Small cell carcinomas (SCCs) are aggressive neuroendocrine tumors that are most commonly found in the lung. SCC is well-known for poor prognosis as the reported median survival is 2 to 4 months without treatment in the most common form, the small cell lung carcinoma (SCLC). Primary SCCs found in extrapulmonary sites are uncommon and account for only 2.5% to 5.0% of all SCCs.[2,3] The frequently reported extrapulmonary sites are esophagus, larynx, and bladder. In the head and neck region, the larynx is the most common extrapulmonary site for SCC, but accounts for <0.5% of all primary laryngeal carcinomas. Despite the anatomical proximity to the larynx, SCC in the pyriform sinus is very rare and approximately 5 cases have been reported in the English literature in the past 10 years. Previous reports have introduced various therapeutic modalities such as chemotherapy and radiation for SCC of the pyriform sinus, but information regarding optimal treatment remains elusive.[6–10]
In this current case, SCC in the pyriform sinus was incidentally detected in a 71-year-old male with a history of SCLC in remission for 4 years after undergoing treatment. Interestingly, the patient also exhibited a complete response in SCC of the pyriform sinus through conventional cisplatin-based chemotherapy with concurrent radiation.
2 Case report
A 71-year-old man was admitted to our hospital for evaluation of an incidental mass in the right pyriform sinus detected on regular follow-up examinations for surveillance of SCLC after being disease free for 4 years. The patient was successfully treated with a chemotherapy regimen consisting of etoposide and cisplatin with concurrent radiation therapy. The patient was a farmer and an ex-smoker with a 50 pack-year smoking history, and had a history of excessive alcohol use.
The mass in the right pyriform sinus of the hypopharynx was a heterogeneously enhancing 1.5 × 1.5-cm mass (Fig. 1A) and had a high glucose metabolism (maximum standardized uptake value = 29.28) (Fig. 1B) on positron emission tomography (PET)-computed tomography (CT) scan. The tumor invaded the lateral and posterior wall of the aryepiglottic fold. Superiorly, the tumor adhered to the inner cortex of the thyroid cartilage. No evidence of cervical lymph node enlargement and recurrence of previous SCLC in the lung were present, but several hypermetabolic mediastinal lymph nodes were present on PET-CT scan images (Fig. 1C). Bronchoscopy revealed no endobronchial lesions such as masses, infiltration, or obstruction. Hematoxylin and eosin staining of the excisional biopsy sample of the mass in the pyriform sinus showed dense sheets of small cells with a high nuclear-to-cytoplasm ratio, hyperchromasia, nuclear molding, and a high mitotic count, indicating SCC (Fig. 1D and E). Immunohistochemistry was positive for neuroendocrine marker CD56 (123C3, Zymed Laboratories, Inc., South San Francisco, CA) and negative for thyroid transcription factor-1 (SPT24, Leica Biosystems, Newcastle, UK) (Fig. 1F and G). To confirm whether mediastinal lymph nodes showing hypermetabolic signs on PET-CT represented metastatic lesions, we performed surgical biopsy and pathological examination, which indicated that the PET-CT results were false-positive.
Collectively, the patient was diagnosed with localized SCC in the right pyriform sinus and treated with 6 cycles of chemotherapy composed of cisplatin 90.6 mg (75 mg/m2) on day 1 and etoposide (VP-16) 120.7 mg (100 mg/m2) on days 1 to 3 and a total radiation dose of 70 Gray in 35 fractions given over 7 weeks. The patient had exhibited complete response to treatment based on head and neck CT and PET-CT 6 months after initial discovery (Fig. 1H–J). The patient recovered without complications, and there has been no evidence of recurrence over 11 months of follow-up.
The clinical experience of SCC of the pyriform sinus is limited because of its extremely low incidence. According to previous reports, the average patient age was 64.8 years, ranging from 50 to 78 years (Table 1).[6–10] In the previous cases shown in Table 1, 4 patients were male and 1 patient was female. Four patients had a history of smoking, but no patients had a history of malignancies. In all cases, the therapeutic approach was chemotherapy with or without radiation therapy to the primary site of the tumor. Only 3 patients who received platinum-based chemotherapy remained disease free.
Interestingly, unlike the previous cases, our patient had a history of SCLC and was disease free for a total of 4 years. Second primary malignancies can be defined based on previous reports as a diagnosis of cancer that occurs 2 years after the resolution of primary cancer. Thus, this case could be diagnosed initially as a second primary malignancy presenting as extrapulmonary SCC. However, since extrapulmonary SCCs are pathologically indistinguishable from metastatic SCLCs, to confirm the diagnosis we needed to verify that there was no evidence of SCLC on further work-up including chest imaging, bronchoscopy, and pathology. In our current case, chest CT scanning and bronchoscopic examination showed no evidence of SCLC recurrence. Additionally, bronchial washing cytology revealed that there were no malignant cells in the specimen. These laboratory data supported the diagnosis of a second primary extrapulmonary SCC rather a metastatic lesion.
Clinical features of SCC found in extrapulmonary sites are similar to SCLC in many ways. However, therapeutic approaches to SCC in various sites have been reported to be modified by anatomical location and disease extent. Additionally, despite the rarity of SCC in extrapulmonary sites, surgery, chemotherapy, radiation, and combined therapy have been applied to achieve local and systemic disease control. For example, surgery is suggested for early-stage SCCs of the uterine cervix, bladder, and salivary gland.[4,13–17] Chemotherapy with concurrent radiation was efficacious in control of the primary SCC of the larynx.[17–20] Adjuvant chemotherapy, preferably with a platinum-based regimen following local control, was effective in SCCs of the esophagus, larynx, uterine cervix, and advanced-stage SCCs of the bladder. However, no superior method for local control has been documented for SCCs of the esophagus, colon, stomach, gallbladder, and prostate.[4,21–24]
The pyriform sinus is a complex anatomical structure of the hypopharynx that adjoins the larynx and trachea. It is bounded laterally by the ala of the thyroid cartilage and thyrohyoid membrane and medially by the aryepiglottic fold and cricoid cartilage. Therefore, surgical resection of pyriform sinus tumors through laryngopharyngectomy is followed by the loss of deglutition and speech, and requires extensive postsurgical rehabilitation. Considering patient quality of life, chemotherapy may be a more desirable initial choice for localized tumors in this anatomical region. A promising chemotherapy regimen for SCC of the pyriform sinus is the standard treatment for SCLC, cisplatin-based chemotherapy with concurrent radiation. Review of 4 previous reports with specified chemotherapeutic agents revealed that cisplatin-based regimens in combination with etoposide, docetaxel, or 5-fluorouracil have been successful in achieving complete response of primary SCC of the pyriform sinus.[6–9] Except for a single case of metastatic recurrence, all patients achieved disease free status during the follow-up period. In particular, 3 patients had radiation therapy in adjunction to cisplatin-based chemotherapy.[6,7,10] Review of these 3 cases showed that 2 patients were male and that all patients had history of heavy smoking. In 2 cases, the primary tumor was found in the right pyriform sinus. At the time of initial presentation, the patients had locally advanced tumor manifesting symptoms associated with mass effect in the hypopharynx and clinically evident adjacent lymph node invasion. In our patient, chemotherapy with cisplatin and etoposide with concurrent radiation was also successful in treating SCC of the pyriform sinus. Similar to majority of the cases, in our case, SCC in the right pyriform sinus was found in a 71-year-old male with a 50 pack-year history of smoking. Unlike other cases, the tumor was discovered at an early stage confined to the pyriform sinus. In the retrospective view, early detection and successful management of aggressive SCC of the pyriform sinus might have been possible as our patient was on a regular follow-up on a resolved SCLC.
In summary, we report our experience with an extremely rare case of SCC occurring in the right pyriform sinus of the hypopharynx in a patient with a history of SCLC. Complete response of SCC was achieved after etoposide/cisplatin chemotherapy and concurrent radiation, which is the regimen recommended as the standard first-line therapeutic modality for SCLC. This report suggests that platinum-based chemotherapy with concurrent radiation may be preferable over surgical resection for localized extrapulmonary SCC, especially when found in the pyriform sinus.
4 Ethical review and patient consent
The Institutional Review Board of Chonbuk National University Hospital waived the need for IRB approval for this case report, but patient consent was required as the study dealt with retrospective use of the patient's medical record and related images. Written informed consent was obtained from the patient prior to the publication of this case report and accompanying images.
The authors would like to thank Jong Jin Sung, MD for processing histopathologic slides.
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