Plaque-Like Dermatofibroma: Case Report of a Rare Entity

A case of a well-demarcated plaque measuring 11 cm without satellites of several years’ duration is presented. It showed typical histologic findings of dermatofibroma, prompting a diagnosis of plaque-like dermatofibroma. The relationship to multiple clustered dermatofibromas and plaque-like myofibroblastic tumor is discussed.


Introduction
Giant dermatofibromas have been defined by a size of at least 5 cm [1] and typically have a nodular and often pedunculated appearance. A subtype of giant dermatofibroma with a less elevated appearance has been termed "plaque-like dermatofibroma". Only a few cases of this entity have been reported. We here describe an additional case and discuss its relationship to cases that have been termed "multiple clustered dermatofibromas" and "plaque-like myofibroblastic tumor".

Case Report
A 43-year-old female with a past medical history of psoriasis and psoriatic arthritis who recently had been taking immunomodulatory medications presented with a longstanding large plaque on her mid back.
Dermatopathology 2021, 8,2 fusions were identified by targeted next-generation sequencing, however, the RNA expression visualization showed increased expression of FGFR1, and sequencing showed a variant of uncertain significance (VUS) in FGFR3.   A focus of the patient's psoriasis had been biopsied fifteen years earlier at the same location as the current plaque, after which the wound healed with a nodular, painful scar. Since that time, the lesion has been slowly increasing in size and has become more symptomatic with pain and pruritus. Clinically it was suspicious for a keloidal scar. The patient denied any specific treatments directed at the lesion. Examination revealed an irregularly pigmented plaque of irregular outlines measuring 11 × 5 cm ( Figure 1). Six punch biopsies demonstrated typical findings of dermatofibroma. The plaque was excised surgically. Histology of the punch biopsies and of the surgical specimen revealed a moderately cellular infiltrate of bland spindle cells in the dermis and upper subcutis ( Figure 2a) in a haphazard to focally storiform arrangement. The subcutis was involved by pushing broad aggregates of spindle cells, without infiltration between adipocytes (honeycomb pattern) (Figure 2a). The overlying epidermis demonstrated hyperplasia (Figure 2b), and multinucleated cells ( Figure 2c) and foam cells (Figure 2d) were present. These histologic features are typical of a dermatofibroma and exclude a diagnosis of dermatofibrosarcoma protuberans. A few foci of follicular induction in the form of nests of basaloid cells with peripheral palisading situated at the undersurface of the epidermis were identified. Immunohistochemical stains showed expression of Factor XIIIa and no expression of CD34 or WT1, further excluding a diagnosis of dermatofibrosarcoma protuberans. Next-generation sequencing including RNA expression analysis was performed following manual microdissection of lesional tissue using a customized platform (ArcherDx, Boulder, CO, USA). No clinically reportable sequence alterations, copy number changes, or fusions were identified by targeted nextgeneration sequencing, however, the RNA expression visualization showed increased expression of FGFR1, and sequencing showed a variant of uncertain significance (VUS) in FGFR3.
Dermatopathology 2021, 8,2 fusions were identified by targeted next-generation sequencing, however, the RNA expression visualization showed increased expression of FGFR1, and sequencing showed a variant of uncertain significance (VUS) in FGFR3.
Of note, some cases of clustered or plaque-like dermatofibromas appear to be different from the MCDF/PLDF/PLMT group. Most notable among these are four case reports of patients who also had multiple clustered or plaque-like dermatofibromas that, however, differed by their eruptive time course and, in three cases, by coincidence with the administration of immunosuppressive medication [27][28][29][30]. Our patient clearly does not fit into this group because her plaque exhibited very slow growth, and she had taken immunomodulatory medication only in the recent past.
By history, the plaque of our patient was preceded by trauma in the form of a biopsy. This may have been coincidental, as trauma has been observed occasionally [4,6,13] but not consistently as a cause of MCDF, PLDF, or PLMT.
The origin of dermatofibromas is unclear. A cause related to an immune process or to immunosuppressive medication has been suggested based on the observation that a subgroup of dermatofibromas occurring as multiple, widespread eruptive lesions are often associated with an autoimmune disease, most commonly lupus erythematosus [31,32]. In these patients, the dermatofibromas show a wide anatomic distribution without clustering. It is not clear how this group of patients relates to the usual single dermatofibromas or to the above settings of MCDF, PLDF, and PLMT, which in general are not associated with an immune-mediated disease. Some cases of benign fibrous histiocytomas/dermatofibromas have been found to carry gene fusions involving protein kinase C isoenzymes PRKCA, PRKCB, and PRKCD and occasionally involving the ALK gene [33,34], but for the majority of cases the genetic basis is unknown. Furthermore, it is unknown what factors limit the growth of dermatofibromas and which factors are responsible for the development of giant dermatofibromas. We applied two sequencing panels that detect gene mutations or fusions commonly encountered in neoplastic disease (including protein kinase C isoenzymes PRKCA and PRKCB as well as ALK, but not PRKCD) to our plaque-like dermatofibroma but did not find a genetic alteration. In an mRNA expression platform, we identified an overexpression of FGFR1 (fibroblast growth factor receptor 1). This may be related to the increase in expression of FGFR2 and FGFR4 that was reported to have been detected in dermatofibromas by immunohistochemistry [35]. Overexpression of FGFRs results in the activation of MAPK and PI3K/Akt pathways and is found in benign and malignant tumors [36][37][38]; it is therefore possible that a similar growth-stimulatory mechanism is operative in dermatofibromas. Final classification of MCDF, PLDF, and PLMT awaits further support from molecular data to help determine whether they represent separate entities or a single disease process with variable clinical features. Institutional Review Board Statement: Ethical review and approval were waived for this study, due to the number of patients less than three.
Informed Consent Statement: Written informed consent has been obtained from the patient to publish this paper.

Conflicts of Interest:
The authors declare no conflict of interest.