Metachronous occurrence of nonradiation-induced brain cavernous hemangioma and medulloblastoma in a child with neurofibromatosis type I phenotype

Abstract

Cavernous hemangioma (CH) is a sporadic vascular malformation occurring either as an autosomal dominant condition or as a well-known complication of radiation exposure. Medulloblastoma is a primitive neuroectodermal tumor common in children and currently treated with surgical resection, chemotherapy, and radiotherapy. Neurofibromatosis is the most common single-gene disorder of the central nervous system. Posterior fossa malignant tumors in the context of neurofibromatosis type I (NF1) are very infrequent. This is the first documented case of an unusual metachronous occurrence of non-radiation-induced CH and medulloblastoma in a child with NF1 phenotype. We report the case of a 13-month-old boy with café-au-lait skin lesions associated with NF1-like phenotype who underwent surgical resection of a single CH in the temporal lobe due to recurrent seizures. Four years later he presented with signs of raised intracranial pressure associated with a posterior fossa tumor and hydrocephalus, thus requiring gross total resection of the lesion. Histological analysis revealed a medulloblastoma. After being treated with radiotherapy and chemotherapy, he achieved total remission. Six years later a massive recurrence of the tumor was observed and the child eventually died. The interest in this case lies in the rarity of NF1-like phenotype associated with a non-radiation-induced brain CH and medulloblastoma in a child.

Constitutional Mismatch Repair Deficiency Syndromes, a Neurofibromatosis 1 Mimicker That Hinders Timely Management

“…13,16,[36][37][38] Non-neoplastic manifestations such as agenesis of the corpus callosum, gray matter heterotopia, developmental venous anomalies, nontherapy-induced brain cavernomas, mild immunodeficiency with decreased levels of immunoglobulins IgG2/4 and IgA, and bronchiectasis with the presence of multiple pilomatrixoma have been reported in the literature and should raise a high level of suspicion for CMMRD syndrome. [38][39][40][41][42][43][44][45] Some of these findings in our patients have been mentioned in Table 1. In our cohort, multiple Mongolian spots, coloboma, obesity, congenital heart disease, dysmorphism, and clubfoot were also encountered.…”

“…The spectrum of tumors found in CMMRD patients also includes premalignancies and benign tumors such as colorectal polyps, hepatic adenomas, and pilomatricomas 13,16,36–38 . Non-neoplastic manifestations such as agenesis of the corpus callosum, gray matter heterotopia, developmental venous anomalies, nontherapy-induced brain cavernomas, mild immunodeficiency with decreased levels of immunoglobulins IgG2/4 and IgA, and bronchiectasis with the presence of multiple pilomatrixoma have been reported in the literature and should raise a high level of suspicion for CMMRD syndrome 38–45 . Some of these findings in our patients have been mentioned in Table 1.…”

Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium ‘Care for CMMRD’ (C4CMMRD)

“…Equally, it may be speculated that somatic mutations in developmental genes (presumed to occur more frequently in CMMRD) could be responsible also for other malformations that were observed in CMMRD patients. Non-therapy-induced brain cavernomas were seen in two published patients25 40 and one so far unreported patient. The combination of congenital asplenia, left isomerism and a ventricular septum defect was observed in one patient 23.…”

Connections between constitutional mismatch repair deficiency syndrome and neurofibromatosis type 1

“…Other non‐neoplastic findings in CMMRD patients that are seen more frequently in CMMRD patients than in the general population and therefore considered diagnostic signposts of this childhood cancer susceptibility syndrome include agenesis of the corpus callosum, sometimes associated with grey matter heterotopia . Furthermore, non‐therapy induced brain cavernomas have been reported in at least three CMMRD patients and are, therefore, also considered a diagnostic feature of CMMRD.…”