Soft tissue
Fibroblastic / myofibroblastic
Giant cell fibroblastoma
Editorial Board Member: Josephine K. Dermawan, M.D., Ph.D.
Deputy Editor-in-Chief: Borislav A. Alexiev, M.D.
Last author update: 28 August 2024
Last staff update: 28 August 2024
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PubMed Search: Giant cell fibroblastoma
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Cytology description | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Molecular / cytogenetics images | Videos | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Maharjan D, Dehner C. Giant cell fibroblastoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissuegiantcellfibro.html. Accessed December 23rd, 2024.
Definition / general
- Locally aggressive subcutaneous fibroblastic neoplasm, arising predominantly in pediatric population
- Considered to be in a spectrum of dermatofibrosarcoma protuberans (DFSP)
Essential features
- Rare fibroblastic neoplasm in dermis, usually affecting children and closely related to DFSP
- Histologically characterized by the presence of spindle to stellate cells, multinucleated / floret-like giant cells lining the ectatic pseudovascular spaces and diffuse CD34 positivity
- Chromosomal translocation t(17:22) resulting in COL1A1::PDGFB fusion
- Increased risk of recurrence if incompletely excised
Terminology
- Giant cell fibroblastoma (GCF)
ICD coding
- ICD-O: 8834/1 - giant cell fibroblastoma
- ICD-11: FB51.Y & XH9AV8 - other specified fibroblastic disorders & giant cell fibroblastoma
Epidemiology
- Rare neoplasm
- M > F
- Median age of 6 years (Ann Diagn Pathol 2007;11:81)
- Infrequent in adults
Sites
- Predilection for trunk, back of the thigh, inguinal region and axilla region
- Rarely head and neck / extremities
Pathophysiology
- Chromosomal translocation t(17:22) resulting in COL1A1::PDGFB fusion; breakpoint in COL1A1 is variable but occurs in region encoding alpha helical domain
- Breakpoint in PDGFB always occurs in exon 2 and encodes beta chain of the PDGF ligand, a tyrosine kinase receptor with mitogenic potential
- Fusion of these genes results in overexpression of a chimeric protein or native PDGFB (Cancer Genet Cytogenet 2003;140:1)
- Closely related to DFSP in histogenesis, with studies showing DFSP recurring as giant cell fibroblastoma and hybrid tumor as well as giant cell fibroblastoma recurring as DFSP (J Plast Reconstr Aesthet Surg 2010;63:e785, Arch Pathol Lab Med 1996;120:1052)
- Amplification / gain of COL1A1::PDGFB is absent in giant cell fibroblastoma but present in DFSP component of hybrid forms, indicating association of genomic gains in the evolution of giant cell fibroblastoma to DFSP (Genes Chromosomes Cancer 2008;47:260)
Etiology
- Unknown
Clinical features
- Superficial painless slow growing plaque to protuberant nodule attached to overlying skin
Diagnosis
- Diagnosis is based on location, morphological features and CD34 positivity by immunohistochemistry
- COL1A1::PDGFB fusion may be detected by different molecular methods; useful for diagnosis but not required
Radiology description
- Ultrasound
- Hypoechoic with well defined margins and internal, irregular, septum-like echogenic structures (Taehan Yongsang Uihakhoe Chi 2020;81:237)
- Magnetic resonance imaging (MRI)
- Different signal intensity in the center and the periphery on fluid sensitive T2 weighted images with a bright edge and lower signal in the center (Taehan Yongsang Uihakhoe Chi 2020;81:237)
- Low T1 signal intensity and high T2 signal intensity with marked contrast enhancement (Am J Dermatopathol 2006;28:228)
Radiology images
Images hosted on other servers:
Ultrasonographic findings, MRI
Prognostic factors
- Recurrence in 50% of cases, especially in cases of incomplete, marginal excision
- Excellent prognosis and low risk of recurrence with wide excision (Am J Surg Pathol 2003;27:27)
- No metastasis reported
Case reports
- 1.5 year old boy with swelling in the occipital area of scalp and encephalocele (BMJ Case Rep 2014;2014:bcr2013203420)
- 3 year old boy with painless swelling at right ankle (Oman Med J 2012;27:e037)
- 3 year old boy with well circumscribed soft tissue mass at left lower abdomen (Taehan Yongsang Uihakhoe Chi 2020;81:237)
- 25 year old man with painless tumor in right lumbar with multiple recurrences (Int J Clin Exp Pathol 2018;11:4052)
Treatment
- Wide local excision with follow up
- Mohs surgery in recurrent cases (Dermatol Surg 2010;36:417)
- DFSP can be treated with imatinib (Ann Diagn Pathol 2016;25:64, Clin Exp Dermatol 2023;48:297, J Clin Med 2020;9:1752)
Clinical images
Images hosted on other servers:
Trunk lesion
Gross description
- Infiltrative and ill defined lesions with a gray to yellowish color and mucoid cut surface
- Variable size ranging from < 1 cm to 8 cm with a median size of 3 - 4 cm (Cancer 1989;64:2154)
Gross images
Images hosted on other servers:
Right ankle tumor
Microscopic (histologic) description
- Dermal tumor with infiltration into subcutaneous fat in honeycomb or parallel growth pattern; spared cutaneous adnexal structures
- Fibrous to myxoid stroma with variable cellularity
- Bland uniform spindled and stellate tumor cells
- Multinucleated / floret-like giant cells with wreath-like nuclei lining irregular pseudovascular spaces
- Perivascular lymphocytic infiltration in an onion skinning pattern; intralesional hemorrhage; myoid whorls in rare cases (Ann Diagn Pathol 2007;11:81)
- Tumors with DFSP components, fibrosarcomatous and pigmented Bednar tumor component reported (Mod Pathol 1998;11:491, Cesk Patol 2002;38:173, Arch Pathol Lab Med 1996;120:1052)
- Tumors may recur as DSFP and may then develop fibrosarcomatous change (Histopathology 1994;24:197)
Microscopic (histologic) images
Contributed by Carina Dehner, M.D., Ph.D., Mark R. Wick, M.D. and AFIP
Ill defined dermal tumor
Honeycomb pattern
Pseudovascular spaces
Multinucleated / floret giant cells
Giant cells and spindled cells
Myoid whorls
Hybrid tumor with DFSP component
Ectatic pseudovascular spaces
Stroma
Fibrotic stroma
Multinucleated stromal giant cells
Breast skin
CD34
Virtual slides
Images hosted on other servers:
20 year old woman with lump on back
Cytology description
- Singly scattered or occasional clusters of mononuclear cells with scant bipolar cytoplasm, vesicular nuclei and inconspicuous to single, small nucleoli (Arch Pathol Lab Med 2001;125:1091)
- Nuclear membranes with frequent notches, creases or folds; rare or no mitotic figures (Diagn Cytopathol 2002;26:398)
- Metachromatic stromal fragments associated with small aggregates of cells in the background
- Absence of necrosis
Positive stains
- CD34: strong and diffusely positive (Med Arh 2006;60:389)
Negative stains
Electron microscopy description
- Ultrastructural finding supports both mononuclear cells and multinucleated giant cells to be of fibroblastic origin (Am J Clin Pathol 1985;83:165, Mod Pathol 1992;5:639)
Molecular / cytogenetics description
- Balanced or unbalanced chromosomal translocation t(17;22) resulting in the fusion gene COL1A1::PDGFB
- Other less common translocations occurring in DFSP / giant cell fibroblastoma include COL1A2::PDGF, COL6A3::PDGFD, EMILIN2::PDGFD and TNC::PDGFD (JAMA Dermatol 2015;151:1330, Mod Pathol 2018;31:1683)
Molecular / cytogenetics images
Images hosted on other servers:
Karyotype
Molecular events
FISH
Videos
Giant cell fibroblastoma
Sample pathology report
- Skin and soft tissue, right thigh, excision:
- Giant cell fibroblastoma with a dermatofibrosarcoma protuberans component (see comment)
- Deep surgical margin free
- Comment: Immunohistochemical stains using the modified avidin biotin technique are performed with appropriate controls. The neoplasm is CD34 positive and S100 protein negative. Controls stain appropriately.
Differential diagnosis
- Fibrous hamartoma of infancy:
- Commonly occurs in infants and young children
- Triphasic morphology with bland fibroblastic / myofibroblastic cell bundles, primitive mesenchyme nodules and mature adipose tissue arranged in an organoid pattern
- Pseudoangiomatous areas lined by plump tumor cells in 33 - 50% of cases
- Immunohistochemistry shows SMA positive fibroblastic areas, CD34 and BCL2 positive primitive mesenchymal cells and S100 positive adipocytic areas
- EGFR exon 20 insertion / duplication mutations
- Giant cell angiofibroma:
- Rare soft tissue tumor occurring predominantly in mesenchymal tissue of orbit and head and neck region
- Well circumscribed tumor with patternless spindle cell proliferation, pseudovascular spaces and floret-like multinucleated giant cells
- Prominent hyalinized blood vessels
- CD34 and BCL2: strong and diffusely positive
- CD31, SMA, desmin, CD117, S100: negative (Case Rep Pathol 2012;2012:408575, Am J Surg Pathol 1995;19:1286)
- Spindle cell / pleomorphic lipoma:
- Arising mainly in men 45 - 60 years of age
- Most common locations are posterior neck, shoulder and back
- Solitary, circumscribed, slowly growing nodule in the subcutaneous tissue
- Histologically characterized by the triad of mature adipocytes, bland spindle cells and thick ropy collagen in varying proportion
- Multinucleated floret-like giant cells present in pleomorphic lipoma
- Pseudoangiomatous variant is characterized by irregular branching spaces with well formed connective tissue projections
- Strong and diffuse CD34 positivity, loss of nuclear RB1 protein expression
- Loss of 16q or 13q
- Pleomorphic fibroma:
- Common in adults and presenting as a slow growing solitary skin colored papule
- Well circumscribed tumor involving papillary and reticular dermis
- Histologically characterized by predominant thick haphazardly arranged collagen and low cellularity
- Presence of scattered spindle or stellate cells and pleomorphic multinucleated giant cells
- Variable immunoreactivity for CD34 and actin
- CD56, CD68, S100 and factor XIII: negative (Cureus 2023;15:e37018)
- Loss of expression of RB1 protein
- Cytogenetic abnormality consists of loss of 13q
Additional references
Board review style question #1
A 5 year old boy presents with a slow growing painless nodule on the back. Histological examination reveals the above given picture. What is the cytogenetic finding in this tumor?
- t(12;15)(p13;q26)
- t(12;16)(q13;p11)
- t(17;22)(q22;q13)
- t(21;22)(q12;q12)
Board review style answer #1
C. t(17;22)(q22;q13) is the cytogenetic finding in giant cell fibroblastoma. Answer A is incorrect because t(12;15)(p13;q26) is not seen in giant cell fibroblastoma but is present in infantile fibroblastoma and congenital mesoblastic nephroma. Answer D is incorrect because t(21;22)(q12;q12) is seen in Ewing sarcoma but not in giant cell fibroblastoma. Answer B is incorrect because giant cell fibroblastoma lacks t(12;16)(q13;p11) and is present in myxoid liposarcoma.
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Board review style question #2
Which of the following immunoprofiles is consistent with giant cell fibroblastoma?
- CD34-, CD31-, S100+, SMA-
- CD34+, CD31+, S100-, SMA-
- CD34+, CD31-, S100-, SMA-
- CD34+, CD31-, S100+, SMA+
Board review style answer #2
C. CD34+, CD31-, S100-, SMA-. Giant cell fibroblastoma is diffuse and strongly positive for CD34. Both the spindle cells and multinucleated giant cells stain with CD34. Answer A is incorrect because giant cell fibroblastoma is negative for S100 and positive for CD34. Myxoid liposarcoma is positive for S100 but negative for CD34. Answer B is incorrect because giant cell fibroblastoma is positive for CD34 but negative for CD31. Vascular tumors are positive for both CD31 and CD34. Answer D is incorrect because giant cell fibroblastoma is negative for SMA. Fibrous hamartoma of infancy has CD34 positive primitive mesenchymal area along with SMA positive fibroblastic areas and S100 positive adipocytic area.
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