Multifocal medulloblastoma in Fanconi Anemia

We present the case of a two-year-old female with known history of Fanconi Anemia (FA) with a PALB2 germline biallelic pathogenic variant; in the context of her disease, she had radial ray anomalies, unilateral renal agenesis, growth retardation, and skin hyperpigmented spots.

She was brought to the emergency department for a two-week-long history of progressive irritability, vomiting and ataxia.

MR imaging in the emergency setting showed an intra-axial large, round and well-demarcated expansile lesion in the cerebellar vermis, with intermediate T2 and low T1 signal, restricted water diffusion and mild contrast enhancement (Figures 1, 2 and 3). In addition, three other smaller lesions with similar characteristics were found in the cerebellar hemispheres (Figure 1). There were no spine lesions.

Partial surgical excision of the largest lesion in the cerebellar vermis was accomplished. Histologic and genetic testing confirmed the diagnosis of medulloblastoma, SHH-activated, TP53-wildtype, with nodular desmoplastic histology. Although chemotherapy was started, the residual tumour and the smaller lesions still grew. She deceased after four months due to respiratory complications following severe pneumonia.

FA is characterized by a predisposition to malignancies. Specifically, medulloblastoma has been described in cases of FA with biallelic inactivation of the tumour suppressor gene BRCA2/FANCD1 or its associated gene PALB2/FANCN [1,2]; typically, these medulloblastomas are SHH-activated [1]. We hypothesize that, in our patient, the multiple cerebellar lesions represented synchronous primary medulloblastomas rather than metastatic dissemination. The smaller cerebellar lesions were intraparenchymal, and leptomeningeal metastases—which represent the typical way of medulloblastoma tumour spreading—were not present [3]. Intraparenchymal metastases in sporadic medulloblastoma are considerably rare; Zapotocky et al. reported the largest cohort of patients with metastatic medulloblastoma and found only two patients with several intraparenchymal lesions (although they could not confirm whether the lesions were metastatic or primary synchronous tumours) [3]. In cases like these, further proof could have been obtained if all the synchronous lesions had been histologically tested—distinct gene expression patterns would suggest different synchronous tumours, considering that medulloblastoma typically maintains molecular subgroup affiliation in metastatic lesions [4].

Another case of multiple primary medulloblastomas in FA has been previously reported, although the lesions were asynchronous. That patient died of disease progression after 20 months of the diagnosis of the first medulloblastoma [1].

Because of its rarity, the outcomes associated with multiple primary intraparenchymal medulloblastoma are not well established, but incomplete surgical resection is a known poor prognostic factor [5], and multiple synchronous lesions may complicate adequate resection.

All patient data have been completely anonymised throughout the entire manuscript and related files.