Cervical Metastatic Glioblastoma Multiforme John J. Zappia, MD, Gregory
T.
Wolf,
MD
\s=b\ Glioblastoma multiforme is an anaplastic neoplasm of glial origin. In spite of the aggressive histologic features and poor prognosis, metastasis outside the cranial vault is distinctly unusual. A patient with glioblastoma multiforme metastatic to the neck is presented. We also review the topic
of metastatic intracranial tumors. (Arch Otolaryngol Head Neck Surg. 1992;118:755-756) the spectrum of tiforme is the In extracranial is
tumors of glial origin, glioblastoma mul¬ most poorly differentiated. Even with this,
spread extremely unusual. Although there are studies in the neurosurgical literature on cervical mé¬ tastases from this and other intracranial tumors, little is men¬ tioned within the otolaryngologic literature. rare
REPORT OF A CASE
39-year-old man with a chronic seizure disor¬ history of memory loss, headaches, and nau¬ sea was presented. At that time a right-sided parietal mass was discovered and a craniotomy with subtotal resection was per¬ formed. Pathologic findings revealed glioblastoma multiforme. In May, August, and November 1989 he underwent interleukin-2 and activated lymphocyte treatment associated with craniotomies for progressive disease. From January through March 1989 he re¬ ceived 6000 cGy radiation therapy to the brain. In March 1989
der and
a
a
2-month
He remained stable until October 1990 when he noticed
a
pro¬
gressively enlarging mass on the right side of the neck. A com¬ puted tomographic scan revealed multiple enlarged right side cervical lymph nodes in the submandibular, jugulodigastric, and deep cervical and parotid chains (Fig 1). The largest node was 2.5 cm and was in the deep cervical chain. The majority of them
showed central attenuation. Examination at the time of his presentation to our institution in November 1990 revealed three masses in the right tail of the parotid/jugulodigastric area. The smallest was 1.0 X 1.5 cm and the largest was 3.0 X 2.5 cm. Fine-needle aspiration of the mass was
nondiagnostic.
An open neck biopsy was performed. Multiple firm lymph nodes were encountered in the right jugulodigastric area. They appeared free of the parotid gland. A frozen section of one of the nodes was described as a poorly differentiated malignant neo¬ plasm. The permanent report was consistent with metastatic glioblastoma multiforme (Fig 2). Immunohistochemical stains were strongly positive for glial fibrillary acid protein, SI 00, and vimentin and negative for keratin markers (such as K-576) as well as chromogranin. Neuron-specific enolase was equivocal. Subsequently, chemotherapy was resumed, but, 6 months postoperatively, he was experiencing slow progression of his
neurologic symptoms.
COMMENT Neuroglial tumors are derived from the glial elementsastrocytes, oligodendrocytes, and ependymal cells. They are collectively and commonly referred to as gliomas. The astro-
Accepted for publication March 30, 1992. From the Department of Otolaryngology\p=n-\Headand Neck Surgery, University of Michigan Medical Center, Ann Arbor. Reprint requests to
0312 (Dr
Wolf).
1500 E Medical Center
Dr, Ann Arbor, MI 48109\x=req-\
Fig 1.—Top,
This computed tomographic scan with contrast through the soft-tissue window of the neck shows the 2.5-cm right upper cervical mass (M). Bottom, A computed tomographic scan of the brain soon after a biopsy specimen of the neck mass was obtained shows the enhancing parietal glioblastoma and extensive peritumoral and posttreatment
changes.
cytomas are graded histologically from 1 to 4, with grades 1 and 2 neoplasms considered differentiated, grade 3 being
malignant, and grade 4 being glioblastoma multiforme—the anaplastic form. About 25% to 30% of intracranial neoplasms represent metastatic disease with the remainder arising intracranially. Forty percent to 50% of the total are gliomas with 25% to 30% being glioblastoma multiforme.1"3 most
Glioblastoma multiforme may arise de
novo
but fre¬
quently appears in preexisting astrocytomas. The tumors
often contain well-differentiated astrocytic areas as well as undifferentiated areas where astrocytic origin cannot be defined. Because of the degree of anaplasia it can be diffi¬ cult to determine the origin of the neoplastic cells. Glioblastoma multiforme account for more than 50% of primary gliomas. They can occur at any age but peak in¬ cidence is between ages 45 and 55 years. Presentation be¬ fore age 30 years is rare. Males are affected four times more commonly than females.
Downloaded From: http://archotol.jamanetwork.com/ by a University of Michigan User on 06/20/2015
patient showed profound central nervous system symptoms and died 3 months later. Autopsy documented the
frontal lobe glioblastoma multiforme with cervical me¬ tastasis. Several theories have been proposed for the distinct lack of métastases. One of the important considerations is the ab¬ sence of lymphatics in the central nervous system. Another feature of the brain is the presence of a unique vasculature system. The intracranial sinuses are enclosed in a dense durai membrane, making penetration difficult. The cerebral veins, on the other hand, are thin walled. It is believed that these vessels would likely collapse before allowing penetration by an expanding tumor. Intraluminal vessel permeation is rarely seen in patients with gliomas.4 Dolman8 reviewed four cases of intracranial tumors that had metastasized prior to treatment and noted that all of the primary lesions ultimately showed vascular involvement.8 Another reason for the rarity of métastases from these tumors is the poor prognosis, especially with glioblastoma multiforme. It is believed that patients simply do not live long enough to manifest métastases. This idea may indi¬ rectly explain why patients who have undergone treat¬ ment have a higher incidence of spread of disease, because treatment prolongs survival. In addition, some authors have theorized that these tumor cells require an intracra¬ nial environment to survive. The vast majority of extracranial métastases occur after a
Fig 2.—Top, This histopathologic section shows the sheets ofanaplastic
cells of glioblastoma multiforme (hematoxylin-eosin, original magnifi¬ cation X25). Bottom, These cells characteristically react with the immunohistologic markers for gliofibrillary acidic protein, which is a protein more selective for astrocytes and ependymal cells, but absent in neuronal and other nonglial cells (gliofibrillary acidic protein immunostain, original magnification X25).
The signs and symptoms of glioblastoma multiforme are similar to other intracranial masses although onset is more acute and progression more rapid. Average postoperative survival is 10 months.1 In general, 90% of patients are dead within 2 years.2-3 The presence of distant metastatic disease does not appear to affect survival.4 Treatment most com¬ monly consists of surgery followed by radiation with a variety of chemotherapeutic agents being reported as ad¬
juvants.
Glioblastoma multiforme may spread widely within the central nervous system and implant on the meninges or spinal cord. Like other intracranial tumors, dissemination to extracranial sites is unusual. There are case reports, as well as several reviews, of extracranial métastases of intracranial tumors, predominantly in the neurosurgical literature.4"6 The most recent review found 116 welldocumented cases of extracranial métastases.4 The authors noted that 50 of these were glioblastoma multiforme. The most common metastatic site of all primary intra¬ cranial tumors is the lungs and pleura.4-6 Other sites, in or¬ der of frequency, include the liver, mediastinal and cervi¬ cal lymph nodes, and bone, as well as other sites.4"6 El-Gindi et al7 presented two patients similar to our patient. Both patients had been treated with resection fol¬ lowed by radiation for a glioblastoma multiforme before they returned with an increase in their central nervous system symptoms as well as a neck mass. In 1974, Dolman8 described a patient who presented with a parotid mass as well as occipital headaches. A biopsy revealed anaplastic carcinoma metastatic to the lymph node. Soon afterward
treatment intervention, usually after surgery.4,8"11 Liwnicz and Rubinstein4 conclude that the most frequent single factor in the development of extracranial metastasis is di¬ rect access of the glioma to the extrameningeal tissues as a prerequisite for more distant dissemination. It is believed that after a surgical procedure, the lymphatics outside the nervous system are exposed to the tumor. In addition, the intracerebral vasculature will certainly be open and at risk for tumor seeding. A final unusual but documented mode of spread is via a ventriculopleural shunt.12 Of interest to the otolaryngologist is the fact that although rare, cervical lymphatic métastases do occur and have even been the presenting complaint of intracranial tumors.
References
Kelly KA, Kirkwood JM, Kapp DS. Glioblastoma multiforme: pathology, natural history and treatment. Cancer Treat Rev. 1984;11:1-26. 2. Salcman M. The morbidity and mortality of brain tumors: a perspective on recent advances in therapy. Neurol Clin. 1985;3:229-257. 1.
3. Shoene WC. The nervous system. In: Robbins SL, Cotran RS, eds. Basis of Disease. 2nd ed. Philadelphia, Pa: WB Saunders Co; 1979:1566-1569. 4. Liwnicz BH, Rubinstein LJ. The pathways of extraneural spread in metastasizing gliomas: a report of three cases and review of the literature. Hum
Pathologic
Pathol. 1979;10:453-467. 5. Glasauer FE, Yan RH. Intracranial tumors with extracranial metastases: case report and review of the literature. J Neurosurg. 1974;20:474-492. 6. Ley A, Campillo D, Oliveras C. Extracranial metastasis of glioblastoma multiforme. J Neurosurg. 1961;18:313-330. 7. El-Gindi S, Salama M, El-Henawy M, Farag S. Metastases of glioblastoma multiforme to cervical lymph nodes: report of two cases. J Neurosurg.
1973;38:631-634.
Lymph node metastasis as first manifestation of glioblasJ Neurosurg. 1974;41:607-609. 9. Hulbanni S, Goodman PA. Glioblastoma multiforme with extraneural metastases in the absence of previous surgery. Cancer. 1976;37:1577-1583. 10. Myers T, Egelhoff J, Myers M. Glioblastoma multiforme presenting as osteoblastic metastatic disease: case report and review of the literature. AJNR Am J Neuroradiol. 1990;11:802-803. 11. Sadik AR, Port R, Garfinkel B, Bravo J. Extracranial metastasis of cerebral glioblastoma multiforme: case report. Neurosurgery. 1984;15:549-551. 12. Wakamatsu T, Matsuo T, Kawano S, Teramoto S, Matsumua H, et al. Glioblastoma with extracranial metastasis through ventriculopleural shunt. J Neurosurg. 1971;34:697-701. 8. Dolman CL.
toma.
Downloaded From: http://archotol.jamanetwork.com/ by a University of Michigan User on 06/20/2015
T.
Wolf,
MD
\s=b\ Glioblastoma multiforme is an anaplastic neoplasm of glial origin. In spite of the aggressive histologic features and poor prognosis, metastasis outside the cranial vault is distinctly unusual. A patient with glioblastoma multiforme metastatic to the neck is presented. We also review the topic
of metastatic intracranial tumors. (Arch Otolaryngol Head Neck Surg. 1992;118:755-756) the spectrum of tiforme is the In extracranial is
tumors of glial origin, glioblastoma mul¬ most poorly differentiated. Even with this,
spread extremely unusual. Although there are studies in the neurosurgical literature on cervical mé¬ tastases from this and other intracranial tumors, little is men¬ tioned within the otolaryngologic literature. rare
REPORT OF A CASE
39-year-old man with a chronic seizure disor¬ history of memory loss, headaches, and nau¬ sea was presented. At that time a right-sided parietal mass was discovered and a craniotomy with subtotal resection was per¬ formed. Pathologic findings revealed glioblastoma multiforme. In May, August, and November 1989 he underwent interleukin-2 and activated lymphocyte treatment associated with craniotomies for progressive disease. From January through March 1989 he re¬ ceived 6000 cGy radiation therapy to the brain. In March 1989
der and
a
a
2-month
He remained stable until October 1990 when he noticed
a
pro¬
gressively enlarging mass on the right side of the neck. A com¬ puted tomographic scan revealed multiple enlarged right side cervical lymph nodes in the submandibular, jugulodigastric, and deep cervical and parotid chains (Fig 1). The largest node was 2.5 cm and was in the deep cervical chain. The majority of them
showed central attenuation. Examination at the time of his presentation to our institution in November 1990 revealed three masses in the right tail of the parotid/jugulodigastric area. The smallest was 1.0 X 1.5 cm and the largest was 3.0 X 2.5 cm. Fine-needle aspiration of the mass was
nondiagnostic.
An open neck biopsy was performed. Multiple firm lymph nodes were encountered in the right jugulodigastric area. They appeared free of the parotid gland. A frozen section of one of the nodes was described as a poorly differentiated malignant neo¬ plasm. The permanent report was consistent with metastatic glioblastoma multiforme (Fig 2). Immunohistochemical stains were strongly positive for glial fibrillary acid protein, SI 00, and vimentin and negative for keratin markers (such as K-576) as well as chromogranin. Neuron-specific enolase was equivocal. Subsequently, chemotherapy was resumed, but, 6 months postoperatively, he was experiencing slow progression of his
neurologic symptoms.
COMMENT Neuroglial tumors are derived from the glial elementsastrocytes, oligodendrocytes, and ependymal cells. They are collectively and commonly referred to as gliomas. The astro-
Accepted for publication March 30, 1992. From the Department of Otolaryngology\p=n-\Headand Neck Surgery, University of Michigan Medical Center, Ann Arbor. Reprint requests to
0312 (Dr
Wolf).
1500 E Medical Center
Dr, Ann Arbor, MI 48109\x=req-\
Fig 1.—Top,
This computed tomographic scan with contrast through the soft-tissue window of the neck shows the 2.5-cm right upper cervical mass (M). Bottom, A computed tomographic scan of the brain soon after a biopsy specimen of the neck mass was obtained shows the enhancing parietal glioblastoma and extensive peritumoral and posttreatment
changes.
cytomas are graded histologically from 1 to 4, with grades 1 and 2 neoplasms considered differentiated, grade 3 being
malignant, and grade 4 being glioblastoma multiforme—the anaplastic form. About 25% to 30% of intracranial neoplasms represent metastatic disease with the remainder arising intracranially. Forty percent to 50% of the total are gliomas with 25% to 30% being glioblastoma multiforme.1"3 most
Glioblastoma multiforme may arise de
novo
but fre¬
quently appears in preexisting astrocytomas. The tumors
often contain well-differentiated astrocytic areas as well as undifferentiated areas where astrocytic origin cannot be defined. Because of the degree of anaplasia it can be diffi¬ cult to determine the origin of the neoplastic cells. Glioblastoma multiforme account for more than 50% of primary gliomas. They can occur at any age but peak in¬ cidence is between ages 45 and 55 years. Presentation be¬ fore age 30 years is rare. Males are affected four times more commonly than females.
Downloaded From: http://archotol.jamanetwork.com/ by a University of Michigan User on 06/20/2015
patient showed profound central nervous system symptoms and died 3 months later. Autopsy documented the
frontal lobe glioblastoma multiforme with cervical me¬ tastasis. Several theories have been proposed for the distinct lack of métastases. One of the important considerations is the ab¬ sence of lymphatics in the central nervous system. Another feature of the brain is the presence of a unique vasculature system. The intracranial sinuses are enclosed in a dense durai membrane, making penetration difficult. The cerebral veins, on the other hand, are thin walled. It is believed that these vessels would likely collapse before allowing penetration by an expanding tumor. Intraluminal vessel permeation is rarely seen in patients with gliomas.4 Dolman8 reviewed four cases of intracranial tumors that had metastasized prior to treatment and noted that all of the primary lesions ultimately showed vascular involvement.8 Another reason for the rarity of métastases from these tumors is the poor prognosis, especially with glioblastoma multiforme. It is believed that patients simply do not live long enough to manifest métastases. This idea may indi¬ rectly explain why patients who have undergone treat¬ ment have a higher incidence of spread of disease, because treatment prolongs survival. In addition, some authors have theorized that these tumor cells require an intracra¬ nial environment to survive. The vast majority of extracranial métastases occur after a
Fig 2.—Top, This histopathologic section shows the sheets ofanaplastic
cells of glioblastoma multiforme (hematoxylin-eosin, original magnifi¬ cation X25). Bottom, These cells characteristically react with the immunohistologic markers for gliofibrillary acidic protein, which is a protein more selective for astrocytes and ependymal cells, but absent in neuronal and other nonglial cells (gliofibrillary acidic protein immunostain, original magnification X25).
The signs and symptoms of glioblastoma multiforme are similar to other intracranial masses although onset is more acute and progression more rapid. Average postoperative survival is 10 months.1 In general, 90% of patients are dead within 2 years.2-3 The presence of distant metastatic disease does not appear to affect survival.4 Treatment most com¬ monly consists of surgery followed by radiation with a variety of chemotherapeutic agents being reported as ad¬
juvants.
Glioblastoma multiforme may spread widely within the central nervous system and implant on the meninges or spinal cord. Like other intracranial tumors, dissemination to extracranial sites is unusual. There are case reports, as well as several reviews, of extracranial métastases of intracranial tumors, predominantly in the neurosurgical literature.4"6 The most recent review found 116 welldocumented cases of extracranial métastases.4 The authors noted that 50 of these were glioblastoma multiforme. The most common metastatic site of all primary intra¬ cranial tumors is the lungs and pleura.4-6 Other sites, in or¬ der of frequency, include the liver, mediastinal and cervi¬ cal lymph nodes, and bone, as well as other sites.4"6 El-Gindi et al7 presented two patients similar to our patient. Both patients had been treated with resection fol¬ lowed by radiation for a glioblastoma multiforme before they returned with an increase in their central nervous system symptoms as well as a neck mass. In 1974, Dolman8 described a patient who presented with a parotid mass as well as occipital headaches. A biopsy revealed anaplastic carcinoma metastatic to the lymph node. Soon afterward
treatment intervention, usually after surgery.4,8"11 Liwnicz and Rubinstein4 conclude that the most frequent single factor in the development of extracranial metastasis is di¬ rect access of the glioma to the extrameningeal tissues as a prerequisite for more distant dissemination. It is believed that after a surgical procedure, the lymphatics outside the nervous system are exposed to the tumor. In addition, the intracerebral vasculature will certainly be open and at risk for tumor seeding. A final unusual but documented mode of spread is via a ventriculopleural shunt.12 Of interest to the otolaryngologist is the fact that although rare, cervical lymphatic métastases do occur and have even been the presenting complaint of intracranial tumors.
References
Kelly KA, Kirkwood JM, Kapp DS. Glioblastoma multiforme: pathology, natural history and treatment. Cancer Treat Rev. 1984;11:1-26. 2. Salcman M. The morbidity and mortality of brain tumors: a perspective on recent advances in therapy. Neurol Clin. 1985;3:229-257. 1.
3. Shoene WC. The nervous system. In: Robbins SL, Cotran RS, eds. Basis of Disease. 2nd ed. Philadelphia, Pa: WB Saunders Co; 1979:1566-1569. 4. Liwnicz BH, Rubinstein LJ. The pathways of extraneural spread in metastasizing gliomas: a report of three cases and review of the literature. Hum
Pathologic
Pathol. 1979;10:453-467. 5. Glasauer FE, Yan RH. Intracranial tumors with extracranial metastases: case report and review of the literature. J Neurosurg. 1974;20:474-492. 6. Ley A, Campillo D, Oliveras C. Extracranial metastasis of glioblastoma multiforme. J Neurosurg. 1961;18:313-330. 7. El-Gindi S, Salama M, El-Henawy M, Farag S. Metastases of glioblastoma multiforme to cervical lymph nodes: report of two cases. J Neurosurg.
1973;38:631-634.
Lymph node metastasis as first manifestation of glioblasJ Neurosurg. 1974;41:607-609. 9. Hulbanni S, Goodman PA. Glioblastoma multiforme with extraneural metastases in the absence of previous surgery. Cancer. 1976;37:1577-1583. 10. Myers T, Egelhoff J, Myers M. Glioblastoma multiforme presenting as osteoblastic metastatic disease: case report and review of the literature. AJNR Am J Neuroradiol. 1990;11:802-803. 11. Sadik AR, Port R, Garfinkel B, Bravo J. Extracranial metastasis of cerebral glioblastoma multiforme: case report. Neurosurgery. 1984;15:549-551. 12. Wakamatsu T, Matsuo T, Kawano S, Teramoto S, Matsumua H, et al. Glioblastoma with extracranial metastasis through ventriculopleural shunt. J Neurosurg. 1971;34:697-701. 8. Dolman CL.
toma.
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