Case 2-2 -

Follicular Neoplasia: Trichoblastoma Versus Trichoblastic Carcinoma (Basal Cell Carcinoma) Mark A. Hurt, MD Cutaneous Pathology WCP Pathology PC Maryland Heights (St. Louis) MO

There has been a problem, historically, with the classification of neoplasms of the follicular germ. With the key exception of trichoblastic carcinoma (basal cell carcinoma, they have varied patterns and are benign. The chief differential diagnosis, as a rule, is with matrical neoplasms. A variety of different names have been used over the years to describe these lesions. The patient in case #2 was a 78 year old woman with a scalp lesion. This lesion was present for an unknown period of time and was thought to be a melanocytic nevus. There has been no regrowth of this lesion after two years of follow-up. Case 2-2 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer The lesion consisted of small basophilic epithelial nested structures, each of which was surrounded by its own stroma. There was a slight amount of fibrosis between the small islands of basophilic cells. This lesion extended into the deep dermis, but not the subcutis. There was very little advanced differentiation in this lesion. This consisted of small milium sized cysts in one or two areas, and a small zone of eosinophilic material that was somewhat suggestive of hair filament differentiation. A few areas contained follicular papillae. Some areas of these small islands contained peripheral palisading, but mostly they were composed of monomorphous, small, basophilic cells. Historically, the modern era of nomenclature on primary neoplasms of the follicle began in 1962 with Headington's and French's article in the Archives of Dermatology (86:430). They described neoplasms of the hair matrix as "trichomatrioma", which today we know as pilomatricoma and which was known commonly as "calcifying epithelium of Malherbe" prior to the article of Forbis and Helwig (Arch Dermatol 1961; 83:606). The second designation of Headington and French was "trichogenic adnexal tumor". For the "trichogenic adnexal tumor", their concept was a proliferation of thin stranded basophilic cells with abundant stroma and a few infundibular cyst-like structures within it. A year later, Gray and Helwig (Arch Dermatol 1963; 87:102) described patients within the spectrum of what they termed multiple trichoepithelioma vs. solitary trichoepithelioma. The multiple types were the classic Brooke-Fordyce disease patients and the solitary type did not seem to have any syndromic associations. The lesions that they illustrated were neoplasms composed of larger lobules, some with fenestrations, especially in the Brooke-Fordyce patients. Some of these features were present also in solitary lesions. They also described an example of what we know today as desmoplastic (columnar) trichoepithelioma (trichoblastoma). One of their patient's lesions had advanced differentiation, similar to what became known by Headington as "trichogenic trichoblastoma". There were no cases presented that were similar to the patient presented in this seminar. Headington, writing in the Journal of Clinical Pathology in 1970 (23:464), further expanded on his work from 1962, identifying now lesions called "trichoblastoma". These lesions were later called "trichoblastic hamartomas" by Headington in his 1976 review article on the subject. He also expanded his idea of "trichogenic adnexal tumor" to "trichogenic trichoblastoma" when advanced differentiation was identified in the lesions. Czernobilsky reported in 1972 (Arch Dematol 105:587) a lesion he termed "giant solitary trichoepithelioma". This lesion contained small rounded structures in abundance, which would later be termed "trichoblastic fibroma" by Headington and "trichogerminoma" by Sau, et al. Headington's landmark article titled "Tumors of the Hair Follicle. A Review", published in the American Journal of Pathology in 1976 (85:480), introduced an entire classification of tumors and cysts of the hair follicle, one area of which contained the classification of trichogenic tumors. By this time, Headington had formulated his now historic idea of trichoblastoma (without inductive mesenchymal changes), and trichoblastic fibroma and trichogenic trichoblastoma (with inductive mesenchymal change). He also illustrated a lesion he termed "trichoblastic hamartoma", a lesion that I think was very similar to the case #1, which I presented earlier. Headington's concept of trichoblastoma was a purely epithelial neoplasm without stromal induction, and he did not show a scanning magnification of one of these lesions, so it is somewhat difficult to envision its overall structure. Lesions that were termed "trichoblastic fibroma" were illustrated at scanning powers and did show multiple small islands of germinative cells intermixed with larger nests of basophilic (germinative) cells. His idea of "trichogenic trichoblastoma" was a lesion that he formerly considered to be "trichogenic adnexal tumor" and it consisted of thin strands of epithelial cells with advanced differentiation in some areas. Fihlo, et al, writing in 1984 (Arch Dermatol 120:797), described a patient with a large pedunculated lesion in the thigh that contained mostly large nests of basophilic cells with stroma, which would have fulfilled Headington's criteria now for trichoblastic fibroma. In 1988, I and my coworkers, Sherri Long, MD, and Daniel J. Santa Cruz, MD, reported on six patients that we termed "immature trichoepithelioma" (J Cutan Pathol 15:353). The back story of this article is that we had identified lesions that were identical to the patient presented herein. I was unaware of Headington's work and I do not believe it would helped me very much even if I had been aware of it because my sense of his "trichoblastic fibroma" and the lesions we reported were slightly different, ours being composed entirely of small germ-like structures, as opposed to larger lobules mixed with smaller ones. I believe that our lesions were much more stereotyped than those Headington had presented. Nonetheless, the idea was similar; we were describing what we considered to be neoplasms of the follicular germ, just a very stereotyped version. That same year, Grouls and Hay (Pathol Res Pract 1988; 183:462), in the tradition of Headington, described trichoblastic fibroma as a subcutaneous lesion composed of small basophilic islands, but some areas had larger zones, similar in some respects to what later was described as trichogerminoma. Another difference between that lesion of Grouls and Hay and the ones we described was the fact that our cases were mostly dermal whereas those of Grouls and Hay, and many others that were described up to that point, were in the subcutis. In 1989, Gilks, et al, described lesions they termed "trichoblastic fibroma" in the American Journal of Dermatopathology (1989; 11:397). Their lesions were identical, in virtually every respect, to the ones we described. Requena, et al, in 1990, also reporting on a lesion he and his group termed "trichoblastic fibroma" (J Cutan Pathol 1990; 17:381), showed a lesion consisting of relatively large lobules that were, in turn, composed of small strands of basophilic cells. The lesions termed trichogerminoma by Sau, et al, were described in 1992 (J Cutan Pathol 19:357). These lesions were, I think, very similar to some of the lesions that Headington described. They were subcutaneous and composed of rounded "cell ball"-like structures; some areas had clear cell change while others had basophilic cell changes. Other areas contained small cysts. The distinction of this group of lesions was that Sau, et al, did not think they were the same as those of Headington, and they believed that at least one of their patients was different in that there was a metastasis and death. This fact raised the question: how indolent were these lesions? This idea of these lesions being more aggressive than thought originally was also stated by Altman, et al, writing in the Archives of Dermatology about trichoblastic fibroma (1995; 131:198). They described a lesion on the face that they termed "plaque-type trichoblastic fibroma" and illustrated it in their figure 1. These lesions were somewhat firm, but also rather inconspicuous clinically. Their distinguishing feature was that they had relatively infiltrative growth to the subcutis and sometimes deep to it, infiltrating around skeletal muscle. Thus they raised the question about whether these neoplasms could be carcinomas. In a response by Escalonilla and Requena, in follow-up a year later in the Archives of Dermatology (132:1388), they opined that they believed these lesions were nothing more than trichoblastic fibromas and that by location, in areas that contain skeletal muscle, they had the appearance of carcinomas, but had the biology of trichoblastic fibromas. As late as the year 2000, Cowen, et al, described another lesion as "an unusually aggressive trichoblastoma" that I believe would probably be described as plaque-type trichoblastic fibroma according to Altman, et al, and Escalonilla & Requena. In this case the authors believed that the lesion was more aggressive biologically despite the fact that after removal of the lesion there was no persistence of it after a period of time. That lesion also consisted of small islands of basophilic cells and specific stroma (J Am Acad Dermatol 2000; 43:374) very similar to the case presented in this seminar. The interesting follow-up on this case was that the authors submitted it to A. Bernard Ackerman, MD, in New York and later revised their diagnosis of it as trichoblastic carcinoma (basal cell carcinoma) with differentiated zones (J Am Acad Dermatol 2001; 44:547). This was done, despite the fact that there was no persistence of the lesion after Mohs surgery; thus it was not completely clear whether if left alone, this lesion would have been more aggressive than the conventional trichoblastic fibroma. A deeper synthesis of these lesions occurred in 2001 when Ackerman, Reddy, and Soyer, writing in the book, Neoplasms with Follicular Differentiation, made the analogy that all of these follicular germ neoplasms are similar, in fact, to the germ. The idea that they were something different from that was purely a semantic problem. In their view, these lesions should be described as large nodular, small nodular, cribriform, racemiform, and columnar (desmoplastic), yet all trichoblastoma, the benign analog of basal cell carcinoma. Of this spectrum of lesions, the lesion presented in this seminar is similar to what Ackerman, et al, described as "small nodular trichoblastoma". Two years later, writing a somewhat philosophical way, LeBoit posed the question about what should we trust in considering whether trichoblastic neoplasms are a carcinoma or not, (Am J Dermatopathol 2003; 25:260). In that article, Dr. LeBoit recounted some of the histories of these lesions, pointing to the fact that historically the degree of differentiation has determined how pathologists consider the nature of these lesions. The more differentiated, this argument goes, the less likely that they were carcinoma. However, he also pointed out that some lesions described in the literature have seemingly been more aggressive and that the presence of differentiated elements did not necessarily determine their biological outcome. Thus, he stated that "In the end, a basal cell carcinoma is defined by what it does, not by what it resembles. If the lesion invades the subcutis, ulcerates, and recurs after incomplete excision, it is a carcinoma. It is more difficult to apply the same standard to a trichoepithelioma – many basal cell carcinomas are small and indolent, and seem not to change much, even after decades". Despite this point of view, I believe that differentiation as the great determining factor for a given diagnosis follicular neoplasia; it is our window (as dermatopathologists) into their biology. For lesions that have differentiated elements, especially when they are the dominant component of those lesions, I believe one can, realistically, expect them to act like benign neoplasms. That seems to have been the history of these lesions recorded in the literature and in my experience. Thus, I believe that the lesion in this patient is trichoblastoma, small nodular variant, a lesion that Headington would have likely considered to be a trichoblastic fibroma.