#dermpathJC May 2020 summary

#dermpathJC May 2020:

Thursday, May 28th, 9 pm EST

Article discussed: Pleomorphic dermal sarcoma: a more aggressive neoplasm than previously estimated

Authors: Juan C. Tardío, Fernando Pinedo, José A. Aramburu, Dolores Suárez-Massa, Ana Pampín, Luis Requena and Carlos Santonja

Temporary open access courtesy of Journal of Cutaneous Pathology: https://doi.org/10.1111/cup.12603

Summary prepared by: Cacey Peters, M.D. (@caceypeters)

Article Summary:

Pleomorphic dermal sarcoma (PDS) is a rare neoplasm similar to atypical fibroxanthoma, but has fetaures of tumor necrosis, invasion beyond superficial subcutis or vascular or perineural infiltration. Metastatic risk is less than 5%, but ultimately very rare and more studies are needed to ascertain exact risk. The neoplasm fails to show any staining for cytokeratins, S100 protein, desmin or CD34.

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Journal Club Summary:

  • Atypical fibroxanthoma (AFX) is most commonly found on sun-exposed skin of the elderly, particularly the head
  • Histologically characterized by a mixture of spindle, epithelioid, and multinucleated giant cells with marked pleomorphism and many mitoses
  • Architecture may be fascicular, storiform, or haphazard
  • Immunohistochemistry is negative for cytokeratins (CK), S100, desmin, and CD34 while positive for vimentin, CD10, CD99 and variably CD68 and p53
  • 42, a marker of normal and neoplastic follicular dendritic cells (FDC), was shown to be positive in 50% of cases in this study and were negative for other FDC markers such as CD21 and CD23
    • Unfortunately, CNA.42 is positive in AFX, leiomyosarcomas, melanomas and carcinomas (unpublished observations by the authors)
  • According to the WHO, necrosis, invasion into deep subcutis or underlying fascia or skeletal muscle, lymphovascular invasion, or perineural invasion do not constitute a diagnosis of AFX
  • The name “pleomorphic dermal sarcoma” (PDS) has been proposed for such lesions, formally known as cutaneous malignant fibrous histiocytoma (MFH)
  • Confusion has ensued due to the lack of understanding about the true behavior of these lesions as well as some use of both terms as synonyms in the literature
  • Although controversy exists about using different terms for naming members of the same disease spectrum, the differences in clinical behavior between AFX and PDS merits an unambiguous message to the clinicians that is better guaranteed, in the authors opinion, distinguishing them by nomenclature
  • Clinical behavior is indolent with rare recurrence and even rarer metastasis (5% based on limited data and classification criteria)
  • Combining data from this study and a previous study by Miller et al, PDS seems to have a more aggressive clinical behavior, estimated to be 14% metastasis rate, including the skin, regional lymph nodes, and the lungs
  • At least 3 patients died from PDS (7%)
  • When metastasis has occurred, some cases infiltrate beyond the subcutis, contain necrosis, or contained no histopathologic or immunohistochemical information
  • A diagnosis of PDS should be reserved for tumors in sun-damaged skin of the elderly because they are extremely rare in non-sun-damaged skin, if they exist at all
  • TERT promoter mutations with an ultraviolet signature in 76% of PDS supports this view
  • Deletions in chromosomes 9p and 13p are seen in PDS at a similar frequency as AFX and undifferentiated pleomorphic sarcomas (UPS)
  • UPS shows H-ras and K-ras mutations (absent in AFX) and overall, more genetic alterations in complete genomic hybridization (CGH) studies
  • The authors retrospectively studied 18 PDS with emphasis on outcome and the differential diagnosis
  • Out of 12 previously classified PDS/cutaneous MFH and 112 AFX, the inclusion criteria for the series were as follows:
    • Spindle cell and/or pleomorphic dermal-based mesenchymal neoplasms without morphologic or immunohistochemical features diagnostic of any distinct entity
    • Lack of CK, S100 protein, desmin and CD34 expression
    • Invasion of at least the deep subcutis and/or tumor necrosis and/or vascular or perineural infiltration
  • 9 of the 12 PDS were excluded because primary subcutaneous sarcoma infiltration into the dermis could not be ruled out and expression of one or more of the above IHC
  • 15 of the 112 AFX cases were reclassified as PDS making a total of 18 PDS
  • M:F ratio was 1:1 (in contrast to previously reported male predominance)
  • Mean age was 81
  • Patients either had prior trauma or carcinomas in the same vicinity or immunosuppression due to rheumatoid arthritis, renal disease, or their age
  • Clinically they were described as either plaques or tumors, 10 of which were ulcerated
  • Mean size was 22mm with a range from 7-70mm
  • 13 cases showed an asymmetric silhouette and 15 cases showed an infiltrative border
  • Grenz zone, epidermal collarette and epidermal connection were absent in all cases
  • Except in cases with a conventional carcinomatous, melanocytic or sarcomatous component, sarcomatoid carcinoma, melanoma, leiomyosarcoma and angiosarcoma are mainly differentiated from PDS by their immunohistochemical (IHC) features
  • Sarcomatoid carcinoma will stain for cytokeratins, especially high molecular weight, and also p63 and EMA but can also be seen in PDS which makes them less useful
  • There will usually be numerous S100+ dendritic cells in PDS but never the neoplastic cells which helps differentiate PDS from melanoma, which will also likely have a conventional or in situ component
  • Leiomyosarcoma will have desmin and smooth muscle histologic features with marginated fascicles and characteristic elongated blunt-ended nuclei with fibrillary cytoplasm
  • Angiosarcoma has a similar site predilection to PDS, hemorrhage, and is positive for CD31, but is also positive for CD34 and ERG as well as a different clinical appearance with large ill-defined bluish, bruise-like patches that evolve into elevated plaques
  • Dermatofibrosarcoma protuberans (DFSP) is more common in younger patients on the trunk or proximal extremities and has a lace-like pattern that can mimic PDS along with CD34 positivity, however, DFSP has uniform spindle cells arranged in a monotonous storiform pattern somewhere within the lesion, even if there are MFH areas with loss of CD34, that will aid in the diagnosis of DFSP
  • Atypical and cellular dermal fibrous histiocytomas can have spindle to pleomorphic areas that may resemble PDS with similar lack of specific IHC, but usually present on the extremities of young to middle-aged adults with a Grenz zone and peripheral collagen entrapment that is limited to the dermis or, at most, the superficial subcutis
  • If PDS contains myxoid stroma, these must be distinguished from myxofibrosarcoma which differ in that they are often on the extremities, have a multinodular growth patter, broad spectrum of celluarity to stroma ratio, characteristic curvilinear thin-walled vessels and pseudolipoblasts.

Memorable tweets:

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Until next month #dermpathJC, stay safe!

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