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Brain metastasis as the first manifestation of small cell lung cancer in a female adolescent
Lung Cancer 73 (2011) 243–246
Contents lists available at ScienceDirect
Lung Cancer journal homepage: www.elsevier.com/locate/lungcan
Short communication
Brain metastasis as the first manifestation of small cell lung cancer in a female adolescent Li Hui a , Yao Li Qing b,∗ , Chen Zi Qian a , Lin Yu Ning a , Zheng Zhi Yong b a b
Department of Medical Imaging, Fuzhou General Hospital of Nanjing Command, PLA, Fujian Province, China Department of Pathology, Fuzhou General Hospital of Nanjing Command, PLA, Fuzhou 350025, Fujian Province, China
a r t i c l e
i n f o
Article history: Received 28 November 2010 Received in revised form 7 April 2011 Accepted 28 April 2011 Keywords: Brain metastasis Small cell lung cancer Adolescent Smoking
a b s t r a c t Small cell lung cancer is commonly regarded as an old age related disease. Although the brain is a common site of metastasis for this type of lung cancer, the first manifestation is rarely shown from the metastasis site. In this paper, we report a rare case of 19-year-old female patient with small cell lung cancer whose initial presentation was a solitary brain metastasis. The patient was admitted to our hospital for the recurrence of brain tumor, and the histological diagnosis after operation showed small cell lung cancer. Three months later, she suffered from dry cough and was diagnosed as small cell lung cancer by transbronchial biopsy. Due to the identical cell types and immunohistochemical phenotypes, the brain tumor was retrospectively diagnosed as metastasis of small lung cancer by two neurological pathologists. She is the youngest female with brain metastasis as the first manifestation of small cell lung cancer reported so far internationally as to our knowledge. Second-hand smoking was possibly one of the risk factors. © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Lung cancer is one of the most common cancers in the world and 13–20% of the newly diagnosed patients are found to have small cell variety [1]. Small cell lung cancer (SCLC) is universally recognized as an old age related disease. Although it is common for the SCLC to metastasize to other sites, the first symptom is rare from the metastasis site. We report a very rare case of brain metastasis shown as the first manifestation of SCLC in a young female patient. 2. Case report A 19-year-old female patient was admitted to our hospital for the recurrence of ‘brain tumor’ in December 2008. She was diagnosed ‘Tumor in the left temporal and parietal lobes’ based on MRI (Fig. 1A) in February 2005 in another local hospital, and underwent grossly subtotal resection of the brain tumor with a pathological diagnosis of glioma. About three years later, she received the MRI examination again in January 2008, which showed a recurrence of the tumor. She underwent a resection of the brain tumor with a pathological diagnosis of “epithelial malignant tumor and foci of sarcoma, types undetermined” in a big hospital in Shanghai. In November 2008, the patient suffered from weakness in right limbs and activity restriction again, accompanying with severe
∗ Corresponding author. Tel.: +86 13609557019; fax: +86 0591 83717703. E-mail address: [email protected] (Y.L. Qing). 0169-5002/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.lungcan.2011.04.018
headache. The brain MRI indicated the recurrence of occupying lesions of the left temporal and parietal lobes. She had no other medical record, and her family history was unremarkable except her father was a heavy smoker with about 20 years of smoking history. Physical examination revealed that the muscle strength reduced in the right distal extremities. Laboratory tests showed no abnormalities. Peripheral blood cell counts, liver and renal functions, hormonal tests and tumor markers were within normal ranges. The tumor resection operation was performed for her. It was hard to determine the histological diagnosis (Fig. 2B). There was distinct boundary between the tumor area and the normal brain area. Small cells were evenly distributed among the area of tumor without any distinct feature, and large amount of vessels were observed. The relationship between the small cells and the vessels were not clear. Immunohistochemically, CD56 and Vim were strongly positive (Fig. 1C), while CK, CKH , EMA and CKL were mildly positive. CD34, CD99, CgA, CK7, CK20, Des, GFAP, LCA, nestin, Neu-N, S-100, SMA, TTF-1, Syn and Villin were all negative. Ki-67 was about 50% (Fig. 1D). The mitotic count was 62/2 mm2 . Three month later, the patient suffered from cough and fever and was admitted to our hospital again. The chest CT scan showed messes in both pulmonary hila mass with increased lung markings (Fig. 2A and B). The diagnosis of SCLC was made through the trans-bronchial lung biopsy (Fig. 2C). Immunohistochemically, CD56 and Vim were strongly positive (Fig. 2D), while CK, CKL , CKH were mildly positive. TTF-1 and Syn were negative. Ki-67 was about 50% (Fig. 2E). The mitotic count was hard to perform because
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L. Hui et al. / Lung Cancer 73 (2011) 243–246
Fig. 1. MRI image and biopsy sections of the brain focci. (A) The brain MRI in the present case demonstrates a right lobular mass. (B) Histological diagnosis of metastasis of small cell lung cancer was established on the tissue obtained by biopsy. (C) Immunohistochemical analysis of the brain sections (CD56). (D) Immunohistochemical analysis of the brain sections (Ki-67).
the cells were crushed during biopsy. Additionally, the mutation status of EGFR exons 19 and 21 were determined by Real-time fluorescent quantitative PCR, and no mutation was detected at any of the four sites (delE746-A750, delL747-P753insS, L858R, L861Q) (Fig. 3). Based on these findings, she was clinically diagnosed as SCLC. To determine the diagnosis of the brain tumor, we counseled several famous tumor pathologists. The metastasis of SCLC was diagnosed by two pathologists in a hospital in Beijing. Eventually, the patient was diagnosed as SCLC with brain metastasis as the first
manifestation. No other metastasis was found except for the brain. The TNM stage of this case was T4N0M1, stage IV. 3. Discussion The case is impressive in three ways. Firstly, the brain metastasis was shown as the first manifestation of SCLC. Although the brain is a common site for metastasis of SCLC, it rarely occurs that brain metastasis were first presented even before the lung abnormity was detected on the chest CT. Usually the SCLC proliferates rapidly and
Fig. 2. CT image and biopsy sections of the lung focci. (A and B) The chest CT scan in the present case demonstrates both pulmonary hila mass. (C) Histological diagnosis of small cell lung cancer was established on the tissue obtained by trans-bronchial biopsy. (D) Immunohistochemical analysis of the lung sections (CD56). (E) Immunohistochemical analysis of the lung sections (Ki-67).
L. Hui et al. / Lung Cancer 73 (2011) 243–246
Fig. 3. Results of EGFR mutation test in lung section. (A and B) Amplification plot and multicomponent plot of EGFR gene axon 19 ( (C and D) Amplification plot and multicomponent plot of EGFR gene axon 21 ( , L858R; , L861Q).
usually appears as a bulky mass on a chest radiography at the time of diagnosis. Secondly, the patient was very young. She was the youngest patient suffered from SCLC with first manifestation of brain metastasis as reported so far in the international literature. She was only 16 when the brain metastasis was detected and was only 19 when the primary tumor of SCLC was diagnosed. It is quite rare for such a young patient suffering from this disease. Previous studies from Turkey reported that mean age of lung cancer cases at the time of diagnosis was between 56.2 and 60.9 years old [2]. Several studies reported that only 5–10% of all lung cancer patients were in the younger age group below 50 years [3,4]. Elci et al. conducted an investigation on the distribution of histological types of lung cancer by age in Turkey [5]. The youngest patient among the 1354 cases of lung cancer was a 20-year-old male. To our knowledge, she was the youngest patient with SCLC which has been reported up till now. Thirdly, the patient had a history of second-hand smoking. There is no doubt that smoking is the most important risk factor for the development of lung cancer, and the risk increases with the intensity and duration of smoking [6,7]. It was reported that the SCLC had the closest relationship with smoking, and the relative proportion of SCLC increased with smoking intensity [8]. In this reported case,
245
, delE746-A750;
, delL747-P753insS).
the girl suffered from severe second-hand smoking since birth. This case may show the harm of tobacco use even it is second-handed. We believe it is valuable to report this case because of the three aforementioned reasons. In order to further understand the mechanism, diagnosis and treatment of the brain metastasis of SCLC in young people, more case reports of similar cases are needed in the future. Conflict of interest No author has a financial relationship with a commercial entity that has an interest in the topic of this paper. References [1] Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 2006;24(28):4526–7. [2] Karlikaya C, Cakir Edis E. Lung cancer histopathology in the Thrace region of Turkey and comparison with national data. Tuberk Toraks 2005;53(2):132–8. [3] Capewell S, Wathen CG, Sankaran R, Sudlow MF. Lung cancer in young patients. Respir Med 1992;86(6):499–502.
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L. Hui et al. / Lung Cancer 73 (2011) 243–246
[4] Veness MJ, Delaney G, Berry M. Lung cancer in patients aged 50 years and younger: clinical characteristics, treatment details and outcome. Aust Radiol 1999;43(3):328–33. [5] Elci OC, Akpinar-Elci M. The trend of small cell lung cancer among young men. Lung Cancer 2007;57(1):34–6. [6] Collins LG, Haines C, Perkel R, Enck RE. Lung cancer: diagnosis and management. Am Fam Phys 2007;75(1):56–63.
[7] Liu NS, Spitz MR, Kemp BL, Cooksley C, Fossella FV, Lee JS, et al. Adenocarcinoma of the lung in young patients: the M.D. Anderson experience. Cancer 2000;88(8):1837–41. [8] De Stefani E, Boffetta P, Ronco AL, Brennan P, Correa P, Deneo-Pellegrini H, et al. Squamous and small cell carcinomas of the lung: similarities and differences concerning the role of tobacco smoking. Lung Cancer 2005;47(1): 1–8.
Contents lists available at ScienceDirect
Lung Cancer journal homepage: www.elsevier.com/locate/lungcan
Short communication
Brain metastasis as the first manifestation of small cell lung cancer in a female adolescent Li Hui a , Yao Li Qing b,∗ , Chen Zi Qian a , Lin Yu Ning a , Zheng Zhi Yong b a b
Department of Medical Imaging, Fuzhou General Hospital of Nanjing Command, PLA, Fujian Province, China Department of Pathology, Fuzhou General Hospital of Nanjing Command, PLA, Fuzhou 350025, Fujian Province, China
a r t i c l e
i n f o
Article history: Received 28 November 2010 Received in revised form 7 April 2011 Accepted 28 April 2011 Keywords: Brain metastasis Small cell lung cancer Adolescent Smoking
a b s t r a c t Small cell lung cancer is commonly regarded as an old age related disease. Although the brain is a common site of metastasis for this type of lung cancer, the first manifestation is rarely shown from the metastasis site. In this paper, we report a rare case of 19-year-old female patient with small cell lung cancer whose initial presentation was a solitary brain metastasis. The patient was admitted to our hospital for the recurrence of brain tumor, and the histological diagnosis after operation showed small cell lung cancer. Three months later, she suffered from dry cough and was diagnosed as small cell lung cancer by transbronchial biopsy. Due to the identical cell types and immunohistochemical phenotypes, the brain tumor was retrospectively diagnosed as metastasis of small lung cancer by two neurological pathologists. She is the youngest female with brain metastasis as the first manifestation of small cell lung cancer reported so far internationally as to our knowledge. Second-hand smoking was possibly one of the risk factors. © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Lung cancer is one of the most common cancers in the world and 13–20% of the newly diagnosed patients are found to have small cell variety [1]. Small cell lung cancer (SCLC) is universally recognized as an old age related disease. Although it is common for the SCLC to metastasize to other sites, the first symptom is rare from the metastasis site. We report a very rare case of brain metastasis shown as the first manifestation of SCLC in a young female patient. 2. Case report A 19-year-old female patient was admitted to our hospital for the recurrence of ‘brain tumor’ in December 2008. She was diagnosed ‘Tumor in the left temporal and parietal lobes’ based on MRI (Fig. 1A) in February 2005 in another local hospital, and underwent grossly subtotal resection of the brain tumor with a pathological diagnosis of glioma. About three years later, she received the MRI examination again in January 2008, which showed a recurrence of the tumor. She underwent a resection of the brain tumor with a pathological diagnosis of “epithelial malignant tumor and foci of sarcoma, types undetermined” in a big hospital in Shanghai. In November 2008, the patient suffered from weakness in right limbs and activity restriction again, accompanying with severe
∗ Corresponding author. Tel.: +86 13609557019; fax: +86 0591 83717703. E-mail address: [email protected] (Y.L. Qing). 0169-5002/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.lungcan.2011.04.018
headache. The brain MRI indicated the recurrence of occupying lesions of the left temporal and parietal lobes. She had no other medical record, and her family history was unremarkable except her father was a heavy smoker with about 20 years of smoking history. Physical examination revealed that the muscle strength reduced in the right distal extremities. Laboratory tests showed no abnormalities. Peripheral blood cell counts, liver and renal functions, hormonal tests and tumor markers were within normal ranges. The tumor resection operation was performed for her. It was hard to determine the histological diagnosis (Fig. 2B). There was distinct boundary between the tumor area and the normal brain area. Small cells were evenly distributed among the area of tumor without any distinct feature, and large amount of vessels were observed. The relationship between the small cells and the vessels were not clear. Immunohistochemically, CD56 and Vim were strongly positive (Fig. 1C), while CK, CKH , EMA and CKL were mildly positive. CD34, CD99, CgA, CK7, CK20, Des, GFAP, LCA, nestin, Neu-N, S-100, SMA, TTF-1, Syn and Villin were all negative. Ki-67 was about 50% (Fig. 1D). The mitotic count was 62/2 mm2 . Three month later, the patient suffered from cough and fever and was admitted to our hospital again. The chest CT scan showed messes in both pulmonary hila mass with increased lung markings (Fig. 2A and B). The diagnosis of SCLC was made through the trans-bronchial lung biopsy (Fig. 2C). Immunohistochemically, CD56 and Vim were strongly positive (Fig. 2D), while CK, CKL , CKH were mildly positive. TTF-1 and Syn were negative. Ki-67 was about 50% (Fig. 2E). The mitotic count was hard to perform because
244
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Fig. 1. MRI image and biopsy sections of the brain focci. (A) The brain MRI in the present case demonstrates a right lobular mass. (B) Histological diagnosis of metastasis of small cell lung cancer was established on the tissue obtained by biopsy. (C) Immunohistochemical analysis of the brain sections (CD56). (D) Immunohistochemical analysis of the brain sections (Ki-67).
the cells were crushed during biopsy. Additionally, the mutation status of EGFR exons 19 and 21 were determined by Real-time fluorescent quantitative PCR, and no mutation was detected at any of the four sites (delE746-A750, delL747-P753insS, L858R, L861Q) (Fig. 3). Based on these findings, she was clinically diagnosed as SCLC. To determine the diagnosis of the brain tumor, we counseled several famous tumor pathologists. The metastasis of SCLC was diagnosed by two pathologists in a hospital in Beijing. Eventually, the patient was diagnosed as SCLC with brain metastasis as the first
manifestation. No other metastasis was found except for the brain. The TNM stage of this case was T4N0M1, stage IV. 3. Discussion The case is impressive in three ways. Firstly, the brain metastasis was shown as the first manifestation of SCLC. Although the brain is a common site for metastasis of SCLC, it rarely occurs that brain metastasis were first presented even before the lung abnormity was detected on the chest CT. Usually the SCLC proliferates rapidly and
Fig. 2. CT image and biopsy sections of the lung focci. (A and B) The chest CT scan in the present case demonstrates both pulmonary hila mass. (C) Histological diagnosis of small cell lung cancer was established on the tissue obtained by trans-bronchial biopsy. (D) Immunohistochemical analysis of the lung sections (CD56). (E) Immunohistochemical analysis of the lung sections (Ki-67).
L. Hui et al. / Lung Cancer 73 (2011) 243–246
Fig. 3. Results of EGFR mutation test in lung section. (A and B) Amplification plot and multicomponent plot of EGFR gene axon 19 ( (C and D) Amplification plot and multicomponent plot of EGFR gene axon 21 ( , L858R; , L861Q).
usually appears as a bulky mass on a chest radiography at the time of diagnosis. Secondly, the patient was very young. She was the youngest patient suffered from SCLC with first manifestation of brain metastasis as reported so far in the international literature. She was only 16 when the brain metastasis was detected and was only 19 when the primary tumor of SCLC was diagnosed. It is quite rare for such a young patient suffering from this disease. Previous studies from Turkey reported that mean age of lung cancer cases at the time of diagnosis was between 56.2 and 60.9 years old [2]. Several studies reported that only 5–10% of all lung cancer patients were in the younger age group below 50 years [3,4]. Elci et al. conducted an investigation on the distribution of histological types of lung cancer by age in Turkey [5]. The youngest patient among the 1354 cases of lung cancer was a 20-year-old male. To our knowledge, she was the youngest patient with SCLC which has been reported up till now. Thirdly, the patient had a history of second-hand smoking. There is no doubt that smoking is the most important risk factor for the development of lung cancer, and the risk increases with the intensity and duration of smoking [6,7]. It was reported that the SCLC had the closest relationship with smoking, and the relative proportion of SCLC increased with smoking intensity [8]. In this reported case,
245
, delE746-A750;
, delL747-P753insS).
the girl suffered from severe second-hand smoking since birth. This case may show the harm of tobacco use even it is second-handed. We believe it is valuable to report this case because of the three aforementioned reasons. In order to further understand the mechanism, diagnosis and treatment of the brain metastasis of SCLC in young people, more case reports of similar cases are needed in the future. Conflict of interest No author has a financial relationship with a commercial entity that has an interest in the topic of this paper. References [1] Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 2006;24(28):4526–7. [2] Karlikaya C, Cakir Edis E. Lung cancer histopathology in the Thrace region of Turkey and comparison with national data. Tuberk Toraks 2005;53(2):132–8. [3] Capewell S, Wathen CG, Sankaran R, Sudlow MF. Lung cancer in young patients. Respir Med 1992;86(6):499–502.
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L. Hui et al. / Lung Cancer 73 (2011) 243–246
[4] Veness MJ, Delaney G, Berry M. Lung cancer in patients aged 50 years and younger: clinical characteristics, treatment details and outcome. Aust Radiol 1999;43(3):328–33. [5] Elci OC, Akpinar-Elci M. The trend of small cell lung cancer among young men. Lung Cancer 2007;57(1):34–6. [6] Collins LG, Haines C, Perkel R, Enck RE. Lung cancer: diagnosis and management. Am Fam Phys 2007;75(1):56–63.
[7] Liu NS, Spitz MR, Kemp BL, Cooksley C, Fossella FV, Lee JS, et al. Adenocarcinoma of the lung in young patients: the M.D. Anderson experience. Cancer 2000;88(8):1837–41. [8] De Stefani E, Boffetta P, Ronco AL, Brennan P, Correa P, Deneo-Pellegrini H, et al. Squamous and small cell carcinomas of the lung: similarities and differences concerning the role of tobacco smoking. Lung Cancer 2005;47(1): 1–8.