ABSTRACT
The aim of this case report is to introduce the reader to dermatofibrosarcoma protuberans (DFSP). In addition to the general characteristics of this rare skin tumor with possible metastatic potential, we also describe an atypical genetic finding that made our patient's case unique.
Keywords: abdominal wall resistance, case report, COL1A1, dermatofibrosarcoma protuberans, fluorescence in situ hybridization, histopathology, PDGFB
1. Introduction
Dermatofibrosarcoma protuberans (DFSP) is a fibroblastic soft tissue tumor that is locally aggressive, frequently recurrent, but has minimal metastatic potential. It is a relatively rare entity (< 1% of sarcomas); however, it is the most common sarcoma of the skin and subcutaneous tissue. DFSP predominantly affects young adults and middle‐aged individuals. It typically appears on the trunk and proximal parts of the extremities as a persistent, slow‐growing nodular mass.
Histologically, DFSP is characterized by a distinctive morphology in routine staining, locally infiltrative growth, and diffuse CD34 positivity. The most common genetic abnormality in DFSP is the reciprocal translocation t(17;22)(q21.3;q13.1) (in approximately 95% of cases). Characteristic genetic changes described in the literature also include unbalanced translocations, often involving circular chromosomes: der(17)(17;22)(q22;q13), leading to the rearrangement and subsequent fusion of the COL1A1 and PDGFB genes to form the COL1A1::PDGFB fusion gene [1]. This fusion gene arises from the combination of the regulatory region of type I procollagen (COL1A1) and the coding region for PDGFB (platelet‐derived growth factor beta). The COL1A1::PDGFB fusion protein continuously produces active PDGF‐beta, which in turn activates the platelet‐derived growth factor receptor (PDGFRB). This initiates autocrine or paracrine signaling that promotes fibroblast proliferation, migration, and survival. Dysregulation of the PDGF‐beta signaling pathway leads to uncontrolled tumor cell growth and development of DFSP [2]. In the presented case, fluorescence in situ hybridization (FISH) analysis additionally revealed an unusual genetic rearrangement (deletion) in the COL1A1 and PDGFB gene regions (Table 1).
TABLE 1.
Summary of classical and atypical FISH patterns reported in dermatofibrosarcoma protuberans (DFSP), including the novel “double deletion” pattern identified in the present case.
| FISH pattern | Cytogenetic mechanism | Typical FISH signal pattern (COL1A1/PDGFB fusion probe) | Molecular interpretation | Comment/frequency |
|---|---|---|---|---|
| Classical balanced t(17;22)(q22;q13) | Balanced reciprocal translocation between chromosomes 17 and 22 | One fusion (yellow), one red, and one green signal | COL1A1::PDGFB fusion gene formation | Kiuru‐Kuhlefelt et al. (2001) [3], Sirvent et al. (2003) [4]—most common pattern |
| Ring chromosome pattern | Supernumerary ring chromosomes derived from chromosomes 17 and 22 | Multiple fusion signals and/or low‐level amplification (1–3 copies) | COL1A1::PDGFB fusion present and amplified | Kiuru‐Kuhlefelt et al. (2001)—represents unbalanced rearrangement |
| Unbalanced t(17;22) | Gain or loss of chromosomal segments near the breakpoints | One fusion (yellow) with additional red or green signals (2–5 copies possible) | COL1A1::PDGFB fusion plus extra COL1A1 or PDGFB sequences | Sirvent et al. (2003)—frequent unbalanced rearrangement pattern |
| Atypical “double deletion” pattern (present case) | Complex rearrangement involving loss of both telomeric COL1A1 and centromeric PDGFB regions | Fusion signal (break apart probe: with separated or missing probe signals for both genes) | Suggests a cryptic or complex unbalanced rearrangement involving both genes | Novel finding in this study—not previously reported |
2. Case History and Examination
A 38‐year‐old woman was referred from an external facility following histological verification of an endometrioid endometrial carcinoma. A specialized gynecological examination was conducted, confirming the presence of the endometrial lesion. Following the examination, the patient was admitted to the gynecology and obstetrics department for a hysterectomy and bilateral salpingectomy surgery with sentinel lymph node detection. During the procedure, the surgeon noted a firm, nodular tumor measuring approximately 2 cm in the subcutaneous tissue of the abdominal wall, located between the umbilicus and the C‐section scar.
3. Investigations and Diagnosis
After approximately 24 h of fixation in 10% formalin (4% formaldehyde solution), the specimen removed from the abdominal wall was sectioned and processed. Macroscopically, the sample contained a poorly demarcated, firm, gray‐white spherical lesion within the skin and subcutaneous tissue. Three representative samples were selected for further processing and paraffin embedding using standard histopathological techniques.
Microscopic examination with hematoxylin and eosin (H&E) staining revealed a spindle‐cell neoplastic proliferation (Figure 1). The tumor consisted of a uniform population of fibroblast‐like cells with minimal cytological atypia. A storiform and focally whorled growth pattern was observed. Mitotic activity was low. Atypical mitoses were absent. The lesion spared skin adnexa and a narrow band of papillary dermis (the so‐called grenz zone). Tumor cells infiltrated the subcutaneous tissue along fibrous septa in a honeycomb pattern (Figure 2).
FIGURE 1.
Dermatofibrosarcoma protuberans (DFSP)—a spindle cell neoplasm showing a uniform storiform growth pattern with no significant cytologic atypia (H&E staining).
FIGURE 2.
Excised margin demonstrating infiltrative growth of DFSP into the subcutaneous adipose tissue (H&E staining).
Immunohistochemical (IHC) analysis was performed using a basic panel of soft tissue tumor markers. Immunohistochemical staining was performed on the Ventana BenchMark ULTRA system (Roche Diagnostics). The only significant finding was a strong and diffuse CD34 (Agilent DAKO, M7165, clone QBEnd10) positivity, while all other markers were negative (Figure 3).
FIGURE 3.
Immunohistochemical staining shows diffuse CD34 positivity in tumor cells; a characteristic grenz zone is also evident.
For the evaluation of the sample using fluorescence in situ hybridization (FISH), ZytoLight SPEC COL1A1 and ZytoLight SPEC PDGFB break‐apart probes (ZytoVision, Germany) were used, along with the ZytoLight SPEC COL1A1/PDGFB Dual Color Dual Fusion Probe, designed to detect the loci of the COL1A1 and PDGFB genes. The ZytoLight SPEC COL1A1 probe targets sequences at 17q21.33, with a green signal proximal (chr17:47,669,218‐48,223,465) and an orange signal distal (chr17:48,347,800‐48,744,021) to the COL1A1 breakpoint region. The ZytoLight SPEC PDGFB probe targets sequences at 22q13.1, with a green signal distal (chr22:39,720,415‐40,267,687) and an orange signal proximal (chr22:38,928,973‐39,526,228) to the PDGFB breakpoint region. The ZytoLight SPEC COL1A1/PDGFB Dual Color Dual Fusion Probe maps sequences at 17q21.33 (chr17:47,820,343‐48,744,021) containing the COL1A1 gene (orange) and at 22q13.1 (chr22:38,928,973‐40,267,687) carrying the PDGFB gene (green).
The probes were applied to the target tissues and covered with a coverslip. The slides were placed in the TDH500 hybridizer (Hangzhou Allsheng Instruments, China) for denaturation and hybridization, programmed at 75°C for 10 min (for DNA denaturation), followed by 37°C for 16 h (for hybridization). After hybridization, the slides were washed in SSC buffer (Agilent, CA, USA) at 63°C. All post‐hybridization steps were performed in a light‐protected environment to prevent fluorescence signal photobleaching. After drying, the slides were counterstained with 10 μL of DAPI (ZytoVision, Germany) and examined using a fluorescence microscope Olympus BX53 (Olympus, Japan). Images were captured with a Lucia Cytogenetics digital camera (Laboratory Imaging s.r.o., Czechia) and processed using software.
Individual samples were observed using a fluorescence microscope, and 100 nuclei per sample were evaluated. All nuclei exhibiting a fluorescent signal were described, including nuclei with normal arrangement, nuclei with COL1A1 and PDGFB gene disruption, nuclei with t(17;22) translocation, and nuclei displaying other signal patterns (e.g., deletion of a sequence segment from the breakpoint region).
In a normal situation using the “Break Apart” probe, two fusion (orange‐green) signals are observed in the nucleus. In cells with a rearrangement involving the COL1A1 or PDGFB gene, it shows a classical split pattern (one fusion signal and two separate signals). For the qualitative detection of the t(17;22)(q21.3;q13.1) translocation, we use the ZytoLight SPEC COL1A1/PDGFB Dual Color Dual Fusion Probe. With this probe, normal cells exhibit two separate orange and two separate green signals. In contrast, nuclei with the t(17;22) translocation show one separate orange signal, one separate green signal, and two orange‐green (yellow) fusion signals. This indicates a reciprocal translocation. According to the manufacturer, other signal patterns may also be observed in abnormal nuclei.
A deletion of the COL1A1 gene was identified at the 3′ end, proximally from the chromosomal breakpoint at 17q21.33, in 85% of analyzed tumor nuclei (Figure 4). Similarly, a deletion of the PDGFB gene was detected at the 5′ end, distally from the breakpoint at 22q13.1, in 92% of tumor nuclei (Figure 5). This pattern was inconsistent with the expected classical rearrangement pattern of these two genes. Therefore, we proceeded to verify the presence of the t(17;22)(q21.3;q13.1) translocation involving COL1A1::PDGFB using a fusion FISH probe, which confirmed the presence of the translocation in 95% of the tumor nuclei analyzed (Figure 6). This type of rearrangement (deletion detected by FISH) has not yet been reported in the literature for DFSP, highlighting the novelty and significance of this finding for early diagnosis and subsequent treatment of this disease.
FIGURE 4.
Fluorescence in situ hybridization shows deletion of 3′ end COL1A1, proximally from the chromosomal breakpoint at 17q21.33.
FIGURE 5.
Fluorescence in situ hybridization shows deletion of 5′ end PDGFB, distally from the breakpoint at 22q13.1.
FIGURE 6.
Fluorescence in situ hybridization shows translocation t(17;22)(q21.3;q13.1) of COL1A1::PDGFB genes.
Given the typical morphology, immunophenotype, and the presence of the COL1A1::PDGFB fusion gene, we established the diagnosis DFSP.
4. Management and Follow‐Up
Due to the positive resection margins, we recommended a re‐excision of the scar with an adequate safety margin. Based on the decision of a multidisciplinary oncology and dermatology team (and with the patient's consent) a re‐excision with a 2.5 cm margin was performed approximately 1.5 months after the initial surgery. No residual tumor was detected.
The patient was classified as low‐risk for recurrence of both previously identified tumors, and adjuvant therapy was not indicated. She continues to attend regular dermatological follow‐ups using the following schedule: every 3 months during the first year, then (in case of negative findings) every 6 months during the second year and, finally, every 12 months thereafter. Each follow‐up comprises a physical examination (including dermatoscopy), an abdominal ultrasound with meticulous examination of abdominal wall and scar, and a chest x‐ray.
At the time of this article's finalization, no recurrence of malignancy had been detected during her most recent follow‐up.
5. Discussion
According to the current fifth edition of the WHO classification of soft tissue tumors, DFSP is defined as a superficial, locally aggressive fibroblastic neoplasm with a storiform pattern and COL1A1::PDGFB fusion [5].
Genetically, dermatofibrosarcoma protuberans (DFSP) is characterized by a reciprocal translocation t(17;22)(q22;q13). As previously mentioned, the main consequence of the t(17;22)(q22;q13) translocation in DFSP is the overexpression of PDGFB by tumor cells, resulting in constitutive activation of the PDGFB receptor [6].
Kayuri et al. (2016) provided evidence of a split signal pattern of the PDGFB gene, and the COL1A1::PDGFB gene translocation was identified in DFSP cases using FISH analysis [7]. Similarly, Karanian et al. reported the classical split signal pattern of the PDGFB gene and the presence of the COL1A1::PDGFB translocation [8]. A characteristic genetic alteration also described in the literature is an unbalanced translocation, often involving ring chromosomes: der(17)(17;22)(q22;q13), leading to rearrangement and subsequent fusion of the COL1A1 and PDGFB genes [1]. Our case was unique in that we observed a deletion of the 3′ end of the COL1A1 gene segment and a deletion of the 5′ end of the PDGFB gene segment. This pattern was not consistent with the classical rearrangement typically observed between these two genes. Therefore, we proceeded to verify the presence of the t(17;22)(q21.3;q13.1) translocation involving COL1A1::PDGFB using a fusion FISH probe, which confirmed the presence of the translocation in the analyzed tumor nuclei.
DFSP is locally aggressive and has a high recurrence rate if incompletely excised [9]. Surgical excision with 2–3 cm margins significantly reduces the recurrence risk. Mohs surgery has shown excellent results [10]. In selected cases, local radiotherapy may serve as an alternative to surgery. DFSP rarely metastasizes, typically via the bloodstream to the lungs or (less commonly) to regional lymph nodes [11]. For advanced disease with metastases, treatment with tyrosine kinase inhibitors may be considered.
Tyrosine kinase inhibitors (TKIs), most notably imatinib mesylate, selectively block PDGFRβ activity, thereby disrupting the pathological signaling driven by the COL1A1–PDGFB fusion [12]. Imatinib has been approved for the treatment of unresectable, recurrent, or metastatic DFSP, and its efficacy has been demonstrated in several clinical studies. Approximately 50% of patients with locally advanced or metastatic disease achieve an objective response, with a one‐year overall survival rate of around 87%. Meta‐analyses have further confirmed its benefit, including in the neoadjuvant setting, where imatinib can reduce tumor size, facilitate complete surgical resection, and decrease the risk of early postoperative recurrence [13].
Targeted inhibition of the PDGFB/PDGFRβ signaling axis thus represents a cornerstone of therapeutic strategy in DFSP. Ongoing research is now focused on overcoming imatinib resistance, optimizing treatment sequencing, and exploring combination regimens that may further enhance therapeutic efficacy [12]. The diagnostic and therapeutic process is summarized in the following flowchart (Figure 7).
FIGURE 7.
Operational flowchart to facilitate the diagnostic and therapeutic process of DFSP.
6. Differential Diagnoses and Possible Pitfalls
Dermatofibromas typically occur on the limbs, are smaller, display disorganized growth patterns, and often show an inflammatory infiltrate. If CD34 is expressed, it is only focally and weakly positive.
Keloid scar can mimic a clinical appearance of DFSP, especially if it develops months or years after initial injury as some of them tend to do. Histologically, however, it should be readily distinguishable by the presence of typical keloid collagen bundles and lack of honeycomb‐like infiltrating borders.
Dermatomyofibroma can form superficial dermal plaques similar to the initial phase of DFSP. Its histological pattern lacks the typical storiform growth. CD34 is usually only focally positive and the lesion lacks molecular features of DFSP.
Solitary fibrous tumor predominantly arises in subcutaneous and deep soft tissues. It is usually well circumscribed, lacking an infiltrative border with surrounding tissue. While it can express CD34 diffusely, it is distinguished from DFSP by its highly sensitive and specific expression of STAT6.
Spindle cell (desmoplastic) melanoma can pose a diagnostic challenge since it lacks the expression of melanocytic markers HMB45 and Mart1 (MelanA). Location in heavily sun exposed skin of elderly patients, common coexistence with lentigo maligna and diffuse positivity of SOX10 and S100 should steer the diagnostic process in the right direction.
7. Conclusion
Dermatofibrosarcoma protuberans is the most common cutaneous sarcoma. Clinically, it is often difficult to distinguish from other nodular skin and subcutaneous lesions. It is a locally aggressive lesion that frequently recurs if not completely excised, but it carries a low risk of metastasis or sarcomatous transformation. Accurate diagnosis, based on histomorphology supported by immunohistochemistry and increasingly by genetic testing for the COL1A1::PDGFB fusion, is essential for proper patient management.
This study highlights a previously unrecognized FISH pattern characterized by deletions of both COL1A1 and PDGFB probe regions, which was subsequently confirmed to result in a COL1A1::PDGFB fusion. Recognition of this atypical “double deletion” configuration is diagnostically significant, as it may indicate the presence of the fusion even when dedicated fusion probes are not available. This finding is particularly valuable for laboratories with limited molecular resources, helping to avoid false‐negative interpretations and supporting accurate DFSP diagnosis.
Author Contributions
Jakub Bejbl: conceptualization, data curation, formal analysis, writing – original draft. Denisa Drozdková: data curation, formal analysis, writing – original draft. Martina Peřinová: data curation, writing – review and editing. Jiří Ehrmann: project administration, supervision, writing – review and editing.
Funding
This cost is co‐financed by OPST 2021–2027, project Life Environment Research Center Ostrava (LERCO), registration no. CZ.10.03.01/00/22_003/0000003.
Consent
Written informed consent was obtained from the patient for the publication of this case report and any accompanying images.
Conflicts of Interest
The authors declare no conflicts of interest.
Acknowledgments
The authors have nothing to report.
Bejbl J., Drozdková D., Peřinová M., and Ehrmann J., “Atypical Gene Rearrangement of the COL1A1::PDGFB Fusion in Dermatofibrosarcoma Protuberans of the Abdominal Wall: A Case Report,” Clinical Case Reports 14, no. 2 (2026): e71949, 10.1002/ccr3.71949.
Data Availability Statement
Data sharing is not applicable to this article as no new data were generated.
References
- 1. Hornick J. L., “Cutaneous Soft Tissue Tumors: How Do We Make Sense of Fibrous and “Fibrohistiocytic” Tumors With Confusing Names and Similar Appearances?,” Modern Pathology 33, no. Suppl 1 (2020): 56–65, 10.1038/s41379-019-0388-4. [DOI] [PubMed] [Google Scholar]
- 2. Darier J. and Ferrand M., “Dermatofibromes Progressifs et Recidivants ou Fibrosarcomes de la Peau,” Annales de Dermatologie et de Syphiligraphie 5 (1924): 545. [Google Scholar]
- 3. Kiuru‐Kuhlefelt S., El‐Rifai W., Fanburg‐Smith J., Kere J., Miettinen M., and Knuutila S., “Concomitant DNA Copy Number Amplification at 17q and 22q in Dermatofibrosarcoma Protuberans,” Cytogenetics and Cell Genetics 92, no. 3–4 (2001): 192–195, 10.1159/000056901. [DOI] [PubMed] [Google Scholar]
- 4. Sirvent N., Maire G., and Pedeutour F., “Genetics of Dermatofibrosarcoma Protuberans Family of Tumors: From Ring Chromosomes to Tyrosine Kinase Inhibitor Treatment,” Genes, Chromosomes and Cancer 37, no. 1 (2003): 1–19, 10.1002/gcc.10202. [DOI] [PubMed] [Google Scholar]
- 5. The WHO Classification of Tumours Editorial Board , WHO Classification of Tumours Soft Tissue and Bone Tumours, 5th ed. (IARC Press, 2020), 100–103. [Google Scholar]
- 6. Pohlodek K., Mečiarová I., Grossmann P., and Kinkor Z., “Dermatofibrosarcoma Protuberans of the Breast: Case Report,” Oncology Letters 14, no. 1 (2017): 993–998, 10.3892/ol.2017.6206. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Patel K. U., Szabo S. S., Hernandez V. S., et al., “Dermatofibrosarcoma Protuberans COL1A1::PDGFB Fusion Is Identified in Virtually All Dermatofibrosarcoma Protuberans Cases When Investigated by Newly Developed Multiplex Reverse Transcription Polymerase Chain Reaction and Fluorescence in Situ Hybridization Assays,” Human Pathology 39, no. 2 (2008): 184–193, 10.1016/j.humpath.2007.06.009. [DOI] [PubMed] [Google Scholar]
- 8. Karanian M., Pérot G., Coindre J. M., Chibon F., Pedeutour F., and Neuville A., “Fluorescence in Situ Hybridization Analysis Is a Helpful Test for the Diagnosis of Dermatofibrosarcoma Protuberans,” Modern Pathology 28, no. 2 (2015): 230–237, 10.1038/modpathol.2014.97. [DOI] [PubMed] [Google Scholar]
- 9. Taylor H. B. and Helwig E. B., “Dermatofibrosarcoma Protuberans: A Study of 115 Cases,” Cancer 15 (1962): 717–725. [DOI] [PubMed] [Google Scholar]
- 10. Snow S. N., Gordon E. M., Larson P. O., Bagheri M. M., Bentz M. L., and Sable D. B., “Dermatofibrosarcoma Protuberans: A Report of 29 Patients Treated by Mohs Micrographic Surgery With Long‐Term Follow‐Up and Review of the Literature,” Cancer 101, no. 1 (2004): 28–38. [DOI] [PubMed] [Google Scholar]
- 11. Kahn L. B., Saxe N., and Gordon W., “Dermatofibrosarcoma Protuberans With Lymph Node and Pulmonary Metastases,” Archives of Dermatology 114, no. 4 (1978): 599–601. [PubMed] [Google Scholar]
- 12. Huber L., Birk R., Rotter N., et al., “Effect of Small‐Molecule Tyrosine Kinase Inhibitors on PDGF‐AA/BB and PDGFRα/β Expression in SCC According to HPV16 Status,” Anticancer Research 40, no. 2 (2020): 825–835, 10.21873/anticanres.14014. [DOI] [PubMed] [Google Scholar]
- 13. Noguchi R., Ono T., Sasaki K., et al., “Pharmacokinomic Profiling Using Patient‐Derived Cell Lines Predicts Sensitivity to Imatinib in Dermatofibrosarcoma Protuberans,” Cells 14, no. 12 (2025): 884, 10.3390/cells14120884. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Data sharing is not applicable to this article as no new data were generated.