Glioblastoma multiforme after microsurgery for acoustic neuroma without radiotherapy: limitations of the Cahan criteria.
- Cancer 02/1998; 82(1):8-34. · 5.20 Impact Factor
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ABSTRACT: Genetic and immunohistochemical studies may provide insight into the mechanisms of vestibular schwannoma (VS) recurrence following radiation therapy. Stereotactic radiation therapy is an increasingly common alternative to microsurgical resection for the primary management of sporadic VS. The molecular mechanisms associated with recurrent vestibular schwannoma (VS) following radiation therapy are not known. Primary or irradiated VS tumors were fresh-frozen at the time of surgical resection and microdissected to undergo DNA extraction. Lymphocytic control DNA was isolated from blood obtained by venipuncture. Paired normal and tumor DNA specimens were analyzed for allelic loss by PCR amplification of polymorphic dinucleotide repeat sequences. Immunohistochemical studies were performed on paraffin-embedded, irradiated surgical specimens. Using 16 polymorphic microsatellite markers, 20 of 26 non-irradiated VS demonstrated loss of heterozygosity (LOH) in at least one locus of chromosome 22q. In contrast, none of the four irradiated recurrent VS demonstrated LOH on chromosome 22q (p = 0.008). No allelic loss was seen in either the primary or irradiated VS utilizing markers mapping to chromosome 10. Deletions on chromosome 10 are seen in both benign and higher-grade meningiomas and intracranial malignancies associated with radiotherapy. Immunohistochemical studies were performed to detect the protein product of the NF2 gene, merlin, in the four irradiated VS. NF2 staining was not observed. This study represents the first microsatellite and immunohistochemical analysis of recurrent VS following radiation therapy. Our preliminary observations suggest an alternative mechanism of NF2 inactivation that may correlate with radioresistance in VS.Ontology & Neurotology 03/2006; 27(2):213-9. · 2.01 Impact Factor
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ABSTRACT: Indications for the use of radiotherapy in the management of a variety of benign intracranial neoplastic and nonneoplastic pathologies are increasing. Although the short-term risks are minimal, the long-term risks of radiation-induced de novo secondary neoplasms or malignant progression of the primary benign tumor need to be considered. There are currently 19 reported cases of tumors linked with stereotactic radiotherapy/radiosurgery, to which we add our second institutional experience of a patient who succumbed to a glioblastoma multiforme (GBM) after stereotactic radiotherapy for an acoustic neuroma (AN). Review of these 20 cases revealed 10 de novo secondary tumors, of which eight were malignant, with six being malignant gliomas. The majority of the cases (14 of 20) involved AN, with most being in patients with neurofibromatosis-2 (NF2; 8 of 14), reflecting the large numbers and long-term use of radiotherapy for AN. Accelerated growth of the primary benign AN, some 2 to 6 years after focused radiotherapy, was found in six of eight NF2 patients, with pathological verification of a malignant nerve sheath tumor documented in most. The exact carcinogenic risk after radiotherapy is unknown but likely extremely low. However, the risk is not zero and requires discussion with the patient, with specific consideration in young patients and those with a cancer predisposition.Neuro-Oncology 11/2007; 9(4):447-53. · 6.18 Impact Factor
Glioblastoma multiforme after microsurgery for
acoustic neuroma without radiotherapy: Limitations
of the Cahan criteria
Michael Hoa, MD, Richard Rhiew, MD, William J. Kupsky, MD,
Murali Guthikonda, MD, and Edwin M. Monsell, MD, PhD, Detroit, MI
that arose in radiated bone, mostly in children treated for
tuberculosis. They studied only cases that met certain in-
clusion criteria: 1) there must have been histologic or ra-
diographic evidence of the nonmalignant nature of the ini-
tial condition; 2) the sarcoma that arose must have arisen in
the area included in the radiotherapeutic beam; 3) there
must have been a relatively long, asymptomatic period of
latency between radiation and development of the sarcoma;
and 4) the sarcoma must be proved histologically.1,2Since
Cahan’s report, these criteria have often been cited as re-
quirements for considering a case to represent radiation-
Since the 1980s there has been considerable interest in
stereotactic radiosurgery and other forms of focused radia-
tion therapy for nonmalignant conditions. One of the con-
cerns raised by radiation treatments for acoustic neuroma,
which has somewhat limited their use, is the potential for
radiation to induce other intracranial tumors, including ma-
lignancies.3,4Because such cases are rare, it has been dif-
ficult to establish a reliable estimate of their occurrence to
guide selection of treatment and patient counseling. We
report a case that we feel should be taken into consideration
when estimating the risk of radiation-induced malignancy.
Institutional Review Board approval was obtained.
A 58-year-old woman presented to the emergency de-
partment complaining of increasing ataxia for the past two
weeks. She also noted numbness and tingling in the right
face and body, diplopia, blurred vision, nausea, and vomit-
ing for the same period. On the morning of admission she
experienced a severe pressure headache at the right mastoid
process, which spread to include the left side within a few
hours. The past medical history was significant for micro-
surgical excision of a right acoustic neuroma two years
previously. This was conducted as a two-stage procedure at
another center. A few months postoperatively she received
an osseointegrated implant for single-sided deafness. The
patient’s family history was negative for cancer, schwan-
n 1948 Cahan and others reported 11 cases of sarcoma
noma, and neurofibromatosis types I and II. On examination
she avoided head movement. There was brisk spontaneous
right-beating nystagmus with eyes open. Right facial numb-
ness was reported. There was also decreased light-touch
sensation on the left extremities and torso. The deep tendon
reflexes were 2? and strength was 5/5 throughout. The
general physical and neurologic examinations were other-
Magnetic resonance imaging (MRI) (Fig 1) showed a
lobular, infiltrating mass with necrotic centers involving the
right tegmentum, midbrain, pons, middle cerebellar pedun-
cle, and cerebellum. The enhancing area in the right pos-
terolateral cerebellar hemisphere measured 2.5 cm in largest
diameter. The lesion was accompanied by significant
edema, evident on T2-weighted MR sequences, though
there was no evidence of hydrocephalus. A stereotactic
biopsy performed the morning after admission was sugges-
tive of glioma. Stereotactic maximum safe resection of the
tumor in the right cerebellum and brain stem was carried
out. Postoperatively there were no new neurologic deficits.
Numbness of the right face and left body persisted, and the
diplopia resolved. Examination of permanent histologic sec-
tions revealed WHO grade 4 glioblastoma multiforme (Fig 2).
Many tumor cells showed strong immunoreactivity to glial
fibrillary acidic protein and epidermal growth factor. Ki67
labeled 10% to 15% of cells in most regions of the tumor.
Many cells were immunoreactive for p53 and bel-2.
Most authors point out that the occurrence of a second
tumor following radiation does not prove a causal relation-
ship; however, the citation of the “Cahan criteria” and the
publication of a case generally does imply causation. It is
well recognized that radiation damages DNA and is tumor-
igenic and carcinogenic. There is no such suspicion regard-
ing microsurgery. The occurrence of glioblastoma adjacent
Received March 7, 2008; accepted March 20, 2008.
Otolaryngology–Head and Neck Surgery (2008) 139, 323-324
0194-5998/$34.00 © 2008 American Academy of Otolaryngology–Head and Neck Surgery Foundation. All rights reserved.
to the site of microsurgical resection of an acoustic neuroma
points out the hazard of assuming that there is a causal
relationship when two events are associated, ie, that radia-
tion was the cause of all tumors observed following radia-
tion. It would be desirable if more secure criteria, such as
molecular markers, were available to differentiate sponta-
neous versus radiation-induced tumors. Although deletions
in chromosome 10 have been found in both benign and
higher-grade meningiomas and intracranial malignancies
associated with radiotherapy, definitive markers that differ-
entiate spontaneous from radiation-induced tumors have yet
to be identified.4,5
From the Departments of Otolaryngology–Head and Neck Surgery (Drs
Hoa and Monsell), Neurological Surgery (Drs Rhiew and Guthikonda), and
Pathology (Dr Kupsky), Wayne State University School of Medicine.
Corresponding author: Michael Hoa, MD, Dept of Otolaryngology–Head
and Neck Surgery, Wayne State University School of Medicine, 4201 St.
Antoine, 5E-UHC, Detroit, MI 48201.
E-mail address: email@example.com.
Michael Hoa, MD, data collection, writer; Richard Rhiew, MD, data
collection; William J. Kupsky, MD, pathological description, pathologi-
cal specimens, writer; Murali Guthikonda, MD, data collection, writer;
Edwin M. Monsell, MD, PhD, data collection, writer.
1. Cahan WG, Woodward HQ, Higinbotham NL, et al. Sarcoma arising in
irradiated bone: report of eleven cases. Cancer 1948;1:2–29, reprinted in
2. Schrantz JL, Araoz CA. Radiation induced meningeal fibrosarcoma.
Arch Pathol 1972;93(1):26–31.
3. Balasubramanian A, Shannon P, Hodaie M, et al. Glioblastoma multi-
forme after stereotactic radiotherapy for acoustic neuroma: case report
and review of the literature. Neuro Oncol 2007;9(4):447–53.
4. Yang SY, Wang KC, Cho BK, et al. Radiation-induced cerebellar
glioblastoma at the site of a treated medulloblastoma: case report.
J Neurosurg 2005;102(Pediatrics 4):417–22.
5. Lee DJ, Maseyesva B, Westra W, et al. Microsatellite analysis of
recurrent vestibular schwannoma (acoustic neuroma) following stereo-
tactic radiosurgery. Otol Neurotol 2006;27(2):213–9.
gical removal of acoustic neuroma, demonstrating a 2.5-cm en-
hancing right posterolateral cerebellar lesion suggestive of glio-
Axial T1 post-gadolinium MRI two years after sur-
eosin staining of permanent histologic sections showing an infil-
trative glial neoplasm composed of poorly differentiated fibrillated
and small cells. The cells contain either irregular or rounded
nuclei, many showing considerable nuclear atypia and atypical
mitotic figures. There is microvascular proliferation with fibrin
thrombi present in scattered vessels. Small areas of microcystic
degeneration are noted as well as foci of connective tissue prolif-
eration. The tumor engulfed the VIIIth nerve. The VIIIth nerve
was sectioned and did not appear to be the origin of the tumor.
Histopathology of the lesion on hematoxylin and
324Otolaryngology–Head and Neck Surgery, Vol 139, No 2, August 2008