Paediatric case study suggests genetic syndrome link associated with ocular tumor

The clinical and imaging findings were consistent with MECB. Image credit: ©2happy – stock.adobe.com

Italian investigators reported the case of a patient with medulloepithalioma of the ciliary body (MECB), which is a rare tumor that might be associated with DICER1 tumor predisposition syndrome,1 according to first author Francesco Fortarezza, MD, from the University Hospital of Padova, Surgical Pathology and Cytopathology Unit, Padova, Italy.

MECB, a primitive neuroepithelial tumor, is the most common congenital and early childhood neoplasm of the non-pigmented epithelium of the ciliary body.2

The authors pointed out that understanding this link may aid with genetic counseling or surveillance of affected individuals, potentially contributing to improved management and outcomes.

The patient was a 9-year-old boy with vision impairment in the left eye (visual acuity, questionable light perception), microphthalmos and a retrolental cyclitic membrane. Examination revealed a fleshy, whitish-pink ciliary body mass confirmed by B-scan ultrasound with intralesional cysts and total retinal detachment. The right eye (visual acuity, 20/20) was unaffected.

The primary findings were inhomogeneous posterior chamber signals with diffuse, marked and irregular circumferential thickening of the inner choroid and retinal layer, a thickened left ciliary body associated with a hypervascular lesion, 7 × 5 × 2.7 mm3 with intense and anomalous enhancement. The clinical and imaging findings were consistent with MECB and the left eye was enucleated.

Other findings were neoplastic proliferation into the inner surface of the ciliary body positive stains for neuron-specific enolase MNF116 cytokeratins, CK 8/18, weak and focal reactivity for S100, and negativity for acidic glial fibrillar protein, the presence of a mutation in exon 25 (p.E1813D) of the DICER1 gene associated with a diagnosis of malignant MECB. In addition, the thyroid was enlarged and had various mixed solid-cystic and iso-hyperechoic nodules, numerous aggregates of thyrocytes in a microfollicular arrangement with a mildly increased nucleus-cytoplasmic ratio, and no masses or neoplasms in other organs. “The coexistence of intraocular medulloepithelioma and thyroid disease raised suspicions of a genetic syndrome caused by a DICER1 gene mutation,” the authors said.

A DICER1 mutation was identified (NM_177438 .3: c.4465-4468dup p.(Gly1490Valfs*3)). The genetic variant, predicted to introduce a premature stop codon in the protein, is absent in population databases and is likely to be pathogenic (class 4 second American College of Medical Genetics).1

“Most cases are sporadic,” they commented, “but the tumor rarely can occur within the DICER1 syndrome, a rare genetic disorder inherited in an autosomal dominant pattern, caused by mutations in the DICER1 gene, involved in the processing of microRNAs. DICER1 syndrome, which is associated with an increased risk of various types of tumors such as pleuropulmonary blastoma, thyroid tumors, eye abnormalities, and others, has been linked to at least 7 cases of MECB associated with pleuropulmonary blastoma.3-5 Among these cases, only 1 involved both germline and somatic mutations in the tumor tissue. Our case represents an MECB as the initial manifestation of a germline DICER1, highlighting the potential importance of this rare association and genetic consultation of these patients.”

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