Georgia Karpathiou

Prognostic factors in patients presenting with pleural effusion revealing malignancy.

Background: The survival of patients with malignant pleural effusion is considered generally poor. Most of the studies reporting results of prognostic factors are retrospective, using pleural thoracentesis for diagnosis. The objectives of our study were to reveal possible prognostic factors in patients initially presenting with undiagnosed pleural effusion proven to be malignant by diagnostic thoracoscopy. Methods: Ninety consecutive patients, 48 of whom were male (53%), with a median age of 69 years (range 37-93) and a performance status (PS) of 0/1 (63%) and with initially undiagnosed pleural effusion that was proven to be malignant by thoracoscopy were evaluated. Survival time was defined as the time from thoracoscopic diagnosis to death or the last follow-up. A regression analysis was used to determine significant clinical and biological prognostic factors. Results: Lung carcinoma (44.4%), breast carcinoma (24.4%), and mesothelioma (12.2%) were the most frequent tumors diagnosed. The median overall survival was 11 months (range 0.5-55). The survival of the patients was related to the following factors: histology of the primary tumor (p = 0.008), PS (p < 0.001), white blood cells (p = 0.018), and the blood neutrophil-to-lymphocyte (N/L) ratio (p = 0.002). Multiple regression showed PS, histology, and the N/L ratio. Conclusion: The factors affecting survival in our patients were PS, primary tumor histology, and the N/L ratio. These factors may help physicians select patients for treatment and/or interventional procedures.

LC3A-positive "stone-like" structures in cutaneous squamous cell carcinomas.

This study was set to investigate the relation between autophagic activity and the aggressiveness of cutaneous squamous cell carcinomas (SCC), as indicated by tumor thickness and proliferative activity. The anti-LC3A antibody, recognizing both the soluble and the autophagosome-bound forms of the protein, and a standard immunohistochemical technique were applied to 75 cutaneous SCC of variable tumor thickness. The study was complemented by staining for MIB1. Three patterns of LC3A reactivity were recognized: diffuse cytoplasmic, cytoplasmic/perinuclear, and “stone-like” structures (SLS), that is, large, rounded, densely stained amorphous material, 5 μm on average, enclosed within cytoplasmic vacuoles. Higher numbers of SLS were counted in >6-mm-thick SCC compared with the intermediate-thickness tumors (2.1-6 mm) and the <2-mm-thick tumors; the mean recorded values, being 8.8, 4.55, and 1.55, respectively, were statistically significant. The diffuse cytoplasmic staining showed a nearly inverse trend, whereas the perinuclear pattern, expressed in <10% of the total, was not evaluated. With regard to MIB1 proliferation index, this increased with tumor thickness and, in linear regression analysis, was directly linked with SLS counts and inversely with the cytoplasmic pattern. These data suggest that autophagic activity in SCC, when expressed as high LC3A/SLS counts, can be regarded as an indicator of tumor aggressiveness.

Rare Cases of Primary Pleural Hodgkin and Non-Hodgkin Lymphomas

Primary pleural lymphoma is rare. It occurs in only 7% of lymphoma cases. We report herein two cases of primary pleural Hodgkin and non-Hodgkin follicular lymphomas diagnosed by thoracoscopy under local anesthesia. Both patients presented initially with dyspnea revealing pleural effusions. The pleural findings during thoracoscopy differed in the two cases and selective pleural biopsies under optical forceps led to the diagnosis of lymphoma. To date, primary pleural Hodgkin and non-Hodgkin follicular lymphomas have not been reported.

Response of a Patient with Pleural and Peritoneal Mesothelioma after Second-Line Chemotherapy with Lipoplatin and Gemcitabine

We report the case of a 56-year-old patient with malignant pleural mesothelioma of epithelial type, who responded to second-line chemotherapy with lipoplatin plus gemcitabine. Diagnosis and staging of the disease was done by medical thoracoscopy with biopsies of the right pleura in December 2003, when he was treated with talc pleurodesis. Eighteen months later, he presented with pleural effusion of the left side and underwent first-line chemotherapy with cisplatin plus vinorelbine. After 8 cycles, the patient presented renal toxicity limiting further cisplatinum chemotherapy and disease progression with peritoneal invasion of the tumor and ascites. Treatment with lipoplatin-gemcitabine was decided on in November 2006, and the patient showed important improvement in the clinical status and peritoneal effusion. He survived for 36 weeks, with symptom-free survival of 34 weeks.

p16 and p53 expression status in head and neck squamous cell carcinoma: a correlation with histological, histoprognostic and clinical parameters

Different histopathology and prognosis characterise the human papillomavirus (HPV)-related oropharyngeal tumours, but squamous cell carcinomas (SCC) of other localisations have not been exhaustively studied. Tissues from 120 patients with a head and neck SCC were studied for the expression of p16 and p53, and the Brandwein-Gensler (BG) histological risk assessment model. p16 positivity and p53 normal expression were significantly correlated with non-smoking, an earlier T stage and a non-keratinising morphology. The BG risk score was not associated with p16 or p53 expression; p16 expression was associated with a lymphocytic T-cytotoxic response. BG risk score was significantly correlated with overall survival and progression-free survival, while neither p16 nor p53 expression were associated with prognosis. p16 and p53 expression are associated with the histological subtype and the T stage even in non-oropharyngeal-restricted tumours. The BG risk score is not correlated with p16 or p53 and retains its power in non-site-specific SCCs.

Autophagy and Bcl-2/BNIP3 death regulatory pathway in non-small cell lung carcinomas

We recently showed that non‐small cell lung carcinomas (NSCLCs) are of dismal prognosis when encompassing accelerated autophagic activity. The regulation of this abnormally functioning degradation system and its association with hypoxia and apoptosis in lung carcinoma patients is unexplored. In this study we used 115 NSCLC tissues to examine the immunohistochemical expression of four distinct molecules – the major regulator of autophagy Beclin 1, the anti‐apoptotic and anti‐autophagic protein Bcl‐2, the pro‐apoptotic and pro‐autophagic protein BNIP3, and a marker of hypoxia and glucolysis, the glucose transporter Glut 1. Most cases showed reduced reactivity for Beclin 1 (62%) and Bcl‐2 (82%) proteins, almost half of our sample revealed strong BNIP3 expression (57%), whereas most of the carcinomas strongly expressed Glut 1 antigen (71%). Beclin 1 expression showed no association with survival. Bcl‐2 positivity was a marker of good prognosis (p = 0.04), whereas BNIP3 (p = 0.0004) and Glut 1 (p = 0.03) expression correlated with poor outcome in Stage I disease. Autophagic status was negatively associated with Bcl‐2 (p = 0.0006), but positively with Glut 1 expression (p = 0.001). In conclusion, the accelerated autophagic status in NSCLC is unrelated to Beclin 1 and BNIP3 expression, but does show significant association with Bcl‐2 reactivity. Furthermore, we showed important correlations between glucolysis and autophagy, guiding new pathways in future lung carcinoma research.

Prognostic impact of immune microenvironment in laryngeal and pharyngeal squamous cell carcinoma: Immune cell subtypes, immuno-suppressive pathways and clinicopathologic characteristics

Background Immune system affects prognosis of various malignancies. Anti-immune pathways like PD-L1 and CTLA4 are used by the tumor to overcome immune system and they serve as immunotherapy targets. The immune microenvironment of head-and-neck squamous cell carcinoma (SCCHN) has not been sufficiently studied. Patients and Methods 152 SCCHN were immunohistochemically studied for the expression of CD3, CD8, CD57, CD4, granzyme b, CD20, CD163, S100, PD-L1, CTLA4 and CXCR4. Results CD3, CD8, CD57 and stromal S100 higher density is a good prognostic factor (p=0.02, 0.01, 0.02, 0.03 respectively). CTLA4 tumor expression is a poor prognostic factor (p=0.05). The rest immune cells do not affect prognosis. CD3 and CD8 density does not correlate with clinicopathological factors or p16/p53 expression, while CD57 and CD4 higher density is associated with the absence of distant metastases (p=0.03 and 0.07, respectively). Higher CD20 and S100 density is associated with lower T stage (p=0.04 and 0.03, respectively). PD-L1 expression is higher in CD3, CD8, and CD163 infiltrated tumors and in histologically more aggressive tumors. Response to neoadjuvant chemotherapy is better in highly CD3 infiltrated tumors and in tumors with less intraepithelial macrophages. Conclusion Rich T-lympocytic and dendritic cell response is a good prognostic factor in SCCHN, whereas tumors expressing CTLA4 show poor prognosis. PDL1 expression does not affect prognosis, but it is expressed in histologically more aggressive tumors and in T-cells rich tumors. Response to induction chemotherapy is better in tumors less infiltrated by macrophages and mostly infiltrated by T cells.

Clinical and Histologic Predictive Factors of Response to Induction Chemotherapy in Head and Neck Squamous Cell Carcinoma.

Objectives Induction chemotherapy (IC) is occasionally used in head and neck cancer, leading to less extensive surgery and reduced need for irradiation. Factors predicting the response to IC have not been determined. In this study, we investigated the clinical and histopathologic factors that predict the response to IC. Methods Head and neck squamous cell carcinomas from 81 patients were analyzed; clinical factors, histologic parameters, and expression of p16 and p53 were correlated with response to chemotherapy and prognosis. Results Factors predicting a good response to IC were the nonoropharyngeal localization, a rich lymphocytic tissue response, and a low platelet-to-lymphocyte blood ratio before treatment. Response to IC did not correlate with prognosis, whereas a low neutrophil-to-lymphocyte ratio (NLR), the absence of a desmoplastic reaction, a rich lymphocytic tissue response, and the overexpression of p53 were associated with better prognosis. Conclusions Lymphocytic tissue response, NLR, and nonoropharyngeal localization are factors predictive of response to IC.

Pulmonary Mucus Gland Adenomas: Are They Always of Endobronchial Localization?

Mucus gland adenoma is an extremely rare benign lung tumor, presumed to arise from the bronchial mucus glands; it is a TTF-1 negative tumor, centrally located, causing the clinical manifestations of obstruction. We report a TTF-1 negative mucus gland adenoma, arising into the medial bronchopulmonary segment, lacking any relation to a bronchus.

Pleuroscopy in ‘Idiopathic’ eosinophilic pleural effusions

Idiopathic eosinophilic pleural effusions (IEPEs) comprise the eosinophilic pleural effusions for which a specific aetiology cannot be established. There are no reports investigating IEPE on the basis of a systematically applied pleuroscopy approach and entailing an appropriate patient follow‐up till the final outcome is established; existing series rather combine clinical and thoracocentesis criteria to establish the idiopathic character of the diagnosis.