|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 25, No 19 (July 1), 2007: pp. 2848-2850 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.11.3530
Glioblastoma in a Patient With Early-Stage Tonsil CancerDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA A 58-year-old man was referred to the multidisciplinary head and neck clinic with a right tonsil squamous cell carcinoma diagnosed after routine dental examination revealed right tonsillar ulceration. The patient was a lifelong nonsmoker and drank alcohol sparingly. There was no family history of cancer. Physical examination was notable for a right upper tonsil mass infiltrating into the soft palate. There was no trismus, and palate movement was normal. There was no palpable adenopathy. Biopsy showed a well-to-moderately differentiated squamous cell carcinoma. Polymerase chain reaction was positive for human papilloma virus (HPV16), and immunohistochemistry was negative for p16. Chromogenic in situ hybridization (CISH) demonstrated four to six epidermal growth factor receptor (EGFR) copies per nucleus in tumor cells. Evaluation of the oropharynx by neck computed tomography was limited by dental artifact, and small, bilateral cervical lymph nodes smaller than 6 mm in size were present. Positron emission tomography/computed tomography demonstrated intense fluorodeoxyglucose uptake in the right tonsillar region only. Magnetic resonance imaging (MRI), performed to evaluate the extent of the primary or oropharyngeal tumor, showed a 2.4 x 1.6 x 2.0 cm–enhancing mass arising from the right tonsil (Fig 1A). Incidentally, a 1.4-cm ring-enhancing lesion in the anterior left temporal subcortical white matter was noted (Fig 1B). A dedicated brain MRI was performed, confirming the presence of a solitary left temporal mass.
A left craniotomy for gross total resection of the left temporal mass was performed. Microscopically, the mass had atypical, pleomorphic cells with hyperchromatic nuclei, scattered mitoses, vascular proliferation, and pseudopalisading necrosis, consistent with glioblastoma multiforme (GBM), WHO grade 4/4 (Fig 2). CISH for EGFR demonstrated high-level amplification (> 10 signals per nucleus) in rare cells. Next, the patient underwent resection of the tonsillar neoplasm with a modified radical neck dissection and radial forearm free flap reconstruction. Pathology confirmed a T2N0 well-to-moderately differentiated tonsillar squamous cell carcinoma. The tumor had sheets and islands of neoplastic cells with prominent nucleoli, keratin pearl formation, and intercellular bridges. Numerous mitoses were present (Fig 3). The tumor expressed EGFR by immunocytochemistry (Fig 4). Conventional therapy for GBM with external beam radiation plus concurrent temozolomide was administered. Adjuvant radiotherapy for the tonsil carcinoma is now under way. The patient is tolerating treatment well, without any neurological sequealae or significant radiation-induced toxicities. He continues to have some voice change consistent with a palatal defect from his tonsillar surgery. Once tonsillar radiation is completed, adjuvant temozolomide is planned for 6 to 12 months.
Only 10% of patients with head and neck squamous cell carcinoma (HNSCC) will have distant metastases at presentation, whereas more than half of patients will present with locoregionally advanced disease.1 Risk factors for distant metastasis include T4 primary disease, advanced nodal disease at presentation, location of primary tumor in the hypopharynx and nasopharynx, and local or regional recurrence.2 The most common sites of distant metastasis in HNSCC are lung and mediastinum, liver, bone, and skin.2-4 Only a few cases of CNS metastases are reported in the literature.3 The study2 examined the pattern of metastasis in 2,550 HNSCC patients and found only a 3% rate of CNS metastasis. The authors5 reported a series of five cases of HNSCC metastatic to the brain, all of which occurred in the setting of advanced disease or delayed recurrence. In one case, the primary site was the oropharynx, as in our patient, but the staging was T3N2bM0 at presentation. The onset of cerebellar metastasis was delayed from the initial presentation and followed several local recurrences treated extensively with radiation and chemotherapy.5 Given the rarity of brain metastases in HNSCC, as well as the association with advanced recurrent disease, suspicion for another diagnosis should be entertained on finding a brain lesion on routine evaluation for staging in HNSCC. Our patient presented with a T2N0 tonsillar squamous cell carcinoma and an incidental brain lesion. Unlike other solid tumors in which brain metastases are more common and can even be seen at initial diagnosis, CNS metastasis would have been highly unlikely in our patient, whereas the possibility of another etiology for the ring-enhancing brain lesion was entertained. In such cases, it is imperative to assume the possibility of different diagnoses and obtain tissue for evaluation of a second simultaneous diagnosis. The synchronous presentation of two relatively infrequent cancers in this patient prompted us to explore whether a familial syndrome or common mutation could link the two diagnoses. To our knowledge, there has never been a case report of the simultaneous finding of GBM and HNSCC, nor is there a well-described hereditary syndrome involving both of these diagnoses. Familial susceptibility to CNS malignancies is seen, among other syndromes, in Li-Fraumeni syndrome,6 Turcot syndrome, and the neurocutaneous syndromes, but HNSCC is not a component in these disorders. Familial susceptibility to HNSCC is thought to be rare, though Fanconi anemia may be associated with other malignant neoplasms, including HNSCC, leukemia, medulloblastoma, and rarely astrocytoma.7 It is also difficult to postulate a common underlying molecular event specific to both GBM and HNSCC. Our patient had a tonsillar squamous cell carcinoma positive for HPV16, which has never been described in association with GBM. However, the association between HPV16 and oropharyngeal carcinomas is well characterized.8,9 Like several other solid tumor malignancies, both HNSCC and GBM are well known to have overexpression of EGFR.10,11 EGFR is thought to be essential in the pathogenesis of HNSCC, and overexpression is found in up to 90% of HNSCC, correlating with poor prognosis.10 EGFR is also overexpressed in many GBM tumors.11 However, unlike in HNSCC, it appears that EGFR mutations also play a role in GBM. The most common EGFR mutation in GBM is variant III EGFR (EGFRvIII).12 To date, EGFRvIII mutations have only been described in HNSCC in a murine model.13 In our patient, evaluation of EGFR copy number by CISH in the GBM showed amplification in rare cells. The tonsillar cancer cells had an average of four to six EGFR copies. The difference in EGFR copy numbers between the brain and tonsillar neoplasms suggests that there is no etiologic link between the two synchronous tumors. Other potential links between the two tumors for future investigation could be the expression of extracellular matrix metalloproteinase inducer (EMMPRIN), which is thought to stimulate peritumor fibroblasts, contributing to tumor invasion and metastasis.14 In one report,14 EMMPRIN was expressed in 60% to 100% of squamous cell carcinomas and in 79% of glioblastomas multiforme, in addition to several other tumors. Finally, mutations in p5315,16 and tenascin17,18 have also been demonstrated in both tumors. As of yet, there is no obvious association between our patient's synchronous GBM and tonsillar squamous cell carcinoma, but there may be a clearer connection identified in the future. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
REFERENCES 1. Surveillance Epidemiology and End Results: Cancer of the Oral Cavity and Pharynx. http://www.seer.cancer.gov/statfacts/html/oralcav.html 2. Spector JG, Sessions DG, Haughey BH, et al: Delayed regional metastases, distant metastases, and second primary malignancies in squamous cell carcinomas of the larynx and hypopharynx. Laryngoscope 111:1079-1087, 2001[CrossRef][Medline] 3. Kotwall C, Sako K, Razack MS, et al: Metastatic patterns in squamous cell cancer of the head and neck. Am J Surg 154:439-442, 1987[CrossRef][Medline] 4. Ferlito A, Shaha AR, Silver CE, et al: Incidence and sites of distant metastases from head and neck cancer. ORL J Otorhinolaryngol Relat Spec 63:202-207, 2001[Medline] 5. Djalilian HR, Tekin M, Hall WA, et al: Metastatic head and neck squamous cell carcinoma to the brain. Auris Nasus Larynx 29:47-54, 2002[CrossRef][Medline] 6. Hisada M, Garber J, Fung CY: Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst 90:606-622, 1998 7. Alter BP: Cancer in Fanconi anemia, 1927-2001. Cancer 97:425-430, 2003[CrossRef][Medline] 8. Gillison ML, Koch WM, Capone RB, et al: Evidence for causal association between human papilloma virus and a subset of head and neck cancer. J Natl Cancer Inst 92:709-720, 2000 9. Mork J, Lie K, Glattre E, et al: Human papilloma virus infection as a risk factor for squamous cell carcinoma of head and neck. N Engl J Med 344:1125-1131, 2001 10. Rogers SJ, Harrington KJ, Rhys-Evans P, et al: Biological significance of c-erbB family oncogenes in head and neck cancer. Cancer Metastasis Rev 24:47-69, 2005[CrossRef][Medline] 11. Wong AJ, Bigner SH, Bigner DD, et al: Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification. Proc Natl Acad Sci U S A 84:6899-6903, 1987 12. Wikstrand CJ, McLendon RE, Friedman AH, et al: Cell surface localization and density of the tumor-associated variant of the epidermal growth factor receptor, EGFRvIII. Cancer Res 18:4130-4140, 1997 13. Sok JC, Coppelli FM, Thomas SM, et al: Mutant epidermal growth factor receptor (EGFRvIII) contributes to head and neck cancer growth and resistance to EGFR targeting. Clin Cancer Res 12:5064-5073, 2006 14. Riethdorf S, Reimers N, Assmann V, et al: High incidence of EMMPRIN expression in human tumors. Int J Cancer 119:1800-1810, 2006[CrossRef][Medline] 15. Nozaki M, Tada M, Kobayashi H, et al: Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression. Neuro-Oncology 1:124-137, 1999[Abstract] 16. Gasco M, Crook T: The p53 network in head and neck cancer. Oral Oncol 39:222-231, 2003[CrossRef][Medline] 17. Herold-Mende C, Andl T, Laemmler F, et al: Expression and localization profile of Tenascin in squamous cell carcinoma of head and neck. HNO 8:723-729, 1999 18. Leins A, Riva P, Lindstedt R, et al: Expression of Tenascin-C in various human brain tumors and its relevance for survival in patients with astrocytoma. Cancer 11:2430-2439, 2003
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
