Occipital anaplastic oligodendroglioma with multiple organ metastases after a short clinical course: a case report and literature review

Abstract

Background: It is generally believed that malignant gliomas never metastasize outside the central nervous system (CNS). However, the notion that oligodendrogliomas (OGDs) cells cannot spread outside CNS is being challenged.

Methods: We described in detail the clinical story of one patient with anaplastic OGD, which metastasized to lymph nodes, bone marrowand bones Genetic analyses included detection of 1p and 19q chromosomal arms, methylation status of MGMT promoter, and PTEN exon mutations. A search of worldwide literature was conducted for reports of metastatic OGDs using NCBI-PubMed, with the keywords "extracranial", "extraneural", "oligodendroglioma", "oligodendrogliomas", "metastatic", "metastasis", and "metastases", in different combinations.

Results: An open biopsy of the infiltrated bones in our patient revealed that malignant cells had replaced the patient's marrow. Moreover, the diagnosis of multiple-organ metastases of anaplastic OGD was confirmed based on immunohistochemical staining. Genetic analyses showed that the tumors originated from previously resected brain lesions. None of the lesions had 1p and 19q deletions, but hypermethylation of MGMT promoter, and the G → A transversion at codon 234 of PTEN exon 2 were detected. Literatures review yielded 60 reports of metastatic OGDs from 1951 to the present, which with our patient makes 61 cases. Concerning these 61 patients, there were 110 infiltrated sites correlated closely with primary OGDs. The most frequent metastatic sites were bone and bone marrow (n = 47; 42.7%), lymph nodes (n = 22; 20.0%), liver (n = 7; 6.4%), scalp (n = 6; 5.5%), lung (n = 6; 5.5%), pleura (n = 4; 3.6%), chest wall (n = 3; 2.7%), iliopsoas muscle (n = 2; 1.8%), soft tissue (n = 2; 1.8%), and parotid gland (n = 2; 1.8%).

Conclusions: Extracranial metastases in anaplastic OGD are very rare but they do occur; bone and bone marrow may be the most common sites. Detection of certain molecular markers such as deletion of 1p and 19q chromosomal arms, hypermethylation of MGMT promoter, and characteristic PTEN exon mutations may help differentiate subtypes which are more prone to extracranial metastases.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8749838611478560.

Figure 1

Representative axial MR images with gadolinium, taken on initial admission. (A) T₁-weighted MR image (T₁WI); (B) Contrast-enhanced T₁WI and (C) T₂-weighted MR image (T₂WI) showing a left occipital tumor with mild contrast enhancing; (D) at one month follow up, T₁WI; (E) contrast-enhanced T₁WI and (F) T₂WI showing no apparent enhanced lesion; (G) 8 months later after the first surgery, T₁WI; (H) contrast-enhanced T₁WI and (I) T₂WI showing marked enhanced mass on the cavity and recurrence; (J) 48 h after the second surgery, T₁WI; (K) contrast-enhanced T₁WI, and (L) T₂WI showing no apparent enhanced lesion; (M) 8 months later after combination radiotherapy and chemotherapy, T₁WI; (N) contrast-enhanced T₁WI and (O) T₂WI showing marked enhanced mass of the wall in the posterior portion of the removal cavity and left temporal areas, and recurrence of the enhanced tumor. (P, Q) 8 months later after combination radiotherapy and chemotherapy, sagittal spinal contrast-enhanced T₁WI after gadolinium infusion showing high-intensity mass lesion in (P) T7, T10, and T12 vertebral bodies (arrowheads) and (Q) T12, L2, L3, L5, and S1 vertebral bodies (arrows).

Figure 2

Representative photomicrographs of the tumor specimens. Higher cell densities (A, B; 100×, 200×, respectively, H & E) with perinuclear haloes (C; 200×, H & E; arrows), and microscopically round-to-oblong cells with hyperchromatism and pleomorphism (D; 400×, H & E), are compatible with AO. (E, F) Clusters of capillary or plexiform capillaries (arrows), and the irregular mitosis densities were higher (100×, 200×, respectively, H & E). (G, H) Obvious false fence structure (thick arrows)-shaped necrosis (slim arrows; 100×, 200×, respectively, H & E). (I, J) After the right iliac bone marrow needle biopsy, cells in the bone marrow specimen from the patient were small and round with a thin rim of eosinophilic cytoplasm (400×, H & E).

Figure 3

Representative emission computed tomography scans. (A) anterior scans, and (B) posterior scans, showed a hypermetabolically abnormal uptake at the right iliac bone (arrowheads) and T10, and T12 vertebral bodies (arrows).

Figure 4

Representative whole body PET-CT scans. (A) and (B) Multiple foci of increased 18 F-fluoro-2-deoxyglucose (FDG) uptake at the bilateral iliac bones, C4, T7, T11, T10, T12, L2, L3, S1 vertebral bodies and the right acetabulum; (C) Focus of increased ¹⁸ F-FDG uptake at the lymph node near the left side of the T11 vertebral body (arrows); (D) Focus of increased ¹⁸ F-FDG uptake at the lymph node of the right supraclavicular region (arrows).

Figure 5

Representative scans of bone marrow smear. (A, B) No plasmocytoma cells were found (100× and 1000×, respectively).

Figure 6

Representative immunochemical markers in tumor specimens. (A, B) Positive reaction for IDH1 (100×, 200×, respectively). (C) Positive reaction for Ki-67, with proliferating index >80% (200×). (D, E) Tumor cells were positive for GFAP and Oligo-2, respectively (200×). (F, G, H) showed the tumor cells were negative for EMA, MGMT, and vimentin, respectively (200×).

Figure 7

Representative FISH images from the right iliac bone. Some signals are missing due to nuclear truncation. (A) No 1p deletion, with 2 red (1p36, arrows) and 2 green (1q25-q31, arrowheads) signals in scattered nuclei. (B) No 19q deletion with 2 red (19q13, arrows) and 2 green (19p12, arrowheads) signals in scattered nuclei.

Figure 8

Representative MSP-PCR for methylated MGMT promoter. NTC, non DNA template control; +, methylated; –, unmethylated; M, DNA marker; the upper, middle, and lower bands are 140, 120, 100, and 80 bp, respectively.

Figure 9

Representative sequencing data showing the G → A transversion at codon 234 (arrows) of exon 2 in PTEN of the patient. Blue, primer; red, exon 2; purple, the transversion of A, showing the polymorphism.