|LETTER TO THE EDITOR
|Ahead of print
Primary malignant melanoma of the cerebellopontine angle: A rare entity
Siddhi Gaurish Sinai Khandeparkar, Lokesh Ashok Fegade, Bageshri P Gogate, Nikhil Talathi
Department of Pathology, Smt. Kashibai Navale Medical College and General Hospital, Wakad, Pune, Maharashtra, India
|Date of Submission||19-Apr-2020|
|Date of Decision||18-May-2020|
|Date of Acceptance||22-Jun-2020|
|Date of Web Publication||14-Sep-2021|
Siddhi Gaurish Sinai Khandeparkar,
Department of Pathology, Smt. Kashibai Navale Medical College and General Hospital, Wakad, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
About 6–10% of all intracranial tumors arise in or involve the cerebellopontine angle (CPA) of which most are schwannoma (80%) arising from the vestibular division of vestibulocochlear nerve followed by meningioma (10%), epidermoid (about 6%), and the rest consist of an extremely heterogeneous group of tumors that affect the region. The incidence of primary melanocytic lesions of the central nervous system (CNS) is 0.9 per 10 million. Intracranial malignant melanomas (MM) are commonly metastatic. Here, we present a rare case of primary MM of the CPA in a 30-year-old woman with immunohistochemical (IHC) study.
Thirty-year-old woman presented to the neurosurgery outpatient department with complaints of nausea, severe vomiting, occipital headache, and severe imbalance for 2 weeks. On examination, minimal left lower motor neuron facial palsy, left sensorineural hearing loss, papilledema and Romberg's test positive was observed. Computed tomography (CT) of the brain showed an ill-defined hyperdense area in the left CPA cistern measuring 4 × 2.5 cm. [Figure 1] Magnetic resonance imaging (MRI) of the brain showed an ill-defined T2/FLAIR hyperintense lesion appearing iso- to hypointense on T1W1 in the left CPA cistern region and left middle cerebellar peduncle and adjoining left cerebellar hemisphere measuring 4.1 × 2.5 × 2.2 cm with blooming representing subacute hemorrhage. Mild hydrocephalus with ventriculo-peritoneal (VP) shunting in the right atrium with its tip in the right thalamus was seen. Based on clinico-radiological findings, differentials offered were schwannoma and meningioma.
|Figure 1: Computed tomography (CT) brain showing ill-defined hyperdense area in the left cerebellopontine angle cistern measuring 4 × 2.5 cm|
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As informed by the neurosurgeon, gross total resection of the tumor was attempted via a left occipital craniotomy. Intraoperatively, it was seen infiltrating the adjacent brain. Hence, only subtotal resection was possible. On gross examination, multiple soft friable blackish tissue bits were obtained aggregating to 8 mL. Microscopic examination revealed tumor cells arranged in sheets and at places papillary pattern. Individual tumor cells were polygonal with highly pleomorphic and hyperchromatic vesicular nuclei with prominent eosinophilic nucleoli and a moderate amount of eosinophilic cytoplasm. At place, intra- and extra-cytoplasmic coarse black granules of melanin and yellow-brown granules of hemosiderin pigment were seen. Numerous abnormal mitotic figures and a few tumor giant cells were noted. Areas of necrosis, hemorrhage, and calcification were observed [Figure 2]a,[Figure 2]b,[Figure 2]c,[Figure 2]d.
|Figure 2: Photomicrograph of malignant melanoma showing tumor cells arranged in (a) sheets (H&E, ×400) and (b) papillary pattern (H&E, ×100), tumor cells showing (c) mitosis (red circle), intra and extra cytoplasmic melanin pigment and (d) necrosis (H&E, ×400)|
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Histopathological diagnosis of MM was considered. Papillary meningioma (PM) and melanotic schwannoma (MS) were considered as close clinico-pathological differentials. Pearl's Prussian blue stain showed the presence of hemosiderin granules focally in hemorrhagic areas. The tumor cells showed strong vimentin, Melan-A, human melanoma black-45 (HMB-45), and S100 immunoreactivity. They were negative for EMA and collagen IV. Ki-67 labelling index (Ki-67LI) was 20% [Figure 3]a,[Figure 3]b,[Figure 3]c,[Figure 3]d,[Figure 3]e,[Figure 3]f,[Figure 3]g. Diagnosis of MM was confirmed. Cerebrospinal fluid examination was free of tumor cells. Gynecologic and anorectal examination was unremarkable. CT of the chest, abdomen, and pelvis failed to reveal a primary melanoma. Ophthalmological and dermatological evaluation ruled out the possibility of an intraocular melanoma and dermal melanotic lesion, respectively.
|Figure 3: Photomicrograph of malignant melanoma showing tumor cells exhibiting positivity for (a) vimentin, (b) HMB-45, (c) Melan-A and (d) S100, and negativity for (e) collagen IV and (f) EMA (×400) and showing (g) Ki-67LI of 20% (×100)|
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One month later, MRI of the brain showed residual lesion measuring 1.6 × 3.4 × 1.9 cm. Abnormal meningeal enhancement was noted in the posterior fossa region, brainstem surface, and tentorium suggesting the possibility of meningitis. The patient succumbed to meningitis and encephalitis before receiving adjuvant therapy.
Primary focal MM accounts for 1% of all melanoma cases in the CNS. Primary MM of the CPA was first described in 1948 by Bailey. It is exceptionally rare and a thorough clinico-radiological examination for a possible primary melanoma in the body at cutaneous, ocular, and mucosal sites needs to be excluded. Only seventeen CPA melanomas have been reported until 2012.
Earlier reports regarding primary leptomeningeal MM of the CPA have been criticized on the basis that they may represent secondary lesions and criteria for the diagnosis based on post-mortem examinations have been proposed. There is a evidence that an extracranial primary tumor can be found in as many as 90% of patients with MM of the CNS and 10% remain occult. Along with Cranial MRI, 18Flourodeoxyglucose positron emission CT scan completes the search for primary. Hayward in 1976 had suggested based on clinical findings that solitary cerebral lesion, intramedullary, or leptomeningeal involvement, hydrocephalus and pineal/pituitary tumors could be primary melanomas in the absence of melanomas outside the CNS. Clinically primary CPA melanomas are most often seen in under 50 years of age as seen in the present case. The presence of a single intracranial lesion, failure to detect primary elsewhere on detailed clinico-radiological investigation together with 30 years of age suggested the lesion to be primary in this case.
Melanomas originate from melanocyte cell rests which is of neural crest origin. These cells are commonly distributed in the pia mater with a maximum density in the region of the caudal medulla and the high cervical cord which closely correlates with the reported distribution of these rare tumors. Some authors have proposed that dural melanomas may have a possible origin from leptomeningeal deposits where the leptomeninges penetrate the dura. Alternately, heterotopic tissues have been described in dura mater and a melanoma can arise from a heterotopic mass of melanocyte producing neural crest cells.,
The melanocytic tumors range between the relatively indolent melanocytomas to the aggressive MM. Melanocytomas are solitary, circumscribed, non-infiltrating tumor composed of nests of uniform cells with bland oval nuclei exhibiting eosinophilic nucleoli containing melanin with mitosis less than one per 10 high-power fields (HPF). Malignant melanomas have infiltrative margins with sheets and papillae of tumor cells showing marked hyperchromasia, pleomorphism, prominent eosinophilic nucleoli, brisk mitotic activity, necrosis and a varying amount of intra and extracellular melanin pigment as seen in the present case. Considering clinico-radiological and histopathological features differentials taken into account, in this case, were PM and MS.
PM, a rare subtype of malignant meningioma, is classified by the World Health Organization as Grade III and is seen intraoperatively to be a vascular tumor frequently invading the brain and bone. It may exhibit extracranial metastases. In one of the largest studies comprising of 16 cases of PM, the mean age of occurrence in women was 42.3 years. It is histopathologically composed of tumor cells having a perivascular pseudopapillary arrangement with or without other typical features of meningioma such as whorls and psammoma bodies. Tumor cells arranged in whorls and psammoma bodies were not seen in the present case. The tumor cells, in this case, were non-immunoreactive for EMA which ruled out the diagnosis of meningioma.
MS are circumscribed tumors characterized by a spindle and epithelioid cells arranged in interlacing fascicles, with an accumulation of melanin in neoplastic cells and associated melanophages. Nuclei are oval with evenly distributed chromatin and small, distinct nucleoli with rare mitosis. MS associated with Carney's complex show sheets of adipose like cells and psammoma bodies. MS usually lacks Verocay bodies, a well-formed capsule and thick-walled hyalinized blood vessels. Histologic features such as large, vesicular nuclei with macronucleoli, brisk mitotic activity and necrosis raise concern. MS is favored over MM if the tumor arises in ganglia, features psammoma bodies and adipose-like cells, has cells with benign or mildly atypical cytology and demonstrates evidence of pericellular basement membrane synthesis. Also besides, molecular testing for BRAF V600E, a marker that is typically present in more than 90% of melanomas, is negative in MS. In our case the tumor cells were highly atypical with numerous brisk mitosis, at places showing papillary arrangement with no evidence of basement membrane material. In the present case, the tumor cells were vimentin, melan A, HMB45 and S100 immunoreactive which is seen in both MM and MS. However, they were non- immunoreactive for collagen IV which along with histomorphological features and Ki-67LI of 20% ruled out the possibility of MS. Linear, pericellular immunoreaction of both laminin and collagen IV are detected in all cases of MS.,
The prognosis of the patient with solitary primary intracranial melanomas depends upon the degree of mitosis, leptomeningeal dissemination, extent of surgical excision and location of the tumor. Yamane et al. reported mean survival of 20.7 months in patients with solitary primary intracranial MM, while the survival was only 6.7 months in patients with a diffuse leptomeningeal spread. Metastasis from primary intracranial melanomas to lungs, spleen, pancreas, and kidneys although rare, has been reported in the literature. Metastasis from the extracranial primary melanoma is more prone to occur in the brain and is the third most common site of intracranial metastasis after carcinoma of breast and lung.
Surgery remains the key modality of treatment. Sometimes total excision becomes difficult in CPA tumors due to brain infiltration as seen in the present case. In a review, 80% of the cases with subtotal resection of CP angle melanocytomas died within 12 months of diagnosis. Our patient died in a month before receiving adjuvant therapy succumbing to meningitis and encephalitis. The clinical outcome of patients with primary CNS melanoma is reported to be better than that of patients with metastatic disease. Radiotherapy, chemotherapy, and immunotherapy may be considered nonsurgical therapy options for primary MM of the CNS, but their effects have not been established.
Our experience with the present case highlights the occurrence of this lesion in younger age group, need for a high index of suspicion due to rarity of the lesion and a triad of clinical, radiological and immunohistopathological analysis for arriving at an accurate diagnosis and ruling out the differentials.
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There are no conflicts of interest.
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