Almut Böer-Auer (and her colleagues) and a doc in Southern California provoked this correspondent to think a bit more deeply about dermatofibroma. Dermatofibroma, of course, is a common benign tumor that can be seen in any busy dermatopathology practice on a daily basis. Commonly said to be of fibrohistiocytic lineage and alternatively termed fibrous histiocytoma, it is probably better thought of as a tumor with fibrocytic, or better yet myofibrocytic, differentiation. Dermatofibroma is an analogue of atypical fibroxanthoma (AFX), and these two benign and malignant counterparts share a common immunophenotype. With immunoperoxidase stains, one can relatively consistently define expression of both CD10 and actin by both dermatofibroma and AFX, and the latter immunopositivity represents a reflection of their shared myofibrocytic lineage and can be taken by the novice as a false indication of smooth muscle differentiation. There are also a variety of other immunostains that are routinely utilized with varying degrees of frustration in the diagnosis of dermatofibroma. Factor XIIIa remains deployed in pandemic fashion in pathology and dermatopathology despite its ineffectuality. The reagent avidly labels interstitial dendritic cells but less convincingly labels authentic tumor cells, and thus its diagnostic pop is often marginal while its diagnostic value has been overstated. Epithelioid dermatofibroma provides noteworthy divergence from its conventional cousin, as its polygonal cells typically are avidly decorated by factor XIIIa. CD68 is also commonly used but provides irritation and dissatisfaction similar to that provoked by factor XIIIa, as poor target cell sensitivity and specificity represent the rule rather than the exception.
How did Böer-Auer et al. spark a neuron? Their recent report of multinucleate cell angiohistiocytoma with associated hyperneury (neural hyperplasia, nerve hypertrophy) rekindled two independent mental fires. First, does multinucleate cell angiohistiocytoma truly exist as an entity sui generis, or is it merely a fancy dermatofibroma? Second, especially if multinucleate cell angiohistiocytoma might simply represent a swanky dermatofibroma, could any associated neural hyperplasia/hypertrophy constitute secondary induction?
How did a Southern California practitioner precipitate deeper contemplation of a benign fibrous tumor? Simply by indicating that an acral dermatofibroma was impossible (footnote1, which details the exchange, follows the references for this essay). Telephone conversations with clinicians over the years have sounded a similar theme when one renders a diagnosis of dermatofibroma at an unusual site, be it the hand, the foot, or the nose. Such telephone discussions beg the question: is an acral dermatofibroma a fact or a fiction?
Invoking a diagnosis of multinucleate cell angiohistiocytoma can be practical and invaluable for the occasional case, particularly when the affected patient has multifocal or agminated clinical involvement, as is the situation for the patient reported by Böer-Auer et al. and other similar patients. Diagnosing a dermatofibroma in such a context is likely to generate unsolicited feedback just as quickly as a diagnosis of acral dermatofibroma did in Southern California. But excepting the extraordinary patient with segmental or multifocal disease, the debate as to whether there is one entity or two in this realm is much more difficult to resolve. Multinucleate cell angiohistiocytoma lacks a unique immunophenotype that permits it to be unquestionably cleaved from dermatofibroma, and the histomorphology encountered in conventional sections in both entities is extensively overlapping. Table 1 from the manuscript of Böer-Auer et al. is reasonably telling, as the lists of key characteristics for multinucleate cell angiohistiocytoma and dermatofibroma read similarly. It is essentially the same list for both.
|With granular cells||23||0.2%|
|Pseudosarcomatous (atypical fibrous histiocytoma)||100||0.9%|
|With osteoclastic giant cells||11||0.1%|
|With dermal atrophy (atrophic dermatofibroma)||174||1.6%|
|Lipidized with cholesterol clefts||11||0.1%|
|With marked hemosiderosis||668||6.3%|
|With marked hemosiderosis and ‘aneurysmal’ clefts||155||1.5%|
|With prominent ‘collagen balls’||1131||10.7%|
|With nuclear palisading (palisaded dermatofibroma)||22||0.2%|
Induction of hyperplasia in various nearby non-tumoral epithelial or mesenchymal structures – innocent bystanders that get tweaked by the adjacent fibrous proliferation via a mechanism that has not yet been specifically defined – represents a common theme in association with dermatofibroma. To estimate the prevalence of induction in its various guises and to approximate the prevalence of dermatofibroma in standard dermatopathology practice, a data set of 10,561 consecutive dermatofibromas diagnosed at the University of California (UCSF) over a 10 year period was reviewed, and these data are presented in Table 1. Over 850,000 cases were evaluated during the decade between November, 2003, and November, 2013, and thus the prevalence of dermatofibroma in routine practice is at least 1.2% of all cases entering the laboratory (all data included in this essay are probably underestimated; footnote2 details the factors underlying this).
Follicular germinative and sebaceous glandular induction are well established as secondary visual delights for dermatopathologists, and both in combination can be found in association with dermatofibroma in roughly 6% of cases. Melanocytic induction, a circumstance more stereotypically associated with angiofibroma (fibrous papule), is noted only occasionally in the setting of dermatofibroma and was documented in far less than 1% of cases in this data set. The identification of a secondary smooth muscle proliferation induced by a dermatofibroma represents a distinct rarity, and thus the fact that LeBoit and Barr found only three cases for their seminal observation makes complete sense as viewed through the lens of the present (indeed, it can be construed as a small miracle that they even found that many, since nearly a million cases were required to identify the three additional examples documented in Table 1). Hyperneury or induced nerve hypertrophy, as coded in the UCSF database, is only marginally more common, with only one dermatofibroma in a thousand cases exhibiting the phenomenon.
With respect to the Southern California question, can a dermatofibroma occur on a finger, a toe, or on the tip of the nose? The data presented in Table 2 provide a resounding affirmative answer. This subset of 4841 fibromas represents a sizable sample (46%) of the larger complete data set in which the specimen site was easily retrievable and could be tabulated by computer. Per these data, it is clear that conventional dermatofibromas most commonly occur on the extremity but are also routinely found on the trunk. Perhaps predictably for a tumor in which trauma is common cited as a pathogenetic cofactor, the leg is the most common single site of involvement (humans are apparently endlessly bumping into things during ambulation). Dermatofibromas can be found on the hand or foot roughly 6% of the time, and about 1 in 50 dermatofibromas will involve the finger or toe. Table 2 additionally lays bare that conventional dermatofibromas unquestionably but uncommonly involve the head and neck, representing <3% of all examples in this large sample. On a frequency basis, diagnosing a dermatofibroma on the ear or eyelid constitutes an incomparable moment to be cherished just as much as the identification of a dermatofibroma with associated smooth muscle hyperplasia, although one suspects the intellectual triumph induced by (pun intended) the latter are greater.
|Site (frequency)||Sub-site (frequency)||Sub-sub-site (frequency)||N|
|Elbow / forearm / wrist (8.3%)||400|
|Knee / shin / calf / ankle (15.8%)||767|
|Shoulder / axilla (8.2%)||395|
|Chest / breast (3.6%)||172|
|Head / neck (2.8%)||138|
Over a decade ago, Mentzel, Kutzner, and colleagues reported that facial dermatofibromas may be more deeply situated and more prone to local persistence. Spurred by this observation, 10 year topographic distribution data for tumors coded as ‘deep’ dermatofibromas were tabulated independently from the larger data set and are presented in Table 3. Comparing the distributions delineated in Tables 2 and 3, it becomes clear that deep dermatofibromas are far more common to be found on the trunk, neck, or face, or at least are far more common to be biopsied at those sites. In a relative sense, a deep dermatofibroma (in comparison to a conventional one) is 10 times more common to affect the neck and 5 times more prone to involve the face. This may reflect differences in the factors that incite superficial and deep tumors, with deep fibromas on the face, scalp, neck, and trunk potentially being more highly correlated with deep inflammatory triggers, such as folliculitis.
|Site (frequency)||Sub-site (frequency)||Sub-sub-site (frequency)|
|Elbow / forearm / wrist (8.5%)|
|Knee / shin / calf / ankle (4.7%)|
|Back / buttock (15.2%)|
|Shoulder / axilla (10.8%)|
|Chest / breast / abdomen (10.1%)|
|Head / neck (19.8%)|
Tables 1-3 reveal a variety of other tiny facts regarding dermatofibroma. Interestingly, dermatofibromas are comparatively more common on one's backside rather than on the chest or abdomen. Surprisingly, the scalp is a relatively uncommon site of occurrence irrespective of whether the dermatofibroma is superficial or deep. Epithelioid and ‘pseudosarcomatous’ dermatofibromas are not uncommon, comprising roughly 2% and 1% of all tumors, respectively, while the diagnosis of a granular cell or osteoclastic dermatofibroma should justify an office party, given their scarcity. Similarly, two of the favorite variants of yours truly, namely palisaded and ‘cholesterolotic’ dermatofibroma, are much like a four-leaf clover, as they are easily sought but not readily found.
This brief discourse will not (and cannot) resolve whether multinucleate cell angiohistiocytoma and dermatofibroma deserve to be melded or to remain independent, but nosologists should at least consider the possibility that the former is best considered a subset of the latter. Certainly the fact that angiohistiocytomas exhibit induced acanthosis and neural hyperplasia, as reported by Böer-Auer et al., suggests that all eyes should be watchful for adnexal induction in the same context (in the thinking of this observer, such a finding would confirm that the two are one). Although the angiohistiocytoma vs. dermatofibroma debate remains open, the matter of whether dermatofibromas have a constrained clinical distribution can be considered closed. When it comes to this common fibroma, no location is verboten.