Anaplastic astrocytoma cells not detectable on autopsy following long‑term temozolomide treatment: A case report

Hirano,Hirofumi; Kawahara,Takashi; Niiro,Masaki; Yonezawa,Hajime; Takajyou,Tomoko; Ohi,Yasuyo; Kitazono,Ikumi; Sakae,Kiyohiro; Arita,Kazunori

doi:10.3892/mco.2017.1160

Anaplastic astrocytoma cells not detectable on autopsy following long‑term temozolomide treatment: A case report

Authors:
- Hirofumi Hirano
- Takashi Kawahara
- Masaki Niiro
- Hajime Yonezawa
- Tomoko Takajyou
- Yasuyo Ohi
- Ikumi Kitazono
- Kiyohiro Sakae
- Kazunori Arita
View Affiliations

Affiliations: Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8520, Japan, Department of Neurosurgery, Imamura Bun‑in Hospital, Kagoshima 890‑0064, Japan, Department of Molecular and Cellular Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890‑8520, Japan, Department of Pathology, Imamura Bun‑in Hospital, Kagoshima 890‑0064, Japan
Published online on: February 7, 2017 https://doi.org/10.3892/mco.2017.1160
Pages: 321-326
Copyright: © Hirano et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

We herein present an autopsy case of a glioma patient who received long‑term treatment with temozolomide (TMZ). The patient, a 35‑year‑old man with a hypointense tumor of the left frontal lobe, without contrast enhancement following gadolinium (Gd) administration on T1‑weighted images, underwent tumor removal surgery, after which the tumor was diagnosed as anaplastic astrocytoma. By the third round of surgery, the tumor had progressed to anaplastic astrocytoma with contrast enhancement following Gd administration, and the patient received 60 Gy of external beam radiotherapy and nimustine hydrochloride (ACNU)‑based chemotherapy. After the fifth tumor removal surgery, TMZ was substituted with ACNU chemotherapy, which suppressed tumor progression. Following the 41st TMZ treatment, hemorrhage was observed in the residual tumor, and the hematoma had been replaced by a hemangioma. The hemangioma and surrounding brain tissue was removed during the sixth surgery. The patient survived for 14 years and 9 months after the initial surgery, but succumbed to hydrocephalus due to bleeding from hemangiomas. The histopathological specimens of the first to the sixth surgeries revealed mutant isocitrate dehydrogenase 1 (IDH1; R132H point mutation) and p53‑positive tumor cells, but cells positive for the R132H mutation or p53 could not be detected by immunohistochemistry in the autopsy specimens of the brain after 108 courses of TMZ treatment. Mutant IDH1 (R132H) cells were also not detected in the autopsy specimens of the brain by polymerase chain reaction analysis.

View Figures

View References

1	Yung WK, Prados MD, Yaya-Tur R, Rosenfeld SS, Brada M, Friedman HS, Albright R, Olson J, Chang SM, O'Neill AM, et al: Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal brain tumor group. J Clin Oncol. 17:2762–2771. 1999.PubMed/NCBI
2	Gilbert MR, Friedman HS, Kuttesch JF, Prados MD, Olson JJ, Reaman GH and Zaknoen SL: A phase II study of temozolomide in patients with newly diagnosed supratentorial malignant glioma before radiation therapy. Neuro Oncol. 4:261–267. 2002. View Article : Google Scholar : PubMed/NCBI
3	Hirano H, Yunoue S and Arita K: Long-term temozolomide treatment in two patients with high-grade glioma (in Japanese with English abstract). CP Neurosurgery. 18:886–892. 2008.
4	Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, et al: IDH1 and IDH2 mutations in gliomas. N Engl J Med. 360:765–773. 2009. View Article : Google Scholar : PubMed/NCBI
5	Arita H, Narita Y, Yoshida A, Hashimoto N, Yoshimine T and Ichimura K: IDH1/2 mutation detection in gliomas. Brain Tumor Pathol. 32:79–89. 2015. View Article : Google Scholar : PubMed/NCBI
6	Capper D, Sahm F, Hartmann C, Meyermann R, von Deimling A and Schittenhelm J: Application of mutant IDH1 antibody to differentiate diffuse glioma from nonneoplastic central nervous system lesions and therapy-induced changes. Am J Surg Pathol. 34:1199–1204. 2010. View Article : Google Scholar : PubMed/NCBI
7	Scoccianti S, Magrini SM, Ricardi U, Detti B, Krengli M, Parisi S, Bertoni F, Sotti G, Cipressi S, Tombolini V, et al: Radiotherapy and temozolomide in anaplastic astrocytoma: A retrospective multicenter study by the central nervous system study group of AIRO (Italian Association of Radiation Oncology). Neuro Oncol. 14:798–807. 2012. View Article : Google Scholar : PubMed/NCBI
8	Hau P, Koch D, Hundsberger T, Marg E, Bauer B, Rudolph R, Rauch M, Brenner A, Rieckmann P, Schuth J, et al: Safety and feasibility of long-term temozolomide treatment in patients with high-grade glioma. Neurology. 68:688–690. 2007. View Article : Google Scholar : PubMed/NCBI
9	Mannas JP, Lightner DD, Defrates SR, Pittman T and Villano JL: Long-term treatment with temozolomide in malignant glioma. J Clin Neurosci. 21:121–123. 2014. View Article : Google Scholar : PubMed/NCBI
10	Takano S, Kato Y, Yamamoto T, Kaneko MK, Ishikawa E, Tsujimoto Y, Matsuda M, Nakai K, Yanagiya R, Morita S, et al: Immunohistochemical detection of IDH1 mutation, p53, and internexin as prognostic factors of glial tumors. J Neurooncol. 108:361–373. 2012. View Article : Google Scholar : PubMed/NCBI
11	Kawano H, Hirano H, Yonezawa H, Yunoue S, Yatsushiro K, Ogita M, Hiraki Y, Uchida H, Habu M, Fujio S, et al: Improvement in treatment results of glioblastoma over the last three decades and beneficial factors. Br J Neurosurg. 29:206–212. 2015. View Article : Google Scholar : PubMed/NCBI
12	Novelli PM, Reigel DH, Gleason P Langham and Yunis E: Multiple cavernous angiomas after high-dose whole-brain radiation therapy. Pediatr Neurosurg. 26:322–325. 1997. View Article : Google Scholar : PubMed/NCBI
13	Maeder P, Gudinchet F, Meuli R and de Tribolet N: Development of a cavernous malformation of the brain. AJNR Am J Neuroradiol. 19:1141–1143. 1998.PubMed/NCBI
14	Baumgartner JE, Ater JL, Ha CS, Kuttesch JF, Leeds NE, Fuller GN and Wilson RJ: Pathologically proven cavernous angiomas of the brain following radiation therapy for pediatric brain tumors. Pediatr Neurosurg. 39:201–207. 2003. View Article : Google Scholar : PubMed/NCBI
15	Aguilera D, Tomita T, Goldman S and Fangusaro J: Incidental resolution of a radiation-induced cavernous hemangioma of the brain following the use of bevacizumab in a child with recurrent medulloblastoma. Pediatr Neurosurg. 46:303–307. 2010. View Article : Google Scholar : PubMed/NCBI
16	Chourmouzi D, Papadopoulou E, Kontopoulos A and Drevelegas A: Radiation-induced intracranial meningioma and multiple cavernomas. BMJ Case Rep. 2013:pii2013.
17	Lew SM, Morgan JN, Psaty E, Lefton DR, Allen JC and Abbott R: Cumulative incidence of radiation-induced cavernomas in long-term survivors of medulloblastoma. J Neurosurg. 104:(Suppl 2). S103–S107. 2006.
18	Furuse M, Miyatake SI and Kuroiwa T: Cavernous malformation after radiation therapy for astrocytoma in adult patients: Report of 2 cases. Acta Neurochir (Wien). 147:1097–1101. 2005. View Article : Google Scholar : PubMed/NCBI
19	Fukushima S, Narita Y, Miyakita Y, Ohno M, Takizawa T, Takusagawa Y, Mori M, Ichimura K, Tsuda H and Shibui S: A case of more than 20 years survival with glioblastoma, and development of cavernous angioma as a delayed complication of radiotherapy. Neuropathology. 33:576–581. 2013.PubMed/NCBI