Background. Small cell carcinomas of unknown origin have been reported to occur in the hilum or mediastinal lymph nodes. Furthermore, there are a few reports describing the independent coexistence of pulmonary small cell cancer and pulmonary adenocarcinoma in a lung field. Case. A ground glass opacity (GGO) lesion was incidentally found in the right upper lobe on a chest CT image of a 67-year-old man. Positron emission tomography (PET) revealed accumulation in the hilar lymph nodes but distant metastasis was not seen, right upper lobectomy and lymph node dissection were performed. A pathological examination revealed that the GGO lesion of the right upper lobe was pulmonary adenocarcinoma, and small cell cancer was detected in the hilar lymph node. A thorough search of the whole range of the upper lobe was performed to detect macroscopic primary lesions. A primary small cell carcinoma of 2.5 mm in size was found in the upper lobe separate from the GGO lesion. The invasion of cancer cells into the lymphatic vessels was found around the small cell carcinoma. It was therefore diagnosed as a primary lesion of small cell carcinoma of the lung. Conclusion. When small cell carcinoma of unknown origin is detected in the hilum or mediastinal lymph nodes, a detailed examination may reveal primary cancer of the lung.
Background. ALK fusion gene-positive (ALK-positive) non-small-cell lung cancer (NSCLC) occasionally develops tolerance for ALK tyrosine kinase inhibitor (ALK-TKI). It is known that leptomeningeal carcinomatosis is difficult to treat and fatal. We herein report a case of ALK-positive NSCLC presenting with leptomeningeal carcinomatosis that was successfully treated with alectinib after gaining crizotinib resistance. Case. A 45-year-old female patient who had been diagnosed with ALK-positive lung adenocarcinoma (cT3N2M1b, OSS, stage IV) was treated with a combination of carboplatin, pemetrexed, and bevacizumab, followed by maintenance therapy with pemetrexed and bevacizumab, which resulted in a partial response. After her disease progressed, a partial response was obtained with crizotinib. However, leptomeningeal carcinomatosis occurred. We changed to alectinib, and a dramatic response was observed in the leptomeningeal carcinomatosis; however, the patient's liver metastasis worsened two months later. The patient's liver metastasis and primary lesion gradually progressed without the worsening of leptomeningeal carcinomatosis, despite various treatments. She eventually died due to Trousseau syndrome. Conclusion. In ALK-positive lung cancers presenting with leptomeningeal carciomatosis, alectinib should be the preferred agent. The continued use of alectinib beyond progressive disease (PD) may be useful even when PD is observed at the other target lesions.
Background. In female patients, choriocarcinoma most commonly occurs from the trophoblasts and is associated with gestation. Primary pulmonary choriocarcinomas are very rare. We herein report a case of pulmonary choriocarcinoma in which the primary tumor was barely distinguishable from a metastatic tumor. Case. A 36-year-old woman who underwent an induced abortion due to a partial hydatidiform mole between two normal pregnancies was referred to our hospital because of a well-defined mass shadow (26×21 mm) in the lower lobe of the right lung. She developed amenorrhea one month later, and a pregnancy test was positive. She was referred for a gynecological examination at our hospital on the suspicion of an extrauterine pregnancy after a sonographic examination did not reveal an embryo. Although a high serum level of human chorionic gonadotrophin (hCG) was found, a gynecological examination revealed no pelvic abnormalities. Tumor enlargement was found on a chest roentgenogram two months later (31×25 mm). Bronchofiberoscopy did reveal any malignancy. The high uptake of FDG in the tumor was observed on PET-CT. A malignant tumor was strongly suspected; thus, lower lobectomy of the right lung was performed. The tumor was microscopically and immunohistochemically diagnosed as a choriocarcinoma. The postoperative serum hCG level dropped to normal levels, and adjuvant chemotherapy consisting of methotrexate, etoposide and actinomycin D was administered three times. Recurrence has not been observed in the year after surgery. The tumor was first diagnosed as being metastasis from the hydatidiform mole. It was difficult to diagnose as a primary pulmonary choriocarcinoma because there were no other tumors in the lung, and there were no apparent primary lesions in the pelvic cavity. We clinically concluded that the tumor was derived from trophoblasts, because the low frequency of primary pulmonary choriocarcinoma as well as her history of pregnancy. Thus, the tumor was considered to have originated from the chorionic tissue in normal pregnancy, not from the hydatidiform mole, due to the normal serum hCG level after the abortion of the mole.
Objective. Pemetrexed is an effective agent for the treatment of non-squamous non-small cell lung cancer; however, the effectiveness of pemetrexed rechallenge chemotherapy remains to be proven. We administered pemetrexed rechallenge chemotherapy when disease progression was observed in advanced lung cancer patients in whom disease control had been achieved with initial pemetrexed treatment. Methods. We retrospectively reviewed five patients with advanced lung adenocarcinoma who had received pemetrexed rechallenge chemotherapy between January 2010 and December 2014. Results. All of the patients (median age, 64 years; range, 61-76) had stage IV lung adenocarcinoma. Four patients responded to the initial pemetrexed-based chemotherapy and stable disease was achieved in one patient. The median interval from the end of initial pemetrexed-based chemotherapy to pemetrexed rechallenge chemotherapy was 14.5 months (range, 11.8-17.4 months). Three patients achieved a partial response, and the median progression free survival period was 7.2 months (95% confidence interval, 3.8-10.6 months) with pemetrexed rechallenge chemotherapy. Conclusion. Pemetrexed rechallenge chemotherapy may be useful for selected patients.
Background. Polymyositis rarely occurs after a diagnosis of lung cancer. Case. A 63-year-old man had been diagnosed with squamous cell lung carcinoma (T4N2M1b, c-stage IV) in February 2015. He had been treated with chemotherapy consisting of carboplatin (CBDCA) and tegafur/gimeracil/oteracil (S-1) and had shown stable disease with this treatment. However, his creatinine kinase (CK) levels began to increase during the chemotherapy. Rhabdomyolysis by S-1 was initially suspected, so the chemotherapy was changed to CBDCA and nanoparticle-albumin-bound-paclitaxel (nab-PTX). However, his CK levels continued to increase, and he presented with a fever and weakness of the muscles. Myositis was suspected, and muscle biopsy was performed. The pathological findings confirmed polymyositis. The polymyositis improved with prednisolone (PSL) and immunosuppressant treatment. Conclusions. We should consider the possibility of polymyositis when the CK levels increase in patients with lung cancer.
Background. The incidence rate of multiple cancers is now increasing due to the improvement of treatments, the development of medical technology, and aging. Case. A 75-year-old woman had a history of surgical resection of pancreatic carcinoma. During the follow-up, abnormal shadows on the lung field were observed. Chest computed tomography revealed a mass 10 mm in diameter with relatively clear borders and ground-glass patterns in the right S2, and small round masses 5 mm in diameter in the right S5 and S8. A partial resection was performed for the three lung masses. A histopathological examination revealed that the mass in S2 had lepidic tumor growth and resembled Clara cells. It was diagnosed as non-mucinous adenocarcinoma in situ. In contrast, while the masses in S5 and S8 also showed lepidic tumor growth, they had large numbers of columnar cells with mucin production and a shift of the nucleus to the basal side. To differentiate pulmonary mucinous adenocarcinoma from metastases of pancreatic adenocarcinoma, a mutation analysis of KRAS was performed. A KRAS gene mutation (G12D) was detected in the primary pancreatic carcinoma and the tumors in S5 and S8. Conclusion. We encountered a case of synchronous resection of pulmonary metastases of pancreatic carcinoma with lepidic growth that required differentiation from pulmonary mucinous and pulmonary adenocarcinomas.
Background. We report three cases of leptomeningeal carcinomatosis with lung adenocarcinoma who experienced responded favorably for both neurological symptoms and performance status (PS) following treatment with afatinib. Case 1. A woman in her 20s with stage IV lung adenocarcinoma with an Exon19 deletion of EGFR gene. The patient developed symptomatic leptomeningeal carcinomatosis during a previous chemotherapy session and was hospitalized with PS 4. She subsequently received afatinib as third-line therapy. Two weeks later, the neurological symptoms were relieved, her headache and nausea had disappeared, and the vomiting had stopped. The PS was dramatically improved when the patient was discharged. Case 2. A woman in her 40s with stage IV lung adenocarcinoma with an Exon19 deletion of EGFR gene. The patient developed symptomatic leptomeningeal carcinomatosis during a previous chemotherapy session and was hospitalized with PS 4. She subsequently received afatinib as third-line therapy. Two weeks later, the neurological symptoms were relieved, her consciousness was back to normal, her headache and nausea had disappeared, and the vomiting had stopped. The PS was dramatically improved when the patient was discharged. Case 3. A woman in her 60s with stage IV lung adenocarcinoma with an L858R Exon21 mutation of EGFR gene. The patient developed symptomatic leptomeningeal carcinomatosis and was hospitalized with PS 4. Tumor cells were suspected in the spinal fluid based on the cytology findings. She received afatinib as first-line therapy. Four weeks later, the neurological symptoms were relieved, her consciousness was back to normal (Japan Coma Scale: III-100→I-1), her headache and nausea had disappeared, and the vomiting had stopped. She is currently still receiving afatinib therapy and is alive 11 months later without disease progression. Conclusion. This is the first report on the effect of afatinib in leptomeningeal carcinomatosis in EGFR mutation-positive lung adenocarcinoma. The neurological symptoms were improved in all cases. The progression-free survival in Cases 1 and 2 after starting afatinib was 8 and 5 months, respectively, and the overall survival after starting afatinib was 19 and 8 months, respectively. Case 3 is still alive 11 months later without progression. These findings suggest that afatinib might improve the symptoms and quality of life of EGFR-mutant lung adenocarcinoma patients with leptomeningeal carcinomatosis.
Background. Patients with pulmonary pleomorphic carcinoma often have hemosputum and hemoptysis. Case. A 46-year-old woman was referred to our hospital because of hemosputum lasting for three weeks. Computed tomography (CT) revealed a nodular shadow surrounding the bulla in the right S1 and dense consolidation in the right upper lung. The nodular shadow and dense consolidation decreased in size when bronchoscopy was performed. The findings for transbronchial brush cytology were negative. Two months later, her hemosputum reappeared, and the nodular shadow surrounding the bulla in the right S1 increased in size again. Transbronchial biopsy of the nodular shadow revealed squamous cell carcinoma. FDG-PET/CT scanning revealed uptake at the nodular shadow surrounding the bulla. We diagnosed her lung tumor as clinical T1bN0M0, stage IA, and right upper lobectomy was performed. The microscopic images of the resected lung tumor showed mainly sarcomatous components consisting of spindle cells and giant round cells, and partially carcinoma cells. The tumor was diagnosed as pulmonary pleomorphic carcinoma. Bleeding from the mass and absorption occurred repeatedly because many vessels were involved in necrosis area, so the shadow of the primary lesion decreased in size without treatment. Conclusion. Pulmonary pleomorphic carcinoma expresses many angiogenic factors and tends to bleed. We should therefore consider a malignant tumor even if the shadow is diminished without treatment.
Background. According to previous reports, aortic invasion is associated with mortality and morbidity rates of almost 12.5% and 31%, respectively. However, the operative outcomes in cases of aortic invasion with no lymphatic metastasis were preferable. The 5-year survival rate is almost 70%. If the operative risk associated with the resection of cancers with aortic invasion can be improved, then it will be a promising treatment strategy. Case. The patient was a 76-year-old man. An abnormal shadow had been pointed out on his chest X-ray. Computed tomography revealed a mass lesion (3.2×3.0 cm) in the upper lobe of the left lung, along the chest wall and invasion of the aortic arch. Further examinations, including transbronchial lung biopsy and positron emission tomography, revealed that the lesion was squamous cell lung carcinoma. The clinical stage was T4N0M0 stage IIIA. We positioned a thoracic aortic endograft after confirming that the lung cancer had infiltrated the thoracic aorta using a thoracic endoscope. Three weeks after the positioning of the endograft, we successfully performed en bloc tumor resection. The operation included the resection of the aortic wall and the left upper lobe, without cardiopulmonary bypass. The patient remained in hospital for only ten days after surgery; no intraoperative or perioperative complications were observed. A pathologic examination revealed that the lung cancer had infiltrated the aortic wall adventitia; however, en bloc tumor resection (R0) was successfully performed. The operation included the resection of the aortic wall adventitia and media. Conclusion. We described the safe and complete resection of lung cancer infiltrating the aortic arch with a thoracic aortic endograft.
Background. Two ALK inhibitors are available for the treatment of lung cancer in Japan, but resistance to both is not uncommon. Case. A 37-year-old female was diagnosed with ALK-rearrangement-positive lung adenocarcinoma at cT2aN3M0, stage IIIB. She was initially treated with alectinib and showed a sustained partial response (PR) for four and a half months. She was then switched from alectinib to cisplatin and pemetrexed due to progressive disease (PD). On the 16th day of the second drug regimen she developed fever, elevated C-reactive protein levels, and rapidly enlarged lymph nodes. Re-treatment with alectinib attenuated her liver metastasis and partially reduced her lymph node enlargement, but several other lymph nodes continued to grow. The alectinib was then switched to crizotinib, which elicited a PR. A re-biopsied sample of the right supraclavicular lymph node tested positive for ALK-rearrangement by immunohistochemistry and fluorescence in situ hybridization analyses and included some MET-positive cells. We diagnosed adenocarcinoma based on the histological findings which were very similar to the findings we observed in the first examination. Conclusion. The patient's disease responded with a flare-like reaction after the alectinib was discontinued. The MET amplification observed after the alectinib was re-administered might have been related to a resistance mechanism in the growing tumor. Further research on ALK inhibitor resistance is therefore warranted.
Background. Evidence of solitary pancreatic metastasis from lung cancer is rarely observed at the initial diagnosis. Case. A 38-year-old man visited our hospital with a chief complaint of upper back pain. Magnetic resonance imaging revealed a mass in the left upper lobe with invasion to the third thoracic spine. Computed tomography (CT)-guided needle biopsy of the left lung tumor indicated both a histological and immunohistochemical diagnosis of squamous cell carcinoma. Fluorodeoxy glucose-positron emission tomography (FDG-PET) showed the accumulation of FDG in both tumors observed in the left lung and the pancreas tail. Abdominal dynamic CT revealed a tumor measuring 26×24 mm in size with rim enhancement in the pancreas tail. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of the pancreatic tumor indicated a histopathological diagnosis of metastasis from squamous cell carcinoma of the lung. Conclusion. EUS-FNA is a useful diagnostic procedure to distinguish metastatic pancreatic tumors from primary pancreatic tumors.