Purpuric Patches as Cutaneous Presentation of Pediatric NTRK‐Rearranged Spindle Cell Neoplasm

ABSTRACT

Neurotrophic tyrosine receptor kinase‐rearranged spindle cell neoplasms (NTRK‐RSCNs) are rare soft tissue tumors with a broad histologic spectrum. Limited data exist on their cutaneous manifestations, particularly in pediatric patients. We present the case of a 4‐year‐old girl with an LMNA‐NTRK1 fusion‐positive spindle cell neoplasm initially presenting as a subcutaneous nodule adjacent to purpuric patches on the abdomen. This case highlights an atypical cutaneous presentation of NTRK‐RSCNs and demonstrates the successful use of larotrectinib, a TRK inhibitor, in achieving both clinical and histological remission.

To the Editors,

1.

A previously healthy 4‐year‐old girl with a stable birthmark on her abdomen developed new‐onset pruritus and a subtle, palpable subcutaneous nodule beneath the lesion. Abdominal ultrasound and magnetic resonance imaging (MRI) in her home country revealed a 0.7 cm nonvascular subcutaneous mass. Histopathologic examination of the excised tissue showed a poorly circumscribed dermal and subcutaneous proliferation of CD34‐ and S100‐positive cells. Molecular testing identified an LMNA‐NTRK1 gene fusion, consistent with a neurotrophic tyrosine receptor kinase‐rearranged spindle cell neoplasm (NTRK‐RSCN). Surgical margins were positive.

Six months later, the patient presented to the oncology clinic at Boston Children's Hospital for further evaluation. Repeat MRI of the abdomen and pelvis, along with chest computed tomography (CT), showed no evidence of residual or metastatic disease. Dermatology was consulted for evaluation of a nearby pigmented lesion, initially presumed to be a congenital melanocytic nevus. On examination, two periumbilical erythematous‐brown patches, measuring 2 × 2 and 5 × 6cm, with a purpuric appearance and no palpable nodularity or induration were noted adjacent to the surgical scar (Figure 1). Given the atypical presentation and their proximity to the prior tumor, two biopsies of the patches were performed, along with re‐excision of the original site for clear margins.

FIGURE 1.

Periumbilical erythematous‐brown patches, measuring 2 × 2 and 5 × 6 cm, with a purpuric appearance and no palpable nodularity or induration were noted adjacent to the surgical scar.

Histopathology of both biopsies and re‐excision specimen revealed a CD34 and S100‐positive dermal spindle cell proliferation with strong nuclear and cytoplasmic pan‐TRK staining, consistent with persistent NTRK‐RSCN (Figure 2). Positron emission tomography‐computed tomography (PET‐CT) and brain MRI were negative.

FIGURE 2.

(A) Hematoxylin and eosin staining of tissue section showing dermal spindle cell proliferation (10×); (B) Positive nuclear and cytoplasmic Pan‐TRK immunohistochemistry (20×).

Given the lesion size and the presence of an NTRK gene rearrangement, the patient was treated with larotrectinib. After 1 year of therapy, she showed progressive lightening of the lesion and remained radiographically stable. End‐of‐treatment biopsies from the tumor site and adjacent skin were pan‐TRK‐negative, showing only basal hyperpigmentation and dermal fibrosis, confirming remission. She is currently undergoing surveillance with clinical evaluations every 6 weeks and abdomen/pelvis MRI every 6 months until 12 months post‐therapy.

NTRK‐RSCNs are rare soft tissue tumors with a wide morphologic spectrum, typically involving the superficial soft tissues of the trunk and extremities [1, 2]. However, cutaneous involvement remains undercharacterized [1, 2]. The few reported pediatric cases with skin manifestations have primarily described violaceous or indurated plaques and nodules, sometimes mimicking vascular malformations [1, 3]. In contrast, our patient presented with purpuric patches lacking induration adjacent to a previously excised subcutaneous nodule. Biopsies revealed persistent tumor, highlighting the importance of dermatologic vigilance and a low threshold for biopsy of atypical lesions near known tumor sites. Histologically, NTRK‐RSCNs demonstrate variable spindle cell morphology with fascicular or haphazard growth patterns, mild cytologic atypia, low mitotic activity, and frequent immunohistochemical coexpression of S100 and CD34 [2, 4].

Treatment with larotrectinib, a first‐generation tropomyosin receptor kinase inhibitor approved by the US Food and Drug Administration [2, 5], achieved both clinical and histologic remission in our patient, demonstrating its therapeutic potential in pediatric soft tissue tumors with NTRK gene fusions. This case underscores the diagnostic and therapeutic complexity of NTRK‐RSCNs and expands the clinical spectrum of their cutaneous presentation. It emphasizes the importance of clinicopathologic correlation, including biopsy of atypical skin findings, in the management of rare pediatric neoplasms.

Funding

The authors have nothing to report.

Consent

Written consent for the publication of all patient photographs and medical information was obtained from the patient/parent.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.