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Journal of Clinical Oncology, Vol 24, No 18 (June 20), 2006: pp. 2961-2963 © 2006 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.04.8736
Small Cell Carcinoma of the Larynx in a Long-Term Survivor of Small-Cell Lung CancerDepartment of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Gunma, Japan A 73-year-old man, diagnosed with small-cell lung cancer (SCLC), was staged as having T1N1M0 disease. He had smoked two packs of cigarettes per day since early adulthood. Tumor markers revealed pro–gastrin-releasing peptide (pro–GRP) level of 965 pg/mL (normal, < 40 pg/mL) and neuron-specific enolase level of 24 ng/mL (normal, < 12 ng/mL). He received concurrent chemoradiotherapy with cisplatin plus etoposide, and achieved complete remission. Prophylactic cranial irradiation was performed. Serum pro–GRP and neuron-specific enolase levels also decreased below the cutoff range. For 4.5 years after chemoradiotherapy, he had been generally well without any signs of recurrence. Five years later, he was noted to have a slightly raised pro–GRP level of 58 pg/mL. He suddenly developed stridor. Chest radiography revealed no abnormalities suggestive of any signs of recurrence. He had been treated for 3 weeks with inhaled and systemic glucocorticoids without satisfactory symptom control. As a computed tomography (CT) scan of the chest revealed no abnormalities, laryngoscopy was performed. The laryngoscopy revealed a smooth-surfaced fleshy tumor, almost completely obstructing the subglottic airway (Fig 1). Emergency tracheostomy was performed. A CT scan of the neck revealed a well defined and well enhanced mass over the subglottic area (Fig 2; arrow). A biopsy was performed, and the histologic examination revealed small cell carcinoma (Fig 3; x400 magnification). Imunohistochemic staining demonstrated the expression of the neuroendocrine markers including neuron-specific enolase, synaptophysin, and chromogranin. Serum pro–GRP levels rose to 163 pg/mL. However, there was no evidence of disease except for this subglottic area. We considered the possibility of the patient developing second primary small cell cancer of the larynx. He was treated with concurrent platinum-based chemotherapy and neck irradiation up to 52 Gy. After chemoradiotherapy, serum pro–GRP levels decreased below the cutoff range, and a CT scan and direct laryngoscopy revealed no evidence of the disease. The patient has had close follow-up and remains in remission.
Second primary small cell carcinoma or redevelopment of the original SCLC in long-term survivors seems to be uncommon. There are reports indicating the risk of second malignancies increase in long-term survivors of SCLC.1-3 In such cases, if second malignant lesions show the same type of pathology as the initial SCLC, it is difficult to distinguish the second lesion from initial SCLC relapse. Johnson et al1 reported 20 patients out of population of 578 with redevelopment of small cell carcinomas 2.0 years to 12.2 years after the initial treatment. The authors stated that among the 20 SCLC redevelopers, two developed second primary small cell carcinomas of the lung and the esophagus. Heyne et al3 reported three cases of second primary small cell carcinomas in 446 patients with original SCLC, two of whom were bronchogenic and another who was a primary unknown. However, there was no report of second primary small cell carcinoma of the larynx in long-term survivors of SCLC. We recently saw a case of redevelopment of small cell carcinoma about 4.5 years after the original diagnosis of SCLC. The case was considered to be a second primary lesion because 4.5 years had passed before redevelopment, the new lesion was previously described as an extrapulmonary site and the original site was clear. Nevertheless, the possibility that the case developed recurrence of the original SCLC cannot be excluded conclusively based on the evidence available. The following definition1 was used for differentiation of these two events: tumor histologic results show SCLC in a lobe or previously described extrapulmonary site different from the lobe in which the first SCLC presented; there is no evidence by chest roentgenogram, CT of chest, and fiberoptic bronchoscopy that SCLC has recurred in the lobe where it originally presented; and the second cancer is identified more than 2 years after diagnosis of the original SCLC. Extrapulmonary small cell carcinoma is relatively rare disease, encompassing approximately 2.5% to 4% of all small cell carcinomas.4,5 Although the larynx is one of the most common extrapulmonary sites, small cell carcinoma is estimated to account for only 0.5% of all primary laryngeal malignancies.5 Laryngeal small cell carcinoma can occur in any region of the larynx with the supraglottic region to be the most commonly reported site.5 However, small cell carcinoma presenting as subglottic tumor is extremely rare. The most common presenting features of subglottic tumor are dyspnea, hoarseness, and dysphagia.5 Although more frequently misdiagnosed as asthma, subglottic tumor has the potential of acute, life-threatening emergency. The majority of patients of localized small cell cancer of the head and neck have been treated with local modalities of surgery, radiation, or both in the absence of systemic chemotherapy.6 But, the median survival of patients with primary small cell carcinoma of the larynx, hypopharynx, and trachea is between 7 months and 11 months.4,6 Although optimal management for these patients is undefined because of the paucity of reported cases, several investigators have reported that the use of concurrent chemoradiotherapy regimens for limited-stage disease offer potential for long-term survival.6,7 Although it may be difficult to distinguish second primary small-cell carcinoma from initial SCLC relapse in long-term survivors of SCLC, early detection of malignant lesions with careful follow-up and adequate therapy are important. Authors' Disclosures of Potential Conflicts of Interest The authors have indicated no potential conflicts of interest.
REFERENCES
1. Johnson BE, Linnoila RI, Williams JP, et al: Risk of second aerodigestive cancers increases in patients who survive free of small-cell lung cancer for more 2 years. J Clin Oncol 13:101-111, 1995 2. Chute JP, Kelley MJ, Venzon D, et al: Retreatment of patients surviving cancer-free 2 or more years after initial treatment of small cell lung cancer. Chest 110:165-171, 1996 3. Heyne KH, Lippman SM, Lee JJ, et al: The incidence of second primary tumors in long-term survivors of small-cell lung cancer. J Clin Oncol 10:1519-1524, 1992 4. Levenson RM Jr, Ihde DC, Matthews MJ, et al: Small cell carcinoma presenting as an extrapulmonary neoplasm: Sites of origin and response to chemotherapy. J Natl Cancer Inst 67:607-612, 1981[Medline] 5. Kim HJ, Hwang EG: Small cell carcinoma of the larynx: Imaging findings. Auris Nasus Larynx 24:423-427, 1997[CrossRef][Medline] 6. Gaba A, Mbaoma R, Breining D, et al: Small-cell carcinoma of the hypopharynx. J Clin Oncol 23:2094-2096, 2005 7. Galanis E, Frytak S, Lloyd RV: Extrapulmonary small cell carcinoma. Cancer 79:1729-1736, 1997[CrossRef][Medline]
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Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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