Solitary splenic metastasis of an adenocarcinoma of the lung

Splenic metastasis of solid tumors is a rare event, most often diagnosed at the time of autopsy. Whereas in cases of widely disseminated cancer, splenic involvement may be fairly common, solitary splenic metastasis in the absence of other metastases is exceedingly rare. The authors report a case of a 63-year-old woman in whom the sole detectable distant metastasis of a lung carcinoma was a splenic mass. The splenic lesion was detected before the resection of the primary lung lesion during a complete metastatic work-up. At that time, however, it was considered unlikely that the mass in the spleen represented a metastasis because of the lack of metastatic disease elsewhere.     

Splenic metastases in a large unselected autopsy series

We analyzed the files of all autopsies performed at the Institute of Pathology of the Philipps-University Marburg between 1980 and 1999 with respect to the presence of splenic metastasis. The total number of autopsies within the study period was 8,563. In 1,898 cases, a solid malignant tumor (1,774 carcinomas, 36 sarcomas, 27 malignant melanomas) was diagnosed. Metastasis to the spleen occurred in 57 cases (3.0%). Compared to the whole study population, patients with splenic metastasis were significantly younger (59 years vs. 67 years, p<0.05) and had significantly more metastastic sites (median: 6 vs. median:1, p<0.05). This underlines the assumption that splenic metastasis is associated with a worse prognosis. Lung cancer, cutaneous malignant melanoma, and breast cancer were the most frequent primary tumors, accounting for 24.6%, 15.8%, and 12.3% of all spleen metastases, respectively. Patients with testicular germ cell tumors (patients: 9, spleen metastasis: 4), malignant melanoma (patients: 27, spleen metastasis: 9, 33%), and small cell lung cancer (patients: 106, spleen metastasis: 8, 7.5%) had the highest frequency of splenic involvement. Most (n=48) metastases were detected macroscopically, the remaining ones were micrometastases (n=2), small tumor cell clusters, and single tumor cells within sinusoids (n=7). The present study underlines the importance of spleen metastasis as an indicator of poor prognosis. There are, however, various aspects as to the detection and morphology of spleen metastasism, which merit further scrutiny.     

Gastrointestinal tract metastasis of lung cancer: The PD-L1 expression and correlated clinicopathological variables

The gastrointestinal tract is a rare site for metastatic lung cancer. Programmed cell death-ligand 1 (PD-L1) expression in lung cancer is a biomarker for the response to anti-PD-1/PD-L1 therapy. We investigated clinicopathological features and PD-L1 expression in 25 gastrointestinal metastatic tumors from the lung and primary adenocarcinoma of the small bowel. The small bowel was the most common site (16/25; 64%) of gastrointestinal tract lung cancer metastasis. A total of 19 (76%) of the gastrointestinal metastasis showed PD-L1 expression in ≥5% of tumor cells, with 14 (56%) showing high expression levels (≥50%). In contrast, 21 (84%) expressed PD-L1 in ≥5% immune cells, including 4 (16%) showing a high expression levels (≥50%). The PD-L1 expression on tumor cells and immune cells in primary lung cancer and corresponding gastrointestinal metastasis was concordant in 13 (68%) and 11 (58%) of the 19 paired cases, respectively. Small-bowel metastasis of lung cancer was characterized by a higher incidence of perforation (31% vs. 0%), ulcerated mass (83% vs. 60%), and neoplastic PD-L1 expression (75% vs. 0%) compared to primary small-bowel adenocarcinoma. Gastrointestinal metastasis from lung cancer might be a potential target for immune checkpoint inhibitor therapy, given its high expression of PD-L1.     

Growth rate analysis of lung metastases appearing 18 years after resection of cutaneous adenoid cystic carcinoma. Case report and review of the literature.

Growth rate analysis of lung metastases of a cutaneous adenoid cystic carcinoma, which appeared 18 years after the resection of the primary tumor from the scalp is presented. The doubling times of the metastases were long compared with that of other lung metastases. They were 22 months for the metastasis in the right lung and 70 months for the metastasis in the left lung, with a shortening of the doubling time in the left side to 10.4 months in the last 4 months of observation. Backward extrapolation showed that the metastases to the lung were disseminated before the diagnosis and surgical resection of the primary tumor. To our knowledge, this is the third reported case of lung metastases from a cutaneous adenoid cystic carcinoma out of 25 documented cases. We present a review of the literature and discuss the clinical implications of our findings.     

Cardiac plasmacytoma.

A 69-year-old white woman presented with a 3-month history of progressive dyspnea, orthopnea, fatigue and weakness. Clinical, diagnostic imaging and echocardiographic investigations suggested an occult primary cancer with metastasis to the heart. The patient's condition deteriorated gradually, and she died 2 months later. At autopsy, a malignant tumor encasing the heart and a 1-cm solitary tumor nodule in the lower lobe of the left lung were found. Histologic and electron microscopic studies revealed a plasmacytoma predominantly involving the epicardium and a small solitary plasmacytoma located in the left lung. The two tumors were further confirmed by immunohistochemical studies that showed monoclonal IgG expression and kappa light chain restriction.     

Artificial metastases and decrease of fibrinolysis in the nude mouse lung after hemithoracic irradiation

X-irradiation to the nude mouse lung and the ensuing pulmonary metastasis of the injected human cancer cells were investigated. Human cancer cells were injected intravenously into nude mice following 20 Gy right hemithoracic irradiation. The right lungs showed evidence of metastasis while metastasis was slight in the non-irradiated left lung. Platelet aggregation and fibrin deposition occurred around the arrested cancer cells in the capillaries of the right lung. The fibrinolytic activity of the irradiated right lung was lower than that of the non-irradiated contralateral lung. Natural killer cell activity was lower in the right-lung-irradiated mice than in the non-irradiated mice. We conclude that when the target organ is exposed to X-irradiation, there will be a decrease in fibrinolytic activity, a condition paving the way toward a metastasis.     

CD44s在肺癌中的表达及其意义

目的:探讨CD44s在肺癌组织中的表达及其临床意义。方法:采用免疫组化方法检测117例原发性肺癌的CD44s异常表达。结果:CD44s在小细胞肺癌(SCLC)不表达,而表达于非小细胞肺癌(NSCLC)中,并且鳞癌的CD44s表达强度明显强于腺癌(P＜0.05);未发生淋巴结转移的肺癌病例中CD44s的表达明显高于已经发生转移的病例(P＜0.01);按照临床肿瘤TNM分期,早期肺癌的CD44s表达显著高于进展期肺癌(P＜0.05)。结论:CD44s对肺癌组织的病理类型、淋巴结转移、临床分期以及预后的判断是一个较好的评价指标。     

Characterization of a highly metastatic, orthotopic lung cancer model in the nude rat

The prevailing subcutaneous nude rodent tumor xenograft models used for biological and preclinical studies do not optimally reflect some important biological properties of cancer, especially invasion and metastasis. Orthotopic models have been developed to address this need. However, for lung cancer none of the available models are optimal, in that none originate from an orthotopic (bronchial) primary site and exhibit extensive extrathoracic metastasis. Our goal was to develop a consistent rodent model of non-small cell lung cancer with both of these properties. Groups of male Rowett nude rats were given 500 rads of gamma radiation and then endobronchially implanted in the right caudal lobe airway with 50 mg of small NCI-H460 tumor fragments taken from an orthotopic donor tumor. They were then sacrificed at selected post-implantation times and evaluated grossly and histologically for animal weight, primary tumor take and size, and metastatic tumor incidence at multiple sites. At a late time point (32–35 days), consistency of primary tumor size and metastasis was estimated by comparing results from four groups of rats implanted on different occasions. The results showed that the primary tumors grew steadily, reaching four grams by days 32–35. Rats gained weight until days 14 to 21, but then began to show cachexia. High metastatic rates (>60%) were seen for mediastinal lymph nodes (by 21 days), and kidney, bone and brain (by 28 days). Mean primary tumor size and the incidences of both regional and systemic metastasis were consistent at 32–35 days in four different groups of six animals. In conclusion, this orthotopic lung cancer model is highly metastatic and consistent in terms of both primary tumor growth and metastatic behavior. It is the only available rodent model of human lung cancer emanating from an endobronchial site and metastasizing to multiple extrapulmonary sites, and should be very useful for both biological and preclinical studies of lung cancer, particularly where studies of antimetastatic activity are of interest, and/or where survival studies are desired.     

Photodynamic ablation of lymphatic vessels and intralymphatic cancer cells prevents metastasis

The dissemination of tumor cells to sites far from the primary tumor (metastasis) is the principal cause of death in cancer patients. Tumor-associated lymphatic vessels are a key conduit for metastatic tumor cells, which typically first colonize the lymph nodes. Although the primary tumor and affected lymph nodes can be removed during surgery, tumor cells inside lymphatic vessels are left behind. Here, we show that in-transit tumor cells inside lymphatic vessels in mice bearing mouse melanomas or human lung tumors give rise to metastases. Using photodynamic therapy with the benzoporphyrin derivative verteporfin, we selectively destroyed lymphatic vessels in mice and pigs. Destruction of tumor-associated lymphatic vessels also eradicated intralymphatic tumor cells and prevented metastasis of mouse melanoma cells and subsequent relapse. Photodynamic therapy, when combined with anti-lymphangiogenic therapy, prevented further tumor invasion of lymphatic vessels. These findings highlight the potential of targeting in-transit tumor cells in patients.     

Cytopathologic evaluation of lung carcinomas presenting as brain metastasis.

Brain metastasis is an uncommon initial presentation of lung carcinoma. One arm of this analysis is a retrospective review of 137 cases of surgically diagnosed solitary brain metastasis, which were eventually found to be of lung origin, encountered at Hines VA Hospital during the period 1958 to 1996. The second arm is composed of fine-needle aspiration biopsy specimens of primary lung tumor in 23 patients with an initial clinical diagnosis of brain metastasis and without the benefit of surgery, seen from 1981 through 1996. Our results in both analyses indicate that pulmonary adenocarcinoma is the predominant primary tumor that initially manifests as a brain metastasis, approaching 76% (107 and 17 cases, respectively), followed by small-cell carcinoma at 20% (24 and five cases, respectively) and large-cell undifferentiated carcinoma and squamous-cell carcinoma at 2% each. The predominance of adenocarcinoma as a source of brain metastasis in lung cancer patients probably reflects its rising incidence overall of late. Collateral findings also suggest that surgical resection of a solitary and small brain metastasis as well as of a discrete lung primary, whenever feasible, as the most effective procedure to improve survival and quality of life of patients.     

Palatine tonsillar metastasis of lung cancer during chemotherapy

Malignant tumors in the tonsils are usually primary. Metastases to the tonsils are extremely rare, with nearly one hundred cases reported. Herein we present an unusual case of palatine tonsillar metastasis of non-small cell lung cancer during chemotherapy. The patient was a 39-year-old man who was diagnosed as non-small lung cancer with IIIA4 staging and poor differentiated histology. After two cycles of vinorelbine and cisplatin based chemotherapy, a big mass was developed in the right palatine tonsil which was pathologically confirmed as the metastasis from the lung. There was no hemorrhage and complains except moderate foreign body sensations. No cervical lymphadenopathy and distal metastases to other organs such as brain and liver was found. Because of poor overall performance status, no radiotherapy was given. The disease progressed after docetaxel treatment. To the best of our knowledge, this is the first case with palatine tonsillar metastasis from non-small lung cancer during induction chemotherapy.     

A spontaneous metastasis model reveals the significance of claudin-9 overexpression in lung cancer metastasis

Metastasis causes most cancer related mortality but the mechanisms governing metastatic dissemination are poorly defined. Metastasis involves egression of cancer cells from the primary tumors, their survival in circulation and colonization at the secondary sites. Cancer cell egression from the primary tumor is the least defined process of metastasis as experimental metastasis models directly seed cancer cells in circulation, thus bypassing this crucial step. Here, we developed a spontaneous metastasis model that retains the egression step of metastasis. By repeated in vivo passaging of the poorly metastatic Lewis lung carcinoma (3LL) cells, we generated a cell line (p-3LL) that readily metastasizes to lungs and liver from subcutaneous (s.c.) tumors. Interestingly, when injected intravenously, 3LL and p-3LL cells showed a similar frequency of metastasis. This suggests enhanced egression of p-3LL cells may underlie the enhanced metastatic spread from primary tumors. Microarray analysis of 3LL and p-3LL cells as well as the primary tumors derived from these cells revealed altered expression of several genes including significant upregulation of a tight junction protein, claudin-9. Increased expression of claudin-9 was confirmed in both p-3LL cells and tumors derived from these cells. Knockdown of claudin-9 expression in p-3LL cells by si-RNA significantly reduced their motility, invasiveness in vitro and metastasis in vivo. Conversely, transient overexpression of claudin-9 in 3LL cells enhanced their motility. These results suggest an essential role for claudin-9 in promoting lung cancer metastasis.     

骨髓间充质干细胞促进肺癌转移的机制

BACKGROUND:So far the positive or negative effects of mesenchymal stem cells on tumor growth and metastasis are under discussion. OBJECTIVE:To explore the mechanism of bone marrow mesenchymal cells in promoting lung cancer metastasis. METHODS: Primary rat bone marrow mesenchymal stem cells were obtained by direct adherence method of the whole bone marrow, and differential adherence combined with digestion control method was performed to purify cells. Lung cancer cell lines were cultured, and the effects of bone marrow mesenchymal stem cells on the migration, invasion and metastasis of lung cancer cells were observed by scratch test, cell invasion and migration assays. Orthotopic lung cancer models were established in rats and bone marrow mesenchymal stem cells were seeded onto the left lung of rats. Then, pathological changes of lung tissues were observed at 14 days after transplannation. RESULTS AND CONCLUSION:After the scratch test, the migration rate of lung cancer cells became higher, and the scratches healed with time. And after cell transplantation, the number of migrated lung cancer cells increased, as well as the ability of lung cancer cells penetrating the Matrigel was strengthened. Besides, fibrous connective tissues could be found around the lung cancer tissues, and necrosis with distinct boundary and large tumor nuclei; the metastatic tissues showed obvious infiltration and necrosis with large tumor nuclei. These results suggest that bone marrow mesenchymal stem cells can promote the invasion, migration and metastasis of lung cancer cell lines.       

Isolated splenic metastasis from colorectal carcinoma: a case report

Isolated splenic metastasis arising from colorectal carcinoma is very rare and there has been only 6 cases reported in the English literature. A new case is presented, and its possible pathogenesis was considered with previously reported cases. A 65-year-old male patient had received a right hemicolectomy for ascending colon cancer 36 months earlier. He was followed up regularly with serial measurement of serum carcinoembryonic antigen (CEA). Rising serum CEA was discovered from 33 months postoperatively and CT revealed an isolated splenic metastasis. He therefore underwent splenectomy, which was proven to be a metastatic adenocarcinoma with similar histological feature to the original tumor. As all reported cases showed elevated serum CEA at the time of metastasis, isolated splenic metastasis might be associated with CEA in regard to its biological functions of immunosuppression and adhesion.     

肺肠型腺癌6例诊疗分析并文献复习

目的：肠型腺癌是非小细胞肺癌的一种少见病理类型,本文主要讨论肺肠型腺癌的临床和病理特征,诊断和治疗方法。方法：回顾性分析2013年至2016年5月间诊治的6例肺肠型腺癌患者的临床资料。结果：男2例,女4例,发病年龄25~78岁,以“咳嗽胸闷”起病4例,伴“颈部包块”4例,以“头晕恶心呕吐”起病1例;影像学主要表现为肺部、锁骨上及纵隔占位,病理形态及免疫组化均提示肿瘤来自于结直肠癌,但胃肠镜均未见异常占位;根治性和姑息性手术各1例,其中1例根治术后复发转移;1例行脑单发转移灶射波刀治疗后未再接受治疗,余5例患者均接受了全身化疗。截止随访结束,4例患者死亡,生存时间最短9个月,最长32个月。结论：肺肠型腺癌易与结直肠癌肺转移相混淆,确诊需要排除肠道病变,早期治疗以手术治疗为主,关于系统治疗方案有待临床进一步研究。     

Plasma microRNAs as novel biomarkers for early detection of lung cancer

A diagnosis of lung cancer at its early stages is vital for improving the survival rate of patients. MicroRNAs (miRNAs), a family of 19- to 25-nucleotide non-coding small RNAs, are frequently dysregulated in lung cancer. The objective of this study was to investigate the potential of circulating miRNAs for early detection of lung cancer. We searched the published literature for the miRNA microarray data of primary lung cancer and selected 15 miRNAs that were most frequently up-regulated in lung cancer tissues. Total plasma RNA including miRNAs was isolated, polyadenylated and reverse-transcribed into cDNAs. The levels of miRNAs were determined by real-time RT-PCR in 74 lung cancer patients and 68 age-matched cancer-free controls. We found that the levels of miR-155, miR-197, and miR-182 in the plasma of lung cancer including stage I patients were significantly elevated compared with controls (P<0.001). The combination of these 3 miRNAs yielded 81.33% sensitivity and 86.76% specificity in discriminating lung cancer patients from controls. The levels of miR-155 and miR-197 were higher in the plasma from lung cancer patients with metastasis than in those without metastasis (P<0.05) and were significantly decreased in responsive patients during chemotherapy (P<0.001). These results indicate that miR-155, miR-197, and miR-182 can be potential non-invasive biomarkers for early detection of lung cancer.     

Microwave ablation of primary breast cancer inhibits metastatic progression in model mice via activation of natural killer cells

Surgery is essential for controlling the symptoms and complications of stage IV breast cancer. However, locoregional treatment of primary tumors often results in distant progression, including lung metastasis, the most common type of visceral metastasis. As a minimally invasive thermal therapy, microwave ablation (MWA) has been attempted in the treatment of breast cancer, but the innate immune response after MWA has not yet been reported. Using two murine models of stage IV breast cancer, we found that MWA of primary breast cancer inhibited the progression of lung metastasis and improved survival. NK cells were activated after MWA of the primary tumor and exhibited enhanced cytotoxic functions, and the cytotoxic pathways of NK cells were activated. Depletion experiments showed that NK cells but not CD4+ or CD8+ T cells played a pivotal role in prolonging survival. Then, we found that compared with surgery or control treatment, MWA of the primary tumor induced completely different NK-cell-related cytokine profiles. Macrophages were activated after MWA of the primary tumor and produced IL-15 that activated NK cells to inhibit the progression of metastasis. In addition, MWA of human breast cancer stimulated an autologous NK-cell response. These results demonstrate that MWA of the primary tumor in metastatic breast cancer inhibits metastatic progression via the macrophage/IL-15/NK-cell axis. MWA of the primary tumor may be a promising treatment strategy for de novo stage IV breast cancer, although further substantiation is essential for clinical testing.     

Metastasis of colon cancer to the thyroid gland: A case diagnosed on fine‐needle aspirate by a combined cytological,immunocytochemical, and molecular approach

Fine‐needle aspiration (FNA) with cytological evaluation reliably diagnoses primary and secondary thyroid neoplasms. However, identifying the primary origin of a metastatic process involving the thyroid gland is challenging. In particular, metastasis of colon cancer to the thyroid gland is very rare. In this case report, a right lobe solid thyroid nodule in a 66‐year‐old male was aspirated. FNA cytology showed necrosis and atypical tall columnar cells; since, the patient at age 60 had undergone surgery for a sigmoid‐rectal cancer metastasizing to the liver and subsequently to the lung, a suspicion of metastasis from colon cancer was raised. This was corroborated by cell‐block immunocytochemistry showing a cytokeratin (CK) 7 negative/CK20‐positive staining pattern; thyreoglobulin and TTF‐1 were both negative. Since KRAS codon 12/13 mutations frequently occur in colon cancer, whereas they are extremely uncommon in primary thyroid tumors, DNA was extracted from the aspirated cells, and KRAS mutational analysis was carried out. The codon 12 G12D mutation was found; the same mutation was evident in the primary cancer of the colon and in its liver and lung metastasis. Thus, a combined cytological, immunocytochemical and molecular approach unquestionably correlated metastatic adenocarcinoma cells aspirated from the thyroid to a colo‐rectal origin. Diagn. Cytopathol. 2010;38:932–935. © 2010 Wiley‐Liss, Inc.