Anaplastic Pilomyxoid Astrocytoma
Although, Pilomyxoid astrocytoma (PMA) was first described by Tihan et al in 1999 (10); it's recognition as a distinct clinicopathological entity was established by WHO in 2007 (1). PMA is a piloid neoplasm that is considered as infantile variant of pilocytic astrocytoma (PA) with aggressive course (2). Recent studies have shown histological and genetic overlap between PMA and PA (4). Cell of origin of PMA is unclear. It is suggested that origin is from tanycyte or radial glia in proximity to optic nerve (6). PMA was initially classified as grade 2 tumor by WHO in 2007. However, subsequent studies question the grading of tumor due to its unpredictable behavior (5). Revised WHO classification in 2016, didn't assign any specific grade to PMA (9). Symptoms of PMA depend primarily on site and extent of tumor but may include symptoms of raised intracranial pressure or parenchymal compression like failure to thrive, developmental delay in pediatric age group, altered sensorium, headache, vomiting, and generalized weakness along with focal neurological symptoms, visual and endocrine disturbances (7).
The present case described herein is unusual because of the following features. Firstly, our patient presented in sixth decade in contrast to usual presentation of PMA in infantile age group. Only 21 cases of PMA have been reported in literature in adults till date. Secondly, the tumor was localized in left temporo-parietal region. The commonest site of localization of PMA is in hypothalamo-chiasmatic region and only a few cases have been reported in cerebral cortex. There has been only a single case report of PMA in an adult male of 24 years involving posterior temporal lobe (3). Thirdly, anaplastic nuclear features observed in present case have never been reported in PMA. Microscopic features including brisk mitotic figures, nuclear irregularity, hyperchromasia and highly cellular areas were present in the tumor leading to a diagnosis of anaplastic pilomyxoid astrocytoma.
Post operative radiologic findings showed presence of residual tumor at the periphery. The patient was admitted with repeated symptoms six weeks later. He was then referred for neo-adjuvant radiotherapy and chemotherapy. Patient has been under continuous follow up for last one year with no symptomatic or radiological evidence of tumor recurrence.
Anaplastic pilocytic astrocytoma has been reported in literature predominantly in the form of isolated case reports and small case series. In an exclusive study of 34 cases of anaplastic PA identified amongst 2200 cases of pilocytic astrocytomas by Rodriguez FJ et al, criteria of anaplasia included diffuse brisk mitotic activity (>4mitoses per 10 high power fields), with or without necrosis, hypercellularity and moderate to severe cytologic atypia of non-degenerative type. According to them the anaplastic PA's without necrosis behaved closer to St Anne-Mayo grade II astrocytoma whereas presence of necrosis conferred a behavior closer to grade 3 astrocytoma (8). Extensive search in PubMed and Google scholar did not reveal any case of Anaplastic PMA in medical literature.
Differential diagnoses considered in present case were pilocytic astrocytoma, anaplastic astrocytoma, ependymoma, oligoastrocytoma and pleomorphic xanthoastrocytoma. Pilocytic astrocytoma shows characteristic presence of biphasic pattern, eosinophilic granular bodies (EGB's) and Rosenthal fibers. Myxoid change if present is usually focal. Oligoastrocytoma shows biphasic pattern comprising of oligodendroglial and astrocytic cells with presence of EGB's and Rosenthal fibers but angiocentric arrangement of tumour cells and extensive myxoid change is absent. In ependymoma, regular perivascular arrangement of tumor cells with absence of myxoid areas is noted. These tumors exhibit immunoreactivity for EMA in most cases. Although anaplastic astrocytoma demonstrates increased cellularity, nuclear atypia and mitotic figures but angiocentric pattern and diffuse myxoid change is absent. In pleomorphic xanthoastrocytoma pleomorphic lipidized cells are seen along with spindle cells. Monomorphic bipolar cells are absent. Ki -67 index is usually <1%.
There is no consensus guidelines on management of PMA. Whenever possible, gross total resection (GTR) of tumor is the primary treatment strategy. Indications for adjuvant therapy vary with patient's requirement: 1] Tumor recurrence following initial GTR 2] Partial resected tumor causing neurological impairment 3] Partial resected tumor with high Ki- 67 index or growth on follow up imaging even in absence of symptoms.
To conclude, similar to pilocytic astrocytomas, presence of anaplastic features may rarely be encountered in pilomyxoid astrocytomas also and these patients may be benefited with adjuvant therapy. For assigning any specific grade to PMA's more substantial clinical studies are required to understand the exact nature and behavior of this enigmatic tumor.
ACKNOWLEDGMENT - We thank the technical staff (Histopathology section) at BMHRC for their support.
Contributed by Jawale P M, MD, Gulwani Hanna V, DNB MNAMS