Metachronous primary uterine cancer surgically resected during crizotinib treatment in a ALK-rearranged advanced lung adenocarcinoma

Rearrangements of the anaplastic lymphoma kinase (ALK) gene are present in 3% to 7% of nonsmall-cell lung cancers (NSCLCs). Patients harboring ALK rearrangements show very favourable outcomes if treated with targeted agents, among which crizotinib is the first and best studied. Crizotinib, an oral smallmolecule tyrosine kinase inhibitor of ALK, MET, and ROS1 kinases, is a very active and well tolerated drug. Nevertheless, the optimal therapy management with this new drug is still partially unknown, especially with regard to the safety of combined treatments. Recently, the integration of locoregional treatments has been proposed as a feasible multimodality strategy in selected patients with good clinical conditions and slowgrowing or oligoprogressive disease. In this report, a case of advanced lung adenocarcinoma, progressed after first line chemotherapy and re-biopsied detecting ALK rearrangement, is described. During crizotinib treatment the primary lung tumor showed an excellent regression; meanwhile a major surgery for a metachronous uterine cancer was safely and successfully carried out

Intratumoral, rather than stromal, CD8+ T cells could be a potential negative prognostic marker in invasive breast cancer patients

BACKGROUND: Tumor infiltrating lymphocytes (TILs) are widely considered a key sign of the immune interaction between host and tumor, and potentially prognostic biomarkers of good or bad outcome in many cancers, included invasive breast cancer (BC). However, results about the association between TIL typology, location and BC prognosis, are controversial. The aim of the study was to evaluated the prognostic significance of TIL subtypes (CD4+, CD8+, FOXP3+ T cells) and their location (stromal “s” and intratumoral “i” CD4+ and CD8+) in BC patients, focusing on the association between these markers and immunocheckpoint molecules such as cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death ligand 1 (PD-L1) and its receptor (PD-1). METHODS: CD4+, CD8+, FOXP3+, CTLA4+, PD-L1+ and PD-1+ expression was examined by immunohistochemistry on tissue microarrays (TMAs) from 180 BC patients. Univariate and Kaplan–Meier analyses of disease free survival (DFS) were performed to evaluate the prognostic significance of marker expression. RESULTS: Total CD8+ T cells were not significantly associated with DFS. Differently, patients with iCD8+ and sCD8+ overexpression showed a trend toward respectively a worse (P = .050) and a better 5-years DFS (P = .064). Interestingly, TIL expression of both PD-1+ and PD-L1+, was significantly associated with iCD8+ (P = .0004; P < .0001 respectively), while only TIL expression of PD-1 was associated with sCD8+ (P = .001). CONCLUSION: Our data show that iCD8+ T cells, but no sCD8+ T cells identify a subgroup of patients with poor DFS and this could be due to the overexpression of PD-L1/PD-1 pathway

Primary Malignant Peritoneal Mesothelioma in an Incarcerated Groin Hernia: Report of a Case

Malignant peritoneal mesothelioma arising from the inguinal hernia sac is rare. we report the case of a 71-year-old man examined in our emergency department forr a bilateral inguinoscrotal hernia, which was recurrent in the right groin, and priamry and incarcerated in the left groin. A mesothelioma of the hernial sac peritoneum was the final histological diagnosi

Long-Lasting Remission in De Novo Breast Myeloid Sarcoma Treated with Decitabine and Radiotherapy

Myeloid sarcoma (MS) represents a rare disease with an adverse clinical outcome for patients not candidate to acute myeloid leukemia (AML)-like chemotherapies. Here we present the case of an elderly patient affected by a bilateral breast localization of MS treated with the hypomethylating agent decitabine associated to radiotherapy. The association of the two treatment modalities has allowed an optimal and long-lasting disease control

Pathologic Grading of Malignant Pleural Mesothelioma: A REAL Evidence-Based Proposal

Background: A pathologic grading system (PGS) in malignant pleural mesothelioma (MPM) could be clinically warranted to better identify different risk categories of patients, plan therapy options and activate clinical trials. Design: A cohort of 328 MPM patients was raised between October 1980 and June 2015. All original slides were jointly reviewed for consistency, blindly to asbestos exposure, overall survival, staging and (neo)-adjuvant chemotherapy. Histologic scoring was constructed by attributing to each parameter, independent upon multivariate analysis, different scores based on 50% increments of the corresponding hazard ratios (HR). Accordingly, final scores ranged from 0 to 12 points for each tumor patient. Results: Histology (epithelioid, biphasic, sarcomatoid), necrosis (absent v. present), cell atypia (mild, moderate, severe), mitotic count per 1 mm2 (cut-offs: 1-2, 3-5, 6-9, 10 or more) and Ki-67 labeling index on 2000 cells (cut-off 30%) were independent factors of survival after adjusting for confounding factors (stage, age and chemotherapy). Tumor patterns in epithelioid MGM or type of material (biopsy vs. resection) did not affect survival. PGS (AUC-ROC: 0.79) outperformed mitotic count (AUC-ROC: 0.68) and Ki-67 (AUC-ROC: 0.69). Patient survival progressively deteriorated from score 0 (median: 79.2 mo.) to score 12 (median: 1.3 mo.), with median survival values being 26.6 mo. (CI: 21.6-42.6), 15.1 mo. (CI: 13.3-16.8), 8.8 mo. (CI: 6.8-10.9) and 3.9 mo. (CI: 3.3-4.9) for 0-2, 3-5, 6-7, and 8-12 score, respectively. This PGS was effective not only in MPM considered as a whole, but also within epithelioid, biphasic and sarcomatoid subgroups, with HR values being 1.34 (CI: 1.27-1.41), 1.36 (CI: 1.27- 1.46), 1.29 (1.12-1.49) and 1.44 (1.16-1.79) for each point of increase, respectively. Effectiveness of this PGS was then confirmed in an independent validation set dealing with further 60 MPM patients. Conclusions: The combination of multiple parameters outperformed each single variable to construct a simple PGS, which predicted survival in diversely featuring MPM even at the level of an individual patient’s cancer

Prognostic and Predictive Factors Affecting Course of Disease and Survival in Malignant Pleural Mesothelioma

Background: The aim of this study was to determine both prognostic clinical-morphological and predictive biomolecular factors affecting course of disease and survival in malignant pleural mesothelioma (MPM). Methods: We retrospectively analyzed (2004-2014) clinical and pathological data of 108 consecutive patients with diagnosis of MPM. Age, stage (WHO 2015), chemotherapy, histotype, nuclear atypia, mitotic count (1/mm2), Ki-67 percentage and 9p21 (p16/CDKN2A) deletion (43 cases) were analyzed and correlated to survival. Survival was evaluated with Kaplan-Meier method and statistical significance with Log-Rank test (SPSS software, 18.0). Results: There were 83 (76.9%) males, 25 (23.1%) females (ratio 3.3/1); median age at diagnosis was 68 (mean 67.2±9.8; range 42-90) years; 94 (87%) patients had asbestos exposure. Overall median survival was 13.3 (mean 19.15±22.4; range 1-136) months. Mean survival (months) was: 30.2±4.6 and 12.4±1.6 in age ≤ 65 and &gt; 65 years (p=0.0001); 24±4.3 in stage I, 21.3±4.5 in II, 21.1±5.8 in III, 9.7±1.7 in IV (p=0.005); 25.9±2.8 and 5±1.3 in patients receiving complete (n=73) and palliative (n=35) chemotherapy (p=0.0001); 21.4±2.5, 11.6±2.7 and 8.5±2.3 in epithelioid, biphasic and sarcomatoid histotypes (p=0.0001); 26.3±3.3 and 12.4±2.5 in moderate and severe nuclear atypia (p=0.0001); 26±3.4 and 9.9±1,3 in low (≤ 5 mm2) and high (&gt; 5 mm2) mitotic count (p=0.0001); 27.2±3.4 and 9.1±1.1 in low (≤ 25%) and high (&gt; 25%) Ki-67 expression (p=0.0001); 35.8±7.7 in absence of p16/CDKN2A deletion, 17.4±3.4 in heterozygous and 8.9±1.9 in homozygous deletion (p=0.0001). Mean survival (months) in patients receiving complete chemotherapy compared to those receiving palliative one was: stage I 30.7±5.4 and 8.2±4.4 (p=0.0001), stage II 25.8±5.3 and 4.2±1.0 (p=0.0001), stage III 25.2±6.8 and 3.0±0.4 (p=0.0001), stage IV 17.7±2.5 and 3.8±0.7 (p=0.0001). Conclusion: Age, stage, chemotherapy, histotype, nuclear atypias, mitoses, proliferating index and loss of 9p21 gene are predictors of survival in MPM and strongly influence the therapeutic strategy. Chemotherapy significantly affects survival in different stages of MPM

Prognostic Value of Ki67 Percentage, WT-1 Expression and p16/CDKN2A Deletion in Diffuse Malignant Peritoneal Mesothelioma: A Single-Centre Cohort Study

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare malignant neoplasm with a poor survival. Although some advances in knowledge have been obtained for the pleural form, much less is known about DMPM. Advantages in terms of prognosis are still limited and strong efforts need to be made. The aim of our study was to correlate several histological and molecular factors with survival in a large cohort of 45 DMPMs. We evaluated histotype, nuclear grade, mitotic count, necrosis, inflammation, desmoplastic reaction, Ki67 percentage, WT-1 expression, p16 protein by immunohistochemistry and CDKN2A deletion by FISH. Our results showed that epithelioid histotype, nuclear grade 2, mitotic count &le;5 x mm2, absence of desmoplasia and p16/CDKN2A deletion, low Ki67 value, and high WT-1 expression were correlated with the most prolonged survival (p = 0.0001). Moreover, p16 loss in immunohistochemistry reflected CDKN2A deletion detected with FISH, and both were correlated with the worst survival (p = 0.0001). At multivariate analysis, Ki67 value, WT-1 expression and p16/CDKN2A deletion emerged as independent prognostic factors (p = 0.01, p = 0.0001 and p = 0.01, respectively). These parameters are easy to analyse at the time of DMPM diagnosis and may support better patient stratification, prediction of treatment effectiveness and therapeutic optimization

Anaplastic large-cell periprosthetic lymphoma of the breast: could fibrin be an early radiological indicator of the presence of disease?

The onset characteristics of the anaplastic large cell lymphoma (BI-ALCL) are non-specific and the diagnosis is often difficult and based on clinical suspicion and cytological sampling. The presence of non-pathognomonic radiological signs may delay the diagnosis of BI-ALCL, influencing patient prognosis. This could have an important social impact, considering that the incidence of BI-ALCL correlates with the number of prosthetic implants, which is in constant increase worldwide. The aim of this study was to verify if fibrin can represent a potential early radiological sign of the disease