Disseminated oligodendroglial cell-like leptomeningeal tumors: preliminary diagnostic and therapeutic results for a novel tumor entity

Abstract

Pediatric tumors of the central nervous system composed of oligoid tumor cells showing diffuse leptomeningeal spread without a primary mass lesion seem to represent a novel tumor entity. The terms "diffuse leptomeningeal glioneural tumor" or-preferably-"disseminated oligodendroglial-like leptomeningeal tumor of childhood" (DOGLT) were proposed. Four patients were identified with clinico-neuropathologic findings compatible with DOGLT and a mean follow-up time of 54 months was determined. Seven different biopsies obtained from the four patients were histologically evaluated. Clinical course, diagnostic measures, histopathologic and radiologic features and treatment suggestions were recorded, on the basis of which diagnostic and therapeutic algorithm was proposed. Patients with DOGLT presented with hydrocephalus as first symptom, requiring neurosurgical therapy. Open arachnoid biopsy was necessary to confirm diagnosis. The oligoid cells in a desmoplastic or focally myxoid matrix showed OLIG2-, MAP2-, S-100 and rare HuC/HuD protein-immunopositivity. IDH1 (R132H)- and CD99-immunohistochemistry was negative in all patients. None of the evaluable biopsies of three patients showed chromosome 1p/19q deletion, neither as isolated nor combined allelic loss. Chemotherapy according to the SIOP-LGG 2004 standard induction and consolidation protocol resulted in complete response and partial response, respectively, in 50 % of the patients. However, after discontinuation of chemotherapy, two patients experienced tumor progression and one of them succumbed to the disease after 19 months. Radiological criteria as well as preliminary treatment results are presented after observation of four clinical cases. Prognosis and long-term clinical courses remain to be observed.

Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features

“…Small cystic or nodular T2-hyperintense lesions were frequently encountered along the subpial surface of the brain and spinal cord. Discrete intraparenchymal lesions were also found, especially in the spinal cord [1,12,15,29,31,35]. However, in a recent study by Chiang et al comprising five patients, leptomeningeal dissemination was not seen radiologically in any of the cases, suggesting that DLGNTs do not necessarily present with gross leptomeningeal dissemination on MRI [9].…”

“…A summary of characteristics in previous series is given in Table 1. Although most tumors display a slow progression, aggressive cases were occasionally encountered [12,29,31,36]. The largest series with follow-up data of 24 patients showed 9 deaths within 3-21 years [31].…”

“…Histologically, DLGNTs have been described as low-to moderate-cellularity lesions consisting of relatively monomorphous oligodendrocyte-like cells with round to oval nuclei, inconspicuous nucleoli and a 'glioneural commitment' [15], embedded in a desmoplastic or myxoid leptomeningeal stroma [29,31]. While a low mitotic activity was most commonly observed, features of anaplasia were also seen in a number of cases [31,36].…”

“…Immunostaining for NeuN, EMA and mutant IDH1 (R132H) was negative [9,29,31,35]. Although typically displaying a low Ki-67 proliferation index, several cases with elevated proliferation were reported [29,31,35,36], with less favorable outcome associated with an index > 4% [31,36]. The wide spectrum of histological and radiological features encountered, as well as its rarity and relatively recent inclusion in the WHO classification, can make this tumor entity difficult to diagnose.…”

Primary Leptomeningeal Oligodendroglioma, IDH-Mutant, 1p/19q-Codeleted

“…The other entity in the differential diagnosis is diffuse leptomeningeal glioneuronal tumor (DLGT), which very rarely can show combined 1p/19q codeletion (isolated 1p deletion is more common). IDH mutations have not been described in DLGT (2, 5–7). In contrast, DLGT or disseminated oligodendroglioma-like leptomeningeal neoplasms (DOLN) have been shown to frequently carry the BRAF-KIAA1549 fusion/tandem duplication at 7q34 (6).…”