Disseminated oligodendroglial-like leptomeningeal tumor with malignant (anaplastic) transformation.
Disseminated oligodendroglial-like leptomeningeal tumor of childhood is a rare neoplasm that was first described in 1942, but has only recently been better characterized in a report describing 36 patients (4). The current literature suggests that the tumor cells are of glial, neuronal or glioneuronal origin, and may originate from rests of cells commonly present in the meninges (1, 2, 4). Although intraparenchymal lesions are seen in a number of cases, these foci are generally considered to be secondary involvement of a primary meningeal neoplasm. Most cases are low-grade, but approximately a fifth show anaplastic features, such as seen in our patient's tumor. The oligodendroglial origin of the tumor cells is suggested by histology, which shows clear cells containing round nuclei, but also supported by Olig2 immunohistochemical expression and occasional 1p/19q co-deletion, 1p deletion and/or polysomy. A high rate of concurrent BRAF-KIAA1549 gene fusion and 1p deletion has been seen (5). All cases have S100, synaptophysin and Olig2 positivity, as our case does. In addition, FISH in our case demonstrated 1p/19q co-deletion and polysomy in tumor cells, as seen in 20% of cases, and further molecular testing revealed 1p19 loss and a TERT promoter point mutation, but no mutations in IDH1 or IDH2, and no fusions.
The imaging appearance in our case indicated heterogeneity of the dural lesions, with some areas having features suggesting more aggressive findings of higher cellularity and leptomeningeal involvement. Radiological evaluation favored a chronic process due to the associated calvarial and skull base remodeling, with the differential primarily consisting of meningiomatosis and neurofibromatosis type 2. Inflammatory diseases, particularly neurosarcoidosis, along with lymphoma, histiocytosis and dural metastases, all of which could cause dural masses, were considered less likely both because they would not account for the chronic osseous changes and because of the lack of additional systemic findings.
The differential diagnosis of this tumor may be broad due to the associated reactive changes, and the pathologist must be aware of the disseminated oligodendroglial-like leptomeningeal tumor in order to consider it upon encountering infiltrating atypical clear cells in the leptomeninges and dura in the context of imaging that shows diffuse dural nodularity with no intraparenchymal lesion. The exuberant meningothelial reaction is virtually indistinguishable from meningioma, and if it is the main entity sampled on a biopsy, may lead to misdiagnosis of meningiomatosis. However, as on our patient's initial biopsy, some infiltrating clear cells are present that are not macrophages (Figure 1c). A densely histiocytic reaction may lead to consideration of a histiocytic neoplasm, such as Langerhans cell histiocytosis (LCH), which can present as discrete nodules attached to the dura. However, CD1a staining will be positive in LCH, unlike in our case. In addition, Rosai-Dorman Disease (RDD) may rarely involve the CNS, and very rarely may be isolated to the CNS. In RDD, tumor cells are defined by their positivity for CD68 and S100, and emperipolesis is usually present. Although we do not see emperipolesis, staining for CD68 and S100 in our case highlights infiltrating cells, and it is difficult to determine whether the two antibodies are staining the same population of cells. Finally, the granulomatous inflammation and vascular changes could suggest a granulomatosis with polyangiitis (i.e. a Wegener's granulomatosis-like process). Indeed, ANCA-negative cases with florid dural-based lesions that were diagnosed according to the clinical criteria of 1990 and 1992 have been reported, and these patients respond to cyclophosphamide and prednisone therapy (3).
If areas of the characteristic clear cells are sampled on biopsy, the diagnosis becomes a question of identifying the tumor, and the possibilities of disseminated carcinoma, melanoma and a glioneuronal neoplasm may be entertained. In our case, the areas of small anaplastic blue cells raised additional concerns for lymphoma, undifferentiated sarcoma, Ewing's sarcoma, and poorly differentiated myoepithelial carcinoma. Immunostains and FISH for these entities were negative.
Our patient was initiated on daily temozolomide 90mg/m2/dose, with excellent radiographic and clinical response as early as 4 weeks into treatment. After 11 weeks, MRI revealed marked decrease of the extra-axial masses and he was transitioned to monthly temozolomide monotherapy at 200mg/m2/dose, five days per month, and underwent craniospinal radiation with boost to areas of residual tumor burden with excellent response.
Contributed by MacLean P. Nasrallah, MD PhD; Ilya M. Nasrallah, MD PhD; Marisa S. Prelack, MD; Margaret O. Johnson, MD MPH; Travis B. Lewis, MD PhD; Michael Rubenstein, MD; Jane E. Minturn, MD PhD; Arati Desai, MD; Paul Marcotte, MD; Mariarita Santi, MD PhD; Maria Martinez-Lage, MD