Towards precision oncology for HER2 blockade in gastroesophageal adenocarcinoma

Gastroesophageal adenocarcinoma (GEA) represents a very heterogeneous disease and patients in advanced stages have a very poor prognosis. Although several molecular classifications have been proposed, precision medicine for HER2-amplified GEA patients still represents a challenge. Despite improvement in clinical outcomes obtained by adding trastuzumab to first-line platinum-based chemotherapy, no other anti-HER2 agents used first-line or beyond progression have demonstrated any benefit. Several factors contribute to this failure. Among them, variable HER2 amplification assessment, tumour heterogeneity, molecular mechanisms of resistance and microenvironmental factors could limit the effecti…

464P Exome sequencing of ctDNA portrays the mutational landscape of patients with relapsing colon cancer and indicates new actionable targets

Is It a Metastatic Disease: A Case Report and New Understanding of Rosai-Dorfman Disease?

Pleomorphic cutaneous Rosai-Dorfman disease.

we report three cases of pure cutaneous Rosai-Dorfman disease (RDD) showing prominent nuclear pleomorphism. This unusual finding confers a worrisome appearance to these lesions, challenging their recognition and creating difficulty in the differential diagnosis with malignant neoplasms. This article is protected by copyright. All rights reserved.

Carcinoma colorrectal serrado. Descripción histopatológica, inmunohistoquímica y molecular de un caso

Resumen El adenocarcinoma serrado es una variante del carcinoma colorrectal recientemente tipificada, y es el punto final de una via molecular denominada «via serrada». La lesion precursora en esta via es la mutacion del gen BRAF, que origina lesiones serradas con predisposicion a la metilacion genica y a la inestabilidad de microsatelites. En el presente estudio describimos un caso de adenocarcinoma de colon ascendente, con criterios histologicos compatibles con adenocarcinoma serrado: epitelio serrado, citoplasma amplio, nucleo vesicular y ausencia de necrosis. En el estudio inmunohistoquimico se observo perdida de la expresion del gen MLH1. El estudio molecular revelo altos niveles de in…

Assessing molecular subtypes of gastric cancer: microsatellite unstable and Epstein-Barr virus subtypes. Methods for detection and clinical and pathological implications.

Background The molecular classification of gastric cancer recognises two subtypes prone to immune checkpoint blockade: the microsatellite unstable and the Epstein-Barr virus (EBV)-related tumours. We aim to assess the concordance between immunohistochemistry and PCR for microsatellite status evaluation, and explore the value of microsatellite instability (MSI) and EBV as predictive survival factors. Material and methods We collected 246 consecutively diagnosed gastric cancer cases in all stages and evaluated the microsatellite status using immunohistochemistry for mismatched repair (MMR) proteins and PCR. EBV expression was studied through in situ hybridisation. Results Forty-five (18%) cas…

Detection of postoperative plasma circulating tumour DNA and lack of CDX2 expression as markers of recurrence in patients with localised colon cancer

BACKGROUND: Colon cancer (CC) is a heterogeneous disease. Novel prognostic factors beyond pathological staging are required to accurately identify patients at higher risk of relapse. Integrating these new biological factors, such as plasma circulating tumour DNA (ctDNA), CDX2 staining, inflammation-associated cytokines and transcriptomic consensus molecular subtypes (CMS) classification, into a multimodal approach may improve our accuracy in determining risk of recurrence.; METHODS: One hundred and fifty patients consecutively diagnosed with localised CC were prospectively enrolled in our study. ctDNA was tracked to detect minimal residual disease by droplet digital PCR. CDX2 expression was…

Low miR200c expression in tumor budding of invasive front predicts worse survival in patients with localized colon cancer and is related to PD-L1 overexpression

At the histological level, tumor budding in colon cancer is the result of cells undergoing at least partial epithelial-to-mesenchymal transition. The microRNA 200 family is an important epigenetic driver of this process, mainly by downregulating zinc-finger E-box binding homeobox (ZEB) and transforming growth factor beta (TGF-β) expression. We retrospectively explored the expression of the miR200 family, and ZEB1 and ZEB2, and their relationship with immune resistance mediated through PD-L1 overexpression. For this purpose, we analyzed a series of 125 colon cancer cases and took samples from two different tumor sites: the area of tumor budding at the invasive front and from the tumor center…

Intrasinusoidal HHV8-EBV–Positive Large B-Cell Lymphoma With Features of Germinotropic Lymphoproliferative Disorder

Germinotropic lymphoproliferative disorder (GLPD) is a poorly characterized lymphoproliferative entity, recently included in the World Health Organization classification of hematolymphoid neoplasms. The histological pattern of this disease comprises monotypic plasmablasts that involve the germinal centers of the lymphoid follicles (germinotrophism), forming confluent aggregates positive for both human herpes virus type 8 (HHV8) and Epstein-Barr virus. Currently, after 17 years of its first description, only 18 cases have been reported. In this article, we describe a case of a GLPD presenting in an immunocompetent 79-year-old woman with localized axillary lymphadenopathy, showing a prominen…

Quistes de uraco en adultos. Presentación de 3 casos y revisión de la literatura

Resumen El uraco es un grueso cordon fibroso que aparece a partir del quinto mes de gestacion como consecuencia de la obliteracion de la alantoides. Los quistes de origen uracal se producen como consecuencia de un defecto en la obliteracion de dicho conducto, anomalia que se detecta principalmente en ninos y raramente en adultos. Presentamos 3 casos de quistes uracales en adultos, uno de ellos detectado durante el estudio de dolor abdominal y los otros 2 hallados de forma incidental durante el estudio de otras patologias. En ningun caso se sospecho clinicamente la posibilidad de quistes uracales. Histologicamente, estas lesiones se encuentran revestidas por epitelio de tipo urotelial con ex…

In regard to “A tale of two clones: Caldesmon staining in the differentiation of cutaneous spindle-cell neoplasms”

Desmoplastic primitive nonneural granular cell tumor of the skin.

Abstract Primitive nonneural granular cell tumor of the skin was first described by LeBoit et al in 1991 as "primitive polypoid granular cell tumor." Few cases have been reported to date, all being polypoid or deep well-delimited lesions and formed by large spindle or polygonal granular cells with moderate nuclear atypia and increased mitotic activity. This granular cell population does not have a Schwannian, myogenic, melanocytic, fibroblastic, histiocytic, or epithelial differentiation. We report a case that fully satisfies the criteria for primitive nonneural granular cell tumor of the skin and, in addition, shows an extensive desmoplastic stroma. This desmoplastic variant of primitive n…

Anatomía Patológica para el estudiante de Medicina: videotutoriales con integración de Patología digital como una valiosa herramienta para hacer la asignatura más práctica y atractiva

Resumen Introduccion y objetivo La asignatura de Anatomia Patologica es fundamental en la formacion del estudiante de Medicina. Sin embargo, para muchos estudiantes la asignatura presenta un excesivo contenido teorico, poco trasladable a la practica clinica. Presentamos los resultados de un proyecto de innovacion docente dirigido a facilitar la transmision del conocimiento a distancia y hacer de la Anatomia Patologica una asignatura mas practica y atractiva para el estudiante de Medicina. Materiales y metodos Elaboramos material didactico integrando imagenes de enfermedad digital con videotutoriales para la exposicion de casos clinicos donde los alumnos debian llegar al diagnostico final. C…

Carcinoma epidermoide en un quiste branquial vs. metástasis nodal cervical quística. Presentación de un caso y revisión de criterios diagnósticos

Resumen El quiste branquial es una lesion congenita que resulta de un defecto en la obliteracion de los arcos branquiales cuyo componente epitelial podria ser el origen de una neoplasia de celulas escamosas, lo que antiguamente se llamo «carcinoma branquiogenico». Desde su introduccion, la existencia de esta lesion ha sido objeto de controversia por la falta de criterios diagnosticos reproducibles que permitan diferenciarlo de la metastasis ganglionar quistica por carcinomas epidermoides, especialmente los originados en el anillo de Waldeyer, los cuales pueden presentarse hasta en el 25% de los casos como un carcinoma de origen desconocido. El objetivo de este trabajo es presentar un caso c…

h-caldesmon immunoreactivity in atypical fibroxanthoma: implications for the differential diagnosis.

Pigmented desmoplastic trichilemmoma

Desmoplastic trichilemmoma (DT), the pseudomalignant variant of conventional trichilemmoma described by Hunt et al in 1990, displays a superficial lobular growth pattern of glycogen-rich cells with peripheral nuclear palisading surrounded by a thickened basement membrane. DT differs from its conventional counterpart by showing a central hyalinized area with epithelial cords and strands mimicking invasive carcinoma. We report a case that fully satisfies the criteria for DT and, in addition, shows an extensive melanocytic cell component and prominent melanin deposition. To our knowledge, a pigmented variant of DT has not been reported and should be recognized in order to appropriately face th…

Extra-Adrenal Adult Neuroblastoma With Aberrant Germ Cell Marker Expression: Maturation After Chemotherapy as an Important Clue to a Challenging Diagnosis

Adult neuroblastoma is an extremely infrequent neoplasm, usually occurring in the adrenal medulla or in the paraspinal sympathetic ganglia, as its childhood counterpart. We report a very unusual case of a Schwannian stroma-poor adult neuroblastoma of inguinal location, showing aberrant expression of germ cell markers: SALL4 and OCT4. This aberrant marker expression, the unusual positivity for NKX2.2 and the very scattered (instead of diffuse strong) PHOX2B expression, complicated the initial diagnosis. In this case, the posttreatment histological evaluation revealed the neuroblastic nature of the lesion. Neuroblastoma maturation after treatment is an unusual finding in adults, and in this …

Molecular profile in Paraguayan colorectal cancer patients, towards to a precision medicine strategy

[EN] Somatic mutation analysis and evaluation of microsatellite instability (MSI) have become mandatory for selecting personalized therapy strategies for advanced colorectal cancer and are not available as routine methods in Paraguay. The aims of this study were to analyze the molecular profile as well as the microsatellite status in a series of advanced colorectal patients from two public hospitals from Paraguay, to introduce these methodologies in the routine practice to guide the therapeutic decisions. Thirty-six patients diagnosed with advanced colorectal cancer from two referent public hospitals from Paraguay were recruited from May 2017 to February 2018. Sequenom Mass spectrometry, On…

Downregulation of intratumoral expression of miR-205, miR-200c and miR-125b in primary human cutaneous melanomas predicts shorter survival

AbstractWhile only 15–25 percent of melanoma patients develop distant metastasis and die, this disease is still responsible for the majority of skin cancer-related deaths. The availability of adjuvant therapies makes the selection of high-risk patients essential. We evaluated the intratumoral expression of ten miRNAs in primary melanomas in relation to its ability to predict melanoma survival. To this end, we correlated miRNA expression in 132 cryopreserved primary and metastatic tumors with clinicopathological factors and clinical outcome. We found sequential downregulation of intratumoral expression of miR-125b, miR-182, miR-200c and miR-205 over the full spectrum of melanoma progression.…

In the literature: October 2021

EPDR1 up-regulation in human colorectal cancer is related to staging and favours cell proliferation and invasiveness

The finding of novel molecular markers for prediction or prognosis of invasiveness in colorectal cancer (CRC) constitutes an appealing challenge. Here we show the up-regulation of EPDR1 in a prospective cohort of 101 CRC patients, in a cDNA array of 43 patients and in in silico analyses. EPDR1 encodes a protein related to ependymins, a family of glycoproteins involved in intercellular contacts. A thorough statistical model allowed us to conclude that the gene is significantly up-regulated in tumour tissues when compared with normal mucosa. These results agree with those obtained by the analysis of three publicly available databases. EPDR1 up-regulation correlates with the TNM staging parame…

Improving tumour budding evaluation in colon cancer by extending the assessment area in colectomy specimens.

AIMS It is recommended that tumour budding in colon cancer be counted on haematoxylin and eosin-stained sections in a hotspot area of 0.785 mm2 with a ×20 microscope objective. However, tumour buds may be difficult to visualise on haematoxylin and eosin-stained sections, and counting in such a limited area may result in overestimation in cases with focal budding. The aim of this study was to assess the contributions of various factors to improving tumour budding risk stratification: increasing the number of fields counted, using cytokeratin immunostaining, and recording proliferation, the apoptotic index and the emperipoletic index in tumour buds. METHODS AND RESULTS We created an explorato…

1432P Characterizing diversity in the immune profile by a transcriptomic customized gene signature to potentially personalize treatment in advanced gastric cancer patients

Epigenetic changes in localized gastric cancer: the role of RUNX3 in tumor progression and the immune microenvironment

// Marta Jessica Llorca-Cardenosa 1, * , Tania Fleitas 1, * , Maider Ibarrola-Villava 1 , Maria Pena-Chilet 1 , Cristina Mongort 2 , Carolina Martinez-Ciarpaglini 2 , Lara Navarro 2 , Valentina Gambardella 1 , Josefa Castillo 1 , Susana Rosello 1 , Samuel Navarro 2 , Gloria Ribas 1 , Andres Cervantes 1 1 Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain 2 Department of Pathology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain * These authors contributed equally to this work Correspondence to: Gloria Ribas, email: gribas@incliva.es Andres Cervantes, email: andres.cervantes@uv.es Keywords: RUNX3, ARID1A, gastric ca…

488P Patient-derived organoids as a tool for modelling localized colorectal cancer