Neurofibromatosis type 1‐associated unusual pleomorphic astrocytoma displaying continual malignant progression

Abstract

Patients with neurofibromatosis type 1 (NF1) often have gliomas as a complication, most of which are benign pilocytic astrocytomas which have arisen in optic pathways. In the present case, a 17-year-old girl (at death) with stigmata of NF1, initially had a bulky tumor mass in the left thalamus, developing into the lateral ventricle, at 13 years of age. Partially resected tissue samples showed pleomorphic astrocytoma with abundant xanthoma cells and degenerative structures such as Rosenthal fibers (RF) and eosinophilic granular bodies. Fine eosinophilic granules identical to RF, both immunophenotypically and ultrastructurally, were also seen. The residual tumor was subtotally resected 6 months later, and the tumor histology was essentially similar as before, accompanying the regenerative structures; this was believed to be a good prognostic indicator. However, several anaplastic features such as mitosis, necrosis and vascular proliferation appeared even in areas rich in the regenerative structures. After a 2-year, disease-free interval, multiple tumor relapse occurred in June 1997. Partially resected tumor tissues were composed of monotonous small anaplastic cells with prominent proliferative activity. Surprisingly, the tumor cells had retained eosinophilic granules within the cell bodies. Postoperative chemotherapy with procarbazine, MCNU and vincristine (PCV) suppressed the residual tumor dramatically, but the regrowing tumor finally became uncontrollable, leading to the patient's death. TP53 mutation was not detected, while p27 immunopositivity was constantly high during malignant progression, suggesting acquisition of proliferative activity to overcome p53 and p27 inhibitory functions. A review of previously published reports failed to reveal any cases of this type.

Cerebral pleomorphic xanthoastrocytoma associated with NF1: an updated review with a rare atypical case from Africa

“…In the latter case, the primary lesion was a solid left thalamic-lateral ventricular mass whose histomorphology was reported in part as revealing large pleomorphic and xanthomatous cells. Occasional intracytoplasmic eosinophilic granular inclusions were recognized; the tumor cells were GFAP positive, but in all, the diagnosis of PXA-NF1 did not appear to be in the authors' consideration [26]. Nevertheless, no case as far as we know of PXA-NF1 has so far been reported in an African.…”

“…The case reported by Saikali et al was of particular interest because it was a case of multicentric supratentorial cerebral and infratentorial cerebellar hemispheric PXA in NF1 [23]. Another case of a 13-year-old child reported by Yokoo et al in 2001 is also of interest being an example of NF1-associated unusual pleomorphic astrocytoma with malignant progression [26]. In the latter case, the primary lesion was a solid left thalamic-lateral ventricular mass whose histomorphology was reported in part as revealing large pleomorphic and xanthomatous cells.…”

Pleomorphic xanthoastrocytoma with malignant transformation and multiple recurrences in an Iranian girl

“…Our case is in accordance with these observations. Studies have reported that PXA can exhibit a synchronous multicentric pattern19 or result in multiple recurrences 9. Multifocal occurrence of PXA manifesting at different time frame is extremely uncommon but has been reported 20…”

“…Some studies showed surgery is the most important therapeutic approach,1 9 18 21 if anaplastic PXA is confirmed, the active adjuvant of radio and chemotherapy may be useful. One case has been reported in which the use of neoadjuvant vincristin and carbiplatin was effective for controlling bleeding during surgery, presumably due to devascularisation 23.…”

“…Classically, PXA has been considered as a tumour with relatively favourable prognosis 2 3. However, lethal malignant transformation in PXA has been reported in recent years4–9 and a concept called anaplastic PXA (WHO grade III) has been proposed 1 4 10 11. With a review of the literature, we present a case of PXA with malignant transformation who had repeated local recurrences, cerebral dissemination and eventually developed glioblastoma like on histology.…”