with a computerized image analysis system of scanned images. Statistical analysis was performed to compare immunostaining patterns within the tumor categories by stage and grade, between the different neoplasms, and for correlation between light microscopy observations and computerized image analysis. MAIN OUTCOME MEASURES: Localization of adipophilin immunostain, intensity of immunostaining, percent of immunoreactive cells, percentages of vacuolar staining and granular staining, and vacuole size. RESULTS: Adipophilin expression was observed in 100% of sebaceous carcinomas, 100% of cutaneous squamous cell carcinomas, 95% of basal cell carcinomas, 73% of conjunctival squamous cell carcinomas, and 60% of mucoepidermoid carcinomas. Sebaceous carcinomas demonstrated significantly stronger adipophilin expression, a greater number of intracytoplasmic vacuoles, and larger vacuoles. The specificity and sensitivity of adipophilin immunostaining in the diagnosis of sebaceous carcinoma were both 100% when more than 5% of the staining occurred in vacuoles (<95% granular staining). The diagnostic sensitivity and specificity were 100% and 96%, respectively, when the staining was graded as moderately or strongly intense and were 92% and 85% when the vacuoles were greater than 1.5 µm in diameter. CONCLUSIONS: Although upregulation of neoplastic steatogenesis is observed in both sebaceous and nonsebaceous carcinomas, the pattern and intensity of adipophilin immunostaining are helpful in distinguishing sebaceous carcinoma from other neoplasms with overlapping histology.

Lymphadenoma of the salivary gland: clinicopathological and immunohistochemical analysis of 33 tumors.

Lymphadenomas (LADs) are rare salivary gland tumors. Their clinicopathologic characteristics and etiopathogenesis are poorly understood. We examined 33 LADs in 31 patients (17 women and 14 men) aged 11-79 years (median 65 years). There were 22 sebaceous LADs in 21 patients (9 women and 12 men) and 11 non-sebaceous LADs in 10 patients (8 women and 2 men). Two patients had synchronous double tumors. Twenty-six tumors (79%) arose in parotid, three in the neck, and two each in submandibular gland and oral cavity. Extraparotid tumors were seen in 2 of 21 (10%) patients with sebaceous and 4 of 10 (40%) patients with non-sebaceous LADs. Seven of twenty-three (30%) patients had immunosuppressive therapy for unrelated diseases. The tumors were well circumscribed, encapsulated (n=28, 84%) painless masses, varying in size from 0.6 to 6 cm (median 2.2). The cut surfaces were gray-tan to yellow, homogeneous and multicystic (n=24, 72%). The epithelial cells were basaloid, squamous and glandular, forming solid nests, cords, tubules, and cysts. Sebaceous differentiation was restricted to sebaceous lymphadenoma. The epithelial cells expressed basal cell markers (p63, 34BE12, and/or CK5/6, 18/18, 100%) and the luminal glandular cells expressed CK7 (12/12, 100%). Myoepithelial cells were absent (n=10/16, 63%) or focal. The lymphoid stroma was reactive, with germinal centers in 28 (84%). There was no evidence of HPV (0/11), EBV (0/7), and HHV-8 (0/8). Malignant transformation to sebaceous and basal cell adenocarcinoma was seen in one patient each. None of the 11 patients with follow-up (1-8 years) recurred. In summary, sebaceous and non-sebaceous LADs are benign, encapsulated, solid and cystic tumors affecting older adults. Non-sebaceous LADs affect women and extraparotid sites more frequently than sebaceous LADs. Altered immune status may have a role in their etiopathogenesis. Multiple synchronous tumors, origin in buccal mucosa, and malignant transformation may rarely occur.

Sebaceous carcinoma of the eyelids: thirty cases from Japan.

Sebaceous carcinoma of the eyelids is rare in Western countries but not uncommon in Asian countries. Diagnosis is difficult both clinically and histologically. Thirty cases of sebaceous carcinoma of the eyelids treated at Tokyo Medical University Hospital were reviewed to elicit characteristic features of pathological findings. The tumor cells were infiltrating in a lobular pattern that consisted mainly of large atypical germinative cells. Sebocytes seen in the lobules had conspicuous nucleolus associated with perinucleolar halo. In 17 cases (57%) there was foamy histiocyte infiltration in and around the tumor nests. Sebaceous duct differentiation, namely holocrine secretion indicating a specific type of coagulation necrosis maintaining a cellular framework or maintaining a bubbly cytoplasm associated with nuclear debris in the periphery, was seen in 24 cases (80%). Although unequivocal squamous differentiation was limited to only 11 carcinomas, scattered individual necrosis with nuclear debris in the background of germinative cells appeared in 29 cases (96.7%). Expression of epithelial membrane antigen, perilipin and adipophilin were detected in all cases. In conclusion, to detect sebaceous differentiation in sebaceous carcinoma, it would be helpful to focus on holocrine secretion, squamous differentiation and foamy macrophage infiltration, and to utilize immunohistochemistry involving anti-perilipin and anti-adipophilin stain.

Sebaceous carcinoma of the parotid gland in children: an immunohistochemical and ploidy study.

Sebaceous carcinoma (SC) is a rare malignancy, affecting mainly the periocular glands. To the best of the authors' knowledge, this is the first English-language report of parotid SC affecting children; two cases are presented. Immunohistochemical studies included 29 different antibodies (15 of these were cytokeratins, CKs). For each case, DNA ploidy status was determined using isolated nuclei stained with Feulgen and analysed using a DNA image cytometry system. Most of the tumour cells were positive for CKs AE1/AE3, 34B12, 5 and 7. The CK14 pattern depicted the monolayer of basal cells surrounding the islands of malignant tissue, while the more central sebaceous differentiated cells were negative. Epithelial membrane antigen was strongly positive in the well differentiated cells, while most of the basaloid peripheral cells were negative, and only a few cells were positive for carcinoembryonic antigen. beta catenin, E cadherin and C-erb B2 were expressed by most of the cells including the more differentiated sebaceous cells. Tumour cells were negative for muscle or myoepithelial markers, androgen, oestrogen and progesterone receptors. Both SCs were uniformly diploid, and showed low proliferative indices for p53, Ki-67 and Mcm-2, which is consistent with the good clinical course presented by these patients so far.

Immunolabeling pattern of cytokeratin 19 expression may distinguish sebaceous tumors from basal cell carcinomas.

BACKGROUND: Distinction between sebaceous tumors and basal cell carcinomas can often pose diagnostic problems. Recent work with the antibody to cytokeratin 19 (CK 19) has shown that this marker has high specificity for undifferentiated basaloid cells. Our aim was to evaluate the use of CK 19 staining patterns in differentiating between sebaceous tumors and basal cell carcinomas. The sebaceous tumors that were examined in this study included sebaceous adenomas, sebaceous epitheliomas (sebaceomas) and sebaceous carcinomas. METHODS: Thirty-seven cases including 5 sebaceous adenomas, 16 sebaceous epitheliomas, 6 sebaceous carcinomas and 14 basal cell carcinomas (7 being of the morpheaform type and 7 nodular basal cell carcinomas) were tested with a monoclonal mouse antibody to human CK 19. RESULTS: CK 19 was focally positive in 1/5 (20%) sebaceous adenomas, 8/16 (50%) of sebaceous epitheliomas and 1/6 (17%) of sebaceous carcinomas. Strongly positive expression of CK 19 was not seen in any of the sebaceous adenoma, sebaceous epithelioma or sebaceous carcinoma specimens. CK 19 was found to be strongly positive in 9/14 (64%) and focally positive in 2/14 (14%) of basal cell carcinomas. CONCLUSION: CK 19 expression can be helpful in differentiating sebaceous tumors (including sebaceous adenomas, sebaceous epitheliomas and sebaceous carcinomas) from basal cell carcinomas and may be a useful adjunct when these entities are included in the differential diagnosis.

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.

Sebaceous carcinoma of the breast: case report and review of the literature.

Sebaceous differentiation has been described in only limited examples of benign and malignant epithelial lesions of the breast. We report a rare case of mammary sebaceous carcinoma to further delineate its morphologic features. Microscopically, the tumor, arising in the right mammary gland of a 63-year-old woman, was composed of well-defined solid sheets or lobules of atypical epithelial cells including many large pale or clear cells with often scalloped nuclei and coarsely vacuolated cytoplasm, in which abundant lipid droplets were identified with oil-red-O staining. Immunohistochemical expressions of cytokeratin, epithelial membrane antigen, and receptors of estrogen and progesterone were detected, whereas GCDFP-15, S-100 protein, vimentin, alpha-smooth muscle actin, p63, androgen receptor, and the HER2/neu protein were not expressed. Besides, a subset of the tumor cells co-expressed synaptophysin, neurofilament, and PGP9.5, suggesting neuroendocrine differentiation that is a hitherto undescribed phenomenon in the mammary tumors with sebaceous features. This case would expand the morphologic diversity of carcinoma of the breast.

Collision sebaceous and basal cell carcinomas of the eyelid.

OBJECTIVE: To report a rare case of collision sebaceous and basal cell carcinomas of the eyelid. DESIGN: Interventional case report. METHODS: An 80-year-old woman presented with a nodular lesion at the center of the left lower eyelid. Small ulceration and madarosis were also present. RESULTS: The patient underwent excisional biopsy with frozen section control. Histopathology showed mixed sebaceous as well as basal cell carcinoma with uninvolved surgical margins. Oncologic survey did not disclose any other lesion. At 6-month follow-up, there was no evidence of recurrence, new lesions, or metastasis. CONCLUSION: Sebaceous and basal cell carcinomas can coexist in the eyelid within the same clinical lesion. Because of the potential risk of metastasis of sebaceous carcinoma, close follow-up of the patients is advisable.

Cutaneous mass aspirate from a Golden Retriever: "glandular guile".

A 3-year-old, neutered, male Golden Retriever was presented for evaluation of a 10 X 9 X 5 mm, firm, red, raised, cutaneous mass located over the left cranial thorax and noted incidentally by the owner. On cytologic evaluation of a fine-needle aspirate of the mass, the interpretation was a malignant tumor with predominantly mesenchymal features. Differentials included liposarcoma, atypical amelanotic melanoma, anaplastic sarcoma, and anaplastic carcinoma. Following complete excision of the mass, a diagnosis of sebaceous adenocarcinoma was made based on histologic features, positive immunostaining for pancytokeratin, and negative staining for vimentin, Melan-A, and S-100. There was no evidence of metastasis on physical examination or thoracic radiographs, and the prognosis was good. The unique and previously unreported cytologic features of this small, sebaceous adenocarcinoma were the extreme pleomorphism, including marked anisocytosis, anisokaryosis, and multinuclearity, and the paucity of epithelial features.

Sebaceous gland tumors of the eyelids and conjunctiva in the Muir-Torre syndrome: a clinicopathologic study of five cases and literature review.

PURPOSE: To study the sebaceous tumors of eyelid/conjunctiva associated with Muir-Torre syndrome (MTS) and to determine the role of immunohistochemical markers (MSH2, mismatch repair gene) in the diagnosis of patients with MTS. METHODS: A retrospective, noncomparative case series of 5 patients diagnosed with MTS from our laboratory. We also reviewed all previously reported cases of sebaceous eyelid tumors with a visceral malignancy. RESULTS: Four of the 5 patients were men, with a mean age of 55 years (range, 41 to 76 years). Four of the 5 patients had gastrointestinal carcinoma. On histopathological examination, 4 of the 5 tumors were classified as sebaceous adenomas that exhibited a distinct lobular pattern with prominent basaloid cells at the periphery of the lobules. One tumor was classified as a well-differentiated sebaceous gland adenocarcinoma. The diagnosis of MTS in all 5 patients was made after the diagnosis of the eyelid lesions. Immunohistochemical stains showed a lack of MSH2 expression in two tumors, which is highly consistent with MTS. CONCLUSIONS: Muir-Torre syndrome should be considered in patients who develop sebaceous tumors of the ocular adnexa. Immunohistochemistry for MSH2 is a practical initial approach for screening MTS in patients with sebaceous tumors.

Clinicopathological and immunohistochemical features of a sebaceous carcinoma arising within a benign dermoid cyst of the ovary.

Pure sebaceous neoplasms arising in dermoid cysts of the ovary are exceedingly rare. A 63-year-old female with abdominal swelling and pain underwent a right salpingo-oophorectomy that showed a unilocular cyst weighing 830 g and measuring 15x12x10 cm, filled with sebaceous material containing a few hair shafts. The cyst wall exhibited plaques protruding into the cavity of the cyst. Microscopy revealed a dermoid cyst with nests and lobules of atypical and infiltrating sebaceous cells surrounded by basaloid cells. The tumor cells stained diffusely for high-molecular-weight cytokeratins and focally for cytokeratin 7, cytokeratin 19, epithelial membrane antigen and carcinoembryonic antigen in the immunohistochemistry study. Low-molecular-weight cytokeratins, cytokeratin 20, vimentin, S100, p63, estrogen receptor, progesterone receptor, p53 and c-erbB-2 were negative in tumoral cells. The proliferative labeling index (Ki67 and proliferating cell nuclear antigen) was low. Basal cell carcinoma with sebaceous differentiation and sebaceoma must be considered in the differential diagnosis. However, the presence of obvious malignant sebaceous differentiation in nearly every tumor nest and lack of peripheral palisading and peri-tumoral myxoid stroma excluded these diagnoses. Some histogenetic concepts relevant to this case are discussed along with a brief review of this neoplasm. To our knowledge, this is the sixth case report of a sebaceous carcinoma arising in a mature cystic teratoma of the ovary.

Sebaceous carcinoma with apocrine differentiation.

A 54-year-old male had a dome-shaped and skin-colored nodule on his nose. Histopathologically, we diagnosed this neoplasm as a low-grade sebaceous carcinoma rather than a sebaceoma based on the scanning magnification and cytology. This low-grade sebaceous carcinoma was associated with glandular structures. We regarded the glandular structures as those of apocrine glandular differentiation based on 1) the histopathologic features of the glandular structures formed by columnar luminal cells with evidence of decapitation secretion; 2) the expression of cytokeratin (CK) 19, CK8, CK8/18, and CK7 in the luminal cells; 3) the positive reaction of carcinoembryonic antigen and epithelial membrane antigen on the luminal surface and in the cytoplasm of the luminal cells; and 4) the common embryologic origin of the folliculosebaceous-apocrine unit. We found CK15 expression in undifferentiated cells within the mantles of normal hair follicles, suggesting that sebaceous stem cells might exist in mantles as follicular stem cells exist in bulge areas. Pluripotent stem cells in the folliculosebaceous-apocrine unit can give rise to follicular stem cells, sebaceous stem cells, and apocrine stem cells. Our patient's neoplasm showed apocrine glandular differentiation and partial immunohistochemical positivity for CK15 in the neoplastic aggregations. We believe this neoplasm originated from pluripotent stem cells destined to become sebaceous stem cells or from sebaceous stem cells, which also have the ability to differentiate within apocrine glands.

Sebaceous carcinoma of the breast.

We report on a rare distinctive variant of infiltrating ductal carcinoma characterized by sebaceous differentiation of tumor cells. The neoplasm was identified in a lumpectomy specimen from a 45-year-old woman with extensive metastatic disease. In addition to conventional in situ and invasive ductal components, approximately half of the tumor cells exhibited a phenotype resembling tumors of the sebaceous skin appendage with coarsely vacuolated cytoplasm and peripherally displaced nuclei. The sebaceous moiety was also present in the distant metastatic deposits. There was no evidence of mucin production by tumor cells. Ultrastructurally, empty-appearing non-membrane bound vacuoles attested to the sebaceous cells' lipid content. The immunoprofile of the lesion included positivity for cytokeratin and epithelial membrane antigen. Vimentin, S100 protein and carcinoembryonic antigen were not expressed. Most tumor cell nuclei reacted with antibodies to oestrogen and progesterone receptors but failed to show overexpression of the HER2/neu protein. The MIB-1 labeling index averaged 16%. At variance with sebaceous breast carcinomas on record, the present case is notable for its prolonged clinical course.

Immunohistochemical distinction of ocular sebaceous carcinoma from basal cell and squamous cell carcinoma.

BACKGROUND: Diagnosis of sebaceous carcinoma of the periorbital region is often delayed. Clinically, this lesion can mimic several inflammatory disorders. Histopathologically, it can mimic either squamous cell or basal cell carcinoma. OBJECTIVE: To identify an immunohistochemical approach to assist in the diagnosis of periorbital sebaceous carcinoma. METHOD: The immunohistochemical profiles of several cases of periorbital sebaceous, basal cell, and squamous cell carcinoma were examined. RESULTS: Although at least focal epithelial membrane antigen (EMA) staining can effectively distinguish sebaceous carcinoma (10 of 11 were positive) from basal cell carcinoma (1 of 16 were positive), most squamous cell carcinomas examined were also focally EMA positive (11 of 14). However, Cam 5.2 reactivity was seen in most sebaceous carcinomas (8 of 11) but no squamous cell carcinomas (0 of 14). In addition, at least focal BRST-1 reactivity was also seen in most sebaceous carcinomas (7 of 11) but no basal cell carcinomas (0 of 16). CONCLUSIONS: Periorbital sebaceous, basal cell, and squamous cell carcinomas have different immunohistochemical staining profiles; a panel of commonly available antibodies, including anti-EMA, BRST-1, and Cam 5.2, may help distinguish these diseases from each other when that distinction cannot be clearly made by light microscopy alone.