Medulloblastoma with multi-lineage differentiation including myogenic and melanotic elements: a case report with molecular data

Abstract

We present an unusual medulloblastoma in a 3.9-year-old boy who had a 2-week history of nausea and vertigo. MRI revealed a 5×5.5×5 cm sized tumor located in the fourth ventricle and spinal leptomeningeal dissemination. The patient was treated according to the MET-HIT 2000-BIS4 protocol but showed tumor progression after 6 months and died 9 months postoperatively. Histopathologically and immunohistochemically, the tumor showed PNET-like areas with focal anaplasia, admixed rhabdomyoblastic and pigmented elements, cartilage and bone formation, as well as areas with neurocytic and glial differentiation. Neither CTNNB1 mutation nor MYCC/MYCN amplification was detected. The combination of rhabdomyoblastic and melanotic elements in medulloblastoma is exceptionally rare. Although the histopathological features suggested a teratoid tumor, the endodermal cell lineage required for this diagnosis was not present. An atypical teratoid-rhabdoid tumor was ruled out due to the presence of the INI1-protein. Regarding the molecular profile with 1q and 17q chromosomal gains and loss of chromosome 8, this tumor could be compatible with a molecular medulloblastoma Group 3 or 4. Yet, it cannot be definitively ruled out that medulloblastomas with multi-lineage differentiation represent a distinct subgroup of medulloblastoma, and it remains to be clarified whether these tumors are associated with a distinct clinical behavior.

WNT‐activated medulloblastoma with melanotic and myogenic differentiation: Report of a rare case

“…About 12 cases of MB with melanotic differentiation and 50 cases of MB with rhabdomyoblastic differentiation have been reported. MBs with melanotic and myogenic differentiation are still rarer, with only 10 cases reported in the English literature to date (Table ) . These tumors occurred in young children (mean age: 4 years), showed a male predominance, and the majority were associated with the classic variant, and only two of them were seen in large cell/ anaplastic variants .…”

“…In a recent study, Stefanits et al . noted gain of chromosomes 17q and 1q, and loss of chromosome 8 in their case, while CTNNB1 mutation and MYC amplification were absent, compatible with group 3 or 4 . Our case did not show MYC amplification and was immunopositive for β‐catenin, classifying it as WNT subtype.…”

“…MBs with melanotic and myogenic differentiation are still rarer, with only 10 cases reported in the English literature to date (Table 1). [1][2][3][4][5][6][7][10][11][12] These tumors occurred in young children (mean age: 4 years), showed a male predominance, and the majority were associated with the classic variant, and only two of them were seen in large cell/ anaplastic variants. 11,12 While a single case of melanocytic differentiation has been reported in a desmoplastic/ nodular MB, 13 none of the reported MBs with melanotic and myogenic differentiation showed desmoplastic/ nodular histology.…”

“…MB with melanotic and myogenic differentiation, previously documented as pigmented MB with myogenic differentiation and pigmented / melanotic medullomyoblastoma, is an extremely rare variant of MB showing melanocytic as well as rhabdomyoblastic differentiation. It is not considered as a distinct entity, but as a pattern of differentiation seen in association with any of the four major histological variants of MB, most commonly with the classic subtype . Currently, the treatment of this tumor is the same as that of MB and the prognosis depends on the histological variant it is associated with.…”

“…It is not considered as a distinct entity, but as a pattern of differentiation seen in association with any of the four major histological variants of MB, most commonly with the classic subtype. [1][2][3][4][5][6][7] Currently, the treatment of this tumor is the same as that of MB and the prognosis depends on the histological variant it is associated with. It is not known whether multi-lineage differentiation in MB has any distinct clinical or molecular genetic features, presumably due to rarity of this entity, and its molecular genetics with respect to the four recently described molecular MB subgroups remain to be identified.…”