Primary Malignant Melanoma of the Lung: A Case Report

BACKGROUND: Primary melanoma of the lung is an extremely rare pathological entity and sparsely reported in the literature. CASE PRESENTATION: A case of primary malignant melanoma of the lung in a 41-year-old female is reported. The clinical, radiological and histopathological features are discussed. The initial symptom was cough, whereas the chest radiography showed a round opacity of the right lung. The computed tomography of the chest revealed a well-demarcated mass lesion in the right upper lobe. Endobronchial mass causing obstruction of the upper lobar bronchus was the bronchoscopic finding. Patient underwent pneumonectomy. A diagnosis of melanoma was confirmed postoperatively after the immunohistochemistry. Primary nature of the tumour in the lung results from the demonstration of characteristic junctional pattern of melanoma cells beneath the bronchial epithelium on histopathology, and from exclusion of other potential primary sites in the clinical, paraclinical and laboratory examination. CONCLUSIONS: Primary melanoma of the lung represents a rare pathological entity. Careful interpretation of histopathological information in correlation with all other findings from clinical and paraclinical studies can establish a diagnosis. Follow-up is necessary in order to diagnose potential dissemination or secondary sites of the disease. Due to the small number of cases reported in the literature, there is no experience on the management and the prognosis of the disease, but surgical resection remains the cornerstone of the treatment

Mouse p53-deficient cancer models as platforms for obtaining genomic predictors of human cancer clinical outcomes

Mutations in the TP53 gene are very common in human cancers, and are associated with poor clinical outcome. Transgenic mouse models lacking the Trp53 gene or that express mutant Trp53 transgenes produce tumours with malignant features in many organs. We previously showed the transcriptome of a p53-deficient mouse skin carcinoma model to be similar to those of human cancers with TP53 mutations and associated with poor clinical outcomes. This report shows that much of the 682-gene signature of this murine skin carcinoma transcriptome is also present in breast and lung cancer mouse models in which p53 is inhibited. Further, we report validated gene-expression-based tests for predicting the clinical outcome of human breast and lung adenocarcinoma. It was found that human patients with cancer could be stratified based on the similarity of their transcriptome with the mouse skin carcinoma 682-gene signature. The results also provide new targets for the treatment of p53-defective tumours

Cisplatin-Based Three Drugs Combination (NIP) as Induction and Adjuvant Treatment in Locally Advanced Non-small Cell Lung Cancer: Final Results

IntroductionThis phase III trial was conducted in non-small cell lung cancer patients with locally advanced stage II B (only T3N0) III A and III B (only T4 N0). Primary endpoint was 2-year survival; secondary were toxicity, disease-free survival, and overall survival.MethodsAfter three cycles of vinorelbine (N) 25 mg/m2 on days 1 and 5, ifosfamide/mesna (I) 3 g/m2 on day 1, cisplatin (P) (NIP), patients were treated by surgery and within 45 days were randomized to two additional cycles of NIP versus observation.ResultsMedian tumor diameter was 5.5 cm (1.2–10.6). Overall, 155 of 156 patients received chemotherapy: 133 (85%) men, median age: 59 years (35–75). Sixty-five percentage of patients were stage III A, 28% II B, and 7% III B. The study has been closed prematurely because of the low inclusion rate. After three cycles of induction in 143 assessable patients, 82 reported an objective response (57.3%) (95% CI: 48.8–65.6), with 3.5% complete response and 53.8% partial response. Relative dose intensity during neoadjuvant NIP (%) was 97, 98, and 98.5 for vinorelbine, ifosfamide/mesna, and cisplatin, respectively. Tolerance: G3 to 4 neutropenia in 3% of patients and G3 to 4 anemia in 4%; nonhematological toxicities included G3 nausea/vomiting in 11%, G3 anorexia and G3 to 4 infection in 6.5%, G3 asthenia in 10% and G3 to 4 alopecia in 25.5%. After a median of 32 days after NIP, 107 patients (69%) underwent operation with complete resection (R0) in 74% (79 of 107 patients). Downstaging (N2 to N0) after surgery was 29%. Operative mortality rate was 2.8%. Twenty-one days (median) after surgery, 79 patients were randomized to adjuvant NIP (47%) or control (53%). Tolerance of adjuvant NIP: 12.5% G3 to 4 nausea/vomiting, 19% G3 alopecia, 6% G3 infection, and G3 asthenia. Overall median survival 32.3 versus 31.8 months in the observation and NIP arms, respectively.ConclusionsNIP allows 74% of R0 with no surgery delay. The few number of randomized patients did not allow to conclude on the efficacy of adjuvant chemotherapy

Predictive Indicators of Survival in Patients With Surgically Resected Lung Carcinoid Tumors at a Greek Medical Center

Introduction Lung carcinoid tumors are neuroendocrine neoplasms, less frequent than other lung tumors. They are subdivided into typical carcinoids (TC) and atypical carcinoids (AC), according to the rate of mitosis and the presence of necrosis. Lung carcinoids are often asymptomatic and only discovered incidentally. They may also present with cough, wheezing, asthma, and chronic obstructive pulmonary disease, chest pain, and hemoptysis depending on the location of the tumor and, less commonly, present with carcinoid syndrome. In our study, we describe the clinical and pathological features of patients with surgically resected lung carcinoids at our institution over a period of 14 years. We also examine if these features, including age, gender, tumor size, type of carcinoid, stage, nodal involvement, and Ki-67 expression are associated with patients' survival. Materials and methods We retrospectively reviewed patients that underwent surgery with a final histologic diagnosis of a pulmonary carcinoid tumor from March 2005 to March 2019. The evaluation included history, physical examination, chest radiographs, computerized tomography of the chest, upper abdomen, and brain, and bone scintiscan. All specimens resected during the surgical procedures were sent for pathological examination, including mediastinal and hilar lymph nodes. The patients' age, gender, tumor size, type of carcinoid, nodal involvement, stage, and Ki-67 expression were recorded and correlated to the patients' survival rates. Results The study included 108 patients - 52 males and 56 females - with a mean age of 51.5 years (range 11-80 years). Atypical carcinoid was the diagnosis in 28 patients (16 males and 12 females) and 80 patients had the diagnosis of typical carcinoid (36 males and 44 females). Tumor size was <= 3.7 cm in 84 patients (68 with TC and 16 with AC) and >3.7 cm in 22 patients (12 with TC and 10 with AC). Sixteen patients had nodal deposits, 12 in N1 nodes and four in N2 nodes. Eighty patients were classified in stage I, 18 patients in stage II, and 10 patients in stage III. None of the patients had distant metastases. The Ki-67 proliferation index was examined in 84 specimens and Ki-67 was <2.5 in 50 patients and >= 2.5 in 34 patients. Of the 108 patients, eight died, all with disease-related death. According to the Cox regression univariate analysis, four factors were correlated to shorter survival: atypical histology, tumor size >3.7 cm, nodal involvement, and advanced stage Conclusions In conclusion, we found that histological type, tumor size, nodal involvement, and stage are associated with survival in patients with surgically resected lung carcinoids without distant metastases. Other parameters, such as age at operation, gender, and Ki-67 index, did not have a role in survival in these patients according to the Cox regression univariate analysis

Prognostic value of the immunohistochemistry markers CD56, TTF-1, synaptophysin, CEA, EMA and NSE in surgically resected lung carcinoid tumors

Lung carcinoid tumor is a type of neuroendocrine tumor, which is subdivided into typical carcinoid (TC) and atypical carcinoid (AT), based on the rate of mitosis and the presence of necrosis. Several prognostic factors for lung carcinoids have been reported in the literature, including the type, Ki67 index, stage, chemotherapy and radiation therapy. In the present study, 108 cases with resected carcinoid lung tumors were enrolled and the expression of CD56, thyroid transcription factor 1, synaptophysin, carcinoembryonic antigen, epithelial membrane antigen and neuron-specific enolase (NSE) in the resected tissue specimens was immunohistochemically analyzed. Patients with positive staining for NSE had an unfavorable survival prognosis compared with patients with negative staining for NSE (137.2 vs. 150.0 months, P=0.044). According to univariate analysis, none of the above immunohistochemistry markers was associated with survival, and according to multivariate analysis, NSE was an independent influencing factor for survival inpatients with AT (P=0.046) and furthermore, the stage was an independent factor of survival in patients with TC (P=0.005)

The 682-gene signature expression pattern in mouse carcinomas is dependent on p53 expression.

<p><b>A</b>) SV40 Large-T antigen expression in mammary gland was analysed at various time-points during carcinoma formation in transgenic WAP-TNP8 mice. Heatmaps of 682-gene signature transcripts from normal mammary glands (green), primary breast carcinomas (red) and mammary samples with transgene expression at 1, 2, 3, 4 and 5 months (blue) are shown (upper panel). <b>B</b>) p53 expression was induced in lung adenomas and adenocarcinomas in the Kras^LA2/+;Trp53^LSL/LSL;Rosa26Cre^ERT2 mouse model. The heatmaps of the 682-gene signature transcripts from normal lungs (green), lung adenomas (orange) and adenocarcinomas (red) (treated and untreated) are shown (upper panel). In <b>A</b> and <b>B</b>, sample groups are ordered from left to right based on increasing Pearson correlation with the centroid template based on the 682-gene signature. Probesets are ordered from top to bottom based on T-values (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042494#s4" target="_blank">Materials and Methods</a>). The number of samples in each group is shown under the heatmap. The correlation values for individual samples with the centroid are shown in the middle panel. Values range from −1 (negative correlation, bluish background) to +1 (positive correlation, reddish background). The significance of the correlation for each sample is shown in the lower panel as –log₁₀(p-val). The red line indicates a p-val of 0.01.</p