Remote Recurrent Supratentorial Metastatic Medulloblastoma after Cerebellar Resection without Local Relapse: Reporting a Rare Case

Abstract

Isolated supratentorial metastasis of cerebellar medulloblastoma is a rarity, and subfrontal recurrences, multiple times over a prolonged period, after gross total resection of the cerebellar lesion and that of metastasis with late spinal dissemination without primary relapse is an even rarer phenomenon. We report first such case, to the best of our knowledge, where a 17-year-old male presented with remote recurrent supratentorial metastasis, multiple times over a prolonged time period. Gross total resection of first supratentorial metastasis was done (second surgery) 3 years after removal of primary cerebellar medulloblastoma (first surgery) and spinal metastasis was seen 5 years after the first surgery, in spite of craniospinal irradiation and chemotherapy. He was tumor-free for 2 years, after which he again had a recurrent lesion in the subfrontal region and underwent excision (third surgery). Six months after the third surgery, he was presented with similar recurrence, and underwent complete resection (fourth surgery), but unfortunately he passed away after 3 months. This case shows that medulloblastomas may recur even after appropriate treatment, in the absence of local relapse. Repeated surgical exploration, radiotherapy, and chemotherapy might benefit patients with a satisfactory clinical course, giving additional few years of survival benefit.

 

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Keywords

medulloblastoma - primary relapse - supratentorial recurrences

Introduction

Medulloblastoma, classified as a World Health Organization grade IV tumor, usually originates from the superior medullary velum and is the most prevalent malignant brain tumor in children.[1] Treatment entails surgical excision, adjuvant chemotherapy, and craniospinal irradiation. Recurrence may present at the primary location or remotely due to central nervous system dissemination. Despite various treatment efforts, including reoperation, re-irradiation, and standard and myeloablative chemotherapy regimens, no effective curative treatment has been found. Proposed elements include the use of the prone position, insufficient exposure of the cribriform area to radiation, the treatment of hydrocephalus, and unfavorable histopathological, immunohistochemical, and molecular characteristics.[2]

 

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Case

A 17-year-old male presented with visual impairment for 1 month, drowsiness for 10 days, and vomiting for 1 week. He had undergone operation for cerebellar medulloblastoma ([Fig. 1A]) at the age of 12 (gross total excision via transvermian approach in prone position; histopathology: medulloblastoma with extensive nodularity), and had received irradiation (36 Gy/20 fractions to the whole brain and 30 Gy/20 fractions to the spine, followed by a 3DCRT [three-dimensional conformal radiation therapy] posterior fossa boost of 18 Gy/10 fractions with 6 MV photon). Yearly magnetic resonance imaging showed no new lesion for 3 years ([Fig. 1B]). At age 15, he was diagnosed with a bilateral subfrontal lesion ([Fig. 1C]), which was excised completely (histopathology: medulloblastoma of desmoplastic variety; [Fig. 2A]) And received nine cycles of cisplatin, vincristine, lomustine, cyclophosphamide, and mesna over 45 weeks. He remained tumor-free for 2 years ([Fig. 1D]), until now, when he was found to have recurrent subfrontal lesion ([Fig. 1E]) and D1 drop metastasis ([Fig. 1F]), without primary relapse. Gross total excision for the third time (histopathology: metastatic medulloblastoma grade IV; [Fig. 2B]) provided symptomatic relief. After 6 months of tumor-free interval, he was presented with a subfrontal lesion ([Fig. 1G]) again, for which tumor excision was done. Unfortunately, he passed away 3 months after the fourth surgery, due to multiple-organ failure.

Fig. 1 (A) CEMRI brain axial section showing heterogeneously enhancing cerebellar medulloblastoma. (B) Second-year follow-up CEMRI brain coronal section showing no primary cerebellar lesion. (C) Follow-up CEMRI brain after 3 years, showing heterogeneously enhancing lesion in the bilateral basifrontal region, which was found to be metastatic medulloblastoma on histopathology. (D) Follow-up CEMRI brain, 1 year after second surgery, showing areas of gliosis with no residual or recurrent lesion in the basifrontal region. (E) Follow-up CEMRI brain T2-weighted sequence, 2 years after second surgery, showing recurrent bilateral basifrontal lesion, larger in size than the previous time. (F) CEMRI spinal axis showing contrast enhancing extra-dural drop metastasis at the D1 level. (G) Follow-up CEMRI brain coronal section, 6 months after the third surgery, showing heterogeneously enhancing recurrent lesion in the basifrontal region. CEMRI, contrast-enhanced magnetic resonance imaging.

Fig. 2 (A) Biopsy specimen from basifrontal lesion showing pale nodular reticulin–free areas surrounded by densely packed proliferative cells with hyperchromatic and pleomorphic nuclei, with areas of necrosis and sclerosis. On IHC, cells were positive for synaptophysin and GFAP. (B) Biopsy specimen from recurrent basifrontal lesion showing monomorphic large tumor cells arranged in sheets with large central nucleus and eosinophilic cytoplasm, salt and pepper clumped-up chromatin with nucleoli, and area of brisk mitosis and neurocytic differentiation. On IHC, tumor cells express synaptophysin, retic rich and negative for beta catenin.

 

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Discussion

Taking into account the molecular group of the tumor, medulloblastomas, genetically defined, are classified into WNT-activated (favorable prognosis), SHH-activated and TP53-mutant, SHH-activated and TP53-wild-type (slightly worse prognosis), and group 3 and 4 (worst prognosis). The mechanisms of spread include perineural lymphatics, the hematogenous route, or direct seeding. Medulloblastomas typically recur in the posterior fossa, while metastases in the supratentorial region are rare.[3] Subfrontal recurrences are exceptionally uncommon, with fewer than 50 documented cases reported.[2] While thorough removal of the primary tumor is deemed essential to reduce the risk of local recurrence and distant metastasis, this alone is insufficient to fully safeguard against these outcomes.[2] Interestingly, local tumor relapse, which is a known risk factor for distant recurrence, is not present in this case. The utilization of the prone position during surgery and radiation therapy may play a role in this observation. If a recurrence does occur, having it limited to one site and occurring later than the initial diagnosis is considered a positive prognostic sign.[4] Selected basifrontal lesions can be operated via supraorbital keyhole craniotomy as well.[5] According to Collin's law, a patient is deemed cured after a tumor-free period equal to their age at diagnosis plus an additional 9 months. It is relatively rare for supratentorial recurrences to occur outside of this timeframe.

 

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Conclusion

Medulloblastomas can recur multiple times, with or without local relapse. With surgery and chemoradiotherapy, patient might have satisfactory clinical course, and additional few years of survival benefit. Considering the metastatic possibility of medulloblastomas, the question of whether we need to revisit the definition of their cure demands detailed research.

 

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Conflict of Interest

None declared.

• References

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• 4 Massimino M, Casanova M, Polastri D. et al. Relapse in medulloblastoma: what can be done after abandoning high-dose chemotherapy? A mono-institutional experience. Childs Nerv Syst 2013; 29 (07) 1107-1112
• 5 Chauhan BPS, Hedaoo K, Parihar V. et al. Exoscopic supraorbital keyhole approach for skull base lesions: an institutional experience. Asian J Neurosurg 2025; 20 (02) 350-356

Publication History

Article published online:
19 August 2025