Introduction
Extrapulmonary small cell carcinoma is a heterogeneous group of cancers accounting for 2–4 per cent of all small cell carcinomas and 0.1–0.4 per cent of all cancers.Reference van der Heijden and Heijdra1, Reference Walenkamp, Sonke and Sleijfer2 According to the National Comprehensive Cancer Network (NCCN), the most common extrapulmonary sites of origin, in order of decreasing frequency, are the cervix, oesophagus, head and neck, colon and prostate. In the head and neck region, the larynx is the most common site affected by extrapulmonary small cell carcinoma.Reference Ferlito3
The clinical course of these tumours is known to be aggressive in general, with early dissemination and frequent recurrences.Reference Remick and Ruckdeschel4, Reference Lo Re, Canzonieri, Veronesi, Dal Bo, Barzan and Zancanaro5 Although chemotherapy seems to be an effective therapeutic modality as in small cell lung cancer, surgery and radiation therapy may also play an important role depending on the stage or primary site.Reference Lo Re, Canzonieri, Veronesi, Dal Bo, Barzan and Zancanaro5
The management of extrapulmonary small cell carcinoma has not been standardised to date, but is, by medical consensus, similar to that of small cell lung cancer because of their similar clinicopathological features.Reference Brennan, Gregory, Stillie, Herschtal, Mac Manus and Ball6 This study reviewed the clinical course, management and survival outcomes of patients with extrapulmonary small cell carcinoma in the head and neck region.
Patients and methods
Between 1995 and 2010, nine patients with extrapulmonary small cell carcinoma in the head and neck were treated at Kyushu University Hospital. The data for the nine patients, consisting of seven males and two females, were analysed. The subjects' ages ranged from 53 to 82 years, with a median age of 64 years. The following clinical data were collected from the medical records of the nine patients: age and gender, primary sites, treatment modalities and clinical response, time to progression and overall survival rate.
Results
In the nine patients studied, two cases of extrapulmonary small cell carcinoma were detected in the larynx, two in the sinonasal region, two in the nasopharynx, one in the oropharynx, one in the hypopharynx and one in the external auditory canal. All patients had locoregional disease at the time of first diagnosis. They were treated with a variety of therapeutic modalities, including chemotherapy. Five patients received radical surgery followed by adjuvant chemotherapy or radiotherapy or both. Two other patients were treated with chemotherapy consisting of CPT11 plus cisplatin (CDDP) or CDDP plus VP-16 three times. Two other patients received chemo-radiotherapy consisting of S-1 or CDDP. Their total radiotherapy dose was 70.2 Gy. Stage, primary, treatment modalities and outcome are summarised in Table I. The outcomes of the nine patients were as follows: four died of cancer, two died of other diseases, and three showed no evidence of disease after treatment. The median overall survival was 14.5 months (range 2.6–41.0 months), with a three-year survival rate of 23.7 per cent (Figure 1).
Fig. 1 The three-year disease-free survival time.
Table I Clinicopathological characteristics and clinical course in nine patients with extrapulmonary small cell carcinoma
TNM = tumour-node-metatasis; ORC = operation + radiation + chemotherapy; RC = radiation + chemotherapy; CDDP = cisplatin; PEP = pepleomycin; VP16 = etoposide; CPT11 = :irinotecan; S1 = tegafur, gimeracil, oteracil potassium
Discussion
The vast majority of small cell carcinomas develop from the lung, but only 2.5–4 per cent of all small cell carcinomas are present at extrapulmonary sites.Reference van der Heijden and Heijdra1, Reference Walenkamp, Sonke and Sleijfer2 The primary site of occurrence of extrapulmonary small cell carcinoma has been described as being in a variety of organs and regions, such as the head and neck, oesophagus, stomach, pancreas, gallbladder, uterine cervix, kidney, urinary bladder and prostate.Reference Cicin, Karagol, Uzunoglu, Uygun, Usta and Kocak7 Although extrapulmonary small cell carcinoma is rare, the clinical course of the tumour in patients with extrapulmonary small cell carcinoma, is generally aggressive and often recurrent.Reference Remick and Ruckdeschel4 The optimal therapeutic strategy of extrapulmonary small cell carcinoma is still unknown. In addition, extrapulmonary small cell carcinoma is a difficult to treat cancer with early sensitivity to chemotherapy but a poor overall prognosis. As extrapulmonary small cell carcinoma does not have a proven algorithm for treatment, it has generally been treated in a similar fashion to small cell carcinoma of the lung via systemic chemotherapy. These two diseases are separate clinical entities and risk factors for development of extrapulmonary small cell carcinoma may not apply for pulmonary small cell carcinomas. different strategies are needed.
• This study reviewed the clinical course, management and survival outcomes of patients with extrapulmonary small cell carcinoma in the head and neck region
• Nine patients with extrapulmonary small cell carcinoma in the head and neck treated at Kyushu University Hospital were included in this study
• The median overall survival was 14.5 months, with a three-year survival rate of 23.7 per cent
Multimodality therapy has become increasingly applied, including chemotherapy, radiotherapy and possibly surgery depending on the extent of disease or primary site.Reference Weng, Chu, Liu and Chen8 For the majority of patients with first diagnosed extrapulmonary small cell carcinoma, radical surgery or definite radiotherapy has been frequently employed.Reference Haider, Shahid, Finch, Sami, Ahmad and Yadav9 In this study, five of nine patients underwent radical surgery. Previous reports indicated that the combination of radiotherapy with surgical extirpation was associated with significantly improved ten-year survival for extrapulmonary small cell carcinoma of all sites.Reference Grossman, Pedroso, Byrne, Koniaris and Misra10 No significant reduction in mortality was observed for head and neck extrapulmonary small cell carcinomas for combination therapy. The chemotherapeutic regimen of EPSCC is similar to those utilised in small cell lung cancer, and the combination of etoposide and cisplatin is the first line treatment with a response rate of 69 per cent.Reference Lo Re, Canzonieri, Veronesi, Dal Bo, Barzan and Zancanaro5 The most common regimens used in our study were also the combination of etoposide-CDDP.
However, the prognosis of extrapulmonary small cell carcinoma is generally poor with a five-year survival of 13 per cent and a median survival from diagnosis of 14.5 months, which has also been shown to be partially dependent on the primary disease site.Reference Weiss, deFries, Taxy and Braine11, Reference Kim, Lee, Chun, Shin, Kim and Lee12 Our study has several limitations related to the retrospective design and the small number of patients. However, our results showed that overall three-year tumour-free actuarial survival rate after treatment was 23.7 per cent, and this result closely resembles other reports.Reference Kim, Lee, Chun, Shin, Kim and Lee12, Reference Ochsenreither, Marnitz-Schultze, Schneider, Koehler, Daum and Loddenkemper13 Further prospective multicentre studies are required for better understanding of disease entities and response to treatment modalities.
