Contributed by George A. Alexiou, MD, PhD, Kalliopi Stefanaki, MD, PhD, Maria Moschovi, MD, PhD, George Sfakianos, MD, PhD, Neofytos Prodromou , MD, PhD.
DIAGNOSIS
Medulloblastoma with rhabdomyoblastic differentiation according to the updated WHO Classification 2007 (previously known as "medullomyoblastoma").
DISCUSSION
Differential diagnosis based on imaging findings alone would include ependymoma, astrocytoma, medulloblastoma and an atypical teratoid/rhabdoid tumor (AT/RT). Among them, ependymoma was the more likely diagnosis because the tumor was located within the 4th ventricle and extended through foramen of Luschka into the left cerebello-pontine angle without infiltration of the vermis.
On histological grounds, the presence of a malignant embryonal highly cellular neoplasm with morphological heterogeneity, composed mainly of small round cells with sparse cytoplasm, suggested the presence of medulloblastoma. Furthermore, the presence of neoplastic cells with rhabdomyoblastic differentiation, positive for desmin, myogenin/Myf-4 and MyoD1 suggested that the tumor exhibited a rhabdomyoblastic differentiation, while the coexistence of the undifferentiated areas with neuronal [Synaptophysin +] differentiation excluded metastatic rhabdomyosarcoma. Although AT/RT tumors are also embryonal brain neoplasms that show overlapping morphological features with medulloblastoma and variable polyphenotypic differentiation, the characteristic loss of INI1 immunohistochemical expression in the nucleus plays a major role in the differential diagnosis from other embryonal neoplasms, which retain INI1 nuclear expression, as in our case. Furthermore, the absence of glial, especially astrocytic differentiation, on morphological grounds by the detection of neuronal markers (mainly synaptophysin, Neu-N, neurofilaments) and absence of GFAP expression excluded a high grade astrocytic tumor. Anaplastic ependymoma was also excluded by the absence of perivascular pseudorosettes, the definite neuronal and rhabdomyoblastic differentiation and the absence of EMA immunohistochemical expression.
Medulloblastoma arise in the posterior fossa and constitute the most common malignant tumor in children and the second most common brain tumor following low grade astrocytomas. Their incidence peaks in children between 3 and 9 years (5,6). The current management of medulloblastomas entails gross total resection, followed by radiotherapy and chemotherapy (6). Nevertheless, in children younger than 3 years of age the management is problematic (3). Radiotherapy can produce severe neurocognitive damage; consequently, this treatment modality is reserved for children over the age of 3 years.
Medulloblastoma with rhabdomyoblastic differentiation is a variant of medulloblastoma and is exceedingly rare (1,2,4,7). The clinical features and genetic profile are similar to those of other medulloblastomas. However, the presence of rhabdomyoblastic differentiation has been associated with poor prognosis despite aggressive treatment (2,7). Rao et al reported that only 5 of 21 patients survived longer than six months and more recently Helton et al reported that 3 out of 6 patients died of the disease within 2 years (2,7). In our case due to the young patient's age, radiotherapy was not administered. After gross total excision of the tumor, the patient received high dose chemotherapy. One year later the patient was in good clinical condition and no tumor recurrence was noted.
REFERENCES
Contributed by George A. Alexiou, MD, PhD, Kalliopi Stefanaki, MD, PhD, Maria Moschovi, MD, PhD, George Sfakianos, MD, PhD, Neofytos Prodromou , MD, PhD.
International Society of Neuropathology