Articles

Kourtopoulos Harry, MD, PhD and Drosos Christos MD, Department of Neurosurgery, Mediterraneo Hospital, Glyfada, Greece.

An unusual case of a 17 year old boy who at age οί six was diagnosed and curcd for Hodgkin diseased and at age of 12 was diagnosed glioblastoma. He has successfully survived longer than 5 years after repeated surgical removal, radiotherapy and chemotherapy and removal of a postradiation sarcoma. Analysis of the case.

Keywords: Hodgkin disease, glioblastoma multiform, surgery, irradiation, chemotherapy, post radiation sarcoma.

Introduction

The term, Glioblastoma multiform (GMB) was introduced by Percival Bailey and Harvey Cushing in 1926 based on the idea that the tumour originates from primitive precursors of glial cells – glioblasts - and highly variable appearance due to presence of necrosis, haemorrhage and cysts-multiform (1). It is the second most common central nervous system tumour after meningiomas, corresponding into 3 cases per 100.000 inhabitants that will develop the disease annually (2). Life expectancy without treatment is approximately 3 months while treatment with aggressive/radical excision together with oncologic therapy will increase life expectancy to 12-15 months and median survival time seems to have improved over the last decade (3).

Increasing age e.g. over 60 years of age, carries a worse prognosis. 99% of GBM will have a recurrence with widespread tumour infiltration and subsequent death. Age under 50 is associated with longer survival along with 98% resection and use of temozolomide (3). Data from UCLA Neuro-Oncology group has reported median survival of 36.5 months for age range 18-34, 20.8 months for age range 36-50, 19.7 months for age range 50-70 and 16.2 for ages 70-93. Our ease belongs to an even younger age group, not reported before, carrying a very promising result for the future since he has survived for more than 5 years now.

Report of the case

A 12 year old boy (born 4/8/2000, image 1) was admitted to our hospital with history of headaches for the last month. An MR examination on the 6/8/2012 showed a left temporal tumour (6,1x5,7x5,0 cm, image 2)) with dural attachment. There were multiple cysts and hemorrhagic areas inside the tumour mass. There was significant oedema around the tumour with midline shift of 8mm, pressure on the left cerebral peduncle and erasure of the prepontine cistern. The possible diagnosis was that of a meningioma due to its attachment to the dura or a lemphoma (mostly because he had suffered before from Hodgkin's disease) whereas other mesenchymatic tumours were less possible. He presented a GCS of 15 but with severe headache and obvious speech and cognitive disturbances. The histological diagnosis was GBM with the presence of multiple areas of necrosis, atypical mitoses and giant cell type. The postoperative period was uneventful and a postoperative MR (30/8/2012) showed a complete removal of the tumour. There were no clinical deficits.

His excellent clinical picture along with the MR findings made the oncologists (in Athens, Great Ormond Hospital in London and Mayo Clinic in US) to hesitate for further oncologic treatment, e.g. radiotherapy and chemotherapy, having in mind a new trial that should started after December 2012. However, before completion of three months, he suddenly deteriorated with a recurrence and the patient was reoperated on the 8/12/2012. A new complete tumour removal was performed (5,8x5.8x4.9 cm, image 3) with the same histological diagnosis, glioblastoma multiform gr IV. There were multiple areas of necrosis, atypical mitoses and giant cell type. Ki67 was positive for more than 50-60% of the cells and cellular immune histologic positiveness for EGFR, GFAP, CD31, CD34, P53 and VEGF factors.

As soon as the stiches were removed, he started immediately with radiotherapy and themozolomide. Follow up MR studies showed no recurrent tumour but a year later he presented an extracranial tumour mass, along the radiation area, measuring approximately 7.0x3.5 cm. This tumour was immediately removed and the diagnose was, post radiation sarcoma. There was no intracranial involvement. Since then, he has been yearly followed by the oncologists with an MR brain (November 2017) showing no recurrent tumour (image 4).He is a well developed teen ager, receiving no medication. He is attending his last year of scholar education and will study further in the university.

Discussion

During the last century, thousands and thousands of productive men and women have left relatives and life succumbing due to the diagnosis of glioblastoma multiform. Especially those in the fifth and sixth decade (4). Recurrency is believed to depend on cells left behind (5) while survival is linearly associated with the amount removed (6) or the initial Karnowski grade (7). Not all of these conclusions are justified in our case. In both occasions, there was a complete removal but the tumour recurred after the initial resection, but not the second, which makes us to believe that temozolamide played a significant roll. On the other hand, the very vast the majority of those tumours did not survived even when the oncology protocols have been followed. We do not know what factors influenced upon his survival, so far. We believe that his age was the crucial factor for his survival. Literature dealing with glioblastoma survival is rich but not among teen agers unless we thing, like his parents, that this was a miracle!

References

1. Bailey & Cushing: Tumours of the Glioma Group JB Lippincott, Philadelphia 1926
2. Gallego 0. Nonsurgical treatment of recurrent glioblastoma. Current Oncology (Toronto, Ont.) 22(4) 273-81, August 2015
3. Hart MG, Garside R, Rogers G, Stein K, Grant R.: Tomozolomide for high grade glioma. April 2013
4. Shaw LG, Seiferheld W, Scott C, Coughlin C, Sinica group (RTOG) recursive partitioning analysis (RPA) for glioma multiform (GBM) patients. Internat J of Radiation Oncol "Biology" Physics, 57(2) 135-6, 2003
5. Rajesh Y, Pal S, Banik P, Chakraborty S, Borkar SA, Dey G, Mukherjer A, Mantal M. Insights into molecular therapy of glioma: current challenges and next generation blueprint. Acta Pharmacol Sinica 38(5) 591-613, 2017
6. Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, Demonte F, Lang F, Me Cutheon Ian F et al. A multivariate analysis of 416 patients with glioblastoma multiforme. Prognosis, extension of resection and survival. J Neurosurg 95 (2) 190-198, 2001