Answer of Dermatopathology Case 64

Immunohistochemistry: CD34 is strongly positive.


Dermatofibrosarcoma Protuberans

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Abstract:

Cutaneous CD34+ Spindle Cell Neoplasms: Histopathologic Features Distinguish Spindle Cell Lipoma, Solitary Fibrous Tumor, and Dermatofibrosarcoma Protuberans.Am J Dermatopathol. 2010 Jun 17.
Spindle cell lipoma (SCL), dermatofibrosarcoma protuberans (DFSP), and solitary fibrous tumors (SFT) are cutaneous CD34+ spindle cell tumors that may exhibit histopathologic and immunophenotypic overlap. We sought ways to reliably distinguish among these lesions even in small or superficial biopsies. Ten morphologic characteristics were analyzed in a group of 5 SCLs, 6 cutaneous SFTs, and 12 DFSPs. SFT and DFSP exhibited extensive histopathologic overlap in small or partial biopsies. However, adnexal entrapment, defined as diffuse proliferation of tumor cells around pilosebaceous and eccrine structures with minimal disruption or expansion of the dermis, was a feature seen in 10 of the 12 DFSPs and in none of the SFTs or SCLs. Even when only superficial portions of a lesion were present, this feature was identifiable. Spindle cell lipomas posed little diagnostic difficulty, in part because excisional biopsies were performed in all cases of SCL. The number of samples included in the study is relatively small, in part due to the rarity of cutaneous solitary fibrous tumors. We conclude that careful attention to these histopathologic features enables reliable distinction among these tumors.

Dermatofibrosarcoma protuberans: how wide should we resect?Ann Surg Oncol. 2010 Aug;17(8):2112-8. Epub 2010 Mar 31.
BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare dermal tumor with local recurrence rates ranging from 0 to 50%. Controversy exists regarding margin width and excision techniques, with some advocating Mohs surgery and others wide excision (WE). We reviewed the experience in two tertiary centers using WE with total peripheral margin pathologic evaluation.MATERIALS AND METHODS: Institutional Review Board approved retrospective review of patients with DFSP from 1991 to 2008. Patients had initial WE using 1-2 cm margins with primary or delayed closure; further excision was done whenever feasible for positive margins. Pathologic analysis included en face sectioning. We evaluated margin width, number of WE, reconstruction methods, radiation, and outcomes.RESULTS: A total of 206 DFSP lesions in 204 patients (76 males, 128 females), median age 41 years (range 1-84) were treated. Locations were trunk (135), extremities (43), and head and neck (28). The median number of excisions to achieve negative margins was 1 (range 1-4) with a median excision width of 2 cm (range 0.5-3 cm). Closure techniques included primary closure (142; 69%), skin grafting (52; 25%), and tissue flaps (9; 4%). There were 9 patients who received postoperative radiation, 6 for positive margins after maximal surgical excision. At a median follow-up of 64 months (range 1-210), 2 patients (1%) with head and neck primaries recurred locally.CONCLUSIONS: Using a standardized surgical approach including meticulous pathologic evaluation of margins, a very low recurrence rate (1%) was achieved with relatively narrow margins (median 2 cm), allowing primary closure in 69% of patients. This approach spares the additional morbidity associated with wider resection margins and in our experience represents the treatment of choice for DFSP occurring on the trunk and extremities.

Dermatofibrosarcoma protuberans in the breast of a 2-year-old girl.Ann Diagn Pathol.2010 Aug;14(4):279-83. Epub 2009 Dec 1.
Dermatofibrosarcoma protuberans (DFSP) is a low-grade dermal and subcutaneous spindle cell neoplasm that most commonly occurs in the extremities and trunk of adults. It is rare in children and infants, and only few cases are reported as congenital. A 2-year-old girl presented with a rapidly enlarging left breast mass. The histology of the excised mass revealed a moderately cellular spindle cell tumor with large hypercellular fibrosarcoma-like areas, few myxoid areas, and other areas with multinucleated giant cells. By immunohistochemistry, the tumor cells were focally positive for CD34 and were negative in the fibrosarcomatous areas. The diagnosis of DFSP was confirmed by demonstrating an unbalanced translocation der(22)t(17;22)(q21.3;q13.1) by conventional cytogenetic and fluorescence in situ hybridization analyses. Positive immunoreactivity with PDGFR-beta antibody indicated constitutional activation of PDGF receptor and provided an alternate indirect method of confirming the presence of dysregulated PDGF gene involved in this translocation. Although DFSP has been described in the adult female breast, this is the first such case in the breast of a 2-year-old girl. Dermatofibrosarcoma protuberans should be considered in the differential diagnosis of subcutaneous/dermal spindle cell tumors in children regardless of the site. CD 34 immunostaining should not be relied on, as it may be negative in fibrosarcomatous areas. Confirmation of the diagnosis in unusual sites requires identification of the characteristic t(17;22) chromosomal translocation.

Dermatofibrosarcoma protuberans of the vulva: a clinicopathologic and immunohistochemical study of 13 cases. Am J Surg Pathol. 2010;34(3):393-400.
Dermatofibrosarcoma protuberans (DFSP) is a low-grade sarcoma seldom seen in the vulva with only 29 cases reported. We present the clinicopathologic and immunohistochemical features of 13 such cases seen in our institution over a period of 29 years (1978 to 2007). Patient age ranged from 23 to 76 years (mean, 46 y). Twelve patients had a vulvar mass. One patient presented with a pigmented skin lesion. Tumor size ranged from 1.2 to 15 cm (median, 4 cm). Microscopically, all the cases showed typical features of DFSP. In 1 case, myxoid changes were also noted; 3 cases showed fibrosarcomatous transformation. Of interest, in 7 of our 13 cases, a variety of diagnoses, such as cellular dermatofibroma, cellular leiomyoma, neurofibroma, low-grade leiomyosarcoma, fibrosarcoma, low-grade malignant schwannoma, desmoplastic melanoma, cellular neurofibroma, and low-grade malignant peripheral nerve sheet tumor were initially considered. All 11 cases tested for CD34 were positive, whereas 7/9 cases, 8/9 cases, and 9/9 cases were positive for PDGFR-alpha, PDGFR-beta, and c-abl, respectively. All patients were initially treated with excisional biopsy, wide local excision, or radical vulvectomy. Local recurrences occurred in 7 cases. One patient also developed distant metastases. All recurrences were treated surgically; 1 patient also received chemotherapy and radiotherapy and another received imatinib (Gleevec). Follow-up data ranging from 2 to 444 months was available for all patients. Nine patients had no evidence of disease, 2 patients were alive with disease, 1 patient had died of disease, and 1 patient had died of other causes. DFSP affects women of a wide age range and has a propensity to recur locally. The frequent expression of PDGFR-alpha, PDGFR-beta, and c-abl in these cases agrees with the findings of other investigators and supports the use of imatinib (Gleevec) in cases that are recurrent or not amenable to surgery.

Plaque-like CD34-positive dermal fibroma ("medallion-like dermal dendrocyte hamartoma"): clinicopathologic, immunohistochemical, and molecular analysis of 5 cases emphasizing its distinction from superficial, plaque-like dermatofibrosarcoma protuberans.Am J Surg Pathol.2010 Feb;34(2):190-201.
We analyzed the clinical, histomorphologic, and molecular criteria of 5 DH and 7 DFSP to delineate diagnostically relevant differences between incipient dermal DFSP and its benign look-alike, DH. We expand the clinical and histologic spectrum of DH. As medallion-like dermal DH is neither of dermal dendrocyte lineage nor a genuine hamartoma, we propose instead the descriptive term of plaque-like CD34-positive dermal fibroma (PDF). Both PDF/DH and DFSP presented as slightly pigmented and indurated plaques on neck, trunk, and extremities. Histologically, DFSP was characterized either by horizontally oriented spindle cell fascicles or by diffusely arranged fibroblasts within a slightly myxoid stroma in the upper two-thirds of the dermis, whereas PDF/DH presented with a cellular band-like fibroblastic proliferation mostly in the papillary and adjacent upper reticular dermis. Only one congenital PDF/DH in a 9-year-old boy extended into the septa of the subcutaneous fat. Formalin-fixed paraffin-embedded archival tissue was used for detection of the COL1A1-PDGFB gene rearrangement by multiplex reverse transcription-polymerase chain reaction (RT-PCR) and by dual color fusion fluorescence in-situ hybridization (FISH). Archival blocs older than 4 years did not yield amplifiable RNA because of RNA degradation, whereas FISH analysis was feasible in all investigated cases. FISH analysis revealed COL1A1-PDGFB gene rearrangement in all DFSP cases (n=7), whereas RT-PCR could detect the COL1A1-PDGFB fusion transcript only in 1 DFSP. Two cases were negative. In 4 archival cases with storage between 4.5 and 12 years, RNA had been degraded making these cases unsuitable for RT-PCR. In PDF/DH, both RT-PCR and FISH analysis did not reveal any evidence of COL1A1-PDGFB gene rearrangement. We show that PDF/DH and superficial (plaque-like) DFSP, subtle clinicopathologic differences notwithstanding, are morphologic look-alikes that can be kept apart by molecular studies of the COL1A1-PDGFB gene fusion. For the detection of the COL1A1-PDGFB gene rearrangement in diagnostically difficult cases, RT-PCR and FISH analysis are reliable and helpful diagnostic tools. In archival formalin-fixed paraffin-embedded tissue, however, FISH analysis is more robust and exhibits a higher clinical sensitivity than RT-PCR.