#dermpathJC May 2018:
Thursday, May 24th, 9pm EST
Article discussed: Cutaneous and Superficial Soft Tissue CD34+ Spindle Cell Proliferation
Authors: Hongyu Yang, MD, PhD and Limin Yu, MD, MS
Archives of Pathology & Laboratory Medicine: August 2017, Vol. 141, No. 8, pp. 1092-1100
Open access available at: https://doi.org/10.5858/arpa.2016-0598-RA
Summary author: Patrick Rush, DO (@DrPatrickRush)
Journal Club Summary:
CD34 is an often-utilized stain in dermpath. Unfortunately, a wide array of spindle cell tumors in the superficial soft tissues (dermis and subcutis) are CD34 positive. CD34 expression can be a prominent feature of fibrohistiocytic neoplasms but also of neural neoplasms, lipogenic neoplasms, and neoplasms of uncertain histiogenic lineage. In the discussed Archives article Drs. Yang and Yu gave us a great review of these entities with a nuanced discussion of the unique challenges that this heterogeneous group of superficial CD34+ lesions can present. The discussion was focused around four case-based examples.
Brief summary of the Case-Based Entities Discussed:
Cellular Digital Fibroma:
Clinical: Acral sites, such as fingers and toes, small <0.5cm papule
Demographics: 33-83yo, no sex predilection
Behavior: Indolent (no recurrence after complete excision)
Histology: Proliferation of uniform slender fibroblasts forming fascicles in parallel or haphazard arrangement in the upper dermis with dense dermal collagen.
Negative: S100, EMA, Factor XIIIa
- Early DFSP: Also CD34+. Distinguished clinically, DFSP rarely occurs in the digits of adults. DFSP occurs as a plaque with slow growth, not as a small <0.5cm papule
- Superficial Acral Fibromyxoma (Digital Fibromyxoma): Also CD34+, but larger (0.5-5cm) with a distinct myxoid stroma.
Background: Described by McNiff and colleagues in 2005 where this entity was noted to be a unique subset of digital fibromas in their practice.
Superficial CD34+ Fibroblastic Tumor:
Clinical: Slow growing painless mass (1.5-10cm, mean 4.1cm) occurring in the extremities, most commonly in the lower extremity and buttock.
Demographics: Occurs exclusively in adults, 20-76yo, no sex predilection
Behavior: Indolent (of 13 patients 12 had no recurrence, 1 patient developed a lymph node met after 7-years)
Histology: Proliferation of moderately cellular spindled to epitheloid cells with abundant granular to glassy cytoplasm and bizarre hyperchromic nuclei with “alarming” nuclear pleomorphism and a paradoxically low mitotic count and proliferative index in a proliferation (<1/50 HPF). Often there is a prominent inflammatory infiltrate of lymphocytes and mast cells.
Positive: CD34, keratin (focal weak), Intact INI-1
Negative: S100, Desmin, SMA, ERG, FLI-1, TP53
- AFX & Pleomorphic Dermal Sarcoma: Differentiated by the clinical and histology. Clinically these tumors both more typically occur on more chronically sun damaged skin, such as the head and neck (as opposed to the leg and buttock). These tumors will have a high mitotic count, and expression of TP53.
- Myxoinflammatory Fibroblastic Sarcoma (Inflammatory Myxohyaline Tumor of the Distal Extremities) (MIFS): This tumor also has bizarre nuclear cytology combined with a low mitotic rate, and prominent inflammatory infiltrate with scattered keratin positivity. But MIFS will be CD34- and will have rearrangements of TGFBR3 and MGEA5
- Pleomorphic Hyalinizing Angiectatic Tumor (PHAT): Again Strikingly pleomorphic but with a low mitotic count. Distinguished by the presence of characteristic ectatic hyalinized blood vessels and abundant hemosiderin deposition.
- Epithelioid Sarcoma: May comes into the differential sue to its shared phenotype of Keratin positivity with CD34 positivity. Distinguished by their granulomatous appearance from low power, necrosis, and their loss of INI-1 expression.
Background: Described in Carter and colleagues in 2013 when they determined that there was a distinct morphology in a subset of their low-grade fibroblastic tumors.
Spindle cell Lipoma:
Clinical: Solitary subcutaneous mass on the posterior neck, shoulder, and back, typically 3-5cm.
Demographics: Adult males 40s-60s
Histology: The typical histologic presentation is of mature adipocytes, short, cytologically bland spindle cells, and “ropey” collagen bundles, often with prominent mast cells in the background. This typical histology is not the scenario where there will be much diagnostic difficulty, is in the “fat-free” spindle cell lipoma where the paucity of the mature adipocyte component may cause some befuddlement, in this scenario it can be important to know that the bland spindle cells are CD34+.
Positive: CD34 (spindle cell component), S100 (Adipocyte component)
Negative: S100 (spindle cell component), STAT6
- Neurofibroma: While also a infiltrative tumor of bland spindled cells, these are CD34- and S100+ in the spindle cells.
- Solitary Fibrous Tumor: This histologic differential can be difficult if there is fat infiltration. Though they typically have a biphasic appearance and staghorn vasculature. In addition, when these tumors uncommonly occur in the skin, the head and neck is where they commonly occur. They can be differentiated by STAT6 positivity and clinical correlation.
Background: The “fat-free” or “low-fat” variant of spindle cell lipoma is a well-known diagnostic stumbling block.
Plaque-like CD34+ Dermal Fibroma (Medallion-Like Dermal Dendrocyte Hamartoma):
Clinical: Medallion-like round-to-triangular well-circumscribed brown atrophic plaques (6-10cm in diameter) on the central chest and neck since birth (most but not all are congenital).
Histology: Epidermal atrophy with a distinct band-like proliferation of fusiform cells in the upper dermis, concentrically arranged around small vessels and nerves.
Positive: CD34, Factor XIIIa (positive in original series, negative in other subsequently described cases)
Negative: S100, Cytokeratin AE1/AE3, Actin, Desmin, NSE, Neurofilament
- Congenital/atrophic DFSP: Cytogenetic and molecular analysis can help in this distinction. To date, no cytogenetic profile has been ascribed to this entity, unlike DFSP.
Background: Rodriguez-Juardo et al first described this entity in 2004, where they proposed that these lesions represented a hamartomatous process. Since this time the clinical spectrum has been expanded to include de novo occurring lesions in adults. There is some disagreement amongst authors concerning the consideration of de novo tumors in adults and the congenital lesions with a specific clinical scenario as the same or distinct entities.
In short – The May 2018 #dermpathJC discussed the histologic and clinical differentials of CD34+ tumors that arise within dermis and superficial subcutis, and live discussion with the authors. Here are some selected #pearls from the evening discussion.
There were 1.177 Million impressions of the meeting over the following weekend with 333 tweets and 64 Participants. The discussion was lively, as always, with attendees checking in from around the world from Brooklyn, NY, to Chile and many places in between. We were very happy to have the authors in attendance, Dr. Limin Yu (@Wikilip) and Dr. Hongyu Yang (@HENRYY_MD). Having the authors present to discuss their work with interested readers in real time is just one aspect of the #dermpathJC twitter format that stands it apart from traditional journal club formats; allowing for meaningful insight into the authors struggles and thoughts that you might have otherwise not known.
Silvija Gottesman, MD