Choroidal metastases as the presenting feature of adenocarcinoma of the lung: A case report and an overview of the role of radiotherapy in its management.

Lung cancer is 1 of the major health problems in the world and the leading cause of cancer death in Taiwan. Well-known metastatic sites of lung cancer include the lung, lymph nodes, brain, bone, liver, etc. Choroid metastasis is rare and the diagnosis is based primarily on clinical findings supplemented by imaging studies. However, clinicians do not routinely evaluate the possibility of intraocular metastasis, mainly because of the low incidence of asymptomatic choroid metastasis. The most commonly used treatment in patients with symptomatic intraocular metastasis is radiotherapy. Herein, we report the cases of 2 patients who had blurred vision as the initial presentation, and were diagnosed with adenocarcinoma of the lung with brain and choroid metastasis. They refused radiotherapy of the eye, and commenced systemic chemotherapy and brain radiation therapy. One received plaxitaxel and the other received vinorelbine. Throughout serial follow-ups, their visual acuity subjectively improved, along with a reduction in the size of the intraocular tumor, as seen by ophthalmoscopic examination in 1 case.

Purpose: We present a case of choroidal metastatic tumors achieving a best corrected visual acuity of 20/20 after intravitreal injection of bevacizumab (Avastin) and focal laser photocoagulation.Method: Interventional case report.Results: A 68 y/o male has been diagnosed with pulmonary adenocarcinoma (T4N1M0) in December 2006, and had received surgical intervention, radiotherapy and chemotherapy. He visited our outpatient department in December 2009 and presented with blurred vision in his right eye. His best corrected visual acuity was 20/40. Fundus examination revealed multiple subretinal masses, light orange in color, superotemporal and inferonasal to the fovea, in the right eye. Optical coherence tomography scan showed marked subretinal fluid of the macula. A diagnosis of choroidal metastasis secondary to lung cancer was made. After discovering choroidal metastatic lesions, two sessions of intravitreal injection of bevacizumab and three sessions of focal laser photocoagulation were performed. After three months follow-up, his best corrected visual acuity regained 20/20. Scarring and flattening of choroidal lesions were noted on color fundus photography. Multiple hyperfluorescent spots without leakage were showed on fluorescein angiography. Regression of macular edema and serous detachment were evident on optical coherence tomography scan.Conclusion: For the patient with choroidal metastases who wants to preserve good visual acuity and better quality of remained life, intravitreal injection of bevacizumab plus focal laser photocoagulation may be considered. Longer follow-up period is needed for evaluation of efficacy and effectiveness of such treatment.

Purpose: To report a case of choroidal metastasis as the main presentation in a patient with lung carcinoma. Method: Case report. Results: A 69-year-old woman complained of blurred vision in her right eye for 2 months. The best-corrected visual acuity was counting finger in right eye. Fundoscopy demonstrated a large choroidal mass located inferiotemporally associated with exudative retinal detachment in her right eye. B-scan ultrasound revealed the tumor had a high internal reflectivity. Magnetic resonance imaging of the orbit showed an intraocular mass that was approximately 5 mm in thickness. After enucleation, pathologic study of the enucleated eye demonstrated a choroidal metastasis. Complete systemic survey disclosed that a primary lung adeno-carcinoma with bone and choroidal metastasis count for the ocular lesion. Conclusions: Choroidal metastasis can be the first clinical manifestation of lung adenocarcinoma. Ophthalmologists should be aware of systemic malignancy in choroidal metastasis and initiate a thorough systemic evaluation for early detection of life-threatening malignancies.

Choroid metastasis from primary lung cancer is rare and has a poor prognosis. It can be treated with an external beam of radiation or by laser photocoagulation. However, visual defects or blindness are possible complications related to radiotherapy. Chemotherapy for such a condition has not been widely reported. We report a 26-year-old patient who had stage IV lung adenocarcinoma and suffered from progressive blurred vision during a scheduled chemotherapy regimen. Fundoscopy, fluorescence angiography and optic coherence tomography indicated choroidal metastasis of both eyes. We prescribed a platinum double chemotherapy regimen with pemetrexed and cisplatin. A follow-up examination demonstrated complete remission of the choroid metastasis. Herein, we report the first case of lung cancer with choroid metastasis that underwent complete remission after pemetrexed administration. We share our experience and conduct a literature review. (Thorac Med 2012; 27: 159-166)

So far as we know, the most metastatic site in lung cancer is brain and bone. Choroid metastases rarely occur in clinical diagnosis. We report a case of 57 yearold woman presenting as right blurred vision initially. She came to our hospital for further management due to deteriorating vision. Magnetic resonance (MR) revealed a homogeneous enhancing soft tissues mass occupied in the posterior surface of right eye. Under the impression of primary melanoma, enucleation was performed in June fifth, 2006. Pathologic report proved metastatic adenocarcinoma later. Chest computerized tomography (CT) displayed a spiculated mass at RUL and multiple mediastinal lymphadenopathies. Primary adenocarcinoma of lung with choroid metastases was final diagnosed. We also reviewed related literature and emphasized the importance of differentiating diagnosis in choroidal tumor, especially in cancer patients.

A 68-year-old man was referred because of an abnormal shadow in the right upper lung field on a chest X-ray film. After the diagnosis of adenocarcinoma of the lung, left upper lobectomy was done. Histologically, adenocarcinoma with foci of squamous cell carcinoma was seen. About 11 months after that operation, he suddenly noticed a decrease in visual acuity on the left side. The fundus of the eye was tested and metastatic choroidal cancer was suspected. To prevent rupture, the eyeball was enucleated. The choroidal tumor appeared to have components of squamous cell carcinoma from primary lung cancer. About 7 months after enucleation of his eyeball, the patient was disease-free with no decrease in his quality of life. As a result of a recent increase in the incidence of lung cancer, it is important to pay attention to ophthalmological tests in patients with primary lung cancer.

Objective This paper is to explore the aeromedical evaluation standard of the high performance fighter pilot with pulmonary adenocarcinoma after pulmonary lobectomy. Methods Based on the information of clinical diagnosis, treatment, recovery, aeromedical evaluation, re-flight status of a male high performance fighter pilot with pulmonary adenocarcinoma, we reviewed some literatures, and explored the medical evaluation of the high performance fighter pilot after pulmonary lobeetomy. Results With a solitary pulmonary nodule for 10 years, the patient had no chiefcomplaint. And there was no symptom on him. Lung cancer was diagnosed by examination of computed tomography(CT) and positron emission tomography(PET). Lobectomy of inferior lobe of left lung and radical correction of lymph node were operated. The pathological diagnosis was well-differentiated adenocarcinoma. However neither the radiotherapy nor the chemotherapy was adopted.After one-year medical observation, there was no evidence that the cancer recurrence or metastasis.Because the cardiorespiratory function and the G-tolerance of the patient were examined and qualified,he was allowed to returned to flight and had navigated the high performance fighter for 65 hours in thenext 12 months. Then he returned the hospital to reexamined, and there was no evident clinical abnormity to be found again. Conclusions After the pulmonary lobectomy, there is no evidence that the cancer recurrence or metastasis, The evaluation of the cardiorespiratory function and G-tolerance are examined and qualified, the high performance fighter pilot could be qualified for flying. Key words: Carcinoma, bronchogenic; Pulmonary surgical procedures; Diagnostic imaging; Case report; Eligibility determination

Objective Based on lung cancer center database, we analyzed the clinical characteristics of lung patients with bone metastases. The relationship between bone metastases, skeletal-related events, survival time and different pathological subtypes of lung cancer were also evaluated in this study. Methods A total of 861 patients with lung cancer were studied from May 2010 to April 2012 at Tianjin Medical University Cancer Institute and Hospital. As to follow-up situation, patients' survival status and treatment information were collected by telephone follow-up and (or) examinationsin outpatient. The clinical characteristics, skeletal-related events and survival of bone metastaticpatients with different pathological types of lung cancer were analyzed. Logistic regression analysis was used to identify risk factors for bone metastases. The relationship between histological subtypes and the incidence of bone metastases was evaluated using Odds Ratios (ORs). The chi-square test was used to compare the proportion of bone metastases, synchronous bone metastases and SREs among different histological subtypes patients. The overall survivals was evaluated using the Kaplan Meier. Results A total of861 patients with lung cancerwere enrolled in this study, including 293 cases with bone metastases.The average follow-up of our population was 14.2 months and the last follow-up time was September 2017. Among different pathological types of lung cancer, adenocarcinoma (39.14%, 173/442) has the highest incidence of bone metastases, followed by other types (29.91%, 35/117), squamous cell carcinoma (29.47%, 56/190) and SCLC (25.89%, 29/112). Spine (59.73%, 175/293) was the most common location site of the bone metastases, followed by the ribs (49.15%, 144/293), pelvis (20.48%, 60/293), femur (16.38%, 48/293) and sternal (16.38%, 48/293). Lung adenocarcinoma was a risk factor for bonemetastases (P=0.002). In ORs analyze, adenocarcinoma patients were more likely to develop bone metastases [OR=1.60, 95%CI (1.21~2.13)]. In our cohort, 58.36% of patients with lung cancer had skeletal related events. Among various types of skeletal related events of patients with bone metastases, the most common one was radiotherapy for bone metastases (51.88%, 152/293), followed by pathological fractures (15.02%, 44/293), spinal cord compression (6.48%, 19/293), bone instability requiring surgery (4.78%, 14/293) and hypercalcemia (1.71%, 5/293). There was no significant difference between different types of skeletal related events. The median survival time of the patients with bone metastases was 11.5 months. There was no significant difference in survival between adenocarcinoma patients and non-adenocarcinoma patients (P=0.111). Conclusion This study suggested that the incidence of bone metastasis in lung adenocarcinoma was 39.14% and lung adenocarcinoma was a risk factor for bone metastases, which supported early screening and monitoring of bone metastasis in the patients. Key words: Lung neoplasms; Pathology; Neoplasm metastasis; Prognosis

Synchronous double primary malignancy of the lung and brain is extremely rare, as there were only 2 cases reported in the literature. If patients were found to have both lung and brain malignancy, they would be ordinarily be considered to have lung cancer with brain metastasis. We report a 76-year-old female who came to our hospital due to slurred speech for 2 weeks. Brain magnetic resonance imaging (MRI) showed a heterogeneous mass lesion at the left parietal lobe with perifocal edema. Stereotactic biopsy confirmed anaplastic oligoastrocytoma. In the meantime, the pre-operative chest radiograph accidentally found a patch of opacity at the left hilar area during the same admission. The chest computed tomography (CT) scan showed a mass lesion at the left lingular lobe; bronchoscopic finding was unremarkable. Histology of the CT-guided biopsy specimen showed adenocarcinoma. Due to the poor performance status and the patient's family refusing operation, only palliative radiotherapy to the brain was administered. She was still living 7 months later. This case report highlights the importance of searching for and confirming synchronous tumor in addition to lung cancer, since there is the potential of cure and long-term survival.

Ovarian adenocarcinoma can be either a primary ovarian neoplasm or metastasis from another primary site. Approximately 6% of ovarian cancers are metastatic, usually from the stomach, breast, pancreas, kidney, or colon. Reports of ovarian metastasis from lung cancer are relatively uncommon, even in autopsy series. Only approximately 5% of females with lung cancer have ovarian metastasis at autopsy. We report a 23-year-old woman who was diagnosed with adenocarcinoma of the lung, left upper lobe, with multiple brain metastasis, in December, 2001. She received cranial irradiation for brain metastasis and systemic chemotherapy, beginning in January, 2002. About 1 year later, she complained of lower abdominal tenderness, and a huge pelvic mass, about 20 centimeters in diameter, was disclosed by abdominal CT scan. Left salpingo-oophorectomy and pelvic lymph node dissection were performed in January, 2003. Pathology showed that the tumor cells were in a tubulopapillary pattern; their cytoplasm was clear and the nuclei were pleomorphic. Immunohistochemical staining with thyroid transcription factor-1 (TTF-1) showed nuclear staining in the tumorcells, compatible with lung cancer metastasis to the ovary. Even though ovarian metastasis is a rare presentation of lung cancer, the possibility should always be kept in mind when an ovarian tumor is found after lung cancer has been diagnosed.

Objective: To investigate the high resolution CT (HRCT) features of lung adenocarcinoma for differentiating synchronous multiple lung adenocarcinoma from lung adenocarcinoma with intrapulmonary metastasis. Methods: The clinical and imaging features of 131 lesions from 62 patients of synchronous multiple primary lung adenocarcinoma (primary group) and 67 lesions from 31 patients of lung adenocarcinoma with intrapulmonary metastases (metastasis group) were retrospectively analyzed. According to the types of lesion, including pure ground glass nodule (pGGN), mixed ground glass nodule (mGGN) and solid nodule (SN), the image feature matching types of patients were divided into 7 types. The differences of image feature matching types between the primary group and the metastasis group were compared. Multiple lesions in the lung of patients were classified into the main lesion and the concomitant lesions according to their size. The differences including the size of the main lesion and the concomitant lesion (long diameter of nodule, long diameter of solid component in nodule), whether it contains ground glass components in nodule, shape, lobulation, margin, spiculation, bubble-like lucency, pleural retraction and pleural attachment were recorded and analyzed. The differences of image features of main lesion and the concomitant lesion in the primary group and the metastasis group were compared. Results: The image feature matching types of pGGN + mGGN and mGGN + mGGN were more common in the primary group, and the ground glass component contained pGGN or mGGN was accounted for 62.9%(39/62). At least one lesion containing the ground glass component was accounted for 96.8% (60/62). There were two types in metastatic groups, mGGN+ SN and SN+ SN accounting for 6.5% (2/31) and 93.5% (29/31), respectively. There were significant differences in image feature matching types between the primary group and metastatic group (P<0.01). Univariate analysis of the main lesions between the two groups showed that the gender, smoking history, long diameter of the main lesion, long diameter of the solid component, the ground glass component and pleural attachment were statistically different (P<0.05). Further analysis by multivariate logistic regression showed that the male (OR=5.742, P=0.010), SN (OR=41.291, P<0.01) and pleural attachment (OR=9.288, P=0.001) were the three significant risk factors associated with the main lesions in metastasis group.The most common concomitant lesions in primary group were pGGN, containing the ground glass component. However, all of the concomitant lesions in the metastatic group were SN (P<0.01), showing round lesions with well-defined margin, attaching the pleura (P<0.05). Conclusions: The HRCT features of lung adenocarcinoma can differentiate synchronous multiple lung adenocarcinoma from lung adenocarcinoma with intrapulmonary metastasis. At least one lesion contains ground glass components (pGGN or mGGN) in synchronous multiple primary lung adenocarcinoma, while SN is more common in lung adenocarcinoma with lung metastasis. Lung cancer with intrapulmonary metastasis can be considered when the main lesion is SN with pleural attachment and the intrapulmonary accompanying lesion is also solid nodules without lobular, speculation and bubble-like lucency.

Lung adenocarcinoma with metastasis to the uterine cervix is rare, as is ureteral obstruction attributed to metastasis from lung adenocarcinoma. We report a case of lung adenocarcinoma with metastases to both the uterine cervix and retroperitoneal lymph nodes resulting in obstructive uropathy. We used immunohistochemical staining, the epidermal growth factor receptor gene and the clinical course to differentiate lung adenocarcinoma from cervical adenocarcinoma. An excellent response was achieved with first-line gefitinib treatment for 3 months-both the hydronephrosis and the metastatic cervical tumor had almost disappeared. This is the first case report of metastatic retroperitoneal lymphadenopathy with ureteral obstruction resulting from lung adenocarcinoma treated effectively and safely with gefitinib.

We report a case of lung cancer with an iris metastasis. The 80-year-old man had squamous cell carcinoma of lung with multiple bony metastases, and was treated with radiotherapy. Eight months after this treatment, brain metastases and increased intracranial pressure were diagnosed. Glycerol and corticosteroid were given to lower intracranial pressure. The condition of the patient improved. Systemic chemotherapy or brain radiotherapy was suggested, but rejected by the patient. Furthermore, he complained of blurred vision in both eyes. Best-corrected visual acuity was 20/50 in both eyes. By slit lamp examination, two whitish nodules (1×0.5 and 0.2×0.3 mm in size) without prominent blood vessels were identified at the inferior pupillary margin in the right eye. No secondary glaucoma, hyphema, or iritis was found. Metastasis to the iris from lung cancer without choroidal metastasis was impressed. We suggested a course of radiotherapy to the right eyeball, but the patient refused treatment. Metastatic iris tumors are not common. The characteristics, differential diagnosis, and management of iris metastasis will be reviewed in this report.

Objective To study the expression of microRNA (miRNA, miR)-338 in lung adenocarcinoma cell line and lung adenocarcinoma tissues, and to study the mechanism of lung cancer metastasis. Methods The expression of miR-338 was detected by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) in lung adenocarcinoma cell line A549, and 115 cases of lung adenocarcinoma tissues and normal lung tissues adjacent to tumor. To construct miR-338 over expressing lung cancer cell line and explore the function of miR-338 in the proliferation, invasion and metastasis of lung cancer cells. To detect the expression of integrin β3 in miR-338 over expression lung cancer cell line, and to study the mechanism of miR-338 inhibiting lung cancer metastasis. Results (1)The expression of miR-338 was down regulated in lung adenocarcinoma cell line and lung adenocarcinoma tissues (1.00 vs. 0.15±0.01, P=0.035), (0.00 vs. -2.99±3.69, P=0.001). The expression of miR-338 was correlated with tumor embolus, tumor recurrence, TNM stage (P=0.005, 0.004, 0.025). The 5 years overall survival rate of the low expression group was significantly lower than that of the high expression group (median survival time 44 months vs. 53 months, P=0.001). (2) Up-regulating the expression of miR-338 can inhibit the proliferation of lung cancer cells, migration [average cell count (347±41) cells vs. (190±8) cells, P=0.029] and invasion [average cell count (197±12) cells vs. (68±14) cells, P=0.008]. Xenograft tumor model in nude mice showed that the high expression of miR-338 can effectively inhibit the growth of transplanted tumor [average tumor clone number (20±7) cells vs. (4±2) cells, P=0.004]. (3) In the miR-338 over expression lung adenocarcinoma cell line, the expression of integrin β3 was significantly lower than that in control cells (1.00 vs. 0.35±0.04, P=0.001). Dual luciferase activity assay revealed that the miR-338 over expression group was reduced in the luciferase activity (1.00 vs. 0.75±0.08, P=0.030). Conclusion (1) MiR-338 can inhibit the proliferation, invasion and metastasis of lung cancer cells; (2) MiR-338 play a negative regulation post transcription by targeting the integrin β3 3’untranslated regions (3’UTR) mRNA region. integrin β3 is a new miR-338 lung cancer target gene. Key words: Lung adenocarcinoma; Metastasis; MicroRNA-338; Integrin β3

Objective To investigate the expression of hypoxia inducible factor 1α (HIF-1α) and glucose transporter 1 (GLUT1) in lung adenocarcinoma and its correlation with tumor metastasis. Methods SP immunohistochemistry was used to detect GLUT1 and HIF-1α protein expression in 125 lung adenocarcinoma, including 41 cases without metastasis, 38 cases with lymphatic metastasis and 46 cases with brain metastasis. The correlation of GLUT1 and HIF-1α in lung adenocarcinoma metastasis was analyzed by using χ2 test and Pearson correlation analysis. Results Most lung adenocarcinoma were histologically heterogeneous, which contained more than one adenocarcinoma type. 73.2 % (30/41) cases were acinar predominant adenocarcinoma in lung adenocarcinoma without metastasis; 53.6 % (15/38) cases were acinar predominant adenocarcinoma and 26.3 % (10/38) cases were solid predominant adenocarcinoma in lung adenocarcinoma with lymphatic metastasis; 47.8 % (22/46) cases were papillary predominant adenocarcinoma and 34.8 % (16/46) cases were solid predominant adenocarcinoma in lung adenocarcinoma with brain metastases. The expression level of GLUT1 and HIF-1α in lung adenocarcinoma with lymphatic metastasis group was higher than that of the group without tumor metastasis (P < 0.05); the expression of GLUT1 and HIF-1α were positively correlated (r= 0.407, P= 0.000). Conclusions Papillary adenocarcinoma is the most histological type in lung adenocarcinoma with brain metastasis, suggesting that papillary adenocarcinoma is more prone to brain metastasis. The expression of GLUT1 and HIF-1α play an important role in lymph node metastasis and brain metastasis of lung adenocarcinoma. Key words: Adenocarcinoma, bronchiolo-alveolar; Glucose transporter type 1; Hypoxia inducible factor 1, αsubunit; Immunohistochemistry