CASE REPORT
The Clinical Respiratory Journal
Tonsillar metastasis of small cell lung carcinoma Meftun Unsal1, Gokhan Kutlar2, Yurdanur Sullu3 and Sirin Yurtlu4 1 Department 2 Department 3 Department 4 Department
of of of of
Chest, Faculty of Medicine, Ondokuzmayis University, Samsun, Turkey Otolaryngology, Faculty of Medicine, Ondokuzmayis University, Samsun, Turkey Pathology, Faculty of Medicine, Ondokuzmayis University, Samsun, Turkey Chest, Sinop State Hospital, Sinop, Turkey
Abstract Metastasis to palatine tonsils are rare, accounting from only 0.8% of all tonsillar tumors, so far only 100 cases reported in the English literature. Only a few cases have been reported for small cell and non-small cell lung cancer as a primary site. With a diagnosis of small cell lung cancer, a 68-year-old male patient relapsed after six cycles of chemotherapy in tonsilla palatina and cervical lymph nodes. Patients died 26 months after being diagnosed with lung cancer and 2 months after detection of tonsil metastasis. We present the current case report because of the rarity of metastasis to tonsil in lung cancer. Please cite this paper as: Unsal M, Kutlar G, Sullu Y and Yurtlu S. Tonsillar metastasis of small cell lung carcinoma. Clin Respir J 2015; ••: ••–••. DOI:10.1111/ crj.12275
Key words computed tomography – lymphatic metastasis – small cell lung carcinoma – tonsillar neoplasm Correspondence Gokhan Kutlar, MD, Department of Otolaryngology, Faculty of Medicine, Ondokuzmayis University, 55200, Kurupelit Samsun, Turkey. Tel: +90 530 668 75 66 Fax: +90 362 457 60 41 email: [email protected] Received: 03 August 2014 Revision requested: 23 November 2014 Accepted: 20 January 2015 DOI:10.1111/crj.12275 Authorship and contributorship Dr. Unsal and Dr. Kutlar contributed in collecting data, designing and writing the manuscript. Dr. Sullu and Dr. Yurtlu contributed in collecting data. Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article. Financial support None.
Introduction Metastases to tonsilla palatina are uncommon, and the most common primary tumor sites are the breast, stomach, colorectal tract, melanoma and the kidney (1, 2). Metastasis to the tonsils from lung cancer has been reported in large cell adenocarcinoma, small cell neuroendocrine carcinoma and mostly in small cell lung cancer (3, 4). Palatine tonsils were detected more than the lingual tonsils (5, 6). It may be seen before time
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
of diagnosis or during the treatment (6). In here, we have presented a case of small cell lung cancer that observed recurrence in the palatine tonsil after the treatment.
Case presentation A 75-year-old male patient who had complaints of shortness of breath around a month was admitted to
1
Tonsillar metastasis of lung carcinoma
Unsal et al.
Figure 1. (A) Heterogeneous, irregular, specular and 52 × 75 mm diametric mass (*) that encased the left main bronchus and invaded the pulmonary artery with 27 × 22 mm diametric subcarinal lymph nodes. (B) Axial CT section of the left tonsillar fossa midline of the neck that comes up about 2 cm in diameter mass (*) is monitored. (C) An exophytic lesion in the left palatine tonsilla, on physical examination. (D) Microscopic findings of tumor in the lung and palatine tonsil (HE, ×100).
Chest Diseases Clinic in 2012. The patient had 60 packyear history of smoking. Physical examination was normal. Laboratory findings show the following: hemoglobin, 2.8 g/dL; leucocyte, 5840 million/L; BUN, 19.8 mg/dL; SGOT, 22.5 U/L; SGPT, 19.3 U/L. There were no metastases observed in other organs. Tumoral infiltration in the medial anterior segment of the right upper lobe was observed in bronchoscopic examination. The computed tomography (CT) scan of the thorax (Fig. 1A) revealed a mass of 53 × 35 mm, which narrowed the right upper and the middle lobe, and a mass of 15 × 13 mm in the upper lobe of anterior segment. However, there was no metastasis observed in any other organs. The biopsy showed small cell lung cancer on histopathological examination (Fig. 1D). Patient was admitted with sore throat and enlargement on the left side of the neck, after six cycles of therapy containing cisplatin and etoposide cycles. Swollen and edematous tonsils are seen during physical examination (Fig. 1C). In the CT scan of the neck (Fig. 1B), in the left tonsillar fossa, about 2 cm in diameter mass was detected. The biopsy of the palatine tonsil confirmed the small cell lung cancer (Fig. 1D). Patients
2
died 26 months after being diagnosed with lung cancer and 2 months after detection of tonsil metastasis.
Discussion Small cell lung carcinoma consists 13% of all lung cancer. The incidence has decreased in the last 20 years. In our case, there was no metastasis observed in other organs. Spread of tumor to tonsil is thought to occur through the lymphatic vessels of the neck because of the ipsilateral location. It is usually observed unilaterally; bilateral involvement is encountered rather rare (6). Pathways of metastasis to tonsils are not fully understood. However, several mechanisms are suggested: (i) Because palatine tonsils do not have efferent lymphatic drainage, tumor cells are transported via retrograde route, and this is only possible in the absence of cervical lymphatic metastasis (4, 7, 8). (ii) Hematogenous, especially intra-abdominal tumors thought to spread this way (5). (iii) By passing through the lungs by paravertebral plexus (5).
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
Unsal et al.
(iv) It may be spread through direct inoculation during bronchoscopy. Especially, it is considered that lung cancer implements to the tonsils this way (9). The metastasis to the tonsils could cause symptoms, such as dyspnea, pain, discomfort and bleeding. Sometimes these symptoms may also cause delays in diagnosis due to the patient’s ignorance on cancer. As with the various organs, there is no standard treatment on metastasis to the tonsils of lung cancer. Surgery, radiotherapy, chemotherapy or chemoradiotherapy has been tried for tonsillar metastases (3–5, 10). Since small cell lung cancer is spreading rapidly, any direct therapy for tonsil is not recommended. Chen et al. reported that in a case after tonsillectomy, neuroendocrine small cell lung cancer metastases were detected. The patient who had two cycles of chemotherapy has died after 6 months with the development of multiple metastases (4). If tonsillar mass is relatively small, surgical treatment will be applied to the area, which can cause considerable difficulty in swallowing and speaking. Radiotherapy or chemotherapy should be recommended in addition to surgery in larger lesions (3). It is reported that radiotherapy is as effective as surgery, and the complication rates are reported to be low in the treatment of primary squamous cell cancer of the tonsils. The effects of radiotherapy are not well defined in metastatic tumors to tonsil. However, it is known that, in some cases, response to radiotherapy or chemoradiotherapy is fine (3, 10). There is no effective and definitive treatment of metastasis to the tonsils, and this is with poor prognosis. Brownson et al. reported that the average life expectancy is less than 9 months in patients who developed tonsillar metastases, unrelated with the histology of the primary tumor (9). Murakawa et al. achieved complete remission of tonsillar and cervical lymph node metastasis from a large cell carcinoma of the lung in a patient who was treated with combined chemoradiotherapy (10). A case of tonsillar metastases from lung adenocarcinomas in stage IIIb survived 8 years after radiotherapy (3). However, recent reports indicate that epidermal growth factor receptor inhibitors significantly improved the prognosis of a lung cancer patient with tonsillar metastasis by achieving a mean progression-free survival of 4.7 months with first- and second-line treatments, a progression-free survival of 58.8 months with gefitinib, and an overall survival of 82.4 months (11). It takes 8 months from the diagnosis of lung cancer to the development of tonsil metastases. Expected mean survival is approximately 5 months due to poor prognosis. However, for a patient who receives chemotherapy, the mean survival was at 6 months. Because of the rapid spread of small cell lung cancer,
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
Tonsillar metastasis of lung carcinoma
tumor has more distance metastases. Both in the diagnosis and the recurrence, the spread is observed in organs such as liver, bone and the brain (12). In our case, there was no metastasis in other organs during recurrence. Because of the ipsilateral lymphadenopathy, the spread of tumor to tonsil is thought to occur through the lymphatic vessels of the neck. As a result, developing metastasis to the tonsils in lung cancer is a rare condition, and this affects survival, which is relatively short.
References 1. Hyams VJ. Differential diagnosis of neoplasia of the palatine tonsil. Clin Otolaryngol Allied Sci. 1978;3: 117–26. 2. Bar R, Netzer A, Ostrovsky D, Daitzchman M, Golz A. Abrupt tonsillar hemorrhage from a metastatic hemangiosarcoma of the breast: case report and literature review. Ear Nose Throat J. 2011;90: 116–20. 3. Tsubochi H, Isogami K, Sato N, Tadashi I. Successfully treated lingual tonsillar from bronchial adenocarcinoma metastasis. Jpn J Thorac Cardiovasc Surg. 2005;53: 455–7. 4. Chen XH, Bao YY, Zhou SH, Wang QY, Zhao K. Palatine tonsillar metastasis of small-cell neuroendocrine carcinoma from the lung detected by FDG-PET/CT after tonsillectomy: a case report. Iran J Radiol. 2013;10: 148–51. 5. Mastronikolis NS, Tsiropoulos GE, Chorianopoulos D, Liava AC, Stathas T, Papadas TA, Hisa Y. Palatine tonsillar metastasis from lung adenocarcinoma. Eur Rev Med Pharmacol Sci. 2007;11: 279–82. 6. Seddon DJ. Tonsillar metastasis at presentation of small cell carcinoma of the lung. J R Soc Med. 1989;82: 688. 7. Yamaguchi E, Uchida M, Makino Y, Tachibana M, Sato T, Yamamoto Y, Kawashima K, Araki A, Maruyama R. Tonsillar metastasis of gastric cancer. Clin J Gastroenterol. 2010;3: 289–95. 8. Arroyo HH, Takehara J, Ogawa AI, Frizzarini R, Imamura R, Paula HM. Small cell lung carcinoma metastasis to palatine tonsils. Braz J Otorhinolaryngol. 2013;79: 645. 9. Brownson RJ, Jaques WE, Lamonte SE, Zollinger WK. Hypernephroma metastatic to the palatine tonsils. Ann Otol Rhinol Laryngol. 1979;88: 235–40. 10. Murakawa T, Nakajima J, Fukami T, Tanaka M, Takeuchi E, Takamoto S. Tonsillar metastasis from large cell carcinoma of the lung. Jpn J Thorac Cardiovasc Surg. 2001;49: 377–80. 11. Gottschling S, Penzel R, Pelz T, Herpel E, Schnabel PA, Dyckhoff G, Thomas M, Kuhnt T. KRAS-mutation positive, metastatic tonsil carcinoma with cancer stem-like cell features and long-term response to gefitinib: a case report and review of the literature. J Clin Oncol. 2011;29: 616–9. 12. Califano R, Abidin AZ, Peck R, Faivre FC, Lorigan P. Management of small cell lung cancer. Drugs. 2012;72: 471–90.
3
The Clinical Respiratory Journal
Tonsillar metastasis of small cell lung carcinoma Meftun Unsal1, Gokhan Kutlar2, Yurdanur Sullu3 and Sirin Yurtlu4 1 Department 2 Department 3 Department 4 Department
of of of of
Chest, Faculty of Medicine, Ondokuzmayis University, Samsun, Turkey Otolaryngology, Faculty of Medicine, Ondokuzmayis University, Samsun, Turkey Pathology, Faculty of Medicine, Ondokuzmayis University, Samsun, Turkey Chest, Sinop State Hospital, Sinop, Turkey
Abstract Metastasis to palatine tonsils are rare, accounting from only 0.8% of all tonsillar tumors, so far only 100 cases reported in the English literature. Only a few cases have been reported for small cell and non-small cell lung cancer as a primary site. With a diagnosis of small cell lung cancer, a 68-year-old male patient relapsed after six cycles of chemotherapy in tonsilla palatina and cervical lymph nodes. Patients died 26 months after being diagnosed with lung cancer and 2 months after detection of tonsil metastasis. We present the current case report because of the rarity of metastasis to tonsil in lung cancer. Please cite this paper as: Unsal M, Kutlar G, Sullu Y and Yurtlu S. Tonsillar metastasis of small cell lung carcinoma. Clin Respir J 2015; ••: ••–••. DOI:10.1111/ crj.12275
Key words computed tomography – lymphatic metastasis – small cell lung carcinoma – tonsillar neoplasm Correspondence Gokhan Kutlar, MD, Department of Otolaryngology, Faculty of Medicine, Ondokuzmayis University, 55200, Kurupelit Samsun, Turkey. Tel: +90 530 668 75 66 Fax: +90 362 457 60 41 email: [email protected] Received: 03 August 2014 Revision requested: 23 November 2014 Accepted: 20 January 2015 DOI:10.1111/crj.12275 Authorship and contributorship Dr. Unsal and Dr. Kutlar contributed in collecting data, designing and writing the manuscript. Dr. Sullu and Dr. Yurtlu contributed in collecting data. Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article. Financial support None.
Introduction Metastases to tonsilla palatina are uncommon, and the most common primary tumor sites are the breast, stomach, colorectal tract, melanoma and the kidney (1, 2). Metastasis to the tonsils from lung cancer has been reported in large cell adenocarcinoma, small cell neuroendocrine carcinoma and mostly in small cell lung cancer (3, 4). Palatine tonsils were detected more than the lingual tonsils (5, 6). It may be seen before time
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
of diagnosis or during the treatment (6). In here, we have presented a case of small cell lung cancer that observed recurrence in the palatine tonsil after the treatment.
Case presentation A 75-year-old male patient who had complaints of shortness of breath around a month was admitted to
1
Tonsillar metastasis of lung carcinoma
Unsal et al.
Figure 1. (A) Heterogeneous, irregular, specular and 52 × 75 mm diametric mass (*) that encased the left main bronchus and invaded the pulmonary artery with 27 × 22 mm diametric subcarinal lymph nodes. (B) Axial CT section of the left tonsillar fossa midline of the neck that comes up about 2 cm in diameter mass (*) is monitored. (C) An exophytic lesion in the left palatine tonsilla, on physical examination. (D) Microscopic findings of tumor in the lung and palatine tonsil (HE, ×100).
Chest Diseases Clinic in 2012. The patient had 60 packyear history of smoking. Physical examination was normal. Laboratory findings show the following: hemoglobin, 2.8 g/dL; leucocyte, 5840 million/L; BUN, 19.8 mg/dL; SGOT, 22.5 U/L; SGPT, 19.3 U/L. There were no metastases observed in other organs. Tumoral infiltration in the medial anterior segment of the right upper lobe was observed in bronchoscopic examination. The computed tomography (CT) scan of the thorax (Fig. 1A) revealed a mass of 53 × 35 mm, which narrowed the right upper and the middle lobe, and a mass of 15 × 13 mm in the upper lobe of anterior segment. However, there was no metastasis observed in any other organs. The biopsy showed small cell lung cancer on histopathological examination (Fig. 1D). Patient was admitted with sore throat and enlargement on the left side of the neck, after six cycles of therapy containing cisplatin and etoposide cycles. Swollen and edematous tonsils are seen during physical examination (Fig. 1C). In the CT scan of the neck (Fig. 1B), in the left tonsillar fossa, about 2 cm in diameter mass was detected. The biopsy of the palatine tonsil confirmed the small cell lung cancer (Fig. 1D). Patients
2
died 26 months after being diagnosed with lung cancer and 2 months after detection of tonsil metastasis.
Discussion Small cell lung carcinoma consists 13% of all lung cancer. The incidence has decreased in the last 20 years. In our case, there was no metastasis observed in other organs. Spread of tumor to tonsil is thought to occur through the lymphatic vessels of the neck because of the ipsilateral location. It is usually observed unilaterally; bilateral involvement is encountered rather rare (6). Pathways of metastasis to tonsils are not fully understood. However, several mechanisms are suggested: (i) Because palatine tonsils do not have efferent lymphatic drainage, tumor cells are transported via retrograde route, and this is only possible in the absence of cervical lymphatic metastasis (4, 7, 8). (ii) Hematogenous, especially intra-abdominal tumors thought to spread this way (5). (iii) By passing through the lungs by paravertebral plexus (5).
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
Unsal et al.
(iv) It may be spread through direct inoculation during bronchoscopy. Especially, it is considered that lung cancer implements to the tonsils this way (9). The metastasis to the tonsils could cause symptoms, such as dyspnea, pain, discomfort and bleeding. Sometimes these symptoms may also cause delays in diagnosis due to the patient’s ignorance on cancer. As with the various organs, there is no standard treatment on metastasis to the tonsils of lung cancer. Surgery, radiotherapy, chemotherapy or chemoradiotherapy has been tried for tonsillar metastases (3–5, 10). Since small cell lung cancer is spreading rapidly, any direct therapy for tonsil is not recommended. Chen et al. reported that in a case after tonsillectomy, neuroendocrine small cell lung cancer metastases were detected. The patient who had two cycles of chemotherapy has died after 6 months with the development of multiple metastases (4). If tonsillar mass is relatively small, surgical treatment will be applied to the area, which can cause considerable difficulty in swallowing and speaking. Radiotherapy or chemotherapy should be recommended in addition to surgery in larger lesions (3). It is reported that radiotherapy is as effective as surgery, and the complication rates are reported to be low in the treatment of primary squamous cell cancer of the tonsils. The effects of radiotherapy are not well defined in metastatic tumors to tonsil. However, it is known that, in some cases, response to radiotherapy or chemoradiotherapy is fine (3, 10). There is no effective and definitive treatment of metastasis to the tonsils, and this is with poor prognosis. Brownson et al. reported that the average life expectancy is less than 9 months in patients who developed tonsillar metastases, unrelated with the histology of the primary tumor (9). Murakawa et al. achieved complete remission of tonsillar and cervical lymph node metastasis from a large cell carcinoma of the lung in a patient who was treated with combined chemoradiotherapy (10). A case of tonsillar metastases from lung adenocarcinomas in stage IIIb survived 8 years after radiotherapy (3). However, recent reports indicate that epidermal growth factor receptor inhibitors significantly improved the prognosis of a lung cancer patient with tonsillar metastasis by achieving a mean progression-free survival of 4.7 months with first- and second-line treatments, a progression-free survival of 58.8 months with gefitinib, and an overall survival of 82.4 months (11). It takes 8 months from the diagnosis of lung cancer to the development of tonsil metastases. Expected mean survival is approximately 5 months due to poor prognosis. However, for a patient who receives chemotherapy, the mean survival was at 6 months. Because of the rapid spread of small cell lung cancer,
The Clinical Respiratory Journal (2015) • ISSN 1752-6981 © 2015 John Wiley & Sons Ltd
Tonsillar metastasis of lung carcinoma
tumor has more distance metastases. Both in the diagnosis and the recurrence, the spread is observed in organs such as liver, bone and the brain (12). In our case, there was no metastasis in other organs during recurrence. Because of the ipsilateral lymphadenopathy, the spread of tumor to tonsil is thought to occur through the lymphatic vessels of the neck. As a result, developing metastasis to the tonsils in lung cancer is a rare condition, and this affects survival, which is relatively short.
References 1. Hyams VJ. Differential diagnosis of neoplasia of the palatine tonsil. Clin Otolaryngol Allied Sci. 1978;3: 117–26. 2. Bar R, Netzer A, Ostrovsky D, Daitzchman M, Golz A. Abrupt tonsillar hemorrhage from a metastatic hemangiosarcoma of the breast: case report and literature review. Ear Nose Throat J. 2011;90: 116–20. 3. Tsubochi H, Isogami K, Sato N, Tadashi I. Successfully treated lingual tonsillar from bronchial adenocarcinoma metastasis. Jpn J Thorac Cardiovasc Surg. 2005;53: 455–7. 4. Chen XH, Bao YY, Zhou SH, Wang QY, Zhao K. Palatine tonsillar metastasis of small-cell neuroendocrine carcinoma from the lung detected by FDG-PET/CT after tonsillectomy: a case report. Iran J Radiol. 2013;10: 148–51. 5. Mastronikolis NS, Tsiropoulos GE, Chorianopoulos D, Liava AC, Stathas T, Papadas TA, Hisa Y. Palatine tonsillar metastasis from lung adenocarcinoma. Eur Rev Med Pharmacol Sci. 2007;11: 279–82. 6. Seddon DJ. Tonsillar metastasis at presentation of small cell carcinoma of the lung. J R Soc Med. 1989;82: 688. 7. Yamaguchi E, Uchida M, Makino Y, Tachibana M, Sato T, Yamamoto Y, Kawashima K, Araki A, Maruyama R. Tonsillar metastasis of gastric cancer. Clin J Gastroenterol. 2010;3: 289–95. 8. Arroyo HH, Takehara J, Ogawa AI, Frizzarini R, Imamura R, Paula HM. Small cell lung carcinoma metastasis to palatine tonsils. Braz J Otorhinolaryngol. 2013;79: 645. 9. Brownson RJ, Jaques WE, Lamonte SE, Zollinger WK. Hypernephroma metastatic to the palatine tonsils. Ann Otol Rhinol Laryngol. 1979;88: 235–40. 10. Murakawa T, Nakajima J, Fukami T, Tanaka M, Takeuchi E, Takamoto S. Tonsillar metastasis from large cell carcinoma of the lung. Jpn J Thorac Cardiovasc Surg. 2001;49: 377–80. 11. Gottschling S, Penzel R, Pelz T, Herpel E, Schnabel PA, Dyckhoff G, Thomas M, Kuhnt T. KRAS-mutation positive, metastatic tonsil carcinoma with cancer stem-like cell features and long-term response to gefitinib: a case report and review of the literature. J Clin Oncol. 2011;29: 616–9. 12. Califano R, Abidin AZ, Peck R, Faivre FC, Lorigan P. Management of small cell lung cancer. Drugs. 2012;72: 471–90.
3
