TERT promoter mutational screening as a tool to predict malignant behaviour in follicular thyroid tumours-three examples from the clinical routine.

Follicular thyroid adenomas (FTAs) and carcinomas (FTCs), collectively the most common thyroid neoplasms, constitute a significant clinical challenge since histological evidence of invasive behaviour is required for a malignant diagnosis. Small subsets of FTAs relapse as manifest malignant FTCs, indicating that histology is not always adequate to predict malignant potential. Lately, recurrent mutations in the promoter of the Telomerase reverse transcriptase (TERT) gene have been coupled to FTCs, whereas FTAs usually lack this aberrancy. We describe three patients with follicular thyroid tumours in which TERT promoter mutational screening was employed as part of the clinical work-up to pinpoint malignant potential. In two retrospective analyses of seemingly benign lesions, the detected mutations predicted future skeletal metastases, and in one prospective case, the mutational screening led to a different clinical management of the afflicted patient. We therefore consider TERT promoter mutational screening an adjunct tool of value in equivocal cases.

A Review of the Use of Fine-Needle Aspiration Biopsy of Mammary Tumors for Diagnosis and Research.

The article "Aspiration Biopsy of Mammary Tumors in Diagnosis and Research - A Critical Review of 2,200 Cases" by Zajicek et al. [Acta Cytol 1967;11:169-175] is composed of two separate parts as can be seen from the title. Both are, however, of great historical interest. The first describes the early days of fine-needle aspiration cytology diagnosis of breast lesions in particular carcinomas. The results are still impressive with a diagnostic accuracy close to 90%. The second deals with the effect of negative pressure on cell viability during the aspiration procedure. These studies were aimed at evaluating the usefulness of aspirated tumor cells to analyze the effects of therapy and the origin of tumor cells.

Digital image analysis outperforms manual biomarker assessment in breast cancer.

In the spectrum of breast cancers, categorization according to the four gene expression-based subtypes 'Luminal A,' 'Luminal B,' 'HER2-enriched,' and 'Basal-like' is the method of choice for prognostic and predictive value. As gene expression assays are not yet universally available, routine immunohistochemical stains act as surrogate markers for these subtypes. Thus, congruence of surrogate markers and gene expression tests is of utmost importance. In this study, 3 cohorts of primary breast cancer specimens (total n=436) with up to 28 years of survival data were scored for Ki67, ER, PR, and HER2 status manually and by digital image analysis (DIA). The results were then compared for sensitivity and specificity for the Luminal B subtype, concordance to PAM50 assays in subtype classification and prognostic power. The DIA system used was the Visiopharm Integrator System. DIA outperformed manual scoring in terms of sensitivity and specificity for the Luminal B subtype, widely considered the most challenging distinction in surrogate subclassification, and produced slightly better concordance and Cohen's κ agreement with PAM50 gene expression assays. Manual biomarker scores and DIA essentially matched each other for Cox regression hazard ratios for all-cause mortality. When the Nottingham combined histologic grade (Elston-Ellis) was used as a prognostic surrogate, stronger Spearman's rank-order correlations were produced by DIA. Prognostic value of Ki67 scores in terms of likelihood ratio χ(2) (LR χ(2)) was higher for DIA that also added significantly more prognostic information to the manual scores (LR-Δχ(2)). In conclusion, the system for DIA evaluated here was in most aspects a superior alternative to manual biomarker scoring. It also has the potential to reduce time consumption for pathologists, as many of the steps in the workflow are either automatic or feasible to manage without pathological expertise.

Nódulo tiroideo como primer signo de progresión de carcinoma de cervix uterino / Thyroid nodule as a first sign of progression in uterine cervical carcinoma

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Overexpression of proCOL11A1 as a stromal marker of breast cancer.

BACKGROUND: Our previous studies demonstrated the expression of procollagen11A1 in fibroblasts of pancreatic cancer desmoplasia and the lack of expression in fibroblasts of pancreatitis by means of the polyclonal antibody (anti-proCOL11A1 pAb) we generated. In a similar way, we decided to compare the expression of procollagen11A1 in fibroblasts of infiltrating ductal carcinoma of the breast and fibroblasts of benign sclerosing lesions of the breast, in order to validate the anti-proCOL11A1 pAb in this setting and to study how proCOL11A1 expression relates to other prognostic and predictive factors, as well as to survival. METHODS: 45 core biopsies of sclerosing adenosis and 50 core biopsies of infiltrating ductal carcinoma of the breast were stained with anti-proCOL11A1 pAb, a polyclonal antibody highly specific to the less homologous fraction of proCOL11A1 (in comparison with proCOL5A1 and proCOL11A2). In addition, the expression of the proCOL11A1 gene was measured by RT-qPCR. On the other hand, the expression of proCOL11A1 was compared to the expression of estrogenic receptors, progestagen receptors, the state of the epidermal growth factor receptor 2 (HER2), the histologic grade and the stage of the disease. We also compared the immunohistochemical expression of proCol11A1 to the disease-free interval, and to overall survival. RESULTS: The immunohistochemical analysis showed that proCOL11A1 was expressed in 100% of infiltrating ductal carcinomas, but only focally expressed in 2.2% (1 case) of sclerosing adenosis, in agreement with RT-qPCR results. ProCOL11A1 expression did not prove to have a prognostic value in relation to the disease-free interval or to overall survival in infiltrating ductal carcinoma. CONCLUSION: The anti-proCOL11A1 pAb is a stromal marker for breast cancer and the expression of proCOL11A1 does not seem to have a prognostic value in infiltrating ductal carcinoma of the breast.

Imagen de carcinomatosis peritoneal secundaria a rotura de carcinoma hepatocelular originado sobre hígado sano / Peritoneal carcinomatosis secondary to spread of hepatocellular carcinoma originated upon a healthy liver

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Adenocarcinomas nasosinusales tipo intestinal. Perfil inmunohistoquímico de 66 casos / Intestinal-type sinonasal adenocarcinomas. Immunohistochemical profile of 66 cases

Introducción y objetivos: Los adenocarcinomas nasosinusales tipo intestinal son tumores epiteliales malignos, que suponen el 8-25% de los tumores malignos nasosinusales. Se relacionan con la exposición al polvo de la madera. Se subdividen histológicamente en papilares, colónicos, sólidos y mucinosos. Realizamos un estudio patológico e inmunohistoquímico con el fin de establecer características con significado pronóstico, diagnóstico e incluso terapéutico, así como comparar con estudios previos. Métodos: Estudiamos 66 muestras tumorales mediante matrices tisulares. Realizamos tinciones inmunohistoquímicas para p53, p16, beta-catenina, E-cadherina, receptor del factor de crecimiento epidérmico (EGFR), receptor 2 de factor de crecimiento epidérmico humano (HER2/neu) y ciclooxigenasa 2 (COX-2). Resultados: Un 63% de los casos son positivos para p53, el 37% para beta-catenina nuclear, el 100% para E-cadherina, el 98% para beta-catenina membranosa, el 7% para EGFR, el 8% para HER2/neu, el 52% para COX-2 y el 59% pierden la expresión de p16. Conclusiones: La invasión intracraneal es el factor clínico pronóstico más importante. Los tumores de tipo sólido y mucinoso son los que muestran un comportamiento más agresivo, siendo los mucinosos los que mayor invasión intracraneal muestran. No existen diferencias inmunohistoquímicas entre los distintos subtipos histológicos, únicamente la tinción débil para E-cadherina y beta-catenina, más frecuente en los de tipo mucinoso. El EGFR, HER2/neu y COX-2 muestran una positividad menos frecuente que en series previas. La positividad para p16 se asocia a una menor supervivencia y mayor frecuencia de enfermedad metastásica.Palabras clave Adenocarcinoma nasosinusal. Carcinoma nasosinusal. Inmunohistoquímica. p53. p16. beta-catenina. E-cadherina. Receptor del factor de crecimiento epidérmico. Receptor 2 de factor de crecimiento epidérmico humano. Cyclooxigenasa-2 (AU)

Introduction and objectives: Intestinal-type sinonasal adenocarcinomas are malignant epithelial tumours. Around 8-25% of all sinonasal malignant tumours are intestinal-type adenocarcinomas, which are related to wood dust exposure. Four histological subtypes have been described: papillary, colonic, solid and mucinous. We performed a pathological and immunohistochemical study in order to describe characteristics with prognostic, diagnostic and therapeutic value, and also to compare our results with previous studies. Methods: Sixty six tumour samples were analysed and protein expression of p53, p16, E-cadherin, beta-catenin, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2/neu) and cyclooxygenase-2 (COX-2) was performed by tissue microarray blocks. Results: The 63% of cases were p53 positive; 37% showed nuclear staining with beta-catenin and 100% with E-cadherin, while 98% showed membrane staining with beta-catenin, 7% with EGFR, 8% with HER2/neu and 52% with COX-2; and 59% of the cases lost p16 expression. Conclusions: Intracranial invasion was the worst prognostic associated event. Solid and mucinous tumours were the most aggressive histological subtypes. Intracranial invasion was more frequent in mucinous subtype tumours. Immunohistochemical results were similar in all tumour subtypes, except for mucinous tumours, which showed weak expression of E-cadherin and beta-catenin. Comparing with previous studies, we found a lower expression of EGFR, HER2/neu and COX-2. The p16 expression was associated with worse survival and metastatic disease (AU)

Embolismo de líquido amniótico. Presentación de un caso / Amniotic fluid embolism. A case report

El embolismo de líquido amniótico (ELA) es un síndrome obstétrico que suele presentarse de manera abrupta en el parto o en el posparto inmediato, con un comienzo agudo de disnea o colapso cardiovascular. El ELA es difícil de diagnosticar en vida, ya que no existen pruebas analíticas específicas para la enfermedad. Presentamos un caso de ELA en una mujer de 37 años de edad que desarrolló un cuadro súbito de disnea y shock cardiovascular en el trabajo de parto. Se estableció la sospecha clínica de ELA y se procedió a una cesárea urgente. La paciente falleció, pero el feto sobrevivió. En la autopsia se demostró la presencia de componentes del líquido amniótico en los vasos del endocérvix uterino y los espacios alveolares pulmonares, confirmando la sospecha clínica(AU)

Amniotic fluid embolism (AFE) is a rare obstetric syndrome occurring abruptly during delivery or the postpartum characterized by acute onset of dyspnea or haemodynamic collapse. Clinical diagnosis is often difficult due to the lack of specific tests. We present a case of AFE in a 37-year-old woman who developed abrupt dyspnea and cardiogenic shock during labour. An emergency caesarian section was performed due to the suspicion of AFE. The patient died but the foetus survived. The autopsy revealed amniotic components within the endocervix vessels and lung alveolar spaces, thus confirming the clinical diagnosis(AU)

Intestinal-type sinonasal adenocarcinomas. Immunohistochemical profile of 66 cases.

INTRODUCTION AND OBJECTIVES: Intestinal-type sinonasal adenocarcinomas are malignant epithelial tumours. Around 8-25% of all sinonasal malignant tumours are intestinal-type adenocarcinomas, which are related to wood dust exposure. Four histological subtypes have been described: papillary, colonic, solid and mucinous. We performed a pathological and immunohistochemical study in order to describe characteristics with prognostic, diagnostic and therapeutic value, and also to compare our results with previous studies. METHODS: Sixty six tumour samples were analysed and protein expression of p53, p16, E-cadherin, ß-catenin, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2/neu) and cyclooxygenase-2 (COX-2) was performed by tissue microarray blocks. RESULTS: The 63% of cases were p53 positive; 37% showed nuclear staining with ß-catenin and 100% with E-cadherin, while 98% showed membrane staining with ß-catenin, 7% with EGFR, 8% with HER2/neu and 52% with COX-2; and 59% of the cases lost p16 expression. CONCLUSIONS: Intracranial invasion was the worst prognostic associated event. Solid and mucinous tumours were the most aggressive histological subtypes. Intracranial invasion was more frequent in mucinous subtype tumours. Immunohistochemical results were similar in all tumour subtypes, except for mucinous tumours, which showed weak expression of E-cadherin and ß-catenin. Comparing with previous studies, we found a lower expression of EGFR, HER2/neu and COX-2. The p16 expression was associated with worse survival and metastatic disease.

Characterization of a novel mouse monoclonal antibody, clone 1E8.33, highly specific for human procollagen 11A1, a tumor-associated stromal component.

A novel IgG1, κ mouse monoclonal antibody (clone 1E8.33) to human procollagen 11A1 has been generated. This antibody is poorly mutated, essentially in germ line configuration; its complementarity determining regions (CDRs) are especially rich in tyrosine and serine residues. The epitope recognized is encompassed in the YNYGTMESYQTEAPR amino acid stretch within the variable region of human procollagen 11A1. Human procollagens 5A1 and 11A1 are very similar. However, this antibody does not cross-react with human procollagen 5A1. In human breast tumors, only the activated peritumoral myofibroblasts show a strong intracytoplasmic staining with this antibody. As procollagen 11A1 is overexpressed in the stroma of human tumors with desmoplastic reaction, this antibody represents a valuable tool for diagnostic purposes.