Clinical Review & Education
JAMA Dermatology Clinicopathological Challenge
Soft, Multilobed Exophytic Mass in a Woman in Her 50s Evan W. Piette, MD; Joseph F. Sobanko, MD; Karolyn A. Wanat, MD
A woman in her 50s presented to the clinic for initial evaluation of a soft, flesh-colored, eroded, exophytic mass arising within a soft plaque in the inguinal region (Figure, A). The lesion had been growing for approximately 6 months, and was described as being sore but otherwise asymptomatic. The patient had no other pertinent medical problems and reported no prior skin
conditions with theexception of a “bump” in the area of the mass that had resolved several months prior to development of the lesion seen in the Figure, A. A biopsy was performed, and histopathologic examination of the mass is shown in the Figure, B and C. What is your diagnosis?
A
B
C
Figure. A, Soft, multilobed, exophytic, eroded mass in the inguinal region. B, Histopathologic examination of the mass (hematoxylin-eosin, original magnification ×200). C, Immunohistochemically stained (CD34 positive) specimen of the mass (original magnification ×200).
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JAMA Dermatology March 2014 Volume 150, Number 3
Copyright 2014 American Medical Association. All rights reserved.
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323
Clinical Review & Education JAMA Dermatology Clinicopathological Challenge
Diagnosis Giant cell fibroblastoma (GCF)
Microscopic Findings and Clinical Course A biopsy specimen was obtained, and the patient was subsequently referred for Mohs micrographic surgery, where excision was extended to the fascia. Histopathologic findings of both the initial biopsy and the excised specimen demonstrated a dermal proliferation of mononuclear spindle cells and multinucleated giant cells associated with a loose connective tissue and areas of myxoid matrix (Figure, B). The histologic differential could include other entities containing spindled cells in a background of variable mucinous stroma, such as neurofibroma, dermatofibroma, nodular fasciitis, atypical fibrous xanthoma, and malignant fibrohistiocytoma (undifferentiated pleomorphic sarcoma). The spindle cells in our patient stained positive for CD34 (Figure, C) and were negative for S-100, smooth muscle actin, AE1/AE3, factor XIIIa, and CD68, consistent with a diagnosis of GCF. Fluorescent in situ hybridization assay for the COL1A1PDGFB fusion via the t(17;22) translocation were performed on both the initial biopsy specimen and excisional specimen, and results were negative.
Discussion Giant cell fibroblastoma was first described in the 1980s, and traditional teaching has suggested it as the juvenile variant of dermatofibrosarcoma protuberans (DFSP).1 However, recent publications have demonstrated that GCF may be seen more frequently in adults than previously thought, and investigators have considered GCF to be on a spectrum with other variants of DFSP, including pigmented, myxoid, myoid, granular cell, sclerotic, atrophic, and DFSP with fibrosarcomatous areas.1,2 In our patient, histopathoARTICLE INFORMATION Author Affiliations: Department of Dermatology, Hospital of University of Pennsylvania, Philadelphia. Corresponding Author: Evan W. Piette, MD, Department of Dermatology, University of Pennsylvania, 3600 Spruce St, 2 Maloney Building, Philadelphia, PA 19104 ([email protected]). Section Editor: Mary S. Stone, MD; Assistant Section Editors: Soon Bahrami, MD; Carrie Ann R. Cusack, MD; Molly A. Hinshaw, MD; Arni K. Kristjansson, MD; Lori D. Prok, MD. Published Online: January 1, 2014. doi:10.1001/jamadermatol.2013.7544. Conflict of Interest Disclosures: None reported. REFERENCES 1. Llombart B, Serra-Guillén C, Monteagudo C, López Guerrero JA, Sanmartín O. Dermatofibrosarcoma protuberans:
324
logic examination revealed an area of a myxoid matrix. This finding of GCF-like areas associated with a myxoid matrix has also recently been described in a case series of 16 patients in China with myxoid DFSP.3 Typically GCF presents similarly to DFSP, with a slowly growing, asymptomatic, protuberant nodule in a truncal distribution with a high local recurrence rate after excision (approximately 50%) and a sex predilection for males.4 In addition, GCF and DFSP demonstrate deep infiltration into the subcutaneous fat. Both tumors show CD34 positivity and more recently have been shown to express the relatively specific immunohistochemical marker apolipoprotein D.5 They also commonly share the t(17;22) chromosomal translocation, resulting in expression of COL1A1-PDGFB.6 Interestingly, our patient was negative for this translocation. Studies have shown over 90% of DFSPs are positive for this translocation7 and have suggested that gain of this translocation is involved in the histologic evolution of GCF into DFSP.8 Primary differences between GCF and DFSP are seen on histopathologic examination. In GCF, there are branching pseudocystic or pseudovascular areas lined by mononuclear spindle cells and multinucleated giant cells. In contrast, DFSP typically shows a storiform pattern of uniform, spindled cells with plump nuclei.6 In addition, no reports of distant metastasis in patients with GCF are currently published in the literature, in contrast to DFSP. Surgical excision is the recommended treatment. Mohs micrographic surgery offers precise microscopic margin evaluation and may reduce the likelihood of recurrence.4,6 Adjuvant therapy with imatinib mesylate can be effective when the COL1A1-PDGFB fusion is present.1 Current recommendations for follow-up include examination every 6 months for the first 3 years, followed by annual examinations for the lifetime of the patient.1
a comprehensive review and update on diagnosis and management. Semin Diagn Pathol. 2013;30(1):13-28. 2. Eminger LA, Shinohara MM, Elenitsas R, Halpern AV, Heymann WR. Giant cell fibroblastoma mimicking a soft fibroma arising within a dermatofibrosarcoma protuberans. J Am Acad Dermatol. 2012;67(4):e137-e139. 3. Ren WM, Sheng WQ, Wang J. Myxoid dermatofibrosarcoma protuberans: a clinicopathologic analysis of 16 cases [in Chinese]. Zhonghua Bing Li Xue Za Zhi. 2012;41(7):456-460. 4. Najarian DJ, Morrison C, Sait SN, et al. Recurrent giant cell fibroblastoma treated with Mohs micrographic surgery. Dermatol Surg. 2010;36(3):417-421.
6. Jha P, Moosavi C, Fanburg-Smith JC. 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. Ann Diagn Pathol. 2007;11(2):81-88. 7. Salgado R, Llombart B, M Pujol R, et al. Molecular diagnosis of dermatofibrosarcoma protuberans: a comparison between reverse transcriptasepolymerase chain reaction and fluorescence in situ hybridization methodologies. Genes Chromosomes Cancer. 2011;50(7):510-517. 8. Macarenco RS, Zamolyi R, Franco MF, et al. Genomic gains of COL1A1-PDFGB occur in the histologic evolution of giant cell fibroblastoma into dermatofibrosarcoma protuberans. Genes Chromosomes Cancer. 2008;47(3):260-265.
5. West RB, Harvell J, Linn SC, et al. Apo D in soft tissue tumors: a novel marker for dermatofibrosarcoma protuberans. Am J Surg Pathol. 2004;28(8):1063-1069.
JAMA Dermatology March 2014 Volume 150, Number 3
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/22/2015
jamadermatology.com
JAMA Dermatology Clinicopathological Challenge
Soft, Multilobed Exophytic Mass in a Woman in Her 50s Evan W. Piette, MD; Joseph F. Sobanko, MD; Karolyn A. Wanat, MD
A woman in her 50s presented to the clinic for initial evaluation of a soft, flesh-colored, eroded, exophytic mass arising within a soft plaque in the inguinal region (Figure, A). The lesion had been growing for approximately 6 months, and was described as being sore but otherwise asymptomatic. The patient had no other pertinent medical problems and reported no prior skin
conditions with theexception of a “bump” in the area of the mass that had resolved several months prior to development of the lesion seen in the Figure, A. A biopsy was performed, and histopathologic examination of the mass is shown in the Figure, B and C. What is your diagnosis?
A
B
C
Figure. A, Soft, multilobed, exophytic, eroded mass in the inguinal region. B, Histopathologic examination of the mass (hematoxylin-eosin, original magnification ×200). C, Immunohistochemically stained (CD34 positive) specimen of the mass (original magnification ×200).
jamadermatology.com
JAMA Dermatology March 2014 Volume 150, Number 3
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/22/2015
323
Clinical Review & Education JAMA Dermatology Clinicopathological Challenge
Diagnosis Giant cell fibroblastoma (GCF)
Microscopic Findings and Clinical Course A biopsy specimen was obtained, and the patient was subsequently referred for Mohs micrographic surgery, where excision was extended to the fascia. Histopathologic findings of both the initial biopsy and the excised specimen demonstrated a dermal proliferation of mononuclear spindle cells and multinucleated giant cells associated with a loose connective tissue and areas of myxoid matrix (Figure, B). The histologic differential could include other entities containing spindled cells in a background of variable mucinous stroma, such as neurofibroma, dermatofibroma, nodular fasciitis, atypical fibrous xanthoma, and malignant fibrohistiocytoma (undifferentiated pleomorphic sarcoma). The spindle cells in our patient stained positive for CD34 (Figure, C) and were negative for S-100, smooth muscle actin, AE1/AE3, factor XIIIa, and CD68, consistent with a diagnosis of GCF. Fluorescent in situ hybridization assay for the COL1A1PDGFB fusion via the t(17;22) translocation were performed on both the initial biopsy specimen and excisional specimen, and results were negative.
Discussion Giant cell fibroblastoma was first described in the 1980s, and traditional teaching has suggested it as the juvenile variant of dermatofibrosarcoma protuberans (DFSP).1 However, recent publications have demonstrated that GCF may be seen more frequently in adults than previously thought, and investigators have considered GCF to be on a spectrum with other variants of DFSP, including pigmented, myxoid, myoid, granular cell, sclerotic, atrophic, and DFSP with fibrosarcomatous areas.1,2 In our patient, histopathoARTICLE INFORMATION Author Affiliations: Department of Dermatology, Hospital of University of Pennsylvania, Philadelphia. Corresponding Author: Evan W. Piette, MD, Department of Dermatology, University of Pennsylvania, 3600 Spruce St, 2 Maloney Building, Philadelphia, PA 19104 ([email protected]). Section Editor: Mary S. Stone, MD; Assistant Section Editors: Soon Bahrami, MD; Carrie Ann R. Cusack, MD; Molly A. Hinshaw, MD; Arni K. Kristjansson, MD; Lori D. Prok, MD. Published Online: January 1, 2014. doi:10.1001/jamadermatol.2013.7544. Conflict of Interest Disclosures: None reported. REFERENCES 1. Llombart B, Serra-Guillén C, Monteagudo C, López Guerrero JA, Sanmartín O. Dermatofibrosarcoma protuberans:
324
logic examination revealed an area of a myxoid matrix. This finding of GCF-like areas associated with a myxoid matrix has also recently been described in a case series of 16 patients in China with myxoid DFSP.3 Typically GCF presents similarly to DFSP, with a slowly growing, asymptomatic, protuberant nodule in a truncal distribution with a high local recurrence rate after excision (approximately 50%) and a sex predilection for males.4 In addition, GCF and DFSP demonstrate deep infiltration into the subcutaneous fat. Both tumors show CD34 positivity and more recently have been shown to express the relatively specific immunohistochemical marker apolipoprotein D.5 They also commonly share the t(17;22) chromosomal translocation, resulting in expression of COL1A1-PDGFB.6 Interestingly, our patient was negative for this translocation. Studies have shown over 90% of DFSPs are positive for this translocation7 and have suggested that gain of this translocation is involved in the histologic evolution of GCF into DFSP.8 Primary differences between GCF and DFSP are seen on histopathologic examination. In GCF, there are branching pseudocystic or pseudovascular areas lined by mononuclear spindle cells and multinucleated giant cells. In contrast, DFSP typically shows a storiform pattern of uniform, spindled cells with plump nuclei.6 In addition, no reports of distant metastasis in patients with GCF are currently published in the literature, in contrast to DFSP. Surgical excision is the recommended treatment. Mohs micrographic surgery offers precise microscopic margin evaluation and may reduce the likelihood of recurrence.4,6 Adjuvant therapy with imatinib mesylate can be effective when the COL1A1-PDGFB fusion is present.1 Current recommendations for follow-up include examination every 6 months for the first 3 years, followed by annual examinations for the lifetime of the patient.1
a comprehensive review and update on diagnosis and management. Semin Diagn Pathol. 2013;30(1):13-28. 2. Eminger LA, Shinohara MM, Elenitsas R, Halpern AV, Heymann WR. Giant cell fibroblastoma mimicking a soft fibroma arising within a dermatofibrosarcoma protuberans. J Am Acad Dermatol. 2012;67(4):e137-e139. 3. Ren WM, Sheng WQ, Wang J. Myxoid dermatofibrosarcoma protuberans: a clinicopathologic analysis of 16 cases [in Chinese]. Zhonghua Bing Li Xue Za Zhi. 2012;41(7):456-460. 4. Najarian DJ, Morrison C, Sait SN, et al. Recurrent giant cell fibroblastoma treated with Mohs micrographic surgery. Dermatol Surg. 2010;36(3):417-421.
6. Jha P, Moosavi C, Fanburg-Smith JC. 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. Ann Diagn Pathol. 2007;11(2):81-88. 7. Salgado R, Llombart B, M Pujol R, et al. Molecular diagnosis of dermatofibrosarcoma protuberans: a comparison between reverse transcriptasepolymerase chain reaction and fluorescence in situ hybridization methodologies. Genes Chromosomes Cancer. 2011;50(7):510-517. 8. Macarenco RS, Zamolyi R, Franco MF, et al. Genomic gains of COL1A1-PDFGB occur in the histologic evolution of giant cell fibroblastoma into dermatofibrosarcoma protuberans. Genes Chromosomes Cancer. 2008;47(3):260-265.
5. West RB, Harvell J, Linn SC, et al. Apo D in soft tissue tumors: a novel marker for dermatofibrosarcoma protuberans. Am J Surg Pathol. 2004;28(8):1063-1069.
JAMA Dermatology March 2014 Volume 150, Number 3
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/22/2015
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