Clinical Presentation and Genetic Paradigm of Diffuse Infiltrating Retinoblastoma: A Review

Abstract

Retinoblastoma is the most common childhood cancer. Thanks to modern technology and good medical access, mortality in Europe has decreased to about 5%. Diffuse infiltrating retinoblastoma is a very rare subtype of this neoplasm and is characterized by its atypical growth pattern. Diffuse infiltrating retinoblastoma may mimic other more innocuous diseases and may therefore be misdiagnosed. The purpose of this paper was to provide a short review of the main symptoms of diffuse infiltrating retinoblastoma presenting to the ophthalmologist and give a comparison to typical retinoblastoma. The second purpose was to set up a discussion of the genetic paradigm of diffuse infiltrating retinoblastoma. It has often been described to occur sporadically; however, in the last years, it has been shown that it might be heritable. A literature search concerning diffuse infiltrating retinoblastoma considering English, German and Spanish cases and case series identified 77 patients. Moreover, an overview of general data, main symptoms, clinical findings and initial working diagnoses or referral diagnoses is given. Males were significantly more often affected than females. Diffuse infiltrating retinoblastoma can be heritable. Genetic analysis should be offered to the patient and relatives. Interdisciplinary medical follow-up care is needed to detect associated cancers.

Conservative management of retinoblastoma: Challenging orthodoxy without compromising the state of metastatic grace. “Alive, with good vision and no comorbidity”

“…Compared to classic retinoblastoma, the diagnosis of diffuse infiltrating retinoblastoma is usually made in older children (mean age 5.7 years) following atypical presenting symptoms such as vision loss, ocular redness or pain, in the context of misleading signs most frequently masquerading inflammation or pointing to other diagnoses, including neovascular glaucoma and cataract (Traine et al, 2016). In addition to frequent diagnostic delay, slow tumor growth could explain the older age at presentation (Bhatnagar and Vine, 1991;Traine et al, 2016). Most cases (> 90%) are unilateral and sporadic.…”

Conservative treatment of diffuse infiltrating retinoblastoma: optical coherence tomography-assisted diagnosis and follow-up in three consecutive cases

“…In the diffuse infiltrating type, the growth remains relatively flat to the retina, with virtually no focal retinal mass nor calcification. A clear-cut definition of this rare subtype has not, however, yet been proposed 4. Most knowledge is based on clinical descriptions of cases before enucleation and histopathology reports.…”

“…Histopathology reports have shown diffuse invasion of the ganglion cells 3. According to a recent review of 77 cases of diffuse infiltrating rb from various publications, boys are more commonly affected than girls (62% vs 38%) 4. Mean age at diagnosis is 5.7 years (range: 1–19 years).…”

“…Because of the later age at presentation and different clinical manifestations compared with typical rb, the diagnosis of diffuse infiltrating rb can be challenging, especially in unilateral cases. Actually, more than half of the cases are misdiagnosed 4. To date, except for four cases of a variant subtype, namely diffuse anterior rb salvaged with intracameral chemotherapy6 or plaque brachytherapy,7 previously published cases of diffuse infiltrating rb have always been managed with enucleation 1 3 5 8…”

Retinoblastoma presenting as haemorrhagic choroidal detachment in a 10-year-old girl

“…The symptoms of this subtype usually mimics inflammatory diseases, thus making its diagnosis difficult. It may present as vitreous cells, pseudohypopyon, subretinal fluid, iris neovascularisations and heterochromia and retinal detachment 17. Retinoblastoma may present atypically in less than 1% of the cases.…”