Cutaneous Malignant Melanoma Mimicking Malignant Peripheral Nerve Sheath Tumor (MPNST) in Meckel's Cave: Utility of Next-Generation DNA Sequencing for Diagnosis

Introduction: Malignant peripheral nerve sheath tumors (MPSNT) and metastatic melanoma in Meckel's cave are exceptionally unusual. Desmoplastic neurotropic metastatic melanoma (DNM), a rare variant, frequents the skull base via perineural invasion of the trigeminal or facial nerves in the setting of previous head/neck cutaneous malignancy, while MPNST arises directly from cranial nerve sheath fibers. Shared embryonic lineage of neural crest origin renders significant histopathologic overlap and limited diagnostic distinction. Poor prognosis and varying therapeutic regimens for both entities necessitate the utilization of next-generation DNA sequencing (NGS) to detail genetic and immunological profiles confirm diagnosis, and guide neuro-oncologic therapy.

Objectives: To present a case of metastatic melanoma mimicking MPNST within Meckel's cave and emphasize early diagnosis with NGS.

Methods: A 73-year-old male presented with subacute hallucinations and right abducens palsy. He had no history of melanoma but reported a nondescript family history of skin cancer. He harbored no suspicious integumentary lesions. Neuroimaging demonstrated a solitary, bilobed, gadolinium-enhancing mass in Meckel's cave extending to the prepontine cistern with an amelanotic appearance on unenhanced sequences ([Fig. 1]). No perineural enhancement of the postganglionic trigeminal nerve or maxillofacial structures was evident nor was osseous foraminal expansion. The patient underwent a right-sided subtemporal craniotomy with transpetrosal approach for a suspected trigeminal schwannoma.

Results: Macroscopic appearance of the tumor was non-pigmented and resembled nerve sheath tumor. Histopathology revealed a high-grade spindle-cell sarcomatoid neoplasm with neurocristic differentiation ([Fig. 2]). Immunohistochemical staining was positive for S100 and SOX10 with no reactivity evident for BCL2, CD34, GFAP, HMB45, Melan A, desmin, or pancytokeratin. Initial diagnosis was interpreted as MPNST.

The patient underwent 27 fractions of 200 Gy external beam radiation. Eventually, NGS led to an integrated diagnosis of poorly differentiated metastatic cutaneous melanoma based on the sarcoma methylation classifier and mutation profile ([Fig. 3]). The patient expired 3 months postoperatively before immunotherapy could be initiated.

Literature review yielded 18 articles with 26 cases of malignant melanoma infiltrating Meckel's cave ([Fig. 4]). 92.3% cases represented DNM with perineural trigeminal invasion. The remaining cases were primary melanoma with one association to NF-1. DNM presented with extensive postganglionic trigeminal nerve enhancement, pterygoid and orbital infiltration, and an amelanotic radiographic appearance. Two cases depicted histopathologic mimicry of MPNST, of which discovery of cutaneous head/neck involvement occurred 9 months after skull base tumor resection in one case. NGS was inconsistently reported.

Conclusion: We present a challenging case of metastatic Meckel's cave melanoma treated as presumptive trigeminal MPNST. Our case represents the second case of MPNST mimicry in Meckel's cave without a history of cutaneous melanoma. A lack of enhancement of post-ganglionic cranial nerves and osseous expansion of maxillofacial foramina precluded consideration for classic DNM on radiography. Histopathology was inconclusive. NGS was ultimately critical for accurate diagnostics and offering result-driven guidance for FDA-approved immunotherapies despite the patient's accelerated demise. NGS should be performed at the time of initial specimen collection for suspected cranial nerve sheath tumors, particularly for those patients with unknown dermatologic history or melanoma risk factors.

 

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
15 February 2022