—  SPECIALTY CONFERENCE  —

Bone & Soft Tissue Pathology

Case 3 - Myxoid Dermatofibrosarcoma Protuberans with Composite Features of Giant Cell Fibroblastoma

Steven Billings


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  • The differential diagnosis of myxoid spindle cell tumors of the skin is broad, including a variety of both benign and malignant entities.

  • Immunohistochemical stains may be useful but need to be interpreted with caution.

  • Careful attention to sometimes subtle histologic features is key to accurate diagnosis.

Clinical History:
A 26-year-old man presented with a painful nodule on the back, clinically thought to be a cyst.


Case 3 - Slide 1
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Case 3 - Figure 1
Scanning magnification demonstrated a myxoid tumor involving the deep dermis and subcutis.
Case 3 - Figure 2
The tumor was composed of randomly arranged cells embedded in a prominent myxoid stroma.
Case 3 - Figure 3
The tumor cells were relatively bland spindled to stellate cells with hyperchromatic nuclei.

Case 3 - Figure 4
High power view demonstrating the spindled and stellate tumor cells.
Case 3 - Figure 5
Within the tumor there were ecstatic thin-walled vessels.
Case 3 - Figure 6
In some areas there were delicate capillaries in the stroma.

Case 3 - Figure 7
The tumor infiltrated through the subcutaneous fat that in areas resulted in a honeycomb pattern.
Case 3 - Figure 8
Scattered multinucleated tumor cells were present.
Case 3 - Figure 9
There was a focal area that was more cellular. In this area the tumor cells had a storiform growth pattern.

Pathologic Findings:
The specimen consisted of a skin ellipse with attached soft tissue that was 2.5 cm in greatest dimension. The soft tissue had a gelatinous cut surface and no cyst was apparent. Microscopically, the tumor involved the deep reticular dermis and extensively involved the subcutaneous fat. The tumor had an infiltrative growth pattern, dissecting between collagen bundles of the dermis. In the subcutis, the tumor had some areas with a relatively blunt interface but also had infiltrative zones where the tumor infiltrated between individual adipocytes in a honeycomb pattern. The tumor was composed of randomly arranged spindled to stellate cells embedded within a myxoid stroma. The cells were fairly monomorphous with hyperchromatic nuclei, but scattered multinucleated cells were present. Focally, some tumor cells lined clefts within the stroma. The underlying vasculature showed scattered ectatic vessels as well as delicate branching capillaries. A focal more cellular area was present where the tumor had a tight storiform pattern. The tumor cells were positive for CD34, but in some of the myxoid areas the staining was less intense.

Diagnosis:
Myxoid Dermatofibrosarcoma Protuberans with Composite Features of Giant Cell Fibroblastoma.

Discussion:
Dermatofibrosarcoma protuberans (DFSP) is a fibrohistiocytic tumor of intermediate malignancy that usually presents in young to middle aged adults. It is locally destructive with a relatively high rate of local recurrence but a minimal risk of metastasis. Classic DFSP is characterized by a tight storiform arrangement of uniform slender hyperchromatic spindled cells that are CD34-positive. DFSP also harbors a characteristic t(17;22) resulting in the fusion of the collagen type I alpha gene with the platelet derived growth factor beta gene with formation of the chimeric COL1A1-PDGFB gene.

Although classic DFSP is a relatively straightforward diagnosis, there are a number of morphologic variants of DFSP that can cause diagnostic problems including pigmented DFSP (Bednar tumor), granular cell DFSP, fibrosarcomatous DFSP, atrophic DFSP, and myxoid DFSP. Myxoid DFSP is a rare variant; less than 50 cases have been described in the literature, with only 2 significant series reported. Myxoid DFSP, unlike the classic variant, lacks the storiform growth pattern secondary to the prominent myxoid stroma. The tumor cells have a more random arrangement and a spindled to stellate morphology. In the myxoid variant a prominent underlying vasculature is frequently present that may contain slightly fibrosed to thin-walled branching vessels. The mitotic rate, similar to conventional DFSP, is typically low with most cases having <5 MF/10 HPF. Key to the diagnosis of myxoid DFSP is recognition of the infiltrative growth pattern. All cases show at least some ares with the classic honeycomb pattern of infiltration into the underlying subcutaneous fat. The majority of cases also have focal areas of classic DFSP with the characteristic tight storiform pattern. Thorough sampling and close examination of all sections may be necessary to find the classic DFSP areas. Like conventional DFSP, the myxoid variant is positive for CD34, but the staining is occasionally patchy and less intense.

A component of giant cell fibroblastoma (GCF) is relatively common in myxoid DFSP. DFSP and GCF are morphologic ends of a spectrum of the same tumor with overlapping clinical, histologic, immunophenotypic, and cytogenetic features. GCF is more common in children and has been referred to as the juvenile form of DFSP. GCF is composed of bland spindled and stellate tumor cells and scattered multinucleated tumor cells in a collagenous to myxoid stroma. Pseudovascular clefts lined by tumor cells are another characteristic feature. Composite tumors with DFSP and GCF are well described, as are cases where recurrent tumors with the opposite morphology (i.e. patients with history of GCF where the recurrence has DFSP morphology).

Myxoid DFSP behaves in a manner similar to conventional DFSP; there does not appear to be an increased risk of local recurrence provided adequate surgical excision. In selected cases where complete excision is difficult or not possible, there is some evidence that DFSP may also be treated with imatinib mesylate.

Differential Diagnosis
The differential diagnosis of cutaneous myxoid tumors is challenging and includes a range of both benign and malignant tumors.

Superficial angiomyxoma may be especially difficult to distinguish on limited biopsy material, as the morphology of the individual tumor cells may show striking similarities and superficial angiomyxoma may also be CD34-positive. The growth pattern is the most important distinguishing factor. Superficial angiomyxoma is usually a dermal-based tumor and has a lobular rather than diffusely infiltrative growth pattern. The presence of entrapped epithelial structures and stromal neutrophils may be helpful, but stromal neutrophils have been reported in up to 30% of myxoid DFSP in one series.

Myxoid perineurioma has a swirling growth pattern, plumper cells and is typically circumscribed. Immunoreactivity for EMA is characteristic, but focal EMA expression may be encountered in myxoid DFSP. CD34 immunoreactivity may be seen in perineurioma but it is typically less intense than in myxoid DFSP. Perineurioma expresses claudin-1 unlike DFSP.

Diffuse neurofibroma with prominent myxoid change (myxoid neurofibroma) could be considered given its similar growth pattern. However, the tumor cells have wavy nuclei and immunoreactivity for S100-protien. Advanced neural differentiation in the form of Wagner-Meissner bodies is also common in diffuse neurofibroma.

Myxofibrosarcoma presents in older patients, has more nuclear atypia, and curvilinear vessels. Pseudolipoblasts are a common feature of myxofibrosarcoma not seen in DFSP.

Low grade fibromyxoid sarcoma has varying fibrous and myxoid zones, a pushing border, and may have collagen rosettes. The myxoid areas also have a swirling growth pattern rather than the more random pattern of myxoid DFSP. Low grade fibromyxoid sarcoma also harbors a specific t(7;16).

Myxoid liposarcoma may be difficult to distinguish from myxoid DFSP. The branching vasculature sometimes seen in myxoid DFSP and the infiltration into the subcutaneous fat may impart a resemblance to myxoid liposarcoma. The vasculature of myxoid DFSP often contains larger, ectatic or slightly hyalinized vessels not seen in myxoid liposarcoma. Individual adipocytes entrapped by myxoid DFSP may be atrophic and resemble lipoblasts. Recognition that the fat is part of the subcutis rather than true lipoblasts is usually straightforward in an adequate biopsy. Immunohistochemistry may be helpful, as myxoid liposarcoma is negative for CD34.

Selected references
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  3. Mentzel T. Scharer L. Kazakov DV. Michal M. Myxoid dermatofibrosarcoma protuberans : clinicopathologic, immunohistochemical, and molecular analysis of eight cases. American Journal of Dermatopathology. 29:443-8, 2007.

  4. McArthur GA. Dermatofibrosarcoma protuberans: a surgical disease with a molecular savior. Current Opinion in Oncology. 18:341-6, 2006l.

  5. Calonje E. Guerin D. McCormick D. Fletcher CD. Superficial angiomyxoma : clinicopathologic analysis of a series of distinctive but poorly recognized cutaneous tumors with tendency for recurrence. American Journal of Surgical Pathology. 23:910-7, 1999.

  6. Hornick JL. Fletcher CD. Soft tissue perineurioma : clinicopathologic analysis of 81 cases including those with atypical histologic features. American Journal of Surgical Pathology. 29:845-58, 2005.

  7. Folpe AL. Billings SD. McKenney JK. Walsh SV. Nusrat A. Weiss SW. Expression of claudin-1, a recently described tight junction-associated protein, distinguishes soft tissue perineurioma from potential mimics. American Journal of Surgical Pathology. 26:1620-6, 2002.

  8. Fujimura T. Okuyama R. Terui T. Okuno K. Masu A. Masu T. Chiba S. Kunii T. Tagami H. Aiba S. Myxofibrosarcoma (myxoid malignant fibrous histiocytoma) showing cutaneous presentation: report of two cases. Journal of Cutaneous Pathology. 32:512-5, 2005.

  9. Huang HY. Lal P. Qin J. Brennan MF. Antonescu CR. Low-grade myxofibrosarcoma : a clinicopathologic analysis of 49 cases treated at a single institution with simultaneous assessment of the efficacy of 3-tier and 4-tier grading systems. Human Pathology. 35:612-21, 2004.

  10. Mansoor A. White CR Jr. Myxofibrosarcoma presenting in the skin: clinicopathological features and differential diagnosis with cutaneous myxoid neoplasms. American Journal of Dermatopathology. 25(4):281-6, 2003 Aug.

  11. Mertens F. Fletcher CD. Antonescu CR. Coindre JM. Colecchia M. Domanski HA. Downs-Kelly E. Fisher C. Goldblum JR. Guillou L. Reid R. Rosai J. Sciot R. Mandahl N. Panagopoulos I. Clinicopathologic and molecular genetic characterization of low - grade fibromyxoid sarcoma , and cloning of a novel FUS/CREB3L1 fusion gene. Laboratory Investigation. 85:408-15, 2005.

  12. Billings SD. Giblen G. Fanburg-Smith JC. Superficial low - grade fibromyxoid sarcoma (Evans tumor): a clinicopathologic analysis of 19 cases with a unique observation in the pediatric population. American Journal of Surgical Pathology. 29:204-10, 2005.