Deconstructing neutrophil to lymphocyte ratio (NLR) in early breast cancer: lack of prognostic utility and biological correlates across tumor subtypes.

PURPOSE: The prognostic utility and biological correlates of neutrophil to lymphocyte ratio (NLR), a potential biomarker of the balance between immune response and the inflammatory status, are still uncertain in breast cancer (BC). METHODS: We analysed a cohort of 959 women with early breast cancer, mostly treated with neoadjuvant or adjuvant chemotherapy. Clinical and pathological data, survival, NLR (continuous and categorical) and stromal tumor infiltrating lymphocytes (sTIL) were evaluated. RESULTS: NLR was only weakly associated with Ki67, while no association was found for grade, histology, immunohistochemical subtype or stage. Lymphocyte infiltration of the tumor did not correlate with NLR (Rho: 0.05, p = 0.30). These results were similar in the whole group and across the different BC subtypes, with no differences in triple negative BC. Relapse free interval (RFI), breast cancer specific survival (BCSS) and overall survival (OS) changed according to pre-treatment NLR neither in the univariate nor in the multivariate Cox models (RFI: HR 0.948, p = 0.61; BCSS: HR 0.920, p = 0.57; OS: HR 0.96, p = 0.59). CONCLUSION: These results question the utility of NLR as a prognostic biomarker in early breast cancer and suggest the lack of correlation of NLR with tumor microenvironment immune response.

Clinical Meaning of Stromal Tumor Infiltrating Lymphocytes (sTIL) in Early Luminal B Breast Cancer.

Luminal breast cancer (BC) is associated with less immune activation, and the significance of stromal lymphocytic infiltration (sTIL) is more uncertain than in other BC subtypes. The aim of this study was to investigate the predictive and prognostic value of sTIL in early luminal BC. The study was performed with an observational design in a prospective cohort of 345 patients with predominantly high-risk luminal (hormone receptor positive, HER2 negative) BC and with luminal B features (n = 286), in which the presence of sTIL was analyzed with validated methods. Median sTIL infiltration was 5% (Q1-Q3 range (IQR), 0-10). We found that sTIL were associated with characteristics of higher biological and clinical aggressiveness (tumor and lymph node proliferation and stage, among others) and that the percentage of sTIL was predictive of pathologic complete response in patients treated with neoadjuvant chemotherapy (OR: 1.05, 95%CI 1.02-1.09, p < 0.001). The inclusion of sTIL (any level of lymphocytic infiltration: sTIL > 0%) in Cox regression multivariable prognostic models was associated with a shorter relapse-free interval (HR: 4.85, 95%CI 1.33-17.65, p = 0.016) and significantly improved its performance. The prognostic impact of sTIL was independent of other clinical and pathological variables and was mainly driven by its relevance in luminal B BC.

A new prognostic model including immune biomarkers, genomic proliferation tumor markers (AURKA and MYBL2) and clinical-pathological features optimizes prognosis in neoadjuvant breast cancer patients.

Background: Up to 30% of breast cancer (BC) patients treated with neoadjuvant chemotherapy (NCT) will relapse. Our objective was to analyze the predictive capacity of several markers associated with immune response and cell proliferation combined with clinical parameters. Methods: This was a single-center, retrospective cohort study of BC patients treated with NCT (2001-2010), in whom pretreatment biomarkers were analyzed: neutrophil-to-lymphocyte ratio (NLR) in peripheral blood, CD3+ tumor-infiltrating lymphocytes (TILs), and gene expression of AURKA, MYBL2 and MKI67 using qRT-PCR. Results: A total of 121 patients were included. Median followup was 12 years. In a univariate analysis, NLR, TILs, AURKA, and MYBL2 showed prognostic value for overall survival. In multivariate analyses, including hormone receptor, HER2 status, and response to NCT, NLR (HR 1.23, 95% CI 1.01-1.75), TILs (HR 0.84, 95% CI 0.73-0.93), AURKA (HR 1.05, 95% CI 1.00-1.11) and MYBL2 (HR 1.19, 95% CI 1.05-1.35) remained as independent predictor variables. Conclusion: Consecutive addition of these biomarkers to a regression model progressively increased its discriminatory capacity for survival. Should independent cohort studies validate these findings, management of early BC patients may well be changed.

Head-tracking as an interface device for image control in digital pathology: a comparative study / Reconocimiento facial como interfaz de usuario para el manejo de la imagen en patología digital: un estudio comparativo

BACKGROUND: Inasmuch as the conventional mouse is not an ideal input device for digital pathology, the aim of this study was to evaluate alternative systems with the goal of identifying a natural user interface (NUI) for controlling whole slide images (WSI). DESIGN: Four pathologists evaluated three webcam-based, head-tracking mouse emulators: Enable Viacam (eViacam, CREA Software), Nouse (JLG Health Solutions Inc), and Camera Mouse (CM Solutions Inc). Twenty WSI dermatopathological cases were randomly selected and examined with Image Viewer (Ventana, AZ, USA). The NASA-TLX was used to rate the perceived workload of using these systems and time was recorded. In addition, a satisfaction survey was used. RESULTS: The mean total time needed for diagnosis with Camera Mouse, eViacam, and Nouse was 18'57", 19'37" and 22'32", respectively (57/59/68seconds per case, respectively). The NASA-TLX workload score, where lower scores are better, was 42.1 for eViacam, 53.3 for Nouse and 60.62 for Camera Mouse. This correlated with the pathologists' degree of satisfaction on a scale of 1-5: 3.4 for eViacam, 3 for Nouse, and 2 for Camera Mouse (p < 0.05). CONCLUSIONS: Head-tracking systems enable pathologists to control the computer cursor and virtual slides without their hands using only a webcam as an input device. - Of the three software solutions examined, eViacam seems to be the best of those evaluated in this study, followed by Nouse and, finally, Camera Mouse. - Further studies integrating other systems should be performed in conjunction with software developments to identify the ideal device for digital pathology

INTRODUCCIÓN: Considerando que el ratón convencional no es el controlador ideal en patología digital, el objetivo del estudio fue evaluar sistemas alternativos y tratar de identificar una interfaz natural de usuario para controlar preparaciones digitalizadas. MATERIAL Y MÉTODOS: Cuatro patólogos evaluaron tres emuladores de ratón con reconocimiento facial a través de webcam: eViacam, Nouse y Camera Mouse. Se seleccionaron 20 casos digitalizados de dermatopatología aleatoriamente para su diagnóstico, empleando el software Image Viewer (Ventana, AZ, USA). Se utilizó el sistema NASA-TLX para registrar la carga de trabajo percibida y se grabaron los tiempos. Adicionalmente, se empleó un cuestionario de satisfacción. RESULTADOS: El tiempo medio requerido para diagnosticar con Camera Mouse, eViacam y Nouse fue de 18'57", 19'37"y 22'32", respectivamente (57/59/68 segundos por caso, respectivamente). La carga de trabajo NASA-TLX, donde registros menores implican menor carga, fue de 42,1 para eViacam, 53,3 para Nouse y 60,62 para Camera Mouse, correlacionándose con el grado de satisfacción de los patólogos en una escala de 1-5: 3,4 para eViacam (3,4), Nouse (3) y Camera Mouse (2) (p < 0,05). CONCLUSIONES: El reconocimiento facial posibilita a los patólogos el control del cursor y las preparaciones virtuales sin utilizar las manos, empleando únicamente una webcam como dispositivo de entrada. - De los tres sistemas, eViacam es el mejor software evaluado en este estudio, seguido de Nouse y, finalmente, de Camera Mouse. - Deben ser desarrollados estudios adicionales, integrando otros sistemas, en conjunción con el desarrollo de software para alcanzar el sistema ideal en patología digital

Head-tracking as an interface device for image control in digital pathology: a comparative study.

BACKGROUND: Inasmuch as the conventional mouse is not an ideal input device for digital pathology, the aim of this study was to evaluate alternative systems with the goal of identifying a natural user interface (NUI) for controlling whole slide images (WSI). DESIGN: Four pathologists evaluated three webcam-based, head-tracking mouse emulators: Enable Viacam (eViacam, CREA Software), Nouse (JLG Health Solutions Inc), and Camera Mouse (CM Solutions Inc). Twenty WSI dermatopathological cases were randomly selected and examined with Image Viewer (Ventana, AZ, USA). The NASA-TLX was used to rate the perceived workload of using these systems and time was recorded. In addition, a satisfaction survey was used. RESULTS: The mean total time needed for diagnosis with Camera Mouse, eViacam, and Nouse was 18'57", 19'37" and 22'32", respectively (57/59/68seconds per case, respectively). The NASA-TLX workload score, where lower scores are better, was 42.1 for eViacam, 53.3 for Nouse and 60.62 for Camera Mouse. This correlated with the pathologists' degree of satisfaction on a scale of 1-5: 3.4 for eViacam, 3 for Nouse, and 2 for Camera Mouse (p<0.05). CONCLUSIONS: Head-tracking systems enable pathologists to control the computer cursor and virtual slides without their hands using only a webcam as an input device. - Of the three software solutions examined, eViacam seems to be the best of those evaluated in this study, followed by Nouse and, finally, Camera Mouse. - Further studies integrating other systems should be performed in conjunction with software developments to identify the ideal device for digital pathology.

Schwannoma epitelioide con cambios tipo ancient. A propósito de un caso / Epithelioid schwannoma with ‘ancient’ changes. A case report

Los tumores benignos de la vaina del nervio periférico son relativamente frecuentes, siendo los principales representantes el neuroma solitario circunscrito, el neurofibroma y el schwannoma. Sin embargo, la variante epitelioide benigna del schwannoma de partes blandas es extremadamente rara y debe plantearse un cuidadoso diagnóstico diferencial con otras entidades benignas y malignas. Se presenta el caso de un schwannoma epitelioide en un varón de 48 años y se revisa la literatura así como su diagnóstico diferencial histológico e inmunohistoquímico (AU)

Benign peripheral nerve sheath tumours are relatively common and the three main types are neuroma, neurofibroma, and schwannoma. However, the benign epithelioid variant of soft tissue schwannoma is extremely rare and a careful differential diagnosis must be made with other benign and malignant entities. A case of an epithelioid schwannoma in a 48 year-old-man is presented and the histological and immunohistochemical differential diagnosis is discussed. The relevant literature is reviewed (AU)

Hiperplasia nodular oncocítica multifocal de glándula parótida. A propósito de un caso con revisión del espectro de lesiones oncocíticas / Multifocal nodular oncocytic hyperplasia in the parotid gland. A case report and review of oncocytic lesions of the parotid gland

La hiperplasia nodular oncocítica multifocal es una lesión infrecuente de la glándula parótida. Se presenta un caso de hiperplasia nodular oncocítica multifocal de la glándula parótida en espacio parafaríngeo de una mujer de 74 años y se revisan las lesiones oncocíticas de la glándula parótida(AU)

Multifocal nodular oncocytic hyperplasia is a rare lesion of the parotid gland. A case of multifocal nodular oncocytic hyperplasia of the parotid gland in the parapharyngeal space in a 74-year-old woman is reported and the oncocytic lesions of the parotid gland are reviewed(AU)

Carcinomatosis meningea por invasión dural de metástasis craneal / Meningeal carcinomatosis caused by dural invasion of cranial metastases

La meningitis carcinomatosa es una entidad poco frecuente, que puede formar parte de la historia natural de muchos procesos neoplásicos. Se presenta habitualmente con síntomas poco específicos, como cefalea, cambios en la conducta o alteraciones motoras y sensitivas. A continuación presentamos el caso de un paciente con carcinomatosis meníngea por cáncer de pulmón y su evolución clínica (AU)

Carcinomatis meningitis is a rare entity, which may be part of the natural history of many neoplasic. It usually present with nonspecific symptoms such as headache, changes in behavior or motor and sensory disturbances. We present the case of a patient with meningeal carcinomatosis from lung adenocarcinoma and its clinical evolution (AU)

Infiltrating ductal carcinoma and synchronous malignant phyllodes tumour. Diagnostic and therapeutic approaches.

Simultaneous presentation of breast cancer and malignant phyllodes tumour is rare. A female patient presented with a nodule in her left breast (infiltrating ductal carcinoma). On magnetic nuclear resonance another suspicious lesion (malignant phyllodes) was found in the right breast. Bilateral mastectomy was performed. Thirty two months later the patient is still free of disease. The approach to dealing with synchronous breast tumours should be the same as that normally used.

Valoración de la 5ª edición de la clasificación TNM para el cáncer gástrico en nuestro medio / Appraisal of the fifth edition of the tumor-node-metastasis (TNM) classification for gastric cancer in our environment

Objetivo. Evaluar el número de casos de carcinoma gástrico que pueden ser estadificados con los criterios de la 5.a edición del sistema TNM y analizar qué factores pueden estar relacionados con la obtención de un número suficiente de ganglios. Pacientes y método. En 164 pacientes a los que se resecó un carcinoma gástrico, se estudiaron distintos factores que podían influir en el número de ganglios aislados, como el tamaño tumoral, el tipo de resección gástrica, el grado de diferenciación tumoral, el tipo histológico, la variabilidad entre patólogos que analizaron las piezas y la experiencia del cirujano. Resultados. La media de ganglios linfáticos analizados por los patólogos fue de 11,4 (intervalo de confianza del 95%, 10,12-12,66). Atendiendo a los criterios de la 5.a edición de la clasificación TNM, sólo se pudo clasificar correctamente al 31% de los pacientes. Encontramos una correlación positiva entre el tamaño tumoral y el número de ganglios aislados (p = 0,0018), así como un mayor número de ganglios analizados en las gastrectomías totales respecto de las subtotales (p = 0,034). No se observó una variación significativa en los ganglios analizados en relación con el patólogo que analizó la pieza ni con la experiencia del cirujano que efectuó la resección. Conclusiones. La 5.a edición del sistema TNM es fácilmente reproducible, aunque el número de ganglios necesarios para corroborar la afección ganglionar metastásica es difícil de conseguir en nuestro medio. Nuestros resultados sugieren que es necesario un esfuerzo conjunto por parte de cirujanos y patólogos para aumentar el número de pacientes estadificables con esta edición (AU)

Aim. To estimate the proportion of patients with gastric carcinoma that can be classified using the criteria of the fifth edition of the TNM system and to analyze which factors could be related to the finding of an adequate number of nodes. Patients and method. The influence of distinct factors that could influence the number of lymph nodes isolated was evaluated in 164 patients who underwent resection of gastric carcinoma. These factors included tumor size, surgical resection, grade, histological type, variability among the pathologists who analyzed the surgical specimens, and the surgeon's experience. Results. The mean number of lymph nodes examined by the pathologists was 11.4 (10.12-12.66). Applying the criteria of the fifth edition of the TNM classification, only 31% of the patients could be correctly classified. A positive correlation was found between tumor size and the number of resected nodes (p = 0.0018). In addition, a greater number of lymph nodes were found in total gastrectomies than in subtotal gastrectomies (p = 0.034). No significant association was found with the pathologist who analyzed the surgical specimen or with the experience of the surgeon who performed the resection. Conclusions. The fifth edition of the TNM system is easily reproducible, although the number of lymph nodes required to evaluate metastatic node involvement is difficult to obtain in our environment. Our results suggest that a combined effort between surgeons and pathologists is needed to increase the number of patients that can be reliably staged with this TNM edition (AU)

[Assessment of the fifth edition of the tumor-node-metastasis (TNM) classification for gastric cancer in our setting]. / Valoración de la 5.a edición de la clasificación TNM para el cáncer gástrico en nuestro medio.

AIM: To estimate the proportion of patients with gastric carcinoma that can be classified using the criteria of the fifth edition of the TNM system and to analyze which factors could be related to the finding of an adequate number of nodes. PATIENTS AND METHOD: The influence of distinct factors that could influence the number of lymph nodes isolated was evaluated in 164 patients who underwent resection of gastric carcinoma. These factors included tumor size, surgical resection, grade, histological type, variability among the pathologists who analyzed the surgical specimens, and the surgeon's experience. RESULTS: The mean number of lymph nodes examined by the pathologists was 11.4 (10.12-12.66). Applying the criteria of the fifth edition of the TNM classification, only 31% of the patients could be correctly classified. A positive correlation was found between tumor size and the number of resected nodes (p = 0.0018). In addition, a greater number of lymph nodes were found in total gastrectomies than in subtotal gastrectomies (p = 0.034). No significant association was found with the pathologist who analyzed the surgical specimen or with the experience of the surgeon who performed the resection. CONCLUSIONS: The fifth edition of the TNM system is easily reproducible, although the number of lymph nodes required to evaluate metastatic node involvement is difficult to obtain in our environment. Our results suggest that a combined effort between surgeons and pathologists is needed to increase the number of patients that can be reliably staged with this TNM edition.

Fibrohistiocitoma maligno pleomórfico del pericardio / Malignant pleomorphic fibrous histocytoma of the pericardium

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