Factores pronóstico en el carcinoma bronquial no microcítico menor de 3 centímetros (análisis actuarial, incidencia acumulativa y grupos de riesgo) / Prognostic factors in non-small cell lung cancer less than 3 centimeters: actuarial analysis, accumulative incidence and risk groups

Introducción: En la clasificación TNM, los factores determinantes del factor T en el carcinoma pulmonar no microcítico apenas han variado con el tiempo y todavía se basan únicamente en características anatómicas. Nuestro objetivo fue estudiar la influencia en la supervivencia de estos y otros factores de tipo morfopatológico. Métodos: Se incluyeron 263 pacientes sometidos a resección pulmonar por carcinoma pulmonar no microcítico en estadio I patológico y diámetro ≤ 3 cm. Se realizó un estudio de supervivencia y de estimación del riesgo competitivo observando variables clínicas, quirúrgicas y patológicas, siguiendo los métodos de análisis actuarial y de incidencia acumulativa, respectivamente. Posteriormente, se creó un modelo de riesgo de acuerdo con los resultados. Resultados: La supervivencia fue de 79,8 y 74,3% a los 5 y 10 años, respectivamente. Los factores con mejor pronóstico, estadísticamente significativo según el método actuarial fueron: presencia de síntomas, hábito tabáquico, FEV1 > 60%, número de ganglios resecados > 7, tipo histológico escamoso, ausencia de invasión vascular, ausencia de invasión pleural visceral y presencia de invasión bronquial lobar proximal. La edad < 50 años rozó la significación estadística. En el análisis multivariante entraron en regresión la invasión pleural visceral y la invasión vascular. El estudio de riesgo competitivo mostró una probabilidad de muerte por cáncer de 14,3 y 35,1% en 5 y 10 años, respectivamente. Las variables significativas en los análisis univariante y multivariante fueron similares excepto el FEV1 > 60%. Conclusiones: La presencia de invasión pleural visceral y la invasión vascular determina la supervivencia o el riesgo de muerte por carcinoma pulmonar no microcítico ≤ 3 cm y permiten elaborar un modelo predictivo de riesgo

Introduction: In TNM classification, factors determining the tumor (T) component in non-small cell lung cancer have scarcely changed over time and are still based solely on anatomical features. Our objective was to study the influence of these and other morphopathological factors on survival. Methods: A total of 263 patients undergoing lung resection due to stage I non-small cell lung cancer ≤ 3 cm in diameter were studied. A survival analysis and competing-risk estimate study was made on the basis of clinical, surgical and pathological variables using actuarial analysis and accumulative incidence methods, respectively. A risk model was then generated from the results Results: Survival at 5 and 10 years was 79.8 and 74.3%, respectively. The best prognostic factors were presence of symptoms, smoking habit and FEV1 > 60%, number of resected nodes > 7, squamous histology, absence of vascular invasion, absence of visceral pleural invasion and presence of invasion more proximal than the lobar bronchus. All these were statistically significant according to the actuarial method. The factor 'age < 50 years' was close to the margin of statistical significance. Pleural invasion and vascular invasion were entered in the multivariate analysis. The competing-risk analysis showed a probability of death due to cancer of 14.3 and 35.1% at 5 and 10 years, respectively. Significant variables in the univariate and multivariate analyses were similar, with the exception of FEV1 > 60%. Conclusions: Pleural invasion and vascular invasion determine survival or risk of death due to non-small cell lung cancer ≤ 3 cm and can be used for generating a predictive risk model

Prognostic Factors in Non-Small Cell Lung Cancer Less Than 3 Centimeters: Actuarial Analysis, Accumulative Incidence and Risk Groups.

INTRODUCTION: In TNM classification, factors determining the tumor (T) component in non-small cell lung cancer have scarcely changed over time and are still based solely on anatomical features. Our objective was to study the influence of these and other morphopathological factors on survival. METHODS: A total of 263 patients undergoing lung resection due to stage I non-small cell lung cancer ≤3cm in diameter were studied. A survival analysis and competing-risk estimate study was made on the basis of clinical, surgical and pathological variables using actuarial analysis and accumulative incidence methods, respectively. A risk model was then generated from the results. RESULTS: Survival at 5 and 10 years was 79.8 and 74.3%, respectively. The best prognostic factors were presence of symptoms, smoking habit and FEV1>60%, number of resected nodes>7, squamous histology, absence of vascular invasion, absence of visceral pleural invasion and presence of invasion more proximal than the lobar bronchus. All these were statistically significant according to the actuarial method. The factor "age<50 years" was close to the margin of statistical significance. Pleural invasion and vascular invasion were entered in the multivariate analysis. The competing-risk analysis showed a probability of death due to cancer of 14.3 and 35.1% at 5 and 10 years, respectively. Significant variables in the univariate and multivariate analyses were similar, with the exception of FEV1>60%. CONCLUSIONS: Pleural invasion and vascular invasion determine survival or risk of death due to non-small cell lung cancer ≤3cm and can be used for generating a predictive risk model.

Multiple granular cell tumors with metachronous occurrence in tongue and vulva. Clinicopathological and immunohistochemical study.

Granular cell tumor (GCT) usually occurs as a single tumor, although sometimes multiple lesions can occur. In present report we analyze the clinicopathological and immunohistochemical features of a multiple GCT involving the tongue of a 14-year-old girl, with no other abnormalities, with a metachronous occurrence of a second GCT in vulva, after a period of 10 years. Both tumors revealed S-100, vimentin and CD57 positivity. In addition, over expression of calretinin was observed in tumor cells located in the vicinity of pseudoepitheliomatous hyperplasia (PEH) of the tongue. Tumor vasculature situated close to the PEH showed marked CD105 reactivity, data not described so far, suggesting an interaction between PEH cells and underlying stroma, since GCT completely lacks CD105 vessels. Our study emphasizes that patients with GCT, especially young patients, should be followed long-term, looking for multiple tumors or other abnormalities suggestive of a systemic syndrome, given the associations described in multiple GCT.

A multiplex real-time PCR method for quantification of BK and JC polyomaviruses in renal transplant patients.

BACKGROUND: Infection of BK or JC human polyomavirus can lead to polyomavirus-associated nephropathy in renal transplant patients. Thus effective management of these patients requires early detection and quantification of these viruses in urine and blood. DESIGN: The aim of this study was to evaluate and validate a multiplex real-time PCR-based method for monitoring BK and/or JC viral loads in renal transplant patients. Analytic parameters such as limit of quantification, linear dynamic range, sensitivity and specificity, as well as reliability of the assays were determined. Seventy-six plasma or urine samples spiked with variable amounts of BK and JC viral DNA ranging from low (7.0 x 10(3) or 1.5 x 10(4)), to medium (1.0 x 10(6) to high (1.0 x 10(8) or 1.0109 copies/mL) levels of viruses were tested. In addition, 45 clinical urine or plasma samples with known copy numbers of BK or JC viruses, which were isolated from the renal transplant patients from 4 US medical centers, were also tested. RESULTS: BK and/or JC viruses can be detected with distinguishable melting temperature of 64 degrees C or 68 degrees C, respectively. On the basis of the need for clinical monitoring of different types of specimens, the low limit of quantification for plasma or urine was set at 7.0 x 10(3) or 1.5 x 10(4) copies/mL, respectively with the linear dynamic range Z6 logs. The assay exhibits 100% specificity, 97.9% sensitivity with low intra-assay and interassay variability (coefficient of variation <4%). CONCLUSIONS: This clinically validated method has the necessary utility to monitor BK and JC viremia and viruria in renal transplant patients.

Guidelines for HER2 testing in breast cancer: a national consensus of the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM).

Identifying breast cancers with HER2 overexpression or amplification is critical as these usually imply the use of HER2-targeted therapies. DNA (amplification) and protein (overexpression) HER2 abnormalities usually occur simultaneously and both in situ hybridisation and immunohistochemistry may be accurate methods for the evaluation of these abnormalities. However, recent studies, including those conducted by the Association for Quality Assurance of the Spanish Society of Pathology, as well as the experience of a number of HER2 testing National Reference Centres have suggested the existence of serious reproducibility issues with both techniques. To address this issue, a joint committee from the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM) was established to review the HER2 testing guidelines. Consensus recommendations are based not only on the panellists' experience, but also on previous consensus guidelines from several countries, including the USA, the UK and Canada. These guidelines include the minimal requirements that pathology departments should fulfil in order to guarantee proper HER2 testing in breast cancer. Pathology laboratories not fulfilling these standards should make an effort to meet them and, until then, are highly encouraged to submit to reference laboratories breast cancer samples for which HER2 determination has clinical implications for the patients.

Recomendación para la determinación de HER2 en cáncer de mama. Consenso nacional de la Sociedad Españolade Anatomía Patológica (SEAP) y de la SociedadEspañola de Oncología Médica (SEOM) / Guidelines for HER2 testing in breast cancer. A national consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

La identificación de los carcinomas de mama con amplificación/sobreexpresión de HER2 es crítica en la práctica clínicadiaria ya que estas neoplasias requieren un tratamientoespecífico que incluye el uso de terapias dirigidas. Tanto lastécnicas de hibridación in situ como las técnicas inmunohistoquímicasson métodos apropiados para la identificación decánceres de mama HER2 positivos. Sin embargo, numerososestudios, incluidos los desarrollados por la Asociación para laGarantía de Calidad en Patología de la SEAP (AGCP) y laexperiencia de centros de referencia nacionales en la determinaciónde HER2 han puesto de manifiesto importantesproblemas de reproducibilidad entre laboratorios. Por estosmotivos, patólogos expertos en la determinación de HER2 deestos centros de referencia, así como oncólogos médicos conuna contrastada actividad en cáncer de mama, en representaciónde las sociedades respectivas (SEAP y SEOM), han trabajadopara debatir y consensuar las recomendaciones nacionalesde determinación de HER2. Estas recomendaciones sebasan no sólo en la experiencia de los participantes en el consenso, sino también en la experiencia internacional publicadaen recientes guías de distintos países, tales como EstadosUnidos, Reino Unido y Canadá.En este consenso, se recomiendan los requisitos mínimosque un laboratorio de Anatomía Patológica debe cumplirpara garantizar la adecuada determinación de HER2 enla práctica diaria. Aquellos laboratorios que carezcan de losestándares mínimos expuestos en esta guía deberían trabajaren alcanzarlos y durante este proceso remitir a laboratoriosde referencia las muestras en las que la determinaciónde HER2 tenga implicaciones clínicas para las pacientes (AU)

Breast cancers with HER2 alterations are critical toidentify because such tumors require unique treatment,including the use of targeted therapies. HER2 alterationsat the DNA (amplification) and protein (overexpression)level usually occur in concert, and both in situ hybridizationand immunohistochemistry can be accurate methodsto assess these alterations. However, recent studies includingthose conducted by the Association for QualityAssessment of the Spanish Society of Pathology and theexperience of several national reference centres for HER2testing have suggested that serious reproducibility issuesexist with both techniques. To address this, a joint committeeof both the Spanish Society of Pathology and theSpanish Society of Medical Oncology has met to reviewguidelines for HER2 testing. Consensus recommendationare based not only on panellist’s experience but also inthose consensus guidelines previously reported in severalcountries, such as United Stated, United Kingdom andCanada . These guidelines include minimal requirements thatPathology Department must meet in order to guaranteeappropriate HER2 testing in breast cancer. Pathology laboratoriesthat do not meet these standards must put effort toreach them and, in the meantime, send clinical cases to referencecentres (AU)

PCR assays for the early detection of BKV infection in 125 Spanish kidney transplant patients.

BK virus (BKV) reactivation arises from immunocompromised conditions and can produce a tubulointerstitial nephropathy (BKVN) in kidney transplant recipients (KTR). Approximately 5% of KTR develop BKVN, and about 45% of these lose their graft. Therefore, using molecular tools to test for BKV may be helpful in early detection. A series of 125 Spanish KTR, originating from a single transplant center, were studied in relation to BKV infection in the first post-transplant year. First, we carried out a urinary cytological study, looking for decoy cells as a possible marker of virus replication. Secondly, in all positive cytological samples and in some negative cytological samples (selected at random), we performed qualitative polymerase chain reaction (PCR) assays in serum and urine amplifying two different genome regions (LT and VP1). A transcription control region (TCR)-BK polymorphism sequence analysis was also performed in those BK PCR positive cases. Twenty-three of 125 (18.4%) KTR presented decoy cells in at least one urinary cytological sample. Molecular studies revealed that 10 of 125 (8%) KTR were BK PCR-serum positive cases (seven LT+/VP1- and three LT+/VP1+); and 13 of 40 (32.5%) KTR were BK PCR-urine positive cases (five LT+/VP1- and eight LT+/VP1+). When we compared PCR-urine and cytological results in 40 KTR, only 15% (six cases) revealed simultaneous positivity in both studies. In the context of clinical graft dysfunction, three patients demonstrated BK DNA presence in the renal biopsy. Finally, sequence analysis of the TCR was performed in 13 BK-PCR positive cases determining the AS, JL, WW, and WW-like viral variants. TCR sequence analysis, allows us to demonstrate the possible implication of the donor in BK infection studying four BK-PCR positive patients paired by donor.

LT, VP1 and TCR-BKV sequence analysis in a patient with post-transplant BKV nephropathy associated with EBV-related PTLD.

A 10-year-old boy kidney transplant recipient (KTR) developed an abdominal post-transplant lymphoproliferative syndrome (PTLD) followed by BK virus nephropathy (BKVN). BK virus (BKV) and Epstein-Barr virus (EBV) were studied in renal and PTLD tissue by polymerase chain reaction (PCR) assay. Afterwards, the patient was monitored in relation to BKV in urine and serum; transcription control region (TCR)-BK polymorphism sequence analysis was also performed. In the PCR assay, both early large T antigen (LT) and late (VP1) transcriptional BKV coding regions were found in renal tissue, whereas EBV and only LT-BK were detected in PTLD abdominal tissue. On the other hand, TCR sequence analysis revealed the AS genomic BK variant.