Non-melanocytic Skin Tumors
Moderator: Dr. Philip E. LeBoit
Case 2-2 -
Trichoblastoma Versus Trichoblastic Carcinoma (Basal Cell Carcinoma)
Mark A. Hurt, MD
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
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
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