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Extraorbital Sebaceous Carcinoma With Rapidly Developing Visceral Metastases ¨ NEY D UMAN ,* MD,* B ERRIN B AGCI C EYHAN , MD, w T URGAY C D ENIZ G U ¸ ELIKEL , MD, w R ENGIN A HISKALI , MD, z AND D URSUN D UMAN , MD n Department of Internal Medicine,wDepartment of Pulmonary Medicine, and zDepartment of Pathology, Marmara University Hospital, Istanbul, Turkey
n
BACKGROUND. Extraorbital sebaceous carcinoma (SC) is a rare carcinoma of the skin but is known to have a good prognosis in terms of metastasis and survival. OBJECTIVE. To discuss and emphasize through the clinical and histopathologic findings and the aggressive potential of extraorbital SC and to review the corresponding literature. METHODS. We present an unusual form of extraorbital SC that has followed an aggressive course and that has metastasized rapidly.
RESULTS. Local excision of the primary cutaneous tumor with negative margins did not prevent the rapid and fatal internal organ metastases. The patient did not benefit from the docetaxel chemotherapy regimen applied after the distant metastases were developed. CONCLUSION. Extraorbital SC may show a poor prognosis. Both the dermatologic surgeon and the dermatologist should be cautious of the risk of local recurrence and distant metastasis when dealing with extraorbital SC.
D. G. DUMAN, MD, B. B. CEYHAN, MD, T. C ¸ ELIKEL, MD, R. AHISKALI, MD, AND D. DUMAN, MD HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS.
SEBACEOUS CARCINOMA (SC) is a rare neoplasm that is derived from sebaceous glands of the skin. It occurs either on eyelids or in extraorbital sites. Orbital SC is more common than the extraorbital counterpart, as only one forth of all SC cases arise from extraorbital sites. Generally, extraorbital SC has a better prognosis than that of orbital SC in terms of metastasis.1 Distant metastases are seen in less than 10% of all the extraorbital SC cases.2 We present an extraorbital SC case with visceral metastasis to five distant organs, including lung, stomach, spleen, liver, and kidney, which developed within 4 months after the wide surgical excision of the primary skin tumor with intact margins.
Case Report A 65-year-old female with no history of previous irradiation was admitted to our hospital for a skin lesion on her forehead in June 1997. The lesion was located in midline and was 3 cm in diameter, yellowish colored, and ulcerated in character, and it was excised under local anesthesia. Light microscopic examination Address correspondence and reprint requests to: Deniz Gu¨ney Duman, MD, Ahmet Refik Sok. Ceylan Apt. No:19/5, 81060 C¸iftehavuzlar, Istanbul, Turkey, or e-mail:
[email protected] bbcey@superonline. com.
revealed a quite well-demarcated epithelial tumor in the dermis with a predominant lobular pattern and a minor invasive component. The lobules were composed of small cells with hyperchromatic nuclei at the periphery and larger cells with clear or bubbly cytoplasm in the center. Although the tumor was well differentiated and the neoplastic lobules were highly reminiscent of their normal counterparts, mitotic activity of tumor cells was prominent. There were occasional areas with more squamoid features with foci of keratinization. There was no pagetoid spread of neoplastic cells in epidermis. The diagnosis was SC with tumor-free surgical borders. Three months later, her skin lesion on forehead recurred and had been re-excised; SC with intact surgical borders was reported again. In the meantime, she developed dyspnea and hemoptysis. On her chest x-ray, a left hilar mass was noted (Figure 1). Computed tomography of the thorax revealed a cavity with a thickened wall and a dense infiltration in left lower posterior lobe. Bronchoscopic examination showed concentric narrowing of left lower lobar bronchus. Light microscopic examination of the bronchial biopsy showed an epithelial neoplasm with lobules of tumor cells infiltrating the bronchial cartilage. The periphery of the lobules contained a basaloid layer and cells with nuclear atypia and scanty eosinophilic cytoplasm, whereas the cells in the center of the lobules had large, clear, or foamy cytoplasm. These clear cells were
r 2003 by the American Society for Dermatologic Surgery, Inc. Published by Blackwell Publishing, Inc. ISSN: 1076-0512/03/$15.00/0 Dermatol Surg 2003;29:987–989
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DUMAN ET AL.: EXTRAORBITAL SC WITH RAPIDLY DEVELOPING VISCERAL METASTASES
Figure 1. Posteroanterior chest x-ray showing left hilum mass with cavitation.
negative with periodic acid-Schiff and Alcian Blue stain at pH 2.5. There was a prominent pagetoid spread of the neoplastic cells in the ducts of bronchial seromucous glands (Figure 2). Because areas with typical squamous differentiation existed and intracytoplasmic mucin was absent, clear cells were interpreted as squamous cells with hydropic change. Thus, with the initial diagnosis of primary squamous cell carcinoma, single-agent chemotherapy with docetaxel in a dose of 100 mg/m2 was started. One week later, previous skin biopsy slides were available and were examined and compared with bronchus specimens along with the relevant clinical history, and this reassessment yielded the final diagnosis of SC of skin with bronchial metastasis. However, we decided to continue the chemotherapy with docetaxel. One month later, she was readmitted to our medical ward with symptoms of partial intestinal obstruction. Her abdominal computed tomography showed hypodens lesions in liver and spleen, suggesting metastatic disease and an ulcerating mass of 4-cm diameter in stomach corpus and an irregular cystic lesion of 4 cm in left lower kidney. Upper gastrointestinal endoscopy showed an ulcerating mass on the greater curvature of corpus. Pathologic examination of endoscopic biopsies of the stomach also revealed metastatic SC in the submucosa. Interestingly, 6 months before her primary skin lesion appeared, she had had abdominal magnetic resonance imaging taken for the complaint of abdominal discomfort in another center, and this was entirely normal. Three courses of chemotherapy with docetaxel were given in 3-week intervals. There was no response in either lung or abdominal masses after
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Figure 2. Metastatic SC from the bronchus. Respiratory epithelium can be seen at the top; the arrowheads point at SC with pale lipid laden cells (hematoxylin and eosin, 40 and 100). The inset shows the pagetoid spread of the neoplastic cells in the ducts of bronchial glands (arrows) (periodic acid-Schiff–Alcian Blue at pH 2.5 combination, 100).
chemotherapy. She died of intracranial hemorrhage 7 months after initial diagnosis. An autopsy was not performed.
Discussion SC is the adnexal tumor of skin, which is derived from pluripotential cells of the epidermis. SC may arise from orbital or extraorbital sebaceous glands. Among eyelid malignancies, SC ranks as the fourth most common malignancy after basal cell carcinoma, squamous cell carcinoma, and malignant melanoma.1 However, extraorbital SC is rare, as fewer than 150 cases have been reported in the English literature, and we can add our patient to this list. Extraorbital SC occurs most frequently in the 6th and 7th decades of life and is seen almost equally in women and men.3 The most common extraorbital site for SC is the skin of face and neck, where sebaceous glands are mostly populated.4 Other reported origins are parotid and submandibular glands, buccal mucosa, laryngeal and pharyngeal cavities, trunk and upper extremity, sole, the dorsum of great toe, and external genitalia.5 The forehead skin lesion is the primary site of SC in our patient. The bronchial and gastric specimens represent metastases from this primary skin SC, rather than synchronous primary tumors, because all of the biopsies demonstrated almost identical histomorphologic features. The mass lesions in liver, spleen, and kidney visualized on abdominal computed tomography were attributed as visceral metastases of skin SC. Furthermore, literature review yielded only one case report of primary bronchial SC6 but no primary gastric sebaceous tumors. Normal salivary
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glands have sebaceous cells in the glandular ducts, and tumors with sebaceous foci are not very uncommon in these glands.7 Although carcinomas of salivary gland type can be seen in the lung, no sebaceous differentiation is seen in these lung tumors. Sebaceous gland metaplasia in cardiac mucosa of the esophagogastric junction has been reported,8 but sebaceous differentiation or SC has never been described. Moreover gastric tumor of our patient was located in the submucosa, in concordance with metastatic—as opposed to primary carcinomas. The histopathologic criteria for SC are high mitotic activity, nuclear pleomorphism, lobular architecture, and foamy vacuolization in the cytoplasm.2 All of the biopsies of our patient demonstrated these mentioned features. Sebaceous differentiation was recognizable not only in the primary tumor but also in the bronchial and gastric metastases. Although there was no pagetoid spread of neoplastic cells in the primary tumor, such intraepithelial cells were seen in the ducts of bronchial glands. As the bronchial sample was a metastatic SC, this pagetoid spread of neoplastic cells should be evaluated as a pattern of spread of the neoplasm, rather than as an in situ neoplasia, as favored by some authors.9 Because of the rarity of extraorbital SC, calculation of survival rate is difficult. Tumor-free survival of 67% and tumor-related mortality of 20% were reported in a series of 91 patients with extraorbital SC who were followed from several months to 16 years, with a mean follow-up of 4 years, and 10% of these patients had distant metastases such as pulmonary, visceral, and central nervous system.2 Similar to our patient, Wick et al.3 reported two patients in their extraorbital SC series who died of tumor, and one of them survived only 14 months because of distant soft tissue and brain metastases caused by SC, despite excision of primary tumor with tumor-free margins. Wide surgical excision of tumor with involved regional lymph node removal is the accepted treatment for SC currently.10 Relapse after excision may occur.11 In our patient, the forehead SC reoccurred in the same area 3 months later, but no skin lesion reappeared after she received chemotherapy. However, her outcome was poor because of visceral metastases. Chemotherapeutic regimen for SC consists of individual trials of case reports. A case of Meibomian
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gland carcinoma of eyelid with metastasis to lung showed minimal response to cisplatin and doxorubicin, and the patient died 8 months after initial chemotherapy with a response duration of 7 months.12 Our patient survived 6 months after diagnosis and did not give any response to docetaxel chemotherapy. In conclusion, we believe that extraorbital SC may act very aggressive with the potential of early and multiple distant metastases despite prompt surgical excision. Therefore, follow-up with screening for local recurrence and for distant metastases should be scheduled, and further studies are warranted to evaluate the activity of different chemotherapeutic agents on extraorbital SC. ¨ ztek for Acknowledgment The authors thank Dr. Ibrahim O his excellent work in initial pathologic examination of skin tissue samples.
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