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. 2023 Feb 19;35:12–15. doi: 10.1016/j.jdcr.2022.12.028

Pigmented malignant peripheral nerve sheath tumor of the nail unit arising in a patient with neurofibromatosis type I

Courtney Kromer 1,∗, Thomas Knackstedt 1, Stephen Somach 1
PMCID: PMC10106731  PMID: 37078011

Introduction

Malignant peripheral nerve sheath tumors (MPNSTs) are rare, aggressive spindle cell sarcomas that most commonly develop in patients with neurofibromatosis type 1 (NF1) and are the leading cause of death in this population.1,2 These tumors most commonly arise from larger nerve trunks, such as the paraspinal nerves, sacral and brachial plexus, sciatic nerve, and nerves of the chest wall and neck.2 Few cases of MPNSTs arising in the finger have been reported, but to our knowledge, this is the first reported case of a MPNST arising within the nail bed. Here, we report the case of a patient with NF1 presenting with a MPNST arising within the nail bed.

Case report

A 65-year-old African American man with NF1 presented with an expanding tender mass of the right index fingernail bed that had been present for 2 years. Clinical examination revealed a brown to violaceous, dome-shaped nodule occupying most of the nail bed, with nail plate destruction (Fig 1). A nail bed shave biopsy was performed. Histopathology results showed a nodular tumor with epithelial hyperplasia overlying an infiltrative spindle cell tumor in an eosinophilic fibrillary stroma (Fig 2, A). The bulk of the tumor was highlighted with antibodies to S100 protein (Fig 2, B). Portions of the tumor were cellular (Fig 3, A), with some areas highlighted with antibodies to Melan A and neurofilament (Fig 3, B). Some areas of the tumor showed pleomorphic spindle cells (Fig 4, A), whereas other portions showed clustered epithelioid cells with stromal melanophages suggesting melanocytic differentiation (Fig 4, B). These findings were consistent with an MPNST arising within a preexisting neurofibroma. Partial expression of Melan-A was considered a manifestation of limited melanocytic differentiation. The patient underwent treatment with wide local excision via amputation at the level of the distal interphalangeal joint with clear margins.

Fig 1.

Fig 1

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Clinical presentation of a rapidly growing malignant peripheral nerve sheath tumors arising from the thumbnail bed with multiple neurofibromas in a patient with neurofibromatosis type 1.

Fig 2.

Fig 2

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A, Sections from the tumor showed replacement of nail plate and nail bed epithelium with epidermis overlying an infiltrative spindle cell tumor. B, The bulk of the tumor was highlighted by antibodies to S100 protein.

Fig 3.

Fig 3

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A, The bulk of the tumor is composed of spindled cells with mild pleomorphism. B, Neurofilament expression, shown on the right, was seen in the tumor supporting a nerve sheath origin.

Fig 4.

Fig 4

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A, Several areas of the tumor were highly cellular with prominent pleomorphism, which is consistent with a sarcoma. B, Portions of the tumor showed clustered epithelioid cells with numerous stromal melanophages, suggesting melanocytic differentiation.

Consent for the publication of all patient photographs and medical information was provided by the authors at the time of article submission to the journal stating that all patients gave consent for their photographs and medical information to be published in print and online and with the understanding that this information may be publicly available.

Discussion

MPNSTs are rare sarcomas thought to be of neural crest origin, arising from peripheral nerve sheath cells. These tumors are aggressive and characterized by high rates of local recurrence and distant metastases, poor outcomes, and a 5-year survival rate between 23% and 69%. MPNSTs typically arise from preexisting plexiform neurofibromas and atypical neurofibromas in patients with NF1, with incidence in this population ranging from 8% to 15%.3 Progression of these lesions to MPNSTs commonly occur because of loss of additional tumor suppressors, such as p16, p53, and CDKN2A.1, 2, 3, 4 Rapid growth of neurofibromas may indicate malignant transformation, and thus, warranting a biopsy.1, 2, 3, 4

Early recognition of MPNSTs can be challenging, but is critical as, currently, the only effective and curative treatment for these tumors is surgical resection with wide negative margins.1,5, 6, 7, 8 Excision may not be feasible depending on tumor size, location, and metastatic presentation, and even with surgical resection, local recurrence rates range from 25% to 37%.1,9 Currently, there is no consensus on treatment regimens for MPNSTs beyond surgery with wide margins. Given the rarity of these tumors, few clinical trials regarding treatment strictly for MPNSTs have been completed, as they are most often grouped into the larger cohort of soft tissue sarcomas in therapeutic trials.5, 6, 7, 8,10 Few prospective clinical trials have been completed, and those have been in patients with later stage and surgically unresectable MPNSTs.10,11 The SARC006 phase II trial was a prospective study that evaluated response rates to chemotherapies with ifosfamide and doxorubicin, followed by ifosfamide and etoposide in both stage III/IV sporadic and NF1-associated MPNSTs. This study showed that only 32% of all patients had a partial response to the chemotherapy regimen and none had a complete response, leading to the conclusion that these tumors are relatively resistant to chemotherapy.10 Clinical trials using sirolimus and ganetespib, as well as erlotinib, in patients with MPNSTs have failed to yield significant therapeutic responses.11,12 The findings of these trials suggest that NF1-associated MPNSTs may be even less responsive to systemic therapy than sporadic MPNSTs.10,11

Currently, recommendations for adjuvant or neoadjuvant radiation therapy are reserved for high-grade lesions, tumors >5 cm, or tumors with positive margins after resection, and are on the basis of a broader group of high-grade soft tissue sarcomas.5,7,13 To our knowledge, no clinical trials addressing radiation therapy specifically for MPNSTs have been performed. A randomized prospective study of soft tissue sarcomas after limb sparing surgical resection that included patients with MPNSTs showed prevention of local recurrence with postoperative external beam radiotherapy, but no difference in overall survival.14 Any consideration of adjuvant radiation in the setting of NF1-associated MPNSTs should be done with caution, as radiation is a risk factor for development of MPNST and other sarcomas in these patients.15,16

As MPNSTs most commonly arise from larger nerve trunks, their occurrence in the digits is extremely rare.17, 18, 19 To our knowledge, this is the first case of an MPNST arising within the nail bed, and, as such, this tumor should be included in the differential diagnosis of malignant nail bed tumors, such as melanoma and squamous cell carcinoma. Awareness of this unusual presentation of MPNSTs may help lead to early diagnosis and potentially curative treatment of this aggressive disease by surgical resection with wide margins.

Conflicts of interest

None disclosed.

Footnotes

Funding sources: None.

IRB approval status: Not applicable.

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