Brain and spine melanotic schwannoma: A rare occurrence and diagnostic dilemma

Abstract

Purpose

Melanotic schwannoma (MS) was formerly known as a rare variant of schwannoma. The behavior of MS is unpredictable, with a tendency for recurrence and metastasis. The purpose of this study was to illustrate the imaging characteristics of these rare and misdiagnosed tumors. The prognosis of MS is discussed, along with the importance of follow-up exams to assess for recurrence and metastasis. Furthermore, we compare our results with those previously published on MS in order to have a better understanding of this rare entity.

Methods

Three MS cases were encountered between 2008 and 2015 at our institute. All available data were reviewed, including the clinical history, imaging findings, operative notes, and the histopathology results. A follow-up magnetic resonance imaging (MRI) scan was also reviewed up to 23 months post surgery to assess for recurrence.

Results

Three cases of MS are included: one in the brain and two in the spine. The brain lesion was in the occipital region. The spine lesions were thoracic intramedullary and sacral intradural. All cases were hypointense on T2-weighted imaging. Gross total resection was achieved for all lesions without adjuvant therapy. To date, the brain lesion recurred 15 months after surgery.

Conclusions

MS is a rare and distinct entity rather than a variant of schwannoma, and it poses both diagnostic and management dilemmas. Although MS has characteristic MRI features, including T1 and T2 shortening, the preoperative diagnosis is always challenging. Accurate diagnosis is crucial for management planning, including long-term follow-up exams to assess for recurrence and metastasis.

Introduction

Melanotic schwannoma (MS), formerly known as a rare variant of schwannoma, is composed of cells having the ultrastructure and immunophenotype of Schwann cells but containing melanosomes in varying stages of maturation.¹ Several theories for the etiology and histogensis of MS have been proposed, including that Schwann cells and melanocytes are neuroectodermal in origin and that melanocytes migrate with the Schwann cells.² Killeen et al.³ found that MS cells are capable of melanogenesis. Mandybur⁴ suggested a melanomatous transformation of neoplastic Schwann cells.

MS was first described at the thoracic sympathetic ganglion by Millar in 1932.⁵ Currently, up to 200 cases of MS have been reported in the literature at various locations, including the skin, bone, visceral organs, sinuses, adrenal glands, uterus, bronchus, pancreas, orbit, intracranial, and intramedullary.⁶ The lesions most frequently arise close to the midline in the paravertebral nerve roots.⁶ Patients can have various presentations based on tumor location. In 1990, Carney⁷ noted the frequent (about 50%) association of MS with other stigmata of Carney complex, which consists of myxomas (of the heart, breast, and skin), spotty pigmentation, and endocrinopathy (Cushing syndrome, precocious puberty, and acromegaly). The behavior of MS is unpredictable, and although it is considered benign, it can have malignant clinical potential with a tendency for recurrence and metastasis. The rates of local recurrence and distant metastasis have been reported to be 6–35% and 8–41%, respectively, including patients with histologically benign-appearing tumors.^6–9

The purpose of this study was to illustrate the imaging characteristics of these rare and misdiagnosed tumors, which should be considered in the differential diagnosis of uncommon intradural masses. The prognosis of MS is also discussed compared to conventional schwannoma, with the importance of follow-up exams to assess for possible recurrence and metastasis. Furthermore, we compare our results with those previously published for MS in order to have a better understanding of this rare entity.

Methods

Three cases of MS, one intracranial and two intra-spinal, were encountered between 2008 and 2015 at our institute upon review of the radiology database. All available data for the three cases previously described as “MS” were retrieved and reviewed by the authors (A.A. and D.T.), including the clinical history, imaging findings, operative notes, and histopathology results to date. All three patients were women, ranging in age from 40 to 54 years. The brain lesion presented with a headache and visual deficit. The spinal cases presented with back pain without radicular or sphincteric symptoms. In one of the spinal cases, the patient was also known to have breast carcinoma, which made the preoperative diagnosis even more challenging.

Patients were examined by magnetic resonance imaging (MRI) at 1.5 T. The MRI brain protocol included: sagittal T1 spin echo, axial FRFSE T2, axial FSE PD, and diffuse-weighted imaging. The MRI spine protocol included: sagittal T1 TSE, sagittal T2 TSE, and axial T2 TSE. Contrast-enhanced T1-weighted imaging (T1WI) was also obtained after intravenous injection of 1 cc/10 kg of gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany). MRI scans of the lesions were evaluated, with an emphasis on the location, shape, margin, signal intensity, and pattern of contrast enhancement.

All lesions were removed by open surgery with gross total resection. The final diagnoses were established by histopathology, with diffuse positivity of S-100 in all patients. Based on the final diagnosis, follow-up exams by MRI were also reviewed between 15 months after surgery in one patient and 23 months in other patient to assess for recurrence. A detailed review of the literature was also conducted through PubMed using “melanotic schwannoma” as the search term.

Results

Three cases of MS are included: one in the brain and two in the spine (thoracic and sacral). All cases were solitary lesions. The brain lesion was dural based in the right occipital region (Figure 1). The thoracic spine lesion was intramedullary at the T5–T6 level (Figure 2), and the other spinal case was a sacral intradural lesion (Figure 3). T1WI showed isointensity in the brain lesion and in the intramedullary thoracic lesion. However, the sacral lesion was hypointense, with a peripheral rim of spontaneous T1 hyperintensity. All cases were hypointense on T2WI and showed intense contrast enhancement. The intracranial lesion showed peripheral cystic changes with enhancing wall (Figure 1). All tumors showed well-defined, round, or ovoid masses. The microscopic findings showed spindle or epithelioid cells tumor proliferation with brown pigment depositions. There was a lack of cellular atypia or significant mitotic activity. All cases were positive for S-100, Melan-A, and HMB-45, apart from one lesion that was negative for HMB-45.

Figure 1.

A 40-year-old female presented with a history of headache and visual deficit. A dural-based mass was identified in the right occipital region with iso-density on computed tomography, iso-signal intensity on T1-weighted imaging (T1WI), and low signal intensity on T2WI compared to the cerebral cortex associated with diffusion restriction, intense contrast enhancement, and cystic changes (arrow).

Figure 2.

A 45-year-old female presented with a history of back pain. A rounded intramedullary thoracic spine lesion was identified at the T5–T6 level with iso-signal intensity on T1WI and low signal intensity on T2WI associated with intense contrast enhancement (arrow) and adjacent large edema.

Figure 3.

A 54-year-old female presented with a history of back pain. An oval intraspinal sacral lesion was identified at the S2–S3 level with predominantly central low signal intensity on both T1WI and T2WI associated with intense contrast enhancement. There was peripheral rim of spontaneous T1 hyperintense signal (arrow).

To date, the brain lesion recurred 15 months after surgery (Figure 4). However, the intramedullary thoracic lesion and the sacral lesion have shown no evidence of recurrence in the last follow-up exams after 23 and 15 months from the date of surgery, respectively (Figures 5 and 6). None of our cases received radiotherapy, although one case refused to continue treatment with radiotherapy. None of the patients had documented skin or other pigmented lesions. There was no evidence of metastasis in any of the three cases.

Figure 4.

(a) Immediate postoperative magnetic resonance imaging (MRI) shows resection of the occipital lesion without residual. (b) A 15-month postoperative MRI shows a new lesion in the operative site with low signal on T2WI (arrow) and contrast enhancement associated with cystic changes.

Figure 5.

A 23-month follow-up MRI post gross total resection of the intramedullary thoracic spine lesion shows no evidence of tumor residual or recurrence.

Figure 6.

A 15-month follow-up MRI post gross total resection of the sacral lesion shows no evidence of tumor residual or recurrence.

Discussion

The 2016 World Health Organization classification of central nervous system tumors reclassified MS as a distinct entity rather than a variant of schwannoma due to its clinical behavior and genetic difference.¹⁰ Two forms of MS were microscopically described: sporadic and psammomatous.⁹ The psammomatous form is so called due to the fact that some contain psammoma calcifications, and it is often associated with Carney complex in about 50% of cases.⁷ Isolated cases of non-psammomatous MS have been associated with Carney complex as well.¹¹ MS occur in relatively younger adults (M_age = 35 years), and have no sex predilection compared to usual schwannoma, which occur frequently in the fifth decade (M_age = 48 years) with a slight female predilection.^6,9 However, psammomatous MS occurs a decade younger than the sporadic MS.⁷

The clinical presentation is nonspecific based on tumor location and growth rate.⁹ The lesions are most frequently extramedullary in location, arising from the posterior spinal roots.^6,8 Intracranial and intramedullary MS are extremely rare, with only 22 and 11 cases published in the literature to date, respectively (Tables 1 and 2). The average age of the total 35 patients (one patient excluded due to the lack of clinical data and two patients added from our project) was 42.6 years (range 11–77 years), with a slight female predilection (53%). The majority of the intracranial cases were in Meckel’s cave and the cerebellopontine angle region (70%). The most common location of the intramedullary MS was the thoracic spine (67%). Hoover et al.¹² collected some reported and presumed etiologies of intramedullary lesions, including intramedullary nerve fibers displacing Schwann cells during embryogenesis, neoplastic extension of Schwann cells through the insertion site of the dorsal root, neoplastic differentiation of neuroectodermal cells in the pia to form intramedullary MS, and disordered migration of neural crest cells during neural tube closure.

Table 1.

Previously reported intracranial MS cases in the literature including one of our cases.

Author/year	Age	Sex	Location	CT	T1 signal	T2 signal	Cystic	Treatment	Recurrence
Dastur et al.17 1967	38	M	CPA	NA	NA	NA	NA	STR, no AT	Recurrence at 8 months
Quencer et al.23 1979	22	F	Meckel’s cave into CPA	Hyperdense	NA	NA	−	GTR, no AT	No recurrence at 14 months
Miller et al.24 1986	74	M	CPA	NA	NA	NA	NA	GTR, no AT	NA
Beck et al.19 1987	12	M	Meckel’s cave into CPA	NA	NA	NA	NA	GTR, no AT	Recurrence at 24 months (treated by radiotherapy)
Rowlands et al.25 1987	27	M	Cavernous sinus/Meckel’s cave into CPA	NA	NA	NA	NA	Biopsy, + radiotherapy	Detected 10 weeks post resection of MS in the bronchus and recurred at 14 months
Carney7 1990	NA	NA	Trigeminal nerve	NA	NA	NA	NA	NA	NA
Earls et al.26 1994	77	M	CPA	Hyperdense	Isointense	Isointense	+	NA, no AT	NA
Ranjan et al.27 1995	65	F	Cerebellum	Hyperdense	NA	NA	−	GTR, no AT	No recurrence at 6 months
Buhl et al.28 2004	28	M	Meckel’s cave	NA	NA	NA	−	GTR, no AT	Detected 2.5 years from resection of spinal MS
Zhang et al.9 2005	11	M	CN III	NA	NA	NA	NA	STR, + radiotherapy	No recurrence at 3.5 years
Carrasco et al.11 2006	34	F	Meckel’s cave	NA	Hyperintesne	NA	−	STR, no AT	Recurrence at 4 months
Er et al.29 2007	54	M	Foramen magnum	NA	NA	Hypointense	−	GTR, no AT	No recurrence at 24 months
Saint-Blancard et al.30 2008	51	F	CPA	NA	NA	Hypointense	+	STR, no AT	NA
Scheithauer et al.31 2009	41	M	Posterior fossa	NA	NA	NA	NA	NA, + radiotherapy	NA
Ditz et al.22 2011	12	F	Orbit and cavernous sinus	Hyperdense	NA	NA	−	STR, no AT	Recurrence at 20 years
Nenashev et al.32 2012	27	F	Meckel’s cave	NA	NA	NA	NA	STR, + radiotherapy	No recurrence at 6 months
Torres-Mora et al.6 2014	19	F	Meckel’s cave	NA	NA	NA	NA	NA	No recurrence at 49 months
Torres-Mora et al.6 2014	42	M	Cerebellum	NA	NA	NA	NA	NA	NA
Spina et al.33 2015	47	F	CPA	NA	NA	Hypointense	NA	STR, + radiotherapy	NA
Mahato et al.15 2018	43	F	CPA	Hyperdense	NA	Hypointense	+	STR, + radiotherapy	NA
Collart et al.18 2018	64	F	Meckel’s cave	NA	Hyperintesne	Hypointense	+	GTR, no AT	Recurrence at 3 months
Moisak et al.20 2018	23	M	Meckel’s cave	NA	Hyperintense	Hyperintense	−	GTR, + chemotherapy	No recurrence at 3.5 years
Added case	40	F	Occipital	Isodense	isointense	Hypointense	+	GTR, no AT	Recurrence at 15 months

MS: melanotic schwannoma; NA: not available; M: male; F: female; CPA: cerebellopontine angle; CN: cranial nerve; +: present; − : absent; GTR: gross total resection; STR: subtotal resection; AT: adjuvant therapy.

Table 2.

Previously reported intramedullary MS cases in the literature, including one of our cases.

Author/year	Age	Sex	Location	T1	T2	Cystic	Treatment	Follow-up
Solomon et al.34 1987	69	M	Medulla–C3	NA	NA	NA	GTR, no AT	NA
Marchese et al.35 1990	72	F	C4–C6	Hyperintense	NA	NA	STR, no AT	NA
Sola-Perez et al.36 1994	63	F	C7–T1	NA	NA	NA	FNA, no AT	NA
Acciarri et al.37 1999	44	F	T2–T3	Isointense	Hypointense	−	GTR, no AT	No recurrence at 4 months
Santaguida et al.21 2004	35	M	C4–C5	NA	NA	−	GTR, no AT	Recurrence at 10 months (treated by radiotherapy)
Mouchaty et al.38 2008	56	F	T12–L1	NA	NA	−	GTR, no AT	No recurrence at 12 months
Hoover et al.12 2012	62	F	T11	Hyperintense	Hypointense	−	GTR, no AT	No recurrence at 10 months
Pan et al.14 2014	23	F	T4–T5	Hyperintense	Hypointense	−	GTR, no AT	No recurrence at 3 years
Mohamed et al.39 2014	43	M	T9–T10	Hyperintense	Hypointense	−	GTR, no AT	No recurrence at 6 months
Cheng et al.40 2017	47	M	T4–T5	NA	Hypointense	+	STR, no AT	Recurrence at 6 years
Hu et al.41 2018	40	M	C1–C2	Hyperintense	Hypointense	−	STR, no AT	No recurrence at 2 months
Added case	45	F	T5–T6	Isointense	Hypointense	−	GTR, no AT	No recurrence at 23 months

FNA: fine-needle aspiration.

MS is often misdiagnosed as melanoma or conventional schwannoma. The differentiation between MS and other pigmented lesions can be difficult radiologically and pathologically, requiring extensive histopathological and immunohistochemical workup. The preoperative diagnosis is based on MRI, which is the investigation of choice. The radiological diagnosis is very challenging, and cases are usually misdiagnosed as either primary tumor or metastasis such as melanoma. Extramedullary lesions are commonly misdiagnosed as meningioma, conventional schwannoma, or even dermoid. The reason for this is the signal variability of the lesion on MRI due to the distribution and contents of melanin within the tumor and the presence or absence of associated hemorrhage. MS usually exhibits hyperintensity on T1WI and hypointensity on T2WI due to the paramagnetic effect of melanin. However, only lesions comprised of >10% melanin-containing cells exhibit hyperintensity on T1WI and hypointensity on T2WI.¹³ A review of the available imaging data of the intracranial and intramedullary cases showed hyperintensity on T1WI and hypointensity on T2WI in 67% and 87% cases, respectively. The blood components of the lesion are also variable, depending on the hemorrhage stage, which makes the diagnosis more challenging, and it may be confused with other much more common hemorrhagic lesions such as cavernoma.¹⁴ Contrast enhancement after gadolinium administration may be homogenous or heterogeneous based on tumor cellularity, hemorrhage, and cystic changes. Administration of gadolinium can shows nodular enhancement when cystic components are present, but it is mainly useful in differentiating intramedullary lesions from spinal-cord edema. The available data from the reviewed cases demonstrated 33% intralesional cystic changes probably due to an old hemorrhage. Mahato et al.¹⁵ questioned the relationship between cystic changes/necrosis and invasive growth of MS that increases the likelihood of subtotal resection. Confident diagnosis of intramedullary schwannoma can also be made preoperatively when there is continuity of the intramedullary lesion with a contrast-enhanced thickened spinal root.¹⁶ On computed tomography, MS manifests as an iso- or hyperattenuating lesion (100%), which may have areas of calcifications. Underlying bone remodeling and erosion are also observed.^17,18

Surgical resection with tumor-free margins is the treatment of choice for MS if feasible.⁹ The intracranial and intramedullary MS cases underwent gross total resection in 50% and 67% of cases, respectively. Adjuvant radiotherapy remains controversial, with no published clinical series on the effectiveness of radiotherapy or treatment protocol. Vallat-Decouvelaere et al.⁸ and Zhang et al.⁹ observed a lower rate of recurrence and metastasis in patients with MS treated with adjuvant radiotherapy. According to these authors, radiotherapy should be considered in case of histologic criteria of malignancy, incomplete surgical resection, tumor recurrence, or metastasis. Patients with intracranial MS received radiotherapy in 35% of cases either after the initial surgery or as treatment of recurrent disease.¹⁹ One patient received a course of temozolomide chemotherapy.²⁰ None of the intramedullary spinal cases received adjuvant treatment, apart from one patient²¹ who received radiotherapy only after tumor recurrence. Following surgery, the diagnosis of MS relies upon histopathology. The most characteristic features of MS are more or less melanin granules found in Schwann cells. This feature raises a diagnostic problem of whether this is a nerve sheath tumor or a melanoma. Immunohistochemical studies can aid the diagnosis, with strong expression of S-100 in addition to typical dumbbell-shaped growth along the nerve roots grossly and the presence of psammomatous bodies microscopically.⁹ MS stain variably with HMB-45 and Melan-A, as these antibodies are valuable for the diagnosis of malignant melanomas.⁹

The prognosis of MS is really unpredictable. Although it is considered to be benign, malignant clinical behavior has been documented, along with a tendency for recurrence and metastasis. The prognosis can be much worse in case of Carney’s complex with multiple other associated tumors. In Carney’s⁷ series of 31 patients, 6% had local recurrence and 10% died of metastatic disease. This was followed by Vallat-Decouvelaere et al.,⁸ who noted overall local recurrence and metastasis rates of 15% and 26%, respectively. A series of 13 patients reported by Zhang et al. in 2005⁹ showed recurrence in 18.2% and metastasis in 9.1% of cases. Finally, in one of the largest and latest series of MS in the literature, Torres-Mora et al.⁶ reported local recurrence and distant metastatic rates of 35% and 42%, respectively. The results of the present study extend upon these earlier observations, with 39% of the intracranial and intramedullary MS cases having local recurrence between 3 months and 20 years (56% underwent incomplete resection and 89% not received adjuvant therapy). The difference in rate may be explained by the number of patients and longer follow-up exams. Based on the above-described results, Zhang et al.⁹ suggested MS to be a unique neoplasm with potential malignancy. Torres-Mora et al.⁶ suggested reclassification of MS from benign to malignant. The histological criteria for malignancy in MS are not clearly defined, and there is no reliable histological indicator of malignant clinical behavior apart from elevated mitotic activity that may predict malignancy.⁶ Thus, appropriate long-term follow-up is required for all cases, as MS may recur or metastasize, even after two decades of absence of overt malignant histological features.²²

Conclusions

MS is a rare and distinct entity rather than a variant of schwannoma, which poses both diagnostic and management dilemmas. Although MS has characteristic MRI features, including T1 and T2 shortening, the preoperative diagnosis is always challenging due to the rarity of this lesion. Accurate diagnosis is crucial for management planning, including long-term follow-up exams due to the unpredictable prognosis and tendency for recurrence and metastasis.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Conflict of interests

The authors declare that there is no conflict of interest.