Congenital dermatofibrosarcoma protuberans in a seven-month-old infant initially misdiagnosed as infantile myofibroma: A case report

Abstract

BACKGROUND

Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive cutaneous sarcoma predominantly observed in adults 30 years to 50 years of age. It is exceedingly rare in infants and is often misdiagnosed owing to its indolent growth and resemblance to benign lesions such as hemangiomas or fibromas.

CASE SUMMARY

A 7-month-old male infant presented with a congenital dorsal mass that had gradually enlarged since birth. Initial biopsy of the lesion resulted in a misdiagnosis of infantile myofibroma. Given the tumor’s progressive growth, wide local excision was performed with a 2-cm peripheral margin extending to the muscular fascia. Subsequent histopathological examination and immunohistochemical analysis (CD34+, SMA-, Desmin-, S-100-, HMB45-, and Ki-67 approximately 5%) confirmed the diagnosis of classic DFSP. Owing to resource constraints, testing for the COL1A1-PDGFB fusion gene was not performed. The patient experienced an uneventful recovery and underwent close follow-up. At the 2-year postoperative follow-up, clinical examination and ultrasonography revealed no evidence of local recurrence or metastasis.

CONCLUSION

At the 2-year follow-up, the patient exhibited no signs of disease recurrence. However, congenital DFSP requires prolonged surveillance beyond this period because of its potential for late local recurrence.

Key Words: Dermatofibrosarcoma protuberans; Congenital; Infant; Surgical excision; Case report

Core Tip: Dermatofibrosarcoma protuberans (DFSP) is exceptionally rare in infants and is often misdiagnosed as a benign lesion. We report the case of a 7-month-old male infant with congenital DFSP on the back that was initially misdiagnosed as infantile myofibroma. Wide local excision with clear margins resulted in complete remission, with no recurrence at the 2-year follow-up. This case highlights the importance of maintaining a high index of suspicion, establishing an accurate immunohistochemical diagnosis, and achieving complete surgical resection in the management of congenital DFSP.

INTRODUCTION

Dermatofibrosarcoma protuberans (DFSP) is an extremely rare cutaneous tumor in children, with an estimated incidence of approximately 1 case per 1000000 person years in adults and an even lower incidence in children, who account for only 6% of all DFSP cases[1]. The tumor predominantly originates on the trunk, followed by the extremities and the head and neck region.

Histologically, DFSP is characterized by a proliferation of monomorphic spindle cells arranged in a classic storiform pattern within the dermis. Immunohistochemically, the tumor cells typically exhibit strong and diffuse positivity for CD34. Consequently, CD34 immunohistochemical staining is strongly recommended in all suspected cases to confirm the diagnosis.

In contrast to adult-onset DFSP, congenital DFSP often exhibits more rapid local growth when diagnosis is delayed, suggesting a more aggressive clinical course in this context[2]. Given this potential, congenital lesions that remain clinically suspicious despite an initial negative biopsy warrant adequate tissue sampling and consideration of repeat biopsy to facilitate early diagnosis and timely intervention[3]. The pathogenesis of infantile DFSP remains incompletely understood but is frequently linked to the chromosomal translocation t(17;22)(q22;q13), which leads to the formation of the COL1A1-PDGFB fusion gene. This fusion gene induces constitutive activation of the platelet-derived growth factor receptor beta signaling pathway, resulting in uncontrolled proliferation of tumor cells[4].

Herein, we report a case of a 7-month-old male infant with congenital DFSP that was initially misdiagnosed as infantile myofibroma and was successfully treated with wide local excision (WLE).

CASE PRESENTATION

Chief complaints

A slowly enlarging, purplish mass on the mid-back that had been present since birth.

History of present illness

A 7 months old male infant was referred for evaluation of a congenital mass on the back. The parents had noticed a slowly growing, purplish lesion on the midback since birth. Initially, the lesion measured approximately 8 cm × 5 cm × 0.2 cm. An incisional biopsy performed at a local hospital was interpreted as “infantile myofibroma” based on an immunohistochemical profile showing CD34 negativity, vimentin positivity, and S100 negativity (Figure 1A and B). Owing to its benign pathological diagnosis and concerns regarding anesthesia in a young infant, surgical intervention was postponed. Over the subsequent months, the mass continued to enlarge progressively. The infant was otherwise healthy and had no systemic symptoms, such as fever, weight loss, or feeding difficulties.

Figure 1 Initial incisional biopsy (misdiagnosed as infantile myofibroma). A: Low power hematoxylin and eosin image showing a small biopsy specimen composed of spindle cell proliferation (× 40 magnification, scale bar = 500 μm); B: High power hematoxylin and eosin image demonstrating fascicular/nodular arrangement of bland spindle cells without the classic storiform pattern (× 200 magnification, scale bar = 100 μm). Immunohistochemistry showed CD34-, vimentin+, and S100-.

History of past illness

The patient was a full-term infant with an unremarkable perinatal history. There was no history of significant medical illness, previous surgery, or hospitalizations.

Personal and family history

There was no history of trauma to the lesion site or known drug allergies. The family history was negative for DFSP, other soft tissue sarcomas, and neurofibromatosis.

Physical examination

Physical examination revealed a 12 cm × 7 cm × 3 cm, soft, nontender, multinodular, purplish plaque on the right midback with a smooth surface and a visible biopsy scar (Figure 2). No regional lymphadenopathy was detected. The remainder of the physical examination was unremarkable.

Figure 2 Preoperative clinical appearance of the dorsal mass. A: Posterior view showing the overall extent and location of the multinodular, purplish lesion on the lower back; B: Lateral view demonstrating the degree of protrusion/elevation of the lesion; C: Close-up view showing the multinodular surface and purplish discoloration.

Laboratory examinations

Routine laboratory investigations, including a complete blood count, liver and renal function tests, electrolyte panel, and a coagulation profile, were all within normal limits. Serum tumor markers, including carcinoembryonic antigen, alphafetoprotein, neuronspecific enolase, and betahuman chorionic gonadotropin, were also within normal ranges.

Imaging examinations

Ultrasonography: Preoperative ultrasonography demonstrated a heterogeneous, hypoechoic subcutaneous mass measuring approximately 10.9 cm × 2.7 cm, extending from the T11 to L5 vertebral levels, with internal vascularity on doppler examination.

MRI: Magnetic resonance imaging (MRI) revealed a T2 hyperintense lesion measuring 2.0 cm × 13.0 cm that involved the dermis and subcutaneous fat, with ill-defined margins adjacent to the surrounding subcutaneous fat (Figure 3A and B).

Figure 3 Preoperative imaging findings. A: Sagittal T1 weighted magnetic resonance imaging showing the extent of the subcutaneous lesion (outlined by the yellow dashed line); B: Sagittal T2-weighted magnetic resonance imaging demonstrating a T2-hyperintense lesion (white arrow) measuring 20 cm × 13.0 cm, with ill-defined margins against the adjacent subcutaneous fat (yellow arrow); C and D: Contrast-enhanced computed tomography obtained during the arterial (C) and venous (D) phases demonstrating a 10.9 cm × 2.7 cm subcutaneous lesion with marked heterogeneous enhancement and no distinct plane separating the lesion from the underlying deep fascia. The orange arrow (C) indicates a tumor vessel, and the blue arrow (D) indicates an area of significant enhancement. Yellow dashed lines outline the lesion boundaries in (A and B).

Computed tomography: Contrast-enhanced computed tomography (CT) demonstrated marked heterogeneous enhancement, with no definite plane separating the lesion from the underlying deep fascia and no evidence of muscular invasion (Figure 3C and D). Chest and abdominal CT performed on April 24, 2024, revealed no distant metastases or lymphadenopathy. No formal whole body staging (e.g., positron emission tomography CT or bone scan) was performed.

FINAL DIAGNOSIS

Classic DFSP.

TREATMENT

The patient underwent WLE under general anesthesia. Intraoperatively, the tumor appeared well defined and limited to the dermis and superficial fascia. A 2-cm peripheral margin and a deep margin extending to the muscular fascia were excised. The resulting surgical defect measured approximately 12 cm × 5 cm and was closed primarily via direct approximation and interrupted sutures, without the need for skin grafting or flap reconstruction (Figure 4). Histopathological examination of the resected specimen confirmed classic DFSP, with diffuse CD34 positivity and a Ki67 labeling index of approximately 5% (Figure 5A-C). Testing for the COL1A1PDGFB fusion gene was not performed owing to limited resources.

Figure 4 Intraoperative findings during tumor resection. A: The tumor was primarily located in the dermis and appeared relatively well defined on gross inspection; B: Surgical defect following wide local excision with a 2-cm peripheral margin extending to the underlying muscular fascia, demonstrating complete tumor removal before primary wound closure.

Figure 5 Final surgical specimen confirming classic dermatofibrosarcoma protuberans. A: Low power hematoxylin and eosin image showing a dermal based spindle cell tumor with infiltrative extension into the subcutaneous adipose tissue in a characteristic honeycomb pattern (× 40 magnification, scale bar = 500 μm); B: Medium power hematoxylin and eosinimage demonstrating the classic storiform (cartwheel) arrangement of uniform spindle cells (× 100 magnification, scale bar = 200 μm); C: Immunohistochemical staining showing strong, diffuse positivity for CD34 antigen in the tumor cells (× 200 magnification, scale bar = 100 μm).

OUTCOME AND FOLLOW-UP

The postoperative recovery was uneventful. After considering the patient’s age, histopathological findings, and negative deep margins, the multidisciplinary team opted for close monitoring rather than immediate re-excision. The patient underwent clinical examinations and regional ultrasonography every 3 months. At the 6month postoperative follow-up, the surgical scar was well healed, with no palpable masses or tenderness (Figure 6). At the 2 years postoperative follow-up, clinical examination and ultrasonography revealed no evidence of local recurrence or distant metastasis. At the time of writing, the patient remained under follow-up, with long-term surveillance planned for at least 10 years to monitor for potential late recurrence.

Figure 6  Postoperative appearance of the surgical incision at the 6-month follow-up, demonstrating a well-healed linear scar without evidence of wound complications.

DISCUSSION

DFSP is an exceedingly rare soft tissue sarcoma in the pediatric population, with an estimated annual incidence of approximately 1 case per million individuals under the age of 20 years. Congenital DFSP is even rarer[5]. Table 1 summarizes the previously reported case series of congenital DFSP[6-9].

Table 1 Summary of congenital dermatofibrosarcoma protuberans case series (≥ 3 cases).

Ref.	Cases	Presentation/location	Size	Diagnostic delay	Treatment (margin)	Outcome (followup)
Maire et al[6], 2007	9	8 plaques, 1 nodule; trunk (4), lower extremity (2), other (3); all initially suspected benign	< 0.5-10 cm (most > 4 cm)	5.5 months-15 years	Wide excision; reexcision for positive margins (3)	2 cases NED at 7 months and 6 months; 1 untreated (family refused); others NR
Terrier-Lacombe et al[7], 2003	2	Buttock and thigh	2-3 cm	Born with lesions	Wide excision	1 NED at 36 months; 1 NA
Posso-De Los Rios et al[8], 2014	7	Trunk: Back (4), abdomen (1); scalp (1); genital (1); 4 masses, 2 nodules, 1 atrophic plaque	Mean 3.0 ± 1.4 cm	Mean 6.1 years	WLE (majority); margins 1-4 cm; reexcision for positive margins (2), imatinib (1 case)	No recurrence (mean 3.0 years; range 1 months - 8 years)
Weinstein et al[9], 2003	6	Scalp, ankle, back (2), neck, thigh; 50% in atypical locations (scalp, neck, ankle); all initially misdiagnosed	0.7-3 cm	5 months-14 years	WLE (5), MMS (1); 4/6 positive margins → reexcision	3 NED (1-6 years); 1 recurrence; 1 LFU; 0 metastasis

NED: No evidence of disease; NR: Not reported; WLE: Wide local excision; MMS: Mohs micrographic surgery; LFU: Lost to follow-up.

The diagnostic complexity associated with congenital DFSP is not uncommon, as evidenced by Posso-De Los Rios et al[8], who reported an average diagnostic delay of 5.7 years in pediatric DFSP cases, with numerous cases initially misdiagnosed as hemangiomas or vascular malformations. In the current case, the initial incisional biopsy, which sampled tissue to a depth of only 0.2 cm, was misinterpreted as myofibroma based on the immunohistochemical profile (CD34-, vimentin+, and S100-). In hindsight, this misdiagnosis could be attributed to both sampling and interpretive errors. The sampling error may have resulted from the infiltrative honeycomb growth pattern of the tumor, which may have resulted in a specimen lacking the diagnostic storiform component. The interpretive error arose from the assumption that CD34 negativity was sufficient to exclude DFSP. Although CD34 is recognized as the most sensitive immunohistochemical marker for DFSP, with over 90% of cases exhibiting positivity, it is now well established that 5%-10% of DFSPs are CD34-negative[10,11]. Salgado et al[10] demonstrated that all 5 CD34-negative DFSPs in their extensive cohort exhibited the COL1A1-PDGFB translocation, indicating that the absence of CD34 expression does not exclude the diagnosis. Similarly, Cassalia et al[2] emphasized that congenital DFSP frequently mimics benign lesions, including hemangiomas, vascular malformations, and fibrous nevi, and that its indolent growth often creates a false sense of security, leading to diagnostic delays[2].

To mitigate these diagnostic challenges, generous incisional or excisional biopsies that include the dermal-subcutaneous junction should be performed, together with immunohistochemical staining for CD34 and factor XIIIa. In patients with a CD34-negative spindle cell lesion and suspicious morphology, molecular testing, such as fluorescence in situ hybridization (FISH) or reverse transcription-polymerase chain reaction for the COL1A1-PDGFB fusion gene, should be considered. If clinical suspicion persists despite a benign initial biopsy result, repeat biopsy is strongly advised, as early diagnosis facilitates less extensive, tissue-sparing surgery and reduces long-term morbidity in pediatric patients.

The pathogenesis of infantile DFSP remains incompletely understood but is frequently associated with the chromosomal translocation t(17;22)(q22;q13), which results in the formation of the COL1A1-PDGFB fusion gene[4]. The COL1A1-PDGFB fusion is detected in approximately 93% of DFSP cases. Both FISH and reverse transcription-polymerase chain reaction demonstrate 100% specificity, with FISH showing superior sensitivity (91% vs 72%)[10].

We acknowledge the lack of molecular confirmation as a limitation of this report, particularly given the diagnostic challenges inherent to congenital DFSP. In the present case, the characteristic storiform morphology together with diffuse CD34 positivity established the diagnosis with a high degree of confidence. Moreover, as the tumor was completely resected with negative surgical margins, the absence of molecular confirmation does not alter our therapeutic decision, as imatinib is primarily indicated for advanced, unresectable, or metastatic DFSP.

Preoperative MRI demonstrated an ill-defined, T2-hyperintense lesion involving the dermis and subcutaneous fat, reflecting the tumor’s infiltrative edge. In contrast, the tumor appeared relatively well defined on macroscopic visualization. This apparent discrepancy between the imaging and intraoperative findings is complementary rather than contradictory: MRI captures the microscopic infiltrative front, whereas intraoperative assessment reflects the macroscopic tumor-tissue interface. The histologically confirmed honeycomb infiltration of the subcutaneous tissue guided our decision to perform WLE with a 2-cm peripheral margin extending to the underlying muscular fascia.

Complete surgical excision remains the cornerstone of DFSP treatment. Most patients are treated with WLE alone, with no recurrences reported during a mean follow-up of 3 years[8]. More recently, Mohs micrographic surgery (MMS), which facilitates comprehensive microscopic margin assessment while conserving healthy tissue, has been endorsed by several consensus guidelines as the preferred treatment modality, particularly for tumors located in cosmetically sensitive regions[3,12]. Among patients with recurrent DFSP, MMS has been associated with significantly lower disease-specific mortality compared with those undergoing WLE (1.0% vs 3.5%, P < 0.001)[13]. The effectiveness of MMS has also been corroborated in pediatric populations[14,15]. However, pediatric specific comparative data remain limited.

From a recent study of a series of 15 pediatric patients with DFSP, Caussade et al[16] reported no recurrences in either the MMS group (n = 9) or the WLE group (n = 6). Similarly, Aqeel et al[17] reported no recurrences and a 100% 5year recurrencefree survival rate among 17 pediatric patients treated with WLE (mean surgical margin, 1.76 cm). Nevertheless, owing to the rarity of pediatric DFSP, the limited availability of MMS, and concerns about extended anesthesia duration, WLE remains a standard and pragmatic alternative when MMS is not feasible.

Regarding local recurrence, a separate systematic review and meta-analysis by Martin et al[18] found no statistically significant difference in local recurrence rates between MMS and WLE (1.7% vs 3.7%)[18]. However, these findings should be interpreted with caution, as the available evidence is predominantly derived from adult populations, and pediatric-specific data remain limited.

Standard WLE typically involves a peripheral surgical margin of 2-3 cm, extending to the underlying deep fascia[3]. A meta-analysis indicated that margins < 3 cm were associated with a significantly increased risk of recurrence and positive surgical margins compared with margins ≥ 3 cm (relative risk: 0.17 and 0.09, respectively)[19]. However, emerging pediatric-specific evidence suggests that narrower margins may be adequate in carefully selected children. Aqeel et al[17] recently reported outcomes in 17 pediatric patients with DFSP treated with WLE. The mean surgical margin was 1.76 ± 0.54 cm, and 87.5% of evaluable patients were treated with margins of ≤ 2 cm. No local or distant recurrences were observed, and the 5-year recurrence-free survival rate was 100%. The authors concluded that, in appropriately selected patients, WLE with an initial 1-2-cm margin, followed by re-excision when needed to achieve clear margins, does not compromise survival or increase the risk of recurrence and may be considered an effective treatment option in pediatric DFSP. Similarly, Caussade et al[16] found no recurrences in either the MMS or WLE group among 15 pediatric patients with DFSP, suggesting that both approaches can achieve favorable outcomes when guided by multidisciplinary evaluation.

In the present case, a 2-cm surgical margin was chosen for a lumbar lesion in a 7-month-old infant, balancing the recommendations derived from adult studies with the need to preserve normal tissue in a growing child. A larger excision would have required complex reconstruction and increased the risk of functional morbidity. Intraoperative frozen-section analysis was not feasible owing to logistical constraints; however, staged excision remains a reasonable option for future cases when intraoperative margin assessment is unavailable. Fortunately, final histopathological examination confirmed negative surgical margins, eliminating the need for further surgery or adjuvant therapy.

For cases of unresectable, recurrent, or metastatic DFSP, targeted therapy with imatinib mesylate, a tyrosine kinase inhibitor, is a highly effective option. Imatinib functions by inhibiting the constitutively activated platelet-derived growth factor receptor beta signaling pathway driven by the COL1A1-PDGFB fusion, resulting in tumor reduction. This reduction can facilitate subsequent surgical resection or provide palliative benefit in patients with advanced disease. A systematic review indicated that imatinib achieves an objective response rate of 60.5% and disease control rate of 88.1% of patients with locally advanced or metastatic DFSP, although the complete response rate remained low (approximately 5%)[20]. Another review highlighted that tyrosine kinase inhibitors, primarily imatinib, demonstrated efficacy across various subtypes of unresectable DFSP, with a clinical benefit rate ranging from 70% to 96%, despite the occurrence of notable treatment-related side effects. Conversely, radiotherapy provides excellent local control (approximately 90%) with mild toxicity in patients with classic/Low-grade DFSP but may be less effective for high-grade fibrosarcomatous variants[21].

The majority of DFSP recurrences manifest within 2 years to 3 years following surgical intervention. One study documented an overall recurrence rate of 22.7%, with a median recurrence interval of 55.5 months[22]. Consequently, sustained and meticulous surveillance is imperative, particularly in congenital DFSP, where the indolent growth pattern may mask late recurrence. Current guidelines recommend clinical examinations every 6 months for the first 3 years after surgery, followed by annual assessments for at least 10 years[3,12]. Patients exhibiting high-risk features, such as fibrosarcomatous transformation (associated with an approximately 22-fold higher risk of recurrence) or positive surgical margins (associated with an approximately 15-fold higher risk of recurrence), require especially vigilant and extended follow-up[22].

In the present case, the patient achieved negative surgical margins, and histopathological examination demonstrated classic DFSP without fibrosarcomatous transformation, placing him in a lower-risk category for recurrence. Nevertheless, given the congenital presentation and the potential for delayed recurrence, we instituted a long-term surveillance protocol consisting of a clinical follow-up every 6 months for the first 3 years after surgery, annual follow-up thereafter until year 5, and continued biennial or annual assessments thereafter up to 10 years. At the time of writing, the patient remained disease-free after 2 years of follow-up, and we plan to continue this surveillance schedule to monitor for late recurrence.

CONCLUSION

In summary, although DFSP is very rare in infants, it should be considered in the differential diagnosis of persistent, enlarging cutaneous or subcutaneous nodules, regardless of age. Early detection, accurate histopathological diagnosis supported by CD34 staining and molecular testing if needed, and multidisciplinary management with complete surgical excision - through either MMS or WLE - are crucial for achieving optimal outcomes. Complete excision with histologically negative margins is associated with an excellent prognosis in patients with congenital DFSP. Although our patient remains disease-free after 2 years of follow-up, this interval is insufficient to confirm cure because late recurrences may occur. Therefore, long-term surveillance for at least 10 years is recommended to detect any late recurrences.