Sclerosing perineurioma of the anterior chest wall in an active Caucasian toddler: a case report

Introduction

Perineurioma is a rare benign tumor of the peripheral nerve sheath consisting of neoplastic perineural cells. The incidence of pediatric perineurioma is very low, with only a few dozen cases reported in the literature (1-6). Due to its rarity, there are no established statistics on its incidence or prevalence. Since 1978, only 20 cases of pediatric soft-tissue perineurioma have been reported (7-13). Studies have identified that it is a slow-growing, benign tumor that can affect various locations and is most often found in adolescents and young adults. Soft-tissue perineuriomas are benign, slow-growing tumors composed of peripheral nerve sheath cells. The diagnosis is more common in adolescence or young adulthood, though infantile cases have been reported. Pediatric perineuriomas have been found in various locations, including major peripheral nerves (sciatic, median, radial), the head and neck, and the skin and soft tissues. Diagnosis is confirmed through a combination of clinical suspicion, imaging, and a biopsy with specialized immunohistochemical and ultrastructural analysis. Treatment options vary depending on the location and growth rate. Still, because of the slow growth and benign nature, surgical intervention is not always necessary and may be approached cautiously, especially in cases of long-segmental involvement. The condition may be under-recognized due to the need for intensive evaluation and the slow, insidious nature of the tumor’s progression (7-13).

The differential diagnosis of soft-tissue perineurioma includes a range of benign and malignant soft-tissue tumors that share similar microscopic appearances. Key diagnoses to consider are cellular schwannoma, low-grade fibromyxoid sarcoma (LGFMS), solitary fibrous tumor, and neurofibroma. Distinguishing between these entities often relies on immunohistochemical stains and, in some cases, molecular analysis. Benign and low-grade malignant soft-tissue tumors include cellular schwannoma (positive for S-100 protein, unlike perineurioma, which is typically S-100 negative), LGFMS [similar swirling pattern, but negative for S-100 protein and positive for epithelial membrane antigen (EMA) in some cases, and positive for MUC4, a transmembrane or membrane bound mucin that provides a protective layer of mucus and highly sensitive and quite specific immunohistochemical marker for LGFMS], solitary fibrous tumor (positive for CD34, but negative for S-100 protein and EMA), benign fibrous histiocytoma (absent EMA positivity), and neurofibroma (positive for S-100 protein and negative for EMA, unlike perineurioma). Other differential considerations should include dermatofibrosarcoma protuberans (DFSP) (a locally aggressive, superficial mesenchymal neoplasm with fibroblastic differentiation with storiform to whorled pattern, positive for CD34 and some focal EMA expression), smooth muscle tumors [characteristic morphology and positive staining for smooth muscle actin (SMA) and desmin], malignant peripheral nerve sheath tumor (MPNST) (a very aggressive malignant neoplasm to be considered, especially in cases with cellular atypia, necrosis, or high mitotic activity). The key to distinguishing these soft-tissue tumors is immunohistochemistry (IHC). Perineuriomas are typically positive for EMA and negative for S-100 protein (7,14-18). Magnetic resonance imaging (MRI) is particularly useful for the diagnostic workup of soft-tissue tumors (19-21).

Two primary kinds of perineurioma exist: the uncommon intraneural form and the more prevalent extraneural form. Intraneural perineurioma is confined to the borders of peripheral nerves, whereas extraneural perineurioma predominantly occurs in soft tissues and the skin. Extraneural perineurioma is further categorized into conventional, sclerosing, and reticular subtypes based on several clinical and pathological criteria (5,7,10,22). Sclerosing perineurioma is a characteristic variant that predominantly affects young individuals in the hands (8,10,19,23,24). It produces a tiny, asymptomatic subcutaneous lump. As of now, fewer than 60 cases have been reported, and none has been reported in a very young child at this location. We present this article in accordance with the CARE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-625/rc).

Case presentation

A 2-year-6-month-old male presented with a painless nodule on the left pectoral area. Ultrasound at 8 days of life had shown a thin-walled cystic nodule in the subcutaneous fat. There was a nonspecific, well-defined anechoic lesion (5 mm × 11 mm × 8 mm) with mild posterior acoustic enhancement and thin, smooth walls. This cystic lesion was within the subcutaneous fat without involvement of the underlying pectoral muscle. In the two months preceding the presentation, the nodule fluctuated and increased in size without drainage. There was no history of trauma, skin changes, or signs of infection. A repeat ultrasound of the area of interest at the left anterosuperior chest wall revealed that the lesion was still within the subcutaneous fat. The anechoic central component has become smaller, with persistent but less conspicuous posterior acoustic enhancement. There was interval thickening of the walls, which were thick, smooth, and homogenous. The lesion measured 8 mm ×19 mm × 20 mm and was hypovascular (as shown in the Doppler image). No involvement of the underlying pectoral muscle was noted (Figure 1). The lesion was compressible, and the overlying skin and surrounding soft tissues were normal. There was no connection to the overlying skin. In this clinical context, the ultrasound findings remained nonspecific but favored a benign etiology. The primarily cystic and hypovascular nature of the lesion on ultrasound is in favor of a benign lesion. On imaging, the lesion was within the subcutaneous fat, not involving the deep fascia or the underlying muscle. The nodule was entirely removed. Eighteen months after resection, the child has shown no local recurrence or evidence of disease outside of the surgical area. Medical, family, and psychosocial history, including relevant genetic information, was negative.

Figure 1 Ultrasound imaging. (A) Ultrasound at 8 days of life: Nonspecific well-defined anechoic lesion (5 mm × 11 mm × 8 mm) with mild posterior acoustic enhancement and thin, smooth walls. This cystic lesion is within the subcutaneous fat without involvement of the underlying pectoral muscle. (B,C) Ultrasound at 2 years and 6 months: The lesion is still within the subcutaneous fat. The anechoic central component had become smaller, with persistent but less conspicuous posterior acoustic enhancement. There is interval thickening of the walls, which are thick, smooth, and homogenous. The lesion measures 8 mm × 19 mm × 20 mm and is hypovascular (as shown in the Doppler image). No involvement of the underlying pectoral muscle is noted.

Grossly, the specimen consisted of an irregular fragment of yellow-brown fibro-fatty tissue with a ragged surface measuring 15 mm × 13 mm × 7 mm. In the sections, the cut surface was gray in color with a firm consistency, showing no evidence of a cystic component. It was inked, trisected, and embedded in toto in one cassette. Histological sections revealed a compact mass with compact blood vessels exhibiting slit-like lumina. A haphazard proliferation of nerve fibers and sclerotic stroma surrounds these vessels (Figure 2). There was no evidence of atypical cell proliferation, necrosis, or mitotic activity. Immunohistochemical analysis reveals positivity for CD34 and CD31 in the vessels. The spindle cells were positive for CD34 (CD34 highlights endoneurial fibroblasts), GLUT1 (erythrocyte glucose transporter-1 receptor), and EMA but were only focally positive for SMA (Figure 3). There was no staining for S-100, SOX10 (SRY related HMG box 10), MUC4 (mucin 4), ALK1 (anaplastic lymphoma kinase, CD246), CD68, and Factor XIIIa. STAT6 (signal transducer and activator of transcription 6) was negative, ruling out a solitary fibrous tumor, and NTRK (neurotrophic tyrosine receptor kinase) was also negative (Table 1). NTRK-rearranged spindle cell neoplasms are a heterogeneous, emerging group of soft-tissue tumor entities. This kind of neoplasm is an essential recent differential diagnosis (25-29). The tumor proliferation activity was assessed using Ki-67 labeling index, which was less than 5%. The features were in keeping with a diagnosis of a sclerosing perineurioma.

Figure 2 Histology. Small, spindle-shaped neoplastic cells with slightly hyperchromatic nuclei and barely distinguishable cell boundaries are seen. The cells are embedded in a dense stroma (A,B).

Figure 3 Immunohistochemistry. (A) CD34 positivity highlighting endoneurial fibroblasts (×200); (B) low proliferative activity using an antibody against Ki-67 antigen (MIB1, ×100); (C,D) staining of the tumor cells with epithelial membrane antigen at low (C, ×200) and high (D, ×400) magnification; negativity of the tumor cells for STAT6 (E); and STAT6-positive control (F) (E,F, ×200).

Ultrastructurally, the neoplastic perineurial cells have elongated nuclei, marginated chromatin, and thin cytoplasmic processes (Figure 4). Slender, nontapered processes containing large numbers of pinocytotic vesicles and partial encasement by basal lamina are characteristic of perineurioma by electron microscopy. In our case, the partial encasement by basal lamina was barely perceptible because the electron microscopy was performed following tissue retrieval from the formalin-fixed and paraffin-embedded tissue.

Figure 4 Electron microscopy. Ultrastructurally, the neoplastic perineurial cells (arrows) have elongated nuclei, marginated chromatin, and thin cytoplasmic processes (A,B).

Administration of therapeutic intervention (such as dosage, strength, duration) was nil, apart from surgery. The child recovered fully. Changes in therapeutic intervention were likewise nil, because there was no relapse.

All procedures performed in this case were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient’s guardians for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal. The consent form has also been uploaded to the patient’s electronic medical record in the EPIC platform.

Discussion

Ultrasonography is typically the first imaging modality performed to evaluate palpable or visible superficial soft-tissue lesions, which are common in children. Although clinical assessments are essential for differentiating pediatric soft-tissue lesions, ultrasound provides detailed information on the location, characterization (solid versus cystic), vascularity, relationship to adjacent tissues, and compressibility of a lesion. In this case, the sonographic and clinical features of this lesion favored a benign etiology; however, they were still nonspecific and therefore required histological evaluation.

We describe a child with a sclerosing perineurioma of the left anterior chest wall. The histologic findings were consistent with a sclerosing perineurioma, a benign neoplasm arising from perineural cells. This slow-growing, painless mass is usually seen in the extremities. Sclerosing perineurioma was initially described in 1997 by Fetsch and Miettinen, and approximately 60 cases have been well-documented in adults (2,6,7,30-32). It presents as a tiny, painless, dermal or subcutaneous mass with a strong predilection for the digits and palms of young adults. All documented cases of sclerosing perineurioma have had a favorable prognosis, with no instances of recurrence or metastasis. Consequently, local excision is deemed a sufficient treatment. This is the first report of sclerosing perineurioma in a child at this location. The diagnosis necessitates light microscopy and immunohistochemical assessment. Microscopically, a sclerosing perineurioma is characterized by cords of benign epithelioid cells within a highly sclerotic collagenous stroma. Whorled, syncytial, or trabecular patterns are also observed. The differential diagnosis comprises tendon sheath fibroma, epithelioid glomus tumor, giant cell tumor of the tendon sheath, solitary fibrous tumor, and epithelioid sarcoma. Immunohistochemical findings, positive for EMA and negative for S-100 protein, facilitate diagnosis. Claudin-1 and/or the human GLUT1 receptor may aid in validating the diagnosis of perineurioma (22,33). Desmoid tumors may exhibit signal characteristics similar to those of other tumors; however, they are distinctly defined. Calcified lesions may have analogous signal characteristics (34). To our knowledge, the ultrasonographic characteristics of a sclerosing perineurioma have not been previously documented in this location. An ultrasound identified a hypoechoic nodule without calcification or increased vascularity. The hypoechoic nature may be attributed to the abundant collagenous stroma. An initial cystic soft-tissue perineurioma has been identified recently, which nicely fits our case (6,20,35,36).

While perineuriomas are typically positive for both claudin-1 and GLUT1, a perineurioma can be negative for one or both markers. Reports have documented cases of perineuriomas that were negative for GLUT1, claudin-1, or both, though this is considered an unusual presentation. Therefore, the definitive diagnosis must rely on a combination of microscopic findings and additional immunohistochemical markers, such as EMA and CD34. Few reports with claudin 1 and/or GLUT1 negativity have been reported in the literature (37-39). In one case, the diagnosis of cellular neurothekeoma was made. Cellular neurothekeoma is characterized by a multinodular mass with a myxoid matrix and peripheral fibrosis, involving the dermis or subcutis, and showing whorled or focally fascicular patterns of spindled and epithelioid mononuclear cells with abundant cytoplasm, indistinct cell borders, and occasional multinucleated giant cells. None of these features were present in our case.

Perineuriomas, rare and mostly benign peripheral nerve sheath tumors, were first characterized in 1978 by Lazarus and Trombetta (40). Historically, these neoplasms posed a significant diagnostic challenge until the introduction of IHC techniques, which enabled improved characterisation of their pathological features and thus aided diagnosis. In 2022, Wilson et al. reported only 19 cases of pediatric soft-tissue perineurioma and added one of their own (7,9,10,12,13,30,31).

Patient’s parental perspective

The patient expressed verbal satisfaction with the surgical team with complete recovery and no complaints.

Conclusions

In summary, we have delineated the imaging characteristics of a case of sclerosing perineurioma in a young boy in the left pectoral area using ultrasound. Recognition of this uncommon tumor, which preferentially affects digits and palms and exhibits low echogenicity on ultrasound, should lead the interpreter to consider sclerosing perineurioma in the differential diagnosis. This case report illustrates an almost unique pediatric instance of sclerosing perineurioma of the left anterior chest with additional, previously unreported imaging progression since birth. This case report is critical for general pediatrics and pediatric radiology. A description of this case aids in diagnosing extra-acral features of this tumor. Moreover, this case report may improve understanding of the imaging-pathology correlation of this tumor, benefiting both specialists and fellows.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-625/rc

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-625/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-625/coif). C.M.S. serves as an unpaid editorial board member of Translational Pediatrics from March 2024 to February 2026. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this case were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient’s guardians for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Chaturvedi HT, Chaturvedi C. Hybrid peripheral nerve sheath tumours - A Review. J Oral Maxillofac Pathol 2024;28:651-6. [Crossref] [PubMed]
2. Belakhoua SM, Rodriguez FJ. Diagnostic Pathology of Tumors of Peripheral Nerve. Neurosurgery 2021;88:443-56. [Crossref] [PubMed]
3. White B, Belzberg A, Ahlawat S, et al. Intraneural perineurioma in neurofibromatosis type 2 with molecular analysis. Clin Neuropathol 2020;39:167-71. [Crossref] [PubMed]
4. Broski SM, Littrell LA, Howe BM, et al. Extraneural perineurioma: CT and MRI imaging characteristics. Skeletal Radiol 2020;49:109-14. [Crossref] [PubMed]
5. Al-Adnani M. Soft Tissue Perineurioma in a Child With Neurofibromatosis Type 1: A Case Report and Review of the Literature. Pediatr Dev Pathol 2017;20:444-8. [Crossref] [PubMed]
6. Abreu E, Aubert S, Wavreille G, et al. Peripheral tumor and tumor-like neurogenic lesions. Eur J Radiol 2013;82:38-50. [Crossref] [PubMed]
7. Wilson T, Wang S, Bolshom B, et al. Pediatric Soft Tissue Perineurioma in the Head and Neck. Ear Nose Throat J 2024;103:693-5. [Crossref] [PubMed]
8. Siktberg J, Vaishnav Y, Berry J, et al. Sclerosing Perineurioma of the Orbit. Ophthalmic Plast Reconstr Surg 2024;40:e217-20. [Crossref] [PubMed]
9. Duhan A, Rana P, Beniwal K, et al. Perineurioma of scalp in an infant: A case report with short review of literature. Asian J Neurosurg 2016;11:70-1. [Crossref] [PubMed]
10. Johnson C, Brazen B, Ross R, et al. Sclerosing perineurioma: a rare benign tumor in a pediatric patient. Dermatol Online J 2021;
11. Ud Din N, Ahmad Z, Abdul-Ghafar J, et al. Hybrid peripheral nerve sheath tumors: report of five cases and detailed review of literature. BMC Cancer 2017;17:349. [Crossref] [PubMed]
12. Adachi S, Doi R, Mitani K, et al. Atypical soft tissue perineurioma in the tongue of a young girl. Pathol Int 2010;60:787-91. [Crossref] [PubMed]
13. Balarezo FS, Muller RC, Weiss RG, et al. Soft tissue perineuriomas in children: report of three cases and review of the literature Pediatr Dev Pathol 2003;6:137-41. [corrected].
14. Modi MB, Pei S, Hedberg ML, et al. Clinical, pathologic, and molecular analyses of superficial low-grade fibromyxoid sarcoma in two young patients: A rare and deceptive mimic of benignancy. J Cutan Pathol 2022;49:638-44. [Crossref] [PubMed]
15. Magro G, Broggi G, Angelico G, et al. Practical Approach to Histological Diagnosis of Peripheral Nerve Sheath Tumors: An Update. Diagnostics (Basel) 2022;12:1463. [Crossref] [PubMed]
16. Agaimy A, Stachel KD, Jüngert J, et al. Malignant epithelioid peripheral nerve sheath tumor with prominent reticular/microcystic pattern in a child: a low-grade neoplasm with 18-years follow-up. Appl Immunohistochem Mol Morphol 2014;22:627-33. [Crossref] [PubMed]
17. Doyle LA, Möller E, Dal Cin P, et al. MUC4 is a highly sensitive and specific marker for low-grade fibromyxoid sarcoma. Am J Surg Pathol 2011;35:733-41. [Crossref] [PubMed]
18. Thway K, Fisher C, Debiec-Rychter M, et al. Claudin-1 is expressed in perineurioma-like low-grade fibromyxoid sarcoma. Hum Pathol 2009;40:1586-90. [Crossref] [PubMed]
19. Kim HJ, Yang I, Jung AY, et al. Ultrasound and MR findings in sclerosing perineurioma. Skeletal Radiol 2011;40:353-5. [Crossref] [PubMed]
20. Khanna A, Darlow M, Jetly Shridhar R, et al. Periclavicular multifocal, infiltrative extraneural soft tissue perineuriomas: illustrative case. J Neurosurg Case Lessons 2025;9:CASE24388. [Crossref] [PubMed]
21. Thakur U, Ramachandran S, Mazal AT, et al. Multiparametric whole-body MRI of patients with neurofibromatosis type I: spectrum of imaging findings. Skeletal Radiol 2025;54:407-22. [Crossref] [PubMed]
22. Macarenco RS, Ellinger F, Oliveira AM. Perineurioma: a distinctive and underrecognized peripheral nerve sheath neoplasm. Arch Pathol Lab Med 2007;131:625-36. [Crossref] [PubMed]
23. Chavez A, Noland S, Sierra AA. Sclerosing Perineurioma: a Rare Cause of Thumb Mass. J Gen Intern Med 2022;37:3188-9. [Crossref] [PubMed]
24. Macarenco RS, Cury-Martins J. Extra-acral cutaneous sclerosing perineurioma with CD34 fingerprint pattern. J Cutan Pathol 2017;44:388-92. [Crossref] [PubMed]
25. Kakuda Y, Kato I, Kawata T, et al. Soft tissue tumor with BRAF and NRAS mutations sharing features with NTRK-rearranged spindle cell neoplasm: A case report expanding the spectrum of spindle cell tumor with kinase gene alterations. Pathol Int 2025;75:40-5. [Crossref] [PubMed]
26. Kubota Y, Kawano M, Iwasaki T, et al. Current management of neurotrophic receptor tyrosine kinase fusion-positive sarcoma: an updated review. Jpn J Clin Oncol 2025;55:313-26. [Crossref] [PubMed]
27. Malik F, Provine KS, Koo SC, et al. SOX11 is frequently expressed in ETV6::NTRK3-rearranged infantile fibrosarcoma and congenital mesoblastic nephroma. Virchows Arch 2025; Epub ahead of print. [Crossref]
28. Parisi X, Ghosh A, Wang WL, et al. Late Recurrence of Spindle Cell Sarcoma in Association with TPM3::NTRK1 Fusion. Int J Surg Pathol 2025;33:1709-12. [Crossref] [PubMed]
29. Vanacker H, Brahmi M, Pissaloux D, et al. Assessing targetable NTRK1/2/3 fusions in mesenchymal tumors via whole-exome RNA sequencing. ESMO Open 2025;10:105555. [Crossref] [PubMed]
30. Fetsch JF, Miettinen M. Sclerosing perineurioma: a clinicopathologic study of 19 cases of a distinctive soft tissue lesion with a predilection for the fingers and palms of young adults. Am J Surg Pathol 1997;21:1433-42. [Crossref] [PubMed]
31. Hornick JL, Fletcher CD. Soft tissue perineurioma: clinicopathologic analysis of 81 cases including those with atypical histologic features. Am J Surg Pathol 2005;29:845-58. [Crossref] [PubMed]
32. Arunachalam Ganesh R, Selvaraj K, Chandran S, et al. Extraneural Soft Tissue Perineurioma: A Report of a Rare Case of Peripheral Nerve Sheath Tumor. Cureus 2024;16:e73169. [Crossref] [PubMed]
33. Macarenco AC, Macarenco RS. Intradermal monophasic hybrid schwannoma-perineurioma: a diagnostic challenge. Am J Dermatopathol 2010;32:526-8. [Crossref] [PubMed]
34. Horcajadas AB, Lafuente JL, de la Cruz Burgos R, et al. Ultrasound and MR findings in tumor and tumor-like lesions of the fingers. Eur Radiol 2003;13:672-85. [Crossref] [PubMed]
35. Lenartowicz KA, Amrami KK, Torres-Mora J, et al. Perineurioma of the sciatic nerve with reticular, microcystic, and pseudolipoblastic features: illustrative case. J Neurosurg Case Lessons 2023;5:CASE23112. [Crossref] [PubMed]
36. Lazim A, Malik F, Cooper K. Glucose Transporter 1 (GLUT1) Positivity in Ganglion Cysts: A Diagnostic Caveat Due to Overlap With Perineuriomas and Other Fibromyxoid Lesions. Cureus 2025;17:e77142. [Crossref] [PubMed]
37. Ma TS, Zhou L, Zhou Q, et al. Soft tissue perineurioma involving the kidney: a report of two cases with an emphasis on differential diagnosis. Diagn Pathol 2021;16:87. [Crossref] [PubMed]
38. Yamada S, Kitada S, Nabeshima A, et al. Benign cutaneous plexiform hybrid tumor of perineurioma and cellular neurothekeoma arising from the nose. Diagn Pathol 2013;8:165. [Crossref] [PubMed]
39. Yokosuka R, Ikeya T, Yamato H, et al. Perineurioma Diagnosed After Endoscopic Treatment of Suspected Gastric Adenocarcinoma of the Fundic Gland. ACG Case Rep J 2023;10:e01110. [Crossref] [PubMed]
40. Lazarus SS, Trombetta LD. Ultrastructural identification of a benign perineurial cell tumor. Cancer 1978;41:1823-9. [Crossref] [PubMed]