Giant cell fibroblastoma: an update and addition of 86 new cases from the Armed Forces Institute of Pathology, in honor of Dr. Franz M. Enzinger
ABSTRACT A quarter of a century ago at the International Academy of Pathology in Boston, Mass, Drs Enzinger and Shmookler's seminal abstract on giant cell fibroblastoma (GCF) included 20 GCFs on the back and thigh of mostly male children. These tumors involved dermis and subcutis, and had parallel fascicles of wavy uniform spindled cells with wiry collagen, dense sclerosis, and gaping spaces with scattered and rimming pleomorphic giant cells. EM suggested fibroblastic phenotype. All cases had benign behavior, but almost half recurred. The caveat was mistaking this tumor for a malignancy. In 1989, Drs Enzinger, Shmookler, and Weiss published this abstract as 28 cases from the AFIP (1960-1981), including 4 adults up to 55 years old. They proposed a relationship of this childhood tumor to dermatofibrosarcoma protuberans (DFSP). Since these original descriptions of GCF, there has been additional immunohistochemical and molecular support for a relationship between DFSP and GCF. We reviewed additional AFIP cases of GCF since 1981, in honor of Dr Enzinger. These new cases included 60 males and 26 females, whose ages ranged from 6 months to 62 years (median, 6 years; 62%, younger than 10 years; 77%, younger than 20 years; and only 10 patients were older than 40 years). Thirty-nine GCF cases with evaluable epidermis were observed to be protuberant, one with superficial ulceration. Most cases were dermal and subcutaneous, 3 purely dermal, and 5 involved superficial skeletal muscle. Almost all cases demonstrated a honeycomb pattern, and several, a parallel pattern of infiltration. Several cases spared adnexa. Pure GCF areas ranged from solid and collagenized to angiectoid and myxoid, the latter with small to large cystlike spaces. Most cases were relatively hypocellular, except one case with more atypia and mitotic activity. GCF demonstrated myoid whorls in 2 cases, a feature previously described in DFSP. Most remarkable is the peculiar perivascular lymphocytes in an onionskin pattern in GCF, not observed in DFSP. Furthermore, histologic intralesional hemorrhage seems to be common in GCF, particularly near the fascia. Fourteen of our 86 cases demonstrated 5% to 70% (median, 20%) dense nongiant cell storiform areas, interpreted as hybrid GCF-DFSP. Three of these cases demonstrated hypercellular DFSP. One hybrid case had fibrosarcomatous transformation. Two cases of pure GCF recurred as a hybrid tumor with DFSP areas, one of these with hypercellular DFSP. In all but one case, the DFSP was adjacent to GCF with an abrupt transition. Most cases studied were positive for CD34 (more intense in DFSP than relatively hypocellular GCF areas) and negative for smooth muscle actin, desmin, HMB-45, keratin, and S100 protein. GCF is exactly clinically and morphologically the same as Dr Enzinger and colleagues originally described it. Additional observations of marked perivascular and onionskin-like chronic inflammation and consistent hemorrhage may aid in the diagnosis of this previously well-described tumor. Collectively, we now have even more convincing morphologic, immunophenotypic, and molecular evidence that GCF is on a spectrum with DFSP.
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- "Most of the GCFs express CD34. Recurrences have often developed but metastases have not been reported . We should also think of fibrous histiocytoma (FH) in the differential diagnosis. "
ABSTRACT: Giant cell angiofibroma (GCA) was initially described as a potentially recurrent tumor in the orbit of adults. However, it is now recognized that it can also present in other locations. The morphological hallmark is a richly vascularized patternless spindle cell proliferation containing pseudovascular spaces and floret like multinucleate giant cells. Our case was a 32-years-old female complaining of painless solitary nodule arising on the occipital region of the scalp, which was diagnosed as giant cell angiofibroma. We report the case because of its extremely rare localization.04/2012; 2012:408575. DOI:10.1155/2012/408575
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ABSTRACT: More recent techniques to characterize the genetic profile of soft-tissue tumors include the use of gene arrays. Using this technique, Apolipoprotein D (Apo D), a 33-kDa glycoprotein component of high-density lipoprotein, has been found to be highly expressed in dermatofibrosarcoma protuberans. To corroborate these results, we sought to ascertain the utility of Apo D by investigating its sensitivity and specificity in a variety of CD34-positive and CD34-negative cutaneous neoplasms including superficial acral fibromyxoma, sclerotic fibromas, and cellular dermatofibromas. Of interest, we found absence of Apo D expression in all four cases of superficial acral fibromyxoma. Of the remaining CD34-positive lesions, Apo D expression was noted in 35/36 (97%) cases of dermatofibrosarcoma protuberans, 3/5 (60%) giant-cell fibroblastomas, 4/4 (100%) sclerotic fibromas, 8/8 (100%) neurofibromas, and 1/1 (100%) solitary fibrous tumor. Of the CD34-negative lesions, Apo D expression was noted in 2/22 (9%) regular dermatofibroma, 23/45 (51%) cellular dermatofibroma, 10/10 (100%) malignant fibrous histiocytoma, 9/10 (90%) atypical fibroxanthoma, 7/8 (86%) cellular neurothekeoma, 9/9 (100%) malignant melanoma, 8/8 (100%) melanocytic nevi (100%), 0/2 superficial angiomyxoma, 0/15 fibromatosis, 0/1 nodular fasciitis, and 1/2 (50%) desmoplastic fibroblastomas. In summary, our findings indicate that Apo D expression is not specific to dermatofibrosarcoma protuberans. Its principal use as an immunohistochemical adjunct lies in its utility in differentiating superficial acral fibromyxoma from dermatofibrosarcoma protuberans. Although strong positive staining of Apo D in a markedly atypical fibrohistiocytic lesion is suggestive of atypical fibroxanthoma and/or malignant fibrous histiocytoma, further studies with the inclusion of other atypical spindled cell neoplasms are required to conclusively prove the same.Modern Pathology 02/2008; 21(1):31-8. DOI:10.1038/modpathol.3800971 · 6.36 Impact Factor
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ABSTRACT: Dermatofibrosarcoma protuberans (DFSP) is a cutaneous, locally aggressive spindle cell tumor of intermediate malignancy. Tumor cells are reactive for CD34 and characterized by a t(17;22) translocation or a supernumerary ring chromosome that results in the fusion of exon 2 of PDGFB to various exons of the COL1A1 gene. We developed a multiplex reverse transcription polymerase chain reaction (RT-PCR) assay to detect fusion transcripts for all possible COL1A1 breakpoints. Twenty-seven formalin-fixed, paraffin-embedded DFSP cases were analyzed using 18 COL1A1 forward primers and 1 exon 2 PDGFB reverse primer. Sequence analysis was performed to definitively characterize breakpoints. Results were correlated with histology, immunohistochemistry, PDGFB break-apart fluorescence in situ hybridization analysis, and cytogenetics when available. Fusion transcripts were detected by RT-PCR in all but one DFSP case. Sequencing revealed a PDGFB exon 2 breakpoint in all cases. COL1A1 breakpoints were in exons 7 (1 patient), 10 (1), 29 (2), 40 (1), 46 (3), and 49 (2), and intronic between exons 13:14 (1), 26:27 (2), 30:31 (1) 33:34 (1), 43:44 (7), 45:46 (1), and 46:47 (1). Three novel COL1A1 breakpoints were identified, intronic between exons 13:14 (1), 30:31 (1) and in exon 49 (2). There was no correlation found between breakpoints and age, sex, or histologic variants. Using this sensitive multiplex RT-PCR assay in combination with fluorescence in situ hybridization, we found COL1A1-PDGFB rearrangements appear more prevalent in DFSP than previously reported. Its detection may be particularly helpful in the differential diagnosis of atypical, fibrosarcomatous, and metastatic DFSP.Human Pathlogy 03/2008; 39(2):184-93. DOI:10.1016/j.humpath.2007.06.009 · 2.81 Impact Factor