Dermatofibrosarcoma protuberans of the breast with progressive enlargement during pregnancy: Case report and a brief review of the literature

*Corresponding author: Mohamed Aziz. Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. Dermatofibrosarcoma protuberans of the breast with progressive enlargement during pregnancy: Case report and a brief review of the literature Sydni Rivera 2, Hadiyah Page 3, Amanda Canellas 4, Anjali Pagay 2, Natalia Berio-Perez 2, Nadine Akin 3, Anthony Bonilla 4, Jessica Jahoda 1, 2 and Mohamed Aziz 1, 5, * 1 Research Writing and Publication (RWP), LLC, NY, USA. 2 American University of the Caribbean School of Medicine USA. 3 Ross University School of Medicine, Barbados. 4 St. George's University School of Medicine. 5 Saint Vincent's Comprehensive Cancer Center, New York City, NY. World Journal of Biology Pharmacy and Health Sciences, 2025, 23(02), 096-104 Publication history: Received on 27 June 2025; revised on 05 August 2025; accepted on 07 August 2025 Article DOI: https://doi.org/10.30574/wjbphs.2025.23.2.0740 Abstract Dermatofibrosarcoma protuberans (DFSP) is an uncommon low-grade sarcoma that rarely involves the breast and few cases have been reported in literature. It is therapeutically important to distinguish DFSP from other breast malignancies like metaplastic carcinoma and phyllodes tumors. A 37-year-old pregnant woman was referred to the breast clinic for evaluation of an impressive increase of a previously stable breast mass in the second trimester. The lesion was initially thought to be benign, but it grew quite rapidly from a small nodule to a 6 cm, multinodular mass with violaceous discoloration. This gestational growth pattern caused immediate clinical concern and mandated immediate evaluation. However, the diagnostic follow-up was challenging due to lactational physiological changes of pregnancy which created difficulties in overcoming limitations of imaging presentation. Ultrasound and MRI showed overlap of benign and malignant characteristics, highlighting the fact that imaging was insufficient for a definitive diagnosis, necessitating further evaluation. Core needle biopsy was then performed and revealed a storiform pattern of spindle cell proliferation. The diagnosis was established based on extensive immunohistochemical (IHC) analysis and molecular findings (FISH test), revealing the pathognomonic COL1A1-PDGFB fusion gene. Our case was particularly challenging due to concerns related to timing of the surgery during pregnancy, in addition to ensuring en-bloc excision with adequate surgical margins of safety for the mother and fetus. The patient underwent a gross surgical resection; however, the mass recurred locally 14 months post excision, likely due to insufficient surgical margin, emphasizing the necessity of achieving clear margins in the management of DFSP. The case report underscores the importance of a high index of clinical suspicion in the presence of breast masses with rapid growth in pregnant women, the diagnostic challenge of rare breast sarcomas in pregnancy, as well as the necessity for a comprehensive multi-disciplinary management approach in the overall management of these challenging tumors. Keywords: Dermatofibrosarcoma protuberans; Immunohistochemical; Molecular; Breast; Pregnancy; Recurrence World Journal of Biology Pharmacy and Health Sciences, 2025, 23(02), 096-104 97 1. Introduction DFSP is an uncommon mesenchymal tumor classified by the current WHO classification of tumors as an intermediate (rarely metastasizing) fibroblastic and myofibroblastic tumor. The classical DFSP is characterized by a typical storiform (cartwheel) architecture of the proliferation of spindle cells, which may infiltrate the subcutaneous fat in a honeycomb pattern. [1] The finding of the COL1A1PDGFB fusion gene, due to a t(17;22) (q22;q13) translocation, is thought to be pathognomonic and is essential in difficult cases or variants. [2] A few variants are recognized by the WHO classification, such as the fibrosarcomatous variant (DFSP-FS), which has a more aggressive histological appearance, and the pigmented Bednar tumor, which contains melanin-laden dendritic cells, but all of them have the same genetic alteration and biological behavior as classic DFSP. [3] [4] [5] While DFSP typically occurs in other areas of the body, it can, though rarely, present as a primary tumor of the breast. This is considered an unusual location for DFSP. [6] [7] The presence of DFSP in the breast poses a significant diagnostic challenge. It can be difficult to differentiate it from a variety of other benign and malignant breast conditions. [6] [7] Therefore, a high index of suspicion and a strong awareness of DFSP is essential. It is paramount to include DFSP in the differential diagnosis for soft masses in the breast is essential to avoid diagnostic errors. Without this consideration, there is a risk of either over-treating the patient for a more aggressive malignancy or under-treating the patient for what might be mistaken as a benign condition. This case report explains the diagnostic and therapeutic issues related to the management of breast DFSP in pregnancy as well as the possible hormonal impact on the biological behavior of this tumor which may also complicate the decisionmaking process in clinical management. 2. Case presentation A 37-year-old, otherwise healthy multiparous woman (2 previous successful pregnancies) discovered a small, painless, gradually growing, firm mass in the right breast around a year before her pregnancy. The nodule was a firm light brown papule initially thought to be benign and the patient was advised to monitor for any changes. The patient became pregnant one year later. The breast mass was unchanged in size during the first trimester of pregnancy. However, the tumor showed considerable increase in size as pregnancy advanced, particularly since second trimester, forming a mass approximately 6 cm in greatest dimension. The previous solitary lesion had evolved into a multifocal pulsating mass on palpation and had developed a classic violaceous appearance. The dramatic enlargement and visual appearance during pregnancy were of major clinical concern and further work-up was done. Due to suspicious clinical findings, the mass was imaged, and sonography of the right breast revealed an irregular mass in the lower inner quadrant with echogenic bands and suspicious infiltration into the breast fatty tissue. Moderate posterior acoustic enhancement and increased vascularity were also observed. There were lactational changes related to pregnancy throughout the breast tissue which made the ultrasounds difficult to interpret. MRI was then conducted to further characterize the lesion. On T1-weighted imaging, the mass was isoto hypointense to the adjacent tissue. The lesion exhibited strong and homogeneous enhancement after fat saturation sequences post-contrast. The mass appeared hyperintense with an indistinct border on T2-weighted images with fat saturation. The imaging findings were atypical and mimic both benign and malignant lesions, rendering definitive diagnosis difficult by imaging alone. Based on these findings, core needle tissue biopsy with histopathologic evaluation and immunohistochemical analyses was recommended. Core needle biopsy of the mass revealed a spindle cell infiltrating proliferation arranged in a typical storiform pattern with infiltration of surrounding breast fatty tissue and lactating ducts. The tumor appeared to have low nuclear atypia, with low mitotic activity, which was reassuring, but not invariably diagnostic. (Figure 1 A, B, C, D) Significantly, the tumor also seemed to obliterate the normal structures of the skin, the hairs, and the sweat glands as it made its way through the tissue planes. IHC analysis was very essential for establishing the diagnosis. IHC analyses revealed that the tumor cells were positive for CD34, and vimentin and negative for factor XIIIa, S100, HMB45, MelanA, CD31, STAT6, and cytokeratin AE1/AE3. This immunohistochemical staining profile strongly points to DFSP. The differential diagnostic considerations included several breast spindle cell lesions. Dermatofibroma (benign fibrous histiocytoma) was kept in the differential diagnosis as the most frequent mimicker, but was ruled out due to the presence of the infiltrative storiform pattern and the immunoprofile positive for CD 34 and negative for Factor XIIIa of DFSP, as opposed to the well circumscribed nature of the dermatofibroma and its immunoprofile of negative CD 34 and positive Factor XIIIa. Solitary fibrous tumor (SFT) was also a differential diagnosis because the tumors occasionally World Journal of Biology Pharmacy and Health Sciences, 2025, 23(02), 096-104 98 demonstrate spindle cells and react to CD34. SFTs display a “patternless” pattern or small fascicles with prominent branching vasculature, which are two features rarely, if ever, seen in DFSP, as well as the storiform pattern and honeycomb infiltration of fat. Other sarcomas such as leiomyosarcoma, and undifferentiated pleomorphic sarcoma, were excluded due to the uniform, bland spindle cell morphology, low mitotic count, and characteristic IHC profile. These higher-grade tumors tend to show more severe cellular atypia, higher mitotic activity, and other IHC patterns. A diagnosis of desmoplastic melanoma was dismissed due to the S100 negativity and CD34 positivity (in contrast to what is observed in melanocytic lesions, for which these tests are applied). Lastly, spindle cell carcinoma, uncommon in the breast, but excluded by the negative cytokeratin stains. At the patient’s family request, molecular testing by FISH was applied for diagnostic confirmation. Molecular analysis resulted in detection of the specific genetic translocation t(17;22) (q22;q13) giving rise to the COL1A1-PDGFB fusion gene, which is diagnostic for DFSP. Molecular confirmation of this diagnosis was the key defining feature. The case was discussed at the multidisciplinary breast tumor board, and the decision for complete surgical excision with a minimum 2 cm free margin was reached. Considering the patient's pregnancy timing of the surgery was a concern. Surgery was recommended during the second trimester for maternal and fetal safety in the setting of an increasingly growing tumor. Surgical resection was accomplished successfully, and a pathologic review of the excised tumor confirmed the primary core biopsy diagnosis of DFSP. On the other hand, analysis of the surgical margins showed that just 1 cm of safe margins was obtained, and was not sufficient to a 2 cm safe margin. The surgery was well tolerated by the patient without complication, and she had a normal delivery. Yet, a recurrence of a 4 cm mass was diagnosed after 14 months at the same site of surgery. This recurrence was subsequently excised. The patient was free of recurrence at the last follow-up after 26 months of the original surgery. 1A Low power view showing DFSP (Green arrow), lactating ducts (Blue arrow) and benign breast lobules (Yellow arrow) (H&E stain X20); 1B: Intermediate power view showing cellular spindle cells infiltrating the breast fatty tissue (H&E stain X40); 1C: Intermediate power view showing spindle cell proliferation arranged in a typical storiform pattern (H&E stain X40); 1D: High power view showing the tumor spindle cells with low nuclear atypia, and low mitotic activity (H&E stain X60) Figure 1 Histomorphology of breast dermatofibrosarcoma protuberance (DFSP) World Journal of Biology Pharmacy and Health Sciences, 2025, 23(02), 096-104 99 3. Discussion 3.1. History The history of dermatofibrosarcoma protuberans (DFSP) dates to the times when unusual breast skin growths were observed. Darier and Ferrand first described it in 1924 as progressive and recurrent dermatofibroma because of its locally aggressive behavior and its tendency to recur, and initially was called “progressive recurring dermatofibroma.”. [2] Subsequently, in 1925, Hoffmann used the name dermatofibrosarcoma protuberans, a more descriptive term of its sarcomatous nature and protuberant clinical presentation. [8] Over the decades, our knowledge of DFSP has changed greatly, and what was initially described as a purely morphological entity is now better understood in terms of its genetic basis, especially the discovery of the typical COL1A1-PDGFB fusion gene, which has transformed its diagnosis and specific treatment. [9] 3.2. Epidemiology The most recent Surveillance, Epidemiology, and End Results (SEER) registry analysis in the United States of the time 2000-2018 reported an incidence rate of 6.25 cases per million person-years, an upward trend from prior epidemiological studies. [10] [11] Worldwide, the incidence rate in England and Eastern France is 3.0 per million person-years, in Sweden and Denmark between 4-5.3 per million person years. [2] [5] The mean age of diagnosis is 43.5 years (SD 16.6). [12] Both genders are equally affected except in the over 80 age group, where men had a higher incidence. [11] An ethnic disparity exists with DFSP having a preponderance in Black compared to White patients (8.74 vs 4.53) with negligible difference in 1 and 5-year survival rates. [11] Overall mortality is 1.18%, primarily driven by tumor size ≥10 cm or grade III tumors (7.07% and 10.08%, respectively, p < .001). (13) The location of the tumor or surgical procedures did not impact survival. [13) Interestingly, Hispanic populations were found to have a better survival rate, the reasons are still. [12] While DFSP has a high rate of local recurrence (up to 60%), the risk of metastases is minimal at 1% regionally and 45% for distant spread, most commonly to the lungs. [14] [15] Recurrence can be partly explained by the irregular shape and papillary projections of the tumor, posing a challenge for surgical removal. [15] Another aspect to the recurrence and metastases is the presence of high-grade fibrosarcoma with more than 5% tumor volume in 10-15% of all DFSP cases. [4] Large tumour size (≥3 cm), age (≥60 years), primary tumours of the head/ neck and genitalia, had a significantly increased risk of metastases. High socioeconomic status was associated with a significantly decreased risk of metastases. [11] 3.3. WHO classification of fibroblastic/myofibroblastic tumors: The 2020 WHO classification of soft tissue and bone tumors classifies fibroblastic/myofibroblastic tumors into four categories: benign, intermediate (locally aggressive), intermediate (rarely metastasizing), and malignant. [1] Many factors are taken into consideration when categorizing soft tissue sarcomas; a focus on a more rational therapeutic approach has been in use, considering involvement of clinicians, involvement in a broad number of expert sarcoma pathologists, integration of morphology with immunohistochemistry and molecular genetics, and precise definitions of clinicopathological categories. [2]. In this classification, DFSP is classified as an intermediate (rarely metastasizing), fibroblastic and myofibroblastic tumor. [1] DFSP is considered low to intermediate-grade due to its Locally aggressive behavior, high recurrence rate after incomplete excision, and low but real risk of metastasis, especially in fully malignant fibrosarcomatous variants (DFSP-FS). 3.4. Imaging features Imaging features of DFSP may be varied, and may be representative of the infiltrative growth pattern of this tumor. DFSP is usually a hypoechoic, poorly defined, non-homogeneous mass on ultrasound with occasional posterior acoustic enhancement or hyper-vascularity. [18] Although a non-specific mass may be visualized on mammography. [6] MRI will usually offer more information and demonstrate a T1-isointense or hypointense and T2-hyperintense lesion heterogeneously enhanced, reflecting the cellular nature and infiltrative characteristics of the lesion. [16[ Nonetheless, such characteristic attributes are quite likely to be substantially masked by physiological alterations, especially in special clinical situations like pregnancy. [2] The diagnostic process in the case of our patient was extensively complicated by the pregnancy and the related alterations in lactation. The sonography of the fast-growing breast mass showed an irregular mass with echogenic bands, suspicious infiltration of the breast fatty tissue, moderate posterior acoustic enhancement, and increased vascularity, which, although worrying, could not be specifically interpreted because of the widespread lactational World Journal of Biology Pharmacy and Health Sciences, 2025, 23(02), 096-104 100 changes in the breast. Likewise, MRI, which has more advanced features, also demonstrated abnormal results; the mass was isoto hypointense on T1-weighted and hyperintense with an indistinct border on T2-weighted images and demonstrated strong and homogeneous enhancement after contrast administration. More importantly, these imaging results were not specific for a benign or malignant lesion, which highlights the limitations of the use of imaging alone to make a decisive diagnosis of DFSP within the pregnancy context. The case is a clear example of how hormonal environment and physiological changes of pregnancy may produce a difficult diagnostic environment, where imaging findings are insufficient and histopathological, immunohistochemistry (IHC) and molecular confirmation are required. 3.5. Pathological findings The final diagnosis of DFSP is ultimately based on a careful pathological examination which involves gross, microscopic, immunohistochemical and molecular analysis. Grossly, DFSP usually appears as a hard, nodular, frequently protuberant mass, with a typical violaceous or reddish-brown color, due to its origin in the dermis, and vascularity. [17] Microscopically, the typical feature is a monotonous growth of spindle cells in a characteristic storiform, or cartwheel, pattern, and may invade the surrounding subcutaneous fat in a honeycomb pattern. [17] The cells in general have a low cellular atypia and low mitotic activity that makes it a low to intermediate grade sarcoma. [2] IHC analysis has a central role in the distinction of DFSP and its mimics. Most DFSPs are strongly and diffusely positive with CD34, a transmembrane glycoprotein and negative for Factor XIIIa, S100, HMB45, and other markers that would indicate alternative diagnoses. [16] But the real gold standard of diagnosis, especially in the complicated presentation, is molecular analysis. The presence of the COL1A1-PDGFB fusion gene is very characteristic of DFSP. This fusion is caused by reciprocal translocation t(17;22) (q22;q13), which results in an overexpression of platelet-derived growth factor beta (PDGFB) that serves as a strong autocrine growth factor promoting the growth of the tumor cells. [9] The pathological results obtained in our case were very useful in the process of overcoming the diagnostic challenges that were presented by the pregnancy and the rapid development of the tumor. Clinically, the 6 cm multinodular mass with violaceous discoloration was grossly suggestive of DFSP, which, agreed with the clinical appearance that was protuberant. Microscopic evidence was important, and the core needle biopsy revealed an infiltrating spindle cell proliferation that was arranged in storiform pattern with the surrounding breast fatty tissue and lactating ducts infiltration. The low cellular atypia and low mitotic activity were encouraging, but not conclusive in themselves. The IHC that followed was essential, and the tumor cells were found positive to CD34 and negative to Factor XIIIa, S100 and other pertinent markers, which was highly indicative of DFSP. Conclusively, molecular testing, FISH, which revealed the COL1A1-PDGFB fusion gene, gave the conclusive and definitive diagnosis, which supports the significance of such genetic signature in resolving ambiguities of diagnosis, particularly in such rare presentation, as breast DFSP with gestational enlargement. [9] The combination of these pathological observations did not only validate the diagnosis but also provided an explanation of the underlying growth factors of the tumor, which probably played a role in its dramatic growth in the hormonally active condition of pregnancy. 3.6. Differential diagnosis The diagnosis of DFSP, especially in a rare location such as the breast requires a close observation of a wide scope of differentials, including both benign and malignant spindle cell lesions. [18] The high rate of the mass growth during the pregnancy of our patient complicated the clinical picture even further, adding the element of urgency and expanding the range of possible entities. Dermatofibroma (benign fibrous histiocytoma), the most common mimic, was initially one of the main considerations, but the circumscribed appearance of this lesion in most cases, as well as its immunoprofile (negative to CD34, positive to Factor XIIIa), is quite different to the infiltrative storiform pattern and CD34 positivity in our case, which made it possible to rule it out. Other spindle cell tumors, including solitary fibrous tumor (SFT) also made it into the differential, due to its occasional CD34 positivity. Nevertheless, SFTs commonly show a "patternless" pattern or small fascicles with marked branching vasculature. [19] This "patternless" pattern is very uncommon, even absent, in DFSP, and does not exhibit the storiform pattern and honeycomb infiltration of fat that were prominent in the biopsy of our patient. Moreover, leiomyosarcoma and undifferentiated pleomorphic sarcoma of higher grades were ruled out because of the bland uniform and elongated appearance of the spindle cells and low mitotic rate in our case, which are not characteristic of the more cellular atypia and increased mitotic index of the more aggressive lesions. DFSP was also distinguished from these other sarcomas by the specific immunohistochemical profile, especially the intense positivity by CD34. The presence of desmoplastic melanoma as another possible mimic was also ruled out with certainty based on the results of S100 negativity and CD34 positivity of the tumor cells of our patient, as this feature is quite unlike that of the World Journal of Biology Pharmacy and Health Sciences, 2025, 23(02), 096-104 101 melanocytic lesions. [6] Finally, the rare spindle cell carcinoma was also excluded based on the negative cytokeratin stains, which demonstrated that the tumor is of mesenchymal origin. [6] Finally, the full pathological work-up, with the combination of the typical storiform appearance on microscopy, the pathognomonic CD34 positivity on immunohistochemistry, and above all, the presence of the pathognomonic COL1A1-PDGFB fusion gene by molecular testing, gave the definitive evidence to securely arrive at the diagnosis of DFSP and successfully work through this difficult differential, particularly in the unusual clinical scenario of pregnancy. 3.7. Treatments and outcomes Surgical excision with clean margins is the mainstay of DFSP treatment. Wide local excision with a recommended margin of 2-3 cm or Mohs micrographic surgery (MMS) are the most preferred surgical methods of removing tumors completely due to its infiltrative growth pattern and the high rate of local recurrence. [20] Adjuvant treatment, including radiation therapy, can be considered in the presence of positive or close margins, large tumors, or recurrent disease. [20] Targeted treatment with imatinib, a tyrosine kinase inhibitor, has been effective in unresectable or metastatic disease, especially that which contains the COL1A1-PDGFB fusion gene. [21] The case of our patient was a unique and daunting task in treatment planning, which was mainly because of her pregnancy. The multidisciplinary tumor board agreed on the decision to conduct complete surgical excision with at least 2 cm free margin as per standard recommendations. Nevertheless, timing of the operation became a very important factor, weighing between the safety of the mother and the unborn child and the need to deal with the ever-growing tumor. Surgery was tactically advised in the second trimester which is considered relatively safer, when considering surgical intervention during pregnancy. [20] Although a gross surgical resection was successful, it was found that only a safe margin of less than 1 cm was achieved, insufficient to the desired 2 cm. The resultant local recurrence of 4 cm mass 14 months later at the same location is probably due to inadequate margins. This recurrence is a clear indication of the utmost significance of obtaining adequate surgical margins in the management of DFSP since even grossly complete resection may be undermined by microscopic residual disease. Luckily, the recurrent mass was also removed, and the patient has been without recurrence at the final follow-up after 26 months of the first operation. This favorable long-term follow-up post treatment of recurrence demonstrates the overall indolent characteristics of DFSP despite its recurrence, [2] and the importance of close follow-up and aggressive local recurrence treatment to achieve good patient outcomes. It appears that we can have a bright future by incorporating genomics, high-tech imaging, artificial intelligence, and non-invasive surveillance. These accomplishments would entail earlier and more precise diagnoses, more precise and effective treatment, and better control of complex cases resulting in better patient outcomes. The case presents a rare occurrence of breast DFSP in pregnancy and the rapid increase in the size of the tumor was likely to be hormone-mediated. The pregnancy-related growth in the case is not in line with the typical epidemiology, which accentuates the problem of diagnosis and the need to diagnose the atypical manifestation. 3.8. What does the future hold for the DFSP diagnosis and management The future of DFSP management seems to be getting brighter in an age characterized by a swift technological growth, especially when dealing with such difficult presentations as the one in our case. The deep insights that molecular diagnostics provided, namely the discovery of the COL1A1-PDGFB fusion gene, have paved the way for targeted treatment, including such treatment modalities as Imatinib. The future holds the possible emergence of more actionable mutations, or resistance mechanisms may be identified by further genomic profiling. This will likely result in the development of new targeted agents or combination therapy. The future holds a strong promise of more personalized and effective treatment approaches especially for unresectable and recurrent tumors. [9] [22] In addition to therapeutics, there is an ongoing development of advanced imaging. Although our case illustrated the shortcoming of the available imaging modalities as applied to the scenario of pregnancy-related physiological alterations, the evolution of functional imaging (e.g., new MRI sequences, PET scans using new tracers) in the future could allow more accurate tumor details. These will likely include more delineation of the tumor, better evaluation of the response to treatment, and better distinction of benign entities, even in the scenario of complex anatomical or physiological circumstances. The use of artificial intelligence (AI) and machine learning in diagnostic pathology and radiology has a tremendous potential. The training of AI algorithms on large sets of pathological images and clinical data would be able to provide significant contribution diagnosis and management. This trained AI could have the ability to quickly and precisely diagnose DFSP, detect barely noticeable infiltrative patterns, and even predict the effectiveness of World Journal of Biology Pharmacy and Health Sciences, 2025, 23(02), 096-104 102 treatment or the risk of recurrence, supplementing the knowledge of human pathologists and radiologists. [23] [24] [25] Moreover, with the introduction of liquid biopsies that are based on the examination of circulating tumor DNA (ctDNA) in blood, the process of monitoring recurrence and evaluating the effectiveness of therapy may be changed fundamentally. These techniques provide a noninvasive alternative to the existing monitoring strategies. In situations such as DFSP during pregnancy where invasive procedures should be reduced to a minimum and radiation exposure should be avoided as much as possible, these non-invasive methods may be especially revolutionary. In the end, this combination of genomics, advanced imaging, AI, and non-invasive monitoring holds a future where the diagnosis of DFSP is faster, treatment is more accurate, and patient outcomes, even in the most complicated situations, are constantly advancing. [23] [24] This case highlights a rare breast DFSP during pregnancy, with rapid tumor growth likely hormone-influenced. This case’s pregnancy-related growth deviates from typical epidemiology, emphasizing diagnostic challenges and the importance of recognizing atypical presentations. Conclusion: The described case of dermatofibrosarcoma protuberans of the breast which developed a progressive increase in size during pregnancy is an eloquent testimony of the diagnostic and therapeutic difficulties which are related to the management of rare tumors in special physiological conditions. It is a great teaching tool about the value of high index of clinical suspicion of fast-growing breast masses in pregnant women where the physiological effects of pregnancy can be a dire impediment to imaging analysis and the timing of medical intervention. Our case demonstrates the invaluable importance of a multidisciplinary approach to the case, along with the use of pathological and molecular diagnostics, when overcoming such ambiguities and reaching a definitive diagnosis. Moreover, the second local recurrence in the case is a strong reminder of the utmost significance of clear surgical margins, even in anatomically difficult areas, and the necessity of close follow-up in the long term to provide the best patient outcomes in DFSP. Compliance with ethical standards Acknowledgments Special thanks to Tori Richmond, Ramsharan Padhy, and Himabindu Gonuguntla for their assistance in reviewing the final manuscript Disclosure of conflict of interest The following declarations are made by all authors: • Payment/services information: All authors have declared that they received no financial support from any organization for the submitted work. • Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might be interested in the submitted work. Statement of ethical approval Ethical review and approval were not required for this study involving human participants. The paper has been sufficiently anonymized to maintain the patient's confidentiality. Data access statement All relevant data are included in the paper. Author contributions All authors contributed equally to producing this manuscript. Statement of informed consent The patient was lost to follow-up, and all attempts to reach the family members were unsuccessful. Therefore, the paper has been sufficiently anonymized to maintain patient confidentiality. World Journal of Biology Pharmacy and Health Sciences, 2025, 23(02), 096-104 103 References [1] Sbaraglia M, Bellan E, Dei Tos AP. The 2020 WHO classification of soft tissue tumors: news and perspectives. Pathologica. 2020 Nov 3;113(2):70. [2] Jozwik M, Bednarczuk K, Osierda Z. Dermatofibrosarcoma protuberans: an updated review of the literature. Cancers. 2024 Sep 11;16(18):3124. 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