FNA Diagnosis of Giant Cell Fibroblastoma A Case Report of an Unusual Pediatric Soft Tissue Tumor Jessica L. Davis, M.D.,1* Erin Mathes, M.D.,2 and Anna B. Berry, M.D.1

Giant cell fibroblastoma (GCF) is a rare pediatric soft tissue tumor, which exists on a spectrum with dermatofibrosarcoma protuberans (DFSP). Histologic features are well established for these entities; however, cytologic findings have not been well characterized. We report for the first time a case of GCF, confirmed by cytogenetics, with mixed DFSP features. In this case of an 8-month-old boy, a fine needle aspiration specimen showed a low-grade spindle cell tumor, with oval to spindled cells dispersed singly and in patternless groups, and with occasional giant cells. Subsequent histologic features were consistent with GCF, which is an uncommon, CD34 positive, soft tissue neoplasm with a distinct molecular aberration. This case emphasizes the differential diagnosis in pediatric soft tissue tumors and stresses the unique features of GCF. Diagn. Cytopathol. 2015;43:325–328. VC 2014 Wiley Periodicals, Inc. Key Words: dermatofibrosarcoma protuberans (DFSP); fine needle aspiration (FNA); giant cell fibroblastoma (GCF); pediatric; soft tissue

Giant cell fibroblastoma (GCF) is an uncommon, predominantly pediatric mesenchymal neoplasm of the dermis and superficial subcutaneous tissue.1–3 The typical presentation is in boys within the first decade of life with a predilection for the lower extremities and trunk.1–5 A clear relationship between GCF and dermatofibrosarcoma protuberans (DFSP) has been established.3,6–13 While both entities have distinct morphologic features, overlap in histologic appearance exists, with welldocumented hybrid lesions,3,6,7,12,13 and local recurrences 1

Department of Pathology, University of California, San Francisco Departments of Dermatology and Pediatrics, University of California, San Francisco. *Correspondence to: Jessica L. Davis, M.D., 505 Parnassus Ave, M-580, San Francisco, CA 94143. E-mail: [email protected] Disclosure: The authors have no financial disclosures. Received 15 March 2014; Revised 16 June 2014; Accepted 17 July 2014 DOI: 10.1002/dc.23201 Published online 4 August 2014 in Wiley Online Library (wileyonlinelibrary.com). 2

C 2014 WILEY PERIODICALS, INC. V

of pure GCF may demonstrate DFSP morphology.3,8,9 Both neoplasms express cell surface CD343,10,11 and have similar molecular aberrations with fusion of COL1A1 to PDGFB.3,12,13 A supernumerary ring chromosome involving 17;22 is more commonly associated with pure DFSP, while a translocation between 17;22 is more frequently identified in pure GCF.3,12,13 Both neoplasms have a 50% risk of local recurrence. DFSP has a low metastatic potential, while pure GCF has never been shown to metastasize.3 Given the extensive overlap in presentation and pathology, these lesions are thought to exist on a spectrum of disease with GCF representing a juvenile or well differentiated form of DFSP.3,10–13 While the histologic appearance of GCF has been well described, to our knowledge the cytologic features are not well characterized with only two prior case reports of GCF and no prior fine needle aspiration (FNA) cases with features of both GCF and DFSP.4,5 Additionally, this is the first cytologic case to have follow-up molecular data supporting the diagnosis of GCF.

Case Report The patient presented at 8 months of age with a small mass on his left lower back. Initially, the mass was thought to represent an infantile hemangioma; however, follow-up examination at 12-months showed rapid, continued growth of the lesion. Physical examination showed a 5.5 3 5.5 cm soft, subcutaneous mass with adjacent varicosities. Ultrasound demonstrated a solid, heterogenous mass with minimal vascularity and areas of hypoechogenicity suggesting fatty tissue, which raised the possibility of a lipoblastoma. Given the uncertain etiology of the lesion FNA biopsy was recommended. The primary clinical differential diagnosis included a vascular neoplasm or lipoblastoma. FNA biopsy (one pass, 23 gauge needle, divided between direct Papanicolaou stain, May–Grunwald Diagnostic Cytopathology, Vol. 43, No 4

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Fig. C-1. FNA/cytologic features. (a) Bland, patternless, oval to spindle cells. Papanicolaou stain. 6003. (b) Metachromatic stroma. MGG. 2003. (c) Floret-like giant cell. Papanicolaou stain. 6003. (d) Oval cells with scattered giant cells (arrows). MGG. 2003. (e) Spindled to oval cells with vesicular nuclei and small nucleoli with rare giant cells (arrow). H&E, cell block. 4003. (f) CD34 immunohistochemical stain with diffuse membranous to cytoplasmic staining. 4003.

Giemsa [MGG] stain, and cell block) showed a low-grade soft tissue lesion. The smears and cell block sections were moderately cellular with oval to spindled cells dispersed singly or arranged in patternless groups (Fig. C-1a). A background of metachromatic stroma, best visualized on the MGG stain (Fig. C-1b), was present. The individual cells had nuclei with vesicular chromatin, small but distinct nucleoli, and variable amounts of delicate cytoplasm. Scattered floret-like giant cells were seen with similar nuclear and cytoplasmic features (Figs. C-1c and d). No adipocytes, lipoblasts, or prominent vessels were seen. No mitoses or necrosis were identified. Immunohistochemical stains were performed on the cell block sections (Fig. C-1e). Tumor cells showed strong 326

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expression of CD34 (Fig. C-1f). There was no expression of CD31, pan-keratin, S-100, synaptophysin, chromogranin, desmin, myogenin, MSA, SMA, or GLUT-1. The lesion was diagnosed as a low-grade soft tissue lesion, and the possibility of a myofibroma was suggested given the CD34 staining. Complete excision and cytogenetic analysis were recommended. The surgical excision specimen showed an ill-defined, heterogeneous, pale-gray to yellow-red, soft, gelatinous mass in the subcutaneous tissue without epidermal involvement. A portion of the fresh specimen was sent for cytogenetic analysis. Microscopic evaluation showed a dermal and subcutaneous spindle cell neoplasm, which extended to the resection margins. The tumor consisted of two distinct but admixed

Diagnostic Cytopathology DOI 10.1002/dc

GIANT CELL FIBROBLASTOMA: DIAGNOSIS BY FNA

Fig. C-2. Surgical excision/histologic features. (a) Pseudovascular spaces lined by giant cells with myxoid to hyalized stroma. H&E. 2003. (b) Cellular area, with spindled to stellate cells and fat entrapment. H&E. 2003.

morphologic patterns. Areas of hypercellular spindled to stellate cells arranged in a storiform to patternless pattern alternated with hypocellular areas with spindle cells in a slightly myxoid to collagenized background (Figs. C-2a and b). The hypocellular areas had multiple scattered floret-like multinucleated giant cells and prominent dilated pseudovascular spaces lined by compressed mononuclear or multinucleated tumor cells (Fig. C-2a). Numerous small vessels with concentric layers of surrounding lymphocytes in an “onion-skin” pattern were noted. The tumor was poorly circumscribed, infiltrating into surrounding adipose tissue in a “honeycomb-like” pattern and sparing adnexal structures. The morphologic features were that of GCF with areas of histologic overlap with conventional DFSP. An immunohistochemical stain for CD34 was strongly positive. Additional immunohistochemical stains for CD31, desmin, myogenin, CD117, S100, Factor 13A, and pankeratin were negative. Cytogenetic chromosomal analysis showed an abnormal male karyotype with a t(17;22)(q21;q13) translocation. The morphology, immunophenotype, and translocation of 17;22 all supported the diagnosis of GCF. Although the tumor was present at the excision margin, no further surgical therapy was pursued. At 1 year of follow-up there was no evidence of residual disease.

Discussion GCF is an unusual, typically pediatric, soft tissue neoplasm with distinct histologic features, as observed in this case.1,2 While morphologic differences may distinguish GCF from DFSP, these two entities exist on a spectrum with extensive overlap in clinical, histologic, and genetic features.3,6–13 In this case of GCF, while definitive diagnosis was not made on FNA, many clinical concerns were excluded,

including lipoblastoma, hemangioma, or high-grade sarcoma. The FNA specimen was correctly classified as a low-grade spindle cell neoplasm and appropriate management was suggested. However, the significance of the floret-like giant cells was not initially recognized. The cytologic features of GCF include mononuclear spindled to oval cells with vesicular nuclei in a background of metachromatic stroma. These features overlap with aspirate findings in DFSP;14 however, GCF should additionally demonstrate floret-like giant cells.5,6 In either entity, minimal cytologic atypia, a low to absent mitotic index, and expression of CD34 are expected.5,6,14 The differential diagnosis of this pediatric soft tissue neoplasm included a variety of benign to low-grade mesenchymal neoplasms, including nodular fasciitis, inflammatory myofibroblastic tumor, juvenile xanthogranuloma, lipoblastoma, dermatofibroma, and various CD34-positive mesenchymal neoplasms, including myofibroma, fibrous hamartoma of infancy, hemangioma, and solitary fibrous tumor.3,5,6,15 A combination of cytologic/histologic findings in conjunction with immunophenotype can distinguish these entities. An important feature demonstrated on FNA was the presence of floret-like giant cells. These giant cells, in this clinical context, and in conjunction with CD34 positivity, strongly favored a diagnosis of GCF. Additionally, the remaining considerations are not known to share the t(17;22) seen in GCF/DFSP. Prior case series of FNA of DFSP emphasize that cytologic preparations alone are often insufficient to render a diagnosis and cell block material is required for accurate and specific diagnosis.14,16,17 This case highlights the benefit of obtaining additional tissue for cytogenetic studies in pediatric patients who may have soft tissue neoplasms with associated translocations.18 Cytogenetic analysis was performed on the surgical specimen of this case, supporting the Diagnostic Cytopathology, Vol. 43, No 4

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diagnosis of GCF. However, if cytogenetic testing had been pursued and the diagnosis of GCF rendered on the initial FNA, the surgical decision for a wider excision may have been made to decrease the likelihood of recurrence. While FNA is of diagnostic utility, ancillary testing is often essential to establish definitive diagnosis, particularly in rare entities that are infrequently observed in common practice.

References 1. Dymock RB, Allen PW, Stirling JW, Gilbert EF, Thornbery JM. Giant cell fibroblastoma. A distinctive recurrent tumor of childhood. Am J Surg Pathol 1987;11:263–271. 2. Schmookler BM, Enzinger FM, Weiss SW. Giant cell fibroblastoma: A juvenile form of dermatofibrosarcoma protuberans. Cancer 1989;64:2154–2161. 3. Jha P, Moosavi C, Fanburg-Smith JC. Giant cell fibroblastoma: An update and addition of 86 new cases from the Armed Forced Institute of Pathology, in honor of Dr. Franz M. Enzinger. Ann Diagn Pathol 2007;11:81–88. 4. Layfield LJ, Gopez EV. Fine-needle aspiration cytology of giant cell fibroblastoma: Case report and review of the literature. Diagn Cytopathol 2002;26(6):398–403. 5. Maitra A, Timmons CF, Siddiqui MT, Saboorian MH. Fine-needle aspiration biopsy features in a case of giant cell fibroblastoma of the chest wall. Arch Pathol Lab Med 2001;125:1091–1094. 6. Maeda T, Hirose T, Furuya K, Shirakawa K, Kobayashi K. Giant cell fibroblastoma associated with dermatofibrosarcoma protuberans: A case report. Mod Pathol 1998;11:491–495. 7. Zamocnik M, Michal M. Giant cell fibroblastoma with pigmented dermatofibrosarcoma protuberans component. Am J Surg Pathol 1994;18:736–740. 8. Allen PW, Zwi J. Giant cell fibroblastoma transforming into dermatofibrosarcoma protuberans. Am J Surg Pathol 1992;16:1127– 1129.

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9. Denoux Y, Busson A, de Ranieri J, Contesso G, Lemerle J, Mandard AM. Recurrence of giant cell fibroblastoma as dermatofibrosarcoma protuberans in the adult. Ann Pathol 1996;16:457– 459. 10. Cin PD, Sciot R, de Wever I, et al. Cytogenetic and immunohistochemical evidence that giant cell fibroblastoma is related to dermatofibrosarcomaprotuberans. Gene Chromosome Cancer 1996;15: 73–75. 11. Harvell JD, Kilpatrick SE, White WL. Histogenetic relationships between giant cell fibroblastoma and dermatofibrosarcoma protuberans.CD34 staining showing the spectrum and a simulator. Am J Dermatopathol 1998;20:339–345. 12. Simon MP, Florence P, Sirvent N, et al. Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giantcell fibroblastoma. Nat Genet 1997;15:95–98. 13. Terrier-Lacombe MJ, Guillou L, Maire G, et al. Dermatofibrosarcoma protuberans, giant cell fibroblastoma, and hybrid lesions in children: Clinicopathologic comparative analysis of 28 cases with molecular data. Am J Surg Pathol 2003;27(1):27–39. 14. Domanski HA. FNA diagnosis of dermatofibromasarcoma protuberans. Diagn Cytopathol 2005;32(5):299–302. 15. Wood L, Fountaine TJ, Rosamilia L, Helm KF, Clarke LE. Cutaneous CD341 spindle cell neoplasms: Histopathologic features distinguish spindle cell lipoma, solitary fibrous tumor, and dermatofibrosarcoma protuberans. Am J Dermatopathol 2010;32:764–768. 16. Klijanienko J, Caillaud JM, Lagace R. Fine-needle aspiration of primary and recurrent dermatofibrosarcoma protuberans. Diagn Cytopathol 2004;30:261–265. 17. Domanski HA, Gustafson P. Cytologic features of primary, recurrent, and metastatic dermatofibrosarcoma protuberans. Cancer 2002; 25:351–361. 18. Coffin CM, Alaggio R, Dehner LP. Some general consisderations about the clinicopathologic aspects of soft tissue tumors in children and adolescents. Pediatr Dev Pathol 2012;15(1 Suppl): 11–25.

FNA diagnosis of giant cell fibroblastoma: a case report of an unusual pediatric soft tissue tumor.

Giant cell fibroblastoma (GCF) is a rare pediatric soft tissue tumor, which exists on a spectrum with dermatofibrosarcoma protuberans (DFSP). Histolog...
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