CD68 and CD83 immune populations in non-metastatic axillary lymph nodes are of prognostic value for the survival and relapse of breast cancer patients.

BACKGROUND: The foremost cause of death of breast cancer (BC) patients is metastasis, and the first site to which BC predominantly metastasizes is the axillary lymph node (ALN). Thus, ALN status is a key prognostic indicator at diagnosis. The immune system has an essential role in cancer progression and dissemination, so its evaluation in ALNs could have significant applications. In the present study we aimed to investigate the association of clinical-pathological and immune variables in the primary tumour and non-metastatic ALNs (ALNs-) of a cohort of luminal A and triple-negative BC (TNBC) patients with cancer-specific survival (CSS) and time to progression (TTP). METHODS: We analysed the differences in the variables between patients with different outcomes, created univariate and multivariate Cox regression models, validated them by bootstrapping and multiple imputation of missing data techniques, and used Kaplan-Meier survival curves for a 10-years follow-up. RESULTS: We found some clinical-pathological variables at diagnosis (tumour diameter, TNBC molecular profile and presence of ALN metastasis), and the levels of several immune markers in the two studied sites, to be associated with worse CSS and TTP. Nevertheless, only CD68 and CD83 in ALNs- were confirmed as independent prognostic factors for TTP. CONCLUSIONS: The study identified the importance of macrophage and dendritic cell markers as prognostic factors of relapse for BC. We highlight the importance of studying the immune response in ALNs-, which could be relevant to the prediction of BC patients' outcome.

Liquid Biopsy-Based Exo-oncomiRNAs Can Predict Prostate Cancer Aggressiveness.

Liquid biopsy-based biomarkers, including microRNAs packaged within extracellular vesicles, are promising tools for patient management. The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is related to PCa progression and is found in the semen of patients with PCa. TWEAK can induce the transfer of exo-oncomiRNAs from tumor cells to body fluids, and this process might have utility in non-invasive PCa prognosis. We investigated TWEAK-regulated exo-microRNAs in semen and in post-digital rectal examination urine from patients with different degrees of PCa aggressiveness. We first identified 14 exo-oncomiRNAs regulated by TWEAK in PCa cells in vitro, and subsequently validated those using liquid biopsies from 97 patients with PCa. Exo-oncomiR-221-3p, -222-3p and -31-5p were significantly higher in the semen of high-risk patients than in low-risk peers, whereas exo-oncomiR-193-3p and -423-5p were significantly lower in paired samples of post-digital rectal examination urine. A panel of semen biomarkers comprising exo-oncomiR-221-3p, -222-3p and TWEAK was designed that could correctly classify 87.5% of patients with aggressive PCa, with 85.7% specificity and 76.9% sensitivity with an area under the curve of 0.857. We additionally found that TWEAK modulated two exo-oncomiR-221-3p targets, TCF12 and NLK. Overall, we show that liquid biopsy detection of TWEAK-regulated exo-oncomiRNAs can improve PCa prognosis prediction.

Differences in the Immune Response of the Nonmetastatic Axillary Lymph Nodes between Triple-Negative and Luminal A Breast Cancer Surrogate Subtypes.

Breast cancer (BC) comprises four immunohistochemical surrogate subtypes of which triple-negative breast cancer (TNBC) has the highest risk of mortality. Axillary lymph nodes (ALNs) are the regions where BC cells first establish before distant metastasis, and the presence of tumor cells in the ALN causes an immune tolerance profile that contrasts with that of the nonmetastatic ALN (ALN-). However, few studies have compared the immune components of the ALNs- in BC subtypes. The present study aimed to determine whether differences between immune populations in the primary tumor and ALNs- were associated with the luminal A or TNBC subtype. We evaluated a retrospective cohort of 144 patients using paraffin-embedded biopsies. The TNBC samples tended to have a higher histologic grade and proliferation index and had higher levels of immune markers compared with luminal A in primary tumors and ALNs-. Two methods for validating the multivariate analysis found that histologic grade, intratumoral S100 dendritic cells, and CD8 T lymphocytes and CD57 natural killer cells in the ALNs- were factors associated with TNBC, whereas CD83 dendritic cells in the ALNs- were associated with the luminal A subtype. In conclusion, we found that intratumoral regions and ALNs- of TNBC contained higher concentrations of markers related to immune tolerance than luminal A. This finding partially explains the worse prognosis of patients with TNBC.

Biofluid quantification of TWEAK/Fn14 axis in combination with a selected biomarker panel improves assessment of prostate cancer aggressiveness.

BACKGROUND: Conventional clinical biomarkers cannot accurately differentiate indolent from aggressive prostate cancer (PCa). We investigated the usefulness of a biomarker panel measured exclusively in biofluids for assessment of PCa aggressiveness. METHODS: We collected biofluid samples (plasma/serum/semen/post-prostatic massage urine) from 98 patients that had undergone radical prostatectomy. Clinical biochemistry was performed and several cytokines/chemokines including soluble(s) TWEAK, sFn14, sCD163, sCXCL5 and sCCL7 were quantified by ELISA in selected biofluids. Also, the expression of KLK2, KLK3, Fn14, CD163, CXCR2 and CCR3 was quantified by real-time PCR in semen cell sediment. Univariate, logistic regression, and receiver operating characteristic (ROC) analyses were used to assess the predictive ability of the selected biomarker panel in conjunction with clinical and metabolic variables for the evaluation of PCa aggressiveness. RESULTS: Total serum levels of prostate-specific antigen (PSA), semen levels of sTWEAK, fasting glycemia and mRNA levels of Fn14, KLK2, CXCR2 and CCR3 in semen cell sediment constituted a panel of markers that was significantly different between patients with less aggressive tumors [International Society of Urological Pathology (ISUP) grade I and II] and those with more aggressive tumors (ISUP grade III, IV and V). ROC curve analysis showed that this panel could be used to correctly classify tumor aggressiveness in 90.9% of patients. Area under the curve (AUC) analysis revealed that this combination was more accurate [AUC = 0.913 95% confidence interval (CI) 0.782-1] than a classical non-invasive selected clinical panel comprising age, tumor clinical stage (T-classification) and total serum PSA (AUC = 0.721 95% CI 0.613-0.830). CONCLUSIONS: TWEAK/Fn14 axis in combination with a selected non-invasive biomarker panel, including conventional clinical biochemistry, can improve the predictive power of serum PSA levels and could be used to classify PCa aggressiveness.

Tumor de Brenner benigno bilateral asociado a cistadenoma mucinoso. Una aproximación a los tumores de células transicionales del ovario / Bilateral benign Brenner tumour associated with a mucinous cystadenoma. A case report and a reflection on transitional cell tumours of the ovary

Los tumores de células transicionales del ovario constituyen un raro grupo de tumores epiteliales ováricos que, desde su primera descripción en 1932, han sido sujeto de numerosos trabajos para establecer su histogénesis y comprender su actividad endocrina. Comprenden dos categorías clínico-patológicas: los tumores de Brenner (benigno, borderline o proliferante y maligno) y el carcinoma de células transicionales. Presentamos un caso de tumor de Brenner benigno bilateral y de grandes dimensiones asociado a cistadenoma mucinoso en una mujer de 54 años con antecedentes de carcinoma de mama. Discutimos las principales características clínico-patológicas de este grupo de tumores epiteliales ováricos y su asociación con los tumores mucinosos(AU)

Transitional cell tumours constitute a rare group of ovarian epithelial neoplasms, first described in 1932 and still the subject of many studies to determine their histogenesis and endocrine activity. They are classified into two distinct clinicopathological categories: Brenner tumours (benign, borderline or proliferative and malignant) and transitional cell carcinoma. We report a case of a large, bilateral benign Brenner tumour associated with mucinous cystadenoma in a 54 year old woman with a history of breast carcinoma. The main clinical and pathological features of transitional cell ovarian tumours are described and their association with mucinous tumours is discussed(AU)

Cardiomegalia masiva debida a carcinoma de células escamosas de la mucosa oral: descripción de un caso de autopsia / Massive cardiomegaly due to squamous cell carcinoma of oral mucosa: report of an autopsy case

IntroducciónLos tumores de cabeza y cuello producen metástasis a distancia en estadios avanzados. La afectación cardiaca por estos tumores es poco habitual, siendo el origen más frecuente en estos casos los tumores localizados en la lengua.Caso clínicoMujer de 58 años con gran cardiomegalia debida a metástasis de un carcinoma de células escamosas originado en la mucosa yugulogingival, que debutó con clínica inespecífica de un mes de evolución y falleció a los 4 días del ingreso. El estudio necrópsico demostró la afectación cardiaca masiva por carcinoma de células escamosas asociada a metástasis en ambos pulmones, hígado y páncreas, acompañado de tromboembolismo pulmonar, sin recidiva de enfermedad local.DiscusiónPlanteamos la dificultad diagnóstica de las metástasis cardiacas debido a su baja frecuencia y clínica escasa, inespecífica y de presentación tardía.ConclusionesActualmente, las técnicas de imagen y la posibilidad de realizar biopsias cardiacas transvenosas aumentan el número de casos diagnosticados en vida. Sin embargo, aún hoy día la mayoría de estas metástasis continúan diagnosticándose en el estudio necrópsico(AU)

IntroductionTumours of the head and neck tend to metastasize in the late stages of the disease; cardiac metastases are unusual, and when they occur the primary tumour is usually found in the tongue.Case reportA 58 year old woman with cardiac metastasis from a squamous cell carcinoma of the jugular-gingival mucosa was admitted to hospital with non-specific symptoms and died 4 days after admission. The necropsy showed massive cardiac squamous cell carcinoma associated to metastases in lungs, liver, pancreas and pulmonary embolism but no local recurrence of disease.DiscussionCardiac metastases are rare and have non-specific symptoms and are therefore difficult to diagnose.ConclusionsImaging techniques and cardiac biopsies allow more cases to be diagnosed in a living patient, although the majority of cardiac metastases are still diagnosed on necropsy(AU)

[Prevalence of fungal infections detected from biopsies and autopsies in the past 11 years at the University Hospital Joan XXIII in Tarragona, Spain]. / Prevalencia de la patología fúngica en biopsias y autopsias realizadas en el Hospital Universitario Joan XXIII de Tarragona.

Infectious diseases caused by fungal pathogens have increased in the past 10 years. More than 300 pathogenic fungal species have been incriminated as the etiologic agents. We carried out a retrospective study (1994-2004) to evaluate the prevalence of mycoses at the University Hospital Joan XXIII (330 beds). This report found 0.24% of the studied cases (78,310 biopsies and 753 autopsies) were diagnosed as fungal infections (0.21% of the total studied biopsy and 4.25% of the whole autopsies). Skin and mucose were involved in 66% of cases, followed by other less affected anatomical areas. 61% of studied cases were caused by Candida spp (the most frequent in our environment), followed by Aspergillus spp (10%) and the Zygomycetes (5%). The most important underlying illness was obstructive chronic pulmonary disease followed by diabetes and AIDS. The incidence of mycoses increased with the patient's age, especially those patients in their 80s. Antifungal management improved the clinical outcome of the patient but predisposing factors are crucial for diagnosis. Systemic mycoses have poor prognosis with 91% of fatal outcome. Thus, it is important to perform a rapid diagnosis of the fungal infections a diagnostic area in which pathology could play a major role.

Carcinoma de célula pequeña pulmonar combinado con adenocarcinoma y carcinoma escamoso / Pulmonary small cell carcinoma combined with adenocarcinoma and squamous carcinoma

Introducción: De las tumoraciones malignas pulmonares,el carcinoma de célula pequeña (CCP) se presenta en un20-25% de los casos. Se caracteriza por una rápida progresióny gran poder metastásico, disposición central pulmonary asociación a síndromes paraneoplásicos. Se reconocentres subgrupos: CCP puro, carcinoma mezclado con célulasgrandes, y el CCP combinado con carcinoma escamoso y/oadenocarcinoma. Caso clínico: Paciente varón de 58 añoscon hallazgo casual de masa en la radiología de tórax. Labroncoscopia (citología, BAS y biopsia) resultó negativapara células malignas. Ante las características radiológicasmuy sugestivas de malignidad se realizó neumonectomía.En el estudio de la pieza quirúrgica se observó una tumoraciónperibronquial blanquecina de 4 × 3 cm bien delimitada.El estudio microscópico mostró proliferación mixta contres claros patrones bien diferenciados predominando elpatrón de tipo célula pequeña sobre el adenocarcinomatosoy el escamoso. Dos ganglios linfáticos mostraron infiltracióntumoral de patrón glandular. Conclusión: La importanciade este caso radica en su rareza, ya que el CCP combinadorepresenta menos del 1% del total de CCP, siendotodavía más rara la presencia de los tres patrones histológicosdescritos. La supervivencia y tratamiento es similar alCCP puro, mostrando un mejor pronóstico que el CCP mezcladocon células grandes

Introduction: Small cell carcinoma (SCC) representsabout 20-25% of all malignant lung tumors. This type oftumor exhibits some peculiarities such as its rapid progression,aggressive metastatic behavior, central localizationand its association with paraneoplastic syndromes. SCC isclassified as pure, mixed with large-cell carcinoma andcombined with adenocarcinoma and/or squamous carcinoma.Case: A 58-year-old man with a thoracic mass found ina routine x-ray. The bronchoscopic studies (cytology, bronchoalveolaraspirate and biopsy) did not revealed any evidenceof malignancy. The patient eventually underwent surgicalresection of his lung mass, and on gross examination,the specimen received showed a well-defined white peribronchialmass (measuring 4.0 × 3.0 cm in greatest dimensions).Microscopically, the tumor showed a combination ofthree well-differentiated cellular patterns, with a predominanceof a small cell pattern over adenocarcinoma and squamouspatterns. Two lymph nodes were also identified, andthey appeared to be infiltrated by tumor, with predominanceof the adenocarcinoma pattern. Conclusion: This case isinteresting because SCC combined with non-small cell carcinomarepresents less than 1% of all SCC, and the combinedgrowth of the three different patterns is even rarer. Treatmentand survival of SCC combined with non-small cellcarcinoma are the same as pure SCC, both types have a betterprognosis than SCC mixed with large-cell carcinoma