Late-Onset Intracranial Melanotic Schwannoma of the Cerebellopontine Angle: Case Report and Review of the Literature

Abstract

Melanotic schwannoma is a rare malignant tumor of nerve sheaths characterized by melanin-producing cells. It is mostly localized in the posterior roots of spinal nerves or sympathetic ganglia whereas the intracranial localizations are less common. The aim of this study is to describe a case of sporadic melanotic schwannoma of the right cerebellopontine angle, including a literature review of the topic. This is the case of a 79-year-old woman who presented with right-sided hearing loss and vertigo. Magnetic resonance imaging (MRI) of the brain revealed an 8 × 6 mm lesion at the level of the right cerebellar peduncle, hyperintense on T1-weighted sequences. A gross total resection of the lesion was performed through a retrosigmoid approach. The histological and immunohistochemical exams were consistent with a malignant melanotic schwannoma. Research was conducted using Pubmed and a reference list. Only melanotic schwannomas with intracranial localizations were considered. Twenty-nine articles were included in this review, reporting a total number of 32 cases of intracranial melanotic schwannomas. The treatment of choice is the complete surgical excision of the neoplasm; adjuvant radiotherapy correlates with lower rates of recurrence and metastasis. Our case represents the latest onset of an intracranial melanocytic schwannoma with a clinical course similar to a conventional eighth cranial nerve schwannoma.

Introduction

Melanotic schwannoma (MS) is a rare malignant tumor of the nerve sheath, distinguished by the presence of melanin-producing cells. It accounts for approximately 1% of all nerve sheath tumors.^1,2 The majority of cases exhibit thoracic localization, typically involving the posterior roots of spinal nerves or the sympathetic ganglia. Intracranial and craniofacial occurences are uncommon, and only a limited number of cases involving the cerebellopontine angle have been reported in the literature. ²

Previously classified as a benign tumor in the 2013 WHO classification, MS was reclassified in the 2020 WHO classification as a malignant melanotic nerve sheath tumor (MMNST), reflecting its recognized malignant potential.

The development of MS may occur either sporadically or as part of hereditary syndromes (Carney complex; Neurofibromatosis II). In Carney complex, schwannomas are associated with endocrine tumors, cardiac myxomas, and abnormalities in skin pigmentation following an autosomal dominant pattern of inheritance. ³ The present study aims to describe a rare sporadic melanotic schwannoma located in the right cerebellopontine angle, with onset in advanced age. A systematic review of the literature was also conducted.

Materials and Methods

Case Report

A 79-year-old woman was admitted to the Sense Organs Department at “Sapienza” University of Rome. She had a moderate right-sided sensorineural hearing loss, tinnitus, vertigo, and dizziness persisting for several months. Left side hearing was preserved. The patient had no prior history of otologic or vestibular disorders.

Brain Magnetic resonance imaging (MRI) was performed. It revealed an 8 × 6 mm lesion at the level of the right cerebellar peduncle. The lesion appeared hyperintense on T1-weighted sequences and hypointense on T2-weighted sequences.

A retrosigmoid surgical approach was selected to achieve gross total resection of the tumor. Particular attention was directed toward the preservation of cranial nerves VII and VIII.

Histological examination of the excised tumor revealed a tissue mainly composed of spindle cells with a fascicular growth pattern (Figure 1A). In some areas, where the cells were plump and polygonal, a coarsely clumped or finely granular intra-cellular pigment was observed (Figure 1B and C). The pigment tested negative on Perls’ staining and was consistent with melanin (Figure 1D). No significant mitotic activity or necrosis were identified. Immunohistochemical analysis revealed immunoreactivity of the neoplastic cells for S100 in both the non-pigmented (Figure 1E) and pigmented (Figure 1F) areas of the tumor. In contrast, immunostaining for HMB45 was negative in the non-pigmented areas (Figure 1G) and positive in the pigmented ones (Figure 1H). The overall expression of Ki-67 was less than 5%. Based on these findings, a diagnosis of malignant melanotic nerve sheath tumor (MMNST) was established. ⁴

Figure 1.

Representative histological images of the non-pigmented and pigmented areas of the tumor are shown in (A) and in (B and C), respectively. The pigment (arrows in (C)) is negative with Perls’ staining (D); the blue granules in the right top corner are hemosiderin depots. Immunostains for S100 and HMB45 in the non-pigmented and in pigmented areas are shown in (E and F) and in (G and H), respectively. Original magnification for (A, B, E, and F) 10× and for (C and D) 20×. (A-C) Hematoxylin-eosin; (D) Pearls method. For immunohistochemistry, the chromogenic substrate was 3,3′Diaminobenzidine (DAB) for S100 and 3-Amino-9-ethylcarbazole (AEC) for HMB45.

The patient had a regular postoperative course and was discharged on the seventh day after surgery with a prescription for steroid and antiviral therapy. Genetic testing for Carney complex and Neurofibromatosis type II was conducted as part of the diagnostic workup, yielding negative results.

The patient declined postoperative adjuvant therapy and is currently undergoing scrupulous clinical and radiological follow-up.

Six months after surgery, she demonstrated good general and local clinical status, with no signs of cranial nerve VII or VIII dysfunction. Follow-up MRI showed no evidence of tumor recurrence.

Review

The search was conducted using PubMed and a reference list, with the following keywords: “schwannoma,” “melanotic,” and “intracranial.” Publications not written in English were excluded from the review (Figure 2).^5-29

Figure 2.

Prisma flow diagram.

Only intracranial tumors with a histological diagnosis of melanotic schwannoma were included in the review, while melanotic schwannomas with extracranial localization were excluded (Table 1).

Table 1.

Case summaries.

Author	Age	Sex	Location	Carney complex	Resection	Histology	Necrosis	Adjuvant treatment	Recurrence at last follow up
Dastur et al 5 (1967)	34	M	CPA	NA	Subtotal	NPMS	NA	No	Yes, after 8 mo
Quencer et al 6 (1979)	22	M	Trigeminal nerve, Gasserian ganglion	NA	Total	NPMS	No	No	No recurrence at 14 mo
Miller et al 7 (1986)	74	M	CPA	NA	Total	NPMS	NA	No	No recurrence at 9 mo
Beck and Menezes 8 (1987)	12	M	Trigeminal nerve, Meckel’s cave	NA	NA	NA	NA	Radiation (recurrence after 2 y)	No new recurrence at 108 mo
Carney 3 (1990) first case	NA	NA	Trigeminal nerve	Yes	NA	NA	NA	NA	NA
Carney 3 (1990) second case	NA	NA	Trigeminal nerve	Yes	NA	NA	NA	NA	NA
Jensen and Bretlau 9 (1990)	22	M	Orbit	No	Total	NPMS	No	No	Yes, after 36 mo
Earls et al 10 (1994)	77	M	CPA	NA	Subtotal	NA	NA	NA	NA
Ranjan et al 11 (1995)	56	F	Intracerebellar	NA	Total	NPMS	No	No	No recurrence at 6 mo
Buhl et al 12 (2004)	28	M	Trigeminal nerve	No	Total	NPMS	No	No	NA
Zhang et al 13 (2005)	11	M	Oculomotor nerve	No	Subtotal	NPMS	NA	Radiation	No recurrence at 42 mo
Carrasco et al 14 (2006)	34	F	Trigeminal nerve	Yes	Subtotal	NPMS	NA	No	Yes, after 3 mo
Mey et al 15 (2006)	22	M	Orbit	NA	Total	NPMS	No	Radiation	Yes, after 36 mo
Er et al 16 (2007)	54	M	Foramen Magnum	No	Total	NPMS	No	No	No recurrence at 24 mo
Saint-Blancard et al 17 (2008)	52	M	CPA	No	Subtotal	NPMS	Yes	No	NA
Scheithauer et al 18 (2009)	41	F	Posterior fossa	NA	NA	NA	Yes	Radiation	No recurrence at 5 mo
Diaz Beveridge et al. 19 (2010)	60	M	Orbit	Yes	Total	PMS	NA	No	NA
Ditz et al 20 (2011)	12	F	Orbit	No	Total	NPMS	No	No	Yes, recurrence after 240 mo
Torres-Mora et al 21 (2014)	19	F	Trigeminal nerve	No	NA	NA	NA	NA	No recurrence at 49 mo
Moisak et al 22 (2014)	23	M	Trigeminal nerve, Gasserian ganglion	No	Total	PMS	NA	Temozolomide	No recurrence at 42 mo
Spina et al 2 (2015)	47	F	CPA	No	Subtotal	NPMS	No	Radiation	No recurrence at 39 mo
Mahato et al 1 (2017)	43	F	Intracerebellar	No	Subtotal	NPMS	Yes	Radiation	NA
Collart et al 23 (2018)	64	F	Trigeminal nerve, Meckel’s cave, Gasserian ganglion	No	Total	NPMS	NA	Radiation after second surgery for recurrence	Yes, after 3 mo No recurrence after radiation
Mubarak et al 24 (2018)	48	M	CPA	NA	Total	NA	NA	NA	NA
Sahay et al 25 (2020) first case	20	F	Cavernous sinus	No	Total	PSM	No	No	No recurrence at 30 mo
Sahay et al 25 (2020) second case	19	F	Trigeminal nerve	No	Total	NPMS	No	No	No Recurrence at 60 mo
Sahay et al 25 (2020) third case	45	F	CPA	No	Subtotal	NPMS	Yes	NA	NA
Sharath et al 26 (2022)	36	F	Trigeminal nerve	Yes	Total	PMS	NA	NA	NA
Dandekar and Mehta 27 (2023)	23	M	Trigeminal nerve	NA	Total	NA	NA	Radiation	NA
Nicoletti et al. (2024)	79	F	CPA	No	Total	NPMS	No	No	No recurrence at 9 mo
Yoo et al 28 (2024)	76	F	Orbit	No	Total	NPMS	Yes	No	NA
Madesh et al 29 (2025)	42	F	Posterior fossa	No	Total	PMS	Yes	NA	NA

Abbreviations: CPA, pontocerebellar angle; F, female; M, male; NA, not available; NPMS, non-psammomatous; PMS, psammomatous.

Results

A total of 29 studies reporting 32 cases of intracranial melanotic schwannomas (IMS) were analyzed. The mean age at onset was 39,8 years (range 11-79 years), with a balanced gender distribution (15 males and 15 females). Of the cases reviewed, 5 were associated with Carney complex, while the remaining cases were sporadic.

The most frequent intracranial localization of melanotic schwannomas was the trigeminal nerve (12 cases), followed by the cerebellopontine angle (8 cases), orbital cavity (5 cases), intracerebellar region, and posterior cranial fossa (2 cases each). One case involved the foramen magnum, oculomotor nerve and cavernous sinus.

In 19 patients, the lesion underwent gross total resection. In 8 patients, the lesion could not be completely excised. Data regarding the surgical approach were not available for the remaining cases.

On histologic examination, most intracranial melanotic schwannomas did not report any psammomatous bodies: these were identified in 5 patients, 2 of whom had Carney complex. Areas of necrosis were observed in in the lesions of 6 patients.

Radiation therapy was administered as postoperative adjuvant treatment in 33,3% of cases (8 of the 24 patients for whom such data were available). No adjuvant treatment was performed in the remaining 66% of the patients. Follow-up data were available for 19 of the analyzed cases, of which 6 experienced recurrences, with a mean time to recurrence of 54.3 months post-surgery. Interestingly, recurrence of IMS at the cerebellopontine angle was documented in only 1 case.

Discussion

Melanocytic schwannoma arises from 2 distinct cell types: Schwann cells and melanocytes. These cells share a common embryological origin from neural crest cells, which migrate from the neural tube and differentiate under the influence of specific growth factors, such as FOXD3. ¹ Notably, melanocytes and melanosomes are physiologically present in the structures of the vestibule and inner ear as well as in the endolymphatic duct and sac, where they contribute to signal transmission through gap junctions.^30-32

MS has traditionally been regarded as a tumor with benign histological features. However, its clinical behavior can be unpredictable and does not exclude the subsequent or concomitant development of metastases and a non-negligible tendency to recur, particularly in the context of hereditary syndromes. Based on this malignant potential, Torres-Mora et al proposed reclassifying these neoplasms as malignant melanotic nerve sheath tumors (MMNSTs), ²¹ a designation that has been adopted by the 2021 WHO classification of central nervous system tumors.

Currently, strict histopathological criteria for malignancy in MMNSTs are not yet fully established. Nonetheless, the presence of features such as large vesicular nuclei with macronucleoli, high mitotic activity, and areas of necrosis is associated with a more aggressive clinical course.

Two main histologic subtypes of MMNST are recognized: psammomatous and nonpsammomatous. The psammomatous subtype is often linked to Carney complex.

Differential diagnosis must be made with other types of melanin-producing tumors, such as malignant melanoma and melanocytic meningioma, which have different cytological and histological features. ² Additionally, other differential diagnosis to consider are primary leptomeningeal melanocytic neoplasms like the Melanocytoma and uncommon subtypes of nerve sheath tumor such as the Cellular Schwannoma. ³³ Melanocytoma is a solitary, low-grade tumor originating from leptomeningeal melanocytes. It is composed of heavily pigmented, elongate or polygonal cells, with vesicular nucleus and distinct nucleolus.

Patients’ symptoms vary depending on the location of the neoplasm and the intracranial structures involved. In the present case, the lesion mimicked a vestibular schwannoma of the eighth cranial nerve, manifesting with auditory and vestibular symptoms. When involving the fifth cranial nerve, patients may experience pain and unilateral facial dysesthesia.

The radiological features of melanocytic schwannoma are different from those of traditional schwannoma due to the presence of intracytoplasmic melanin deposits. In fact, on MRI, MS appears hyperintense on T1-weighted sequences and hypointense/isointense on T2-weighted sequences. Susceptibility-weighted imaging (SWI) can further assist in identifying areas of intralesional hemorrhage or calcification. ²⁴

Histologically, MS is characterized by spindle and epithelioid cells with eosinophilic to amphophilic cytoplasm. Psammoma bodies are uncommon and more frequently associated with hereditary cases, although they have also been described in sporadic tumors. MSs typically stain positively with Masson-Fontana, Gomori, and periodic acid–Schiff (PAS) stains, indicating the presence of melanin, reticulin, and polysaccharides, respectively. Immunohistochemistry is positive for S-100 protein, HMB-45, laminin, vimentin, Melan-A. The co-expression of S100/SOX10 and melanocytic markers such as HMB45 and MelanA is typical of MSs and crucial for their differential diagnosis with other neoplasms. Ki-67 expression is variable from 1% to 20%. ²³ Mitotic rate has been found to be predictive of clinical outcome: a mitotic rate higher than 2/10 HPF correlates with an increased risk of metastasis. ³⁴

Genetic testing of neoplastic cells is essential for identifying germline mutations, enabling both genetic counseling and long-term surveillance. MMNSTs associated with Carney complex often harbor inactivating mutations of the PRKAR1A tumor suppressor gene on chromosome 17p22. ³⁵

The standard treatment is complete surgical excision of the neoplasm. In our literature review, the recurrence rate was 33.3% following gross total resection and 50% following subtotal resection, with an average time to recurrence of 54.3 months postoperatively.

Adjuvant radiotherapy is the most commonly employed secondary treatment, particularly in cases with histological features suggestive of malignancy or incomplete resection, regardless of histologic grade. Additional adjuvant options include stereotactic radiosurgery (eg, Gamma Knife) and chemotherapeutic agents such as temozolomide. The use of adjuvant radiotherapy has been associated with reduced rates of recurrence and metastasis.^13,36 In the case presented, no adjuvant therapy was administered due to the patient’s preference and the radical nature of the resection.

Following surgery, it is paramount that patients undergo a long follow-up period because of the risk of recurrence and metastasis, even 20 years after the onset of the primary malignancy.

Conclusion

Melanocytic schwannomas are rare neoplasms with radiological, histological and immunohistochemical features that differentiate them from classic schwannomas. To date, only 32 cases of intracranial melanocytic schwannomas have been reported in the literature, and the available data are insufficient to establish a definitive diagnostic and therapeutic strategy. Even rarer is the occurrence of these tumors at the cerebellopontine angle. The optimal treatment approach is complete surgical resection of the neoplasm. Adjuvant therapies should be considered in cases of incomplete mass resection.