PMC4179866_01
Histology of Primary tumor. A) The left chest wall mass excised in 2005 showed an invasive spindle cell neoplasm with B) areas of high grade, fibrosarcomatous transformation with Herringbone architecture. C) The tumor showed CD34 expression and this, along with the fibrosarcomatous areas and high mitotic rate, were consistent with a dermatofibrosarcoma protuberans with fibrosarcomatous transformation (DFSP-FS).
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F1
Histologically, this revealed a neoplasm consisting of atypical spindled cells arranged in a storiform pattern that invaded the dermis and subcutaneous tissue (Figure  1A). Large parts of this tumor showed areas histologically reminiscent of fibrosarcoma (at least 75% of the tumor), characterized by spindled mesenchymal cells with high grade cytologic atypia arranged in broad fascicles forming a "Herringbone" pattern (Figure  1B), with more than 10 mitotic figures per high powered field. This neoplasm showed expression of CD34 by immunohistochemistry (Figure  1C), but was negative for Desmin, S100, Pan-cytokeratin, BCL-2, and CD117 expression.
Radiographs of metastatic disease at diagnosis. A) CT scan demonstrating a large unresectable tumor involving all organs in the left upper abdomen. B) Biopsy of this mass showed malignant high grade spindled cells, C) a COL1A1-PDGFB translocation by dual fusion FISH probe set (yellow signals indicate the fusion signal), consistent with metastatic dermatofibrosarcoma protuberans with fibrosarcomatous transformation (DFSP-FS).
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F2
Surgical Oncology was consulted after an abdominal CT scan revealed a heterogeneous mass in the left upper quadrant involving the pancreas, spleen, adrenal, left lobe of liver, and stomach measuring 17 x 18 x 23 cm (Figure  2A). A core biopsy of this retroperitoneal mass was obtained that showed spindle shaped mesenchymal cells with high grade cytologic atypia (Figure  2B) essentially identical to the fibrosarcomatous areas that were seen in the 2005 chest wall DFSP-FS. A dual fusion DNA FISH probe set for the COL1A1 (17q21) and PDGFB (22q13) genes was positive for a COL1A1-PDGFB translocation (Figure  2C), consistent with DFSP-FS metastasis to the retroperitoneum.Radiographically, this retroperitoneal tumor was unresectable and the patient was started on Imatinib therapy 400 mg BID.
CT scan illustrating post imatinib decrease in size of the tumor now amenable to surgical resection.
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F3
The patient tolerated this dose without any reported side effects and after 18 months of Imatinib therapy, the tumor exhibited a dramatic response with a 70% size reduction and radiographically appeared to be amenable to margin negative (R0) surgical resection (Figure  3).
Gross R0 tumor resection specimen: subtotal distal pancreatectomy, subtotal gastrectomy, splenectomy, adrenalectomy. A) Anterior view B) Posterior view C) Cross sectional view.
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F4
A left upper quadrant exenteration (en-bloc resection including a subtotal distal pancreatectomy, splenectomy, left adrenalectomy, and subtotal gastrectomy) was performed with negative margins on September 1, 2009 (Figure  4A-C).
Histology post-Imatinib Resected retroperitoneal tumor showed a hyalinized hypocellular mass. A) Splenic tissue is demonstrated on the left in the current section. B & C) Focally, the tumor demonstrated residual atypical spindle cells that revealed a COL1A1-PDGFB fusion by interphase FISH (not shown), consistent with a dramatic histologic response of metastatic DFSP-FS to Imatinib.
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F5
Post-Imatinib, this resected tumor showed dramatically altered histology, revealing primarily hyalinized and myxoid fibrous differentiated stroma (Figure  5A) with focal atypical spindle cells (Figure  5B-C) that revealed a COL1A1-PDGFB fusion by interphase FISH analysis, consistent with a dramatic gross and histologic response of the metastatic DFSP-FS to the Imatinib.
Search strategy flow diagrams. A &B Diagrams depicting the search strategy for systematic review of the use of Imatinib in patients with Dermatofibrosarcoma Protuberans.
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F6
Figure  6 describes the search strategy in detail. Twelve studies were excluded (exclusion criteria mentioned in Figure  6).