ORIGINAL ARTICLE Cutaneous Sebaceous Neoplasms With a Focal Glandular Pattern (Seboapocrine Lesions): A Clinicopathological Study of Three Cases Dmitry V. Kazakov, MD, PhD,* Eduardo Calonje, MD,† Dip RCPath, Arno Ru¨tten, MD,‡ Kathrin Glatz, MD,§ and Michal Michal, MD* sebaceous differentiation and different architectural and Abstract: Presented here are three cutaneous sebaceous tumors cytological features, usually allowing clear histopathological (one carcinoma and two sebaceomas), each demonstrating a focal separation, although some histopathological overlap exists. glandular pattern representing apocrine differentiation. The patients, The tumor cells in these sebaceous neoplasms grow mainly in two males and one female, each clinically presented with a small a cohesive fashion, although rare tumors manifest distinctive solitary nodule or tumor on the scalp. None of the patients had growth patterns such as the rippled, labyrinthine/sinusoidal, features of Muir–Torre syndrome. Surgical removal of the lesions was and carcinoid-like ones that are apparently specific for lesions performed in all cases. None of the patients developed recurrence or with sebaceous differentiation and are encountered either sin- metastasis after surgery (follow-up ranged from 18 to 24 months). gly or in combination in cutaneous tumors with sebaceous The glandular areas represented a minor but significant component of differentiation.2–6 So-called adenoid and acinar patterns have the lesions and appeared as glands of various complexity, mostly as been recorded in some examples of ocular sebaceus carcinoma,7 simple round or elongated tubular structures lined by a row of and rare sebaceous neoplasms have been reported to focally cuboidal to columnar cells with eosinophilic cytoplasm and round exhibit apocrine differentiation.8,9 Presented here are three nuclei, with or without a distinct nucleolus. Decapitation secretion further cutaneous sebaceous tumors with a focal glandular was evident but not prominent. In both sebaceomas, at least a portion pattern representing apocrine differentiation. of the glands had a peripheral small-cell layer that appeared similar to the basal/myoepithelial cells of normal eccrine and apocrine ducts. In some glands, the basal/myoepithelial cells seemed to have undergone hyperplasia, resulting in two or more rows of cells that even formed MATERIALS AND METHODS small islands, with an overall appearance reminiscent of basal cell Histological slides from approximately 200 malignant hyperplasia in the prostate, arising in the basal layer of the prostatic and benign cutaneous sebaceous tumors (ocular and extra- glands. The descriptive terms seboapocrine carcinoma or seboapo- ocular carcinomas, sebaceomas, sebaceous adenomas, basal crine sebaceoma are proposed for such lesions. These tumors may be cell carcinoma with sebaceous differentiation, cystic seba- ceous tumor10), including those associated with the Muir– viewed as rare histopathological variants of sebaceous carcinoma and 11 sebaceoma, with a second type of differentiation along the lines of the Torre syndrome, were evaluated. Cases of organoid nevus folliculosebaceous–apocrine unit. (nevus sebaceus of Jadassohn) and secondary tumors arising in it were not studied and, when recognized histologically as Key Words: adnexal tumors, sebaceous neoplasms, apocrine such, were excluded. Eight sebaceous tumors manifesting differentiation, multidirectional differentiation, myoepithelial cells a glandular pattern were found. The term glandular is used to (Am J Dermatopathol 2007;29:359–364) describe structures containing lumina surrounded by epithelial cells, with or without evidence of decapitation secretion. Multiple sections were reviewed to exclude the possibility that these glandular areas might represent preexisting ducts or ebaceous tumors of the skin are most commonly classified represent a pseudoglandular pattern attributable to various Sinto carcinoma (ocular and extraocular), sebaceoma, and causes (holocrine secretion, cell discohesive arrangement 1 sebaceous adenoma. These show different degrees of attributable to necrosis, acantholysis, or myxoid degeneration), as was the case in five tumors that were subsequently excluded from the study. Clinical information and follow-up on the three From the *Sikl’s Department of Pathology, Charles University, Medical included cases were obtained from pathology reports, sub- Faculty Hospital, Pilsen, Czech Republic (D.V.K.,M.M.); †Department of Dermatopathology, St John’s Institute of Dermatology, St Thomas’s mitting pathologists, patients, and their clinicians. Hospital, London, England, UK (E.C.); ‡Dermatohistopathologische Paraffin blocks or reserved unstained slides were Gemeinschaftspraxis, Friedrichshafen, Germany (A.R.); and §Institute of available in two cases for immunohistochemical study. Pathology, University of Basel, Basel, Switzerland (K.G.). Immunohistochemical stains were performed on 5-mM-thick, Reprints: Dmitry V. Kazakov, MD, PhD, Sikl’s Department of Pathology, Charles University Medical Faculty Hospital, Alej Svobody 80, 304 60 formalin-fixed, paraffin-embedded tissue sections, and appro- PILSEN, Czech Republic (e-mail: [email protected]). priate controls were applied using the monoclonal and poly- Copyright Ó 2007 by Lippincott Williams & Wilkins clonal antisera listed in Table 1. The avidin–biotin complex or Am J Dermatopathol Volume 29, Number 4, August 2007 359 Kazakov et al Am J Dermatopathol Volume 29, Number 4, August 2007 complexity, mostly as simple round or elongated tubular TABLE 1. Antibodies Used for Immunohistochemical Study structures lined by rows of cuboidal to columnar cells with Antibody Specificity Clone Dilution Source eosinophilic cytoplasm and round nuclei, with or without a CK7 OV-TL 12/30 1:200 DakoCytomation distinct nucleolus (Fig. 1E and F and Fig. 2D–F). Decapitation CK 14 Ll002 1:1000 NeoMarkers secretion was evident but not prominent (Fig. 2E). In one EMA E29 1:700 DakoCytomation sebaceoma (case 3), the cytoplasm of the luminal cells in CK 8 &18 CAM5.2 1:200 Becton Dickinson glandular structures contained zymogen granules (Fig. 2F). ASMA 1A4 1:200 DakoCytomation In both sebaceomas, at least a portion of the glands had a MSA HHF-35 1:5000 DakoCytomation peripheral small-cell layer that seemed similar to the basal/ GCDFP-15 BRST-2 1:1000 Signet Laboratories myoepithelial cells of normal eccrine and apocrine ducts. The p63 4A4 1:500 Biotex gland structures were numerous and were distributed some- CK, cytokeratin; EMA, epithelial membrane antigen; ASMA, a-smooth muscle what haphazardly. In some glands, the basal/myoepithelial actin; MSA, muscle-specific actin; GCDFP-15, gross cystic disease fluid protein-15. cells seemed to have undergone hyperplasia, resulting in two or more rows of cells that even formed small islands, with an overall appearance reminiscent of basal cell hyperplasia in streptavidin–biotin complex, labeled with peroxidase or the prostate, arising in the basal layer of the prostatic glands. alkaline phosphatase, were employed as the detection systems. (Fig. 2G). Glands with basal/myoepithelilal cells and those Automated immunostaining employing the Lab Vision lacking them were intermingled. automatic stainer was used. In one sebaceoma (case 2), there were foci of immature squamous metaplasia and areas composed of basaloid cells, devoid of sebaceous differentiation, that housed scattered RESULTS lymphocytes, with the resulting picture vaguely resembling a spiradenoma. In both sebaceomas, differentiation toward Clinical Data sebaceous ducts was seen. No other metaplastic phenomena or The patients, two males and one female, each clinically adnexal-type differentiations were observed, nor were there presented with a small solitary nodule or tumor on the scalp any recognizable microscopic features of nevus sebaceus of (Table 2). Ulceration was seen in case 1, which represented Jadassohn. sebaceous carcinoma. None of the patients had features of Muir–Torre syndrome. Surgical removal of the lesions was Immunohistochemical Findings performed in all cases. None of the patients developed Immunohistochemical studies were performed on the recurrence or metastasis after surgery (follow-up ranged from sebaceomas. The glandular areas were positive for CAM5.2 18 to 24 months). and CK7 (Fig. 2H). Stains for CK7 also highlighted sebocytes with multivacuolated cytoplasm, as did the stains for EMA Histopathological Findings (Fig. 2I). CK14 stained the entire tumors, including the One case was classified as sebaceous carcinoma because glandular parts and basaloid cells; GCDFP-15 was tested in of the presence of architectural (asymmetry, infiltrative case 3 and proved positive in the glandular luminal cells. The growth) and cytological atypia (cellular and nuclear pleomor- peripheral basal/myoepithelial-like cells in the glandular areas phism, cell necrosis, atypical mitoses; Fig. 1A–D). Two were positive for p63 in both cases; they tested negative for lesions were classified as sebaceomas (Fig. 2A–C). All three actins in case 3. neoplasms manifested a multinodular architecture and were predominantly composed of basaloid cells and cells with vacuolated cytoplasm and scalloped nuclei. The neoplasm DISCUSSION cells grew mainly in a cohesive fashion, but in both seba- We have presented three sebaceous cutaneous neo- ceomas, labyrinthine/sinusoidal, poorly developed carcinoid- plasms with a focal glandular pattern. The detection of this like, and rippled patterns, as previously reported,2–4 were