Imaging findings in Constitutional Mismatch Repair Deficiency Syndrome


Ariel Kerpel 1 Michalle Soudack 1 Michal Yalon 2 Shai Shrot 1 Chen Hoffmann 1
1Diagnostic Radiology, Chaim Sheba Medical Center, Israel
2Pediatric Hemato-Oncology, Chaim Sheba Medical Center, Israel

BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) is a hereditary childhood cancer syndrome caused by biallelic mutations in an MMR gene. It is characterized by brain tumors as well as colorectal and hematological malignancies. Café au lait macules similar to neurofibromatosis type 1 (NF1) phenotype are present in almost all patients. Diagnostic criteria and surveillance guidelines have been published.

OBJECTIVE: To describe the imaging findings in CMMRD patients.

MATERIALS AND METHODS: We reviewed the imaging studies of all patients with CMMRD who were referred to the pediatric oncology clinic at our institute between 2015 and 2018.

RESULTS: Seven patients from five different families were diagnosed with CMMRD at our institution. The mean age at diagnosis was 9.2 years (range 6-14 years). The commonest presentation was brain malignancy, diagnosed in 6 of 7 patients (85%) between 6-14 years of age. Tumors included three glioblastoma multiforme, two diffuse astrocytoma and one pleomorphic xanthoastrocytoma. Nonspecific brain MRI findings included DVA (developmental venous anomaly), cavernomas, NF1 FASI (focal areas of signal intensity) and subcortical hyperintensities. Two patients showed subcortical hyperintensities transformation to brain tumors. Colorectal tumors were diagnosed in 3 of 7 patients (42%) and included cecal and rectal adenocarcinomas and multiple colonic tubular adenomas at ages 16, 14 and 6 years respectively. Hematological malignancies were diagnosed in 2 of 7 patients (28%) at 6 and 14 years, both were mediastinal non-Hodgkin lymphoma of T-cell lineage. Other imaging findings included duodenal adenoma, gallbladder polyp, pilamatricoma, thymic lymphatic malformation and multiple skeletal lesions. All patients had café au lait macules.

CONCLUSION: As first identifiers of malignancy, radiologists should be familiar with CMMRD syndrome and its associations. A high index of suspicion is warranted in patients with multiple tumors or in young patients with brain and colorectal cancers. Following surveillance protocols is important due to the extremely high risk of malignancy, especially when nonspecific findings are present such as subcortical hyperintensity and colonic polyps.

Ariel Kerpel
Ariel Kerpel