Case 2-3 -

Sebaceous Gland Neoplasm - Adenoma or Carcinoma? Mark A. Hurt, MD Cutaneous Pathology WCP Pathology PC Maryland Heights (St. Louis) MO

The patient was an 81 year old man with a mass in the right axillary region. It was thought clinically to be inflammation. The lesion was diagnosed originally as sebaceous carcinoma, indeterminate margins, by the original pathologist. I received the biopsy as a second opinion consultation. Case 2-3 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer This sebaceous gland neoplasm consisted of lobules of sebaceous glands that vaguely resembled the native sebaceous gland, but with many more basophilic cells at the periphery, forming pyramidal structures that matured to obvious sebocytes with the usual complement of bubbly cytoplasm. In contrast with sebaceoma (sebaceous adenoma), this patient's neoplasm consisted of discrete lobules that radiated from central cyst-like structures, and the sebocytes were found easily within it. Despite the fact that the sebocytes, especially the immature ones, were relatively monomorphous, there were many mitotic figures in this lesion, some of them abnormal. There was also considerable nuclear crowding, especially in the less differentiated zones. Diagnosis: Sebaceous Adenocarcinoma Historically sebaceous neoplasms were divided into sebaceous adenomas and sebaceous carcinomas (ie, sebaceous adenocarcinomas). In the 1940's, the term "sebaceous epithelioma" was introduced and is probably still used by some authors and some diagnosticians. Other names such as "sebomatricoma" have been used, and, of course, the term "sebaceoma" was introduced in 1984 and Troy and Ackerman. Early examples of sebaceous neoplasms, such as the one described by Bock in 1880 in Archiv Für Pathologische Anatomie und Physiologie und Für Klinische Medicin, vol 81, produced a example of a sebaceous gland neoplasm very similar to the one described in the patient in this seminar. In 1909 Karl Reitmann, writing in the Arch Derm Syph ( Berlin) 1909; 99:125 presented another lesion very similar to the one presented herein, again thought to be an adenoma. Another example of a lesion, this time by American authors, Woolhandler and Becker, writing in the Archives of Dermatology and Syphilology 1942;45:734-56, illustrated, in their case #5, what they considered to be a adenoma of sebaceous glands, again very similar to the patient presented herein. In that patient, the authors considered the possibility that the lesion was actually carcinoma. Just one year later, Warren and Warvi, writing in the Am J Pathol (1943; 19:441), illustrated a lesion they interpreted as adenoma; today most would identify it readily as sebaceous hyperplasia. They also identified a lesion they termed carcinoma with invasion of a muscle fiber, it consisting of completely mature sebaceous lobules. It was Walter F. Lever, MD, writing in the Arch Derm Syph (Chicago) 1948;57:102, who presented a lesion consisting of very tightly nested basophilic cells, some of which had clear-cut sebaceous differentiation, but with relatively monomorphous small basophilic cells. One could compare Lever's cases to those of Troy and Ackerman in 1984, and I believe they are very close to each other. Writing that same year, in an article on the "pathogenesis of benign tumors of cutaneous appendages of basal cell epithelioma", Lever described a lesion he termed "sebaceous epithelioma". In that article he argued that sebaceous epithelioma stood "between sebaceous adenoma with its more typical lobules, on the one hand, and cystic basal cell epithelioma in which there is only a little differentiation toward sebaceous cells, on the other" (Arch Derm Syph (Chicago) 1948; 57:679). However, when one looks at Lever's figure 7 from that paper, it is clear, in retrospect, that the lesion is not an adenoma; it is carcinoma. Zackheim, writing in the Archives of Dermatology in 1964 (89:711), in an article about sebaceous epithelioma, regarded these lesions as epitheliomas if "at least half of the cell mass consists of undifferentiated cells". Yet, in some of the cases that Zackheim presented, it is clear that some of these lesions are carcinomas with very infiltrative strands of basophilic cells in a dense stroma. A decade later, Rulon and Helwig, writing in the Am J Clin Pathol (1973;60:745), regarding patients with the Muir-Torre Syndrome, showed sebaceous gland proliferations very similar to those described by Zackheim in 1964, the difference being that Zackheim termed those lesions "sebaceous epitheliomas" while Rulon and Helwig considered them to be "adenomas". One year later, in 1974, Rulon and Helwig again wrote of "cutaneous sebaceous neoplasms" in Cancer (1974; 33:82), in which they divided sebaceous gland neoplasms into adenomas, basal cell carcinomas with sebaceous differentiation, and sebaceous carcinomas. Their concept of sebaceous adenoma consisted of lobular lesions of glands that had relatively mature sebocytes within them and maintained a lobular, pyramidal structure, similar in many respects, to the neoplasm presented herein. Some of the lesions they described were cystic and some were mostly solid. In today's terms, the cystic lesions vs. the relatively solid ones are very different in pattern and the mostly solid basophilic ones are very similar to those described by Troy and Ackerman in 1984, under the term "sebaceoma". The concept of sebaceous adenocarcinoma, according to Rulon and Helwig was a malignancy of pleomorphic sebocytes, one that would often have perineural or intraneural involvement and would be unmistakable as a malignant neoplasm by virtually any pathologist. In 1984, the now classic article by Troy and Ackerman was published in the Am J Dermatopathol (6:7-13). The lesions that they termed "sebaceoma" consisted mainly of nests of basophilic cells with some cystic structures, but mostly monomorphous basophilic cells studded with sebocytes. These lesions were very different from the sebaceous adenomas in the literature up to that point, those being more like mature sebaceous glands but with a periphery of immature sebaceous glands eventually becoming mature in pyramidal structures. The sebaceoma, however, had the structural pattern much like a cylindroma or spiradenoma, but without the prominent basement membrane components with "jigsaw puzzle"-like patterns in cylindroma, or the ducts and two-cell pattern of spiradenoma. In recent years a lesion that has been termed "rippled pattern trichoblastoma" has been described. Ohata and Ackerman, in 2001, argued that these so-called rippled pattern trichoblastomas were nothing more than sebaceomas because they were all studded with sebocytes. (Dermatopathol Pract and Concept 2001; 7:355). In the time between Troy's and Ackerman's description of what they termed "sebaceoma", and the present, other authors such as Sánchez Yus and colleagues attempted to unify the idea of sebaceous adenoma under the term "sebomatricoma". It became clear from looking at their figures that were published in the Am J Dermatol 1995 (17:213) that this conglomeration of neoplasms included outright sebaceous adenocarcinomas as well as some sebaceous gland neoplasms that were well differentiated and very similar to those described by Rulon and Helwig as sebaceous adenoma. Some of the lesions they described were very much like Troy's and Ackerman's lesions, and it becomes clear from looking at these lesions that they were a conglomeration of different kinds of sebaceous gland neoplasms. Thus, from the arguments and examples historic, beginning as sebaceous "adenomas" with abundant sebocytic differentiation, to sebaceous adenocarcinomas, which were pleomorphic malignancies, it became clear that abundant confusion had persisted in the literature about which lesions were malignant and which ones were benign. In 1998, Nussen and Ackerman challenged the concept of sebaceous adenoma one again by introducing the idea that the classical sebaceous adenomas in the literature were nothing more than well differentiated adenocarcinomas of sebaceous glands (Dermatopathol Pract Concept 4: 5-14). In that article, they recounted previously published examples of lesions that were thought to be sebaceous adenomas. Their take on this was that these lesions had enough nuclear pleomorphism and enough structural abnormalities to be considered outright adenocarcinomas, and they included in this mixture of cases ones that they had originally described as sebaceomas, so they themselves admitted that even they had the same problem of prior authors. They went as far to say that, "We have changed our opinions about sebaceous adenomas and cystic sebaceous adenoma not because of metastases but because of histopathological findings." What were these findings? They believed that 1) the carcinomas contained confluence of aggregations of neoplastic cells in an anastomotic patterns, 2) crowding of immature sebocytes, 3) slight pleomorphism of immature sebocytes, 4) heterochromia of nuclei of immature sebocytes, 5) many sebocytes, especially immature and even some mature ones in mitoses, 6) some mitotic figures were abnormal, 7) many individual sebocytes were necrotic, indicated by pyknosis and karyorrhexis, 8) incipient necrosis en mass in some cases. All of these criteria were recounted in their article in 1998. Writing in 2001, Mones and Ackerman, in the book, Resolving quandaries in dermatology, pathology, and dermatopathology, cited that the reason for the confusion of sebaceous adenoma and sebaceous carcinoma over the years was that the low-grade adenocarcinomas had been mistakenly interpreted as adenomas. They believed that the concept of carcinoma should be expanded greatly and that the true adenomas were actually a very small group of sebaceous gland neoplasms. Thus, from 1998 to the present, there has been somewhat of a "buzz" in the community of those who follow adnexal neoplasms because the way that sebaceous gland neoplasms have been studied historically in light of the different interpretation by Ackerman, et al. I believe that Nussen's and Ackerman's hypothesis of 1998 must be tested with real patients over a period of time, and the hypothesis they have put forward needs to be taken seriously. At present, my approach to these lesions is to state in reports that there is some controversy about the nature of many sebaceous gland neoplasms. I tend to be more aggressive today in recommending excision of sebaceous gland neoplasms, as I have expanded my own spectrum to consider more of them to be adenocarcinomas. My bottom line is that one should think of sebaceous gland neoplasms today more seriously with carcinoma in mind rather than writing them off as mostly adenomas.