0000000000056604
AUTHOR
Antonio Ferrández
Controversial issues in soft tissue solitary fibrous tumors: A pathological and molecular review
The clinical evolution of solitary fibrous tumor (SFT) remains unclear. Although various clinical, morphological and molecular criteria may indicate increased risk of malignancy, some SFT can still progress despite having a clearly benign appearance. Various risk stratification systems have been proposed, but unfortunately they are not sufficient to precisely determine the malignant potential. In this review, we discuss current knowledge on SFT, focusing on the following controversial issues: (i) the diverse morphologic spectrum: 'the great simulator;' (ii) malignant transformation or dedifferentiation; (iii) current risk stratification systems; and (iv) molecular factors associated with cl…
Digital Pathology Enables Automated and Quantitative Assessment of Inflammatory Activity in Patients with Chronic Liver Disease
Traditional histological evaluation for grading liver disease severity is based on subjective and semi-quantitative scores. We examined the relationship between digital pathology analysis and corresponding scoring systems for the assessment of hepatic necroinflammatory activity. A prospective, multicenter study including 156 patients with chronic liver disease (74% nonalcoholic fatty liver disease-NAFLD, 26% chronic hepatitis-CH etiologies) was performed. Inflammation was graded according to the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network system and METAVIR score. Whole-slide digital image analysis based on quantitative (I-score: inflammation ratio) and morphometric (C-sco…
Psammomatous malignant melanoma arising in an intradermal naevus
Psammomatous malignant melanoma arising in an intradermal naevus Aims: A wide variety of differentiation patterns may be found in malignant melanoma. Schwannian features are unusual, and mostly present in the desmoplastic variant. We report the first description of psammoma bodies in malignant melanoma. Methods and results: A malignant melanoma arose in an intradermal naevus of the scalp in a 51-year-old woman, displaying focal neural-like features in the form of rosette-like pseudo-meissnerian alveolar nests, as well as numerous psammoma bodies grouped in a few areas. Tumour cell immunostaining for S100, HMB45, NKI-C3, and vimentin was detected. In addition, both malignant and benign melan…
Metabolic profile of chronic liver disease by NMR spectroscopy of human biopsies.
Among the different processes occurring during the evolution of liver disease, fibrosis has a predominant role. Liver fibrosis mechanisms are fairly constant irrespective of the underlying etiology. Cirrhosis is the end-stage of this reaction. Metabolic profiles, which are affected by many physiological and pathological processes, may provide further insight into the metabolic consequences of this severe liver disease. The aim of this study was to demonstrate the applicability of 1H high resolution magic angle spinning (HR-MAS) NMR spectroscopy in the biochemical profile determination of human liver needle biopsy samples for the characterization of metabolic alterations related to the sever…
Urea cycle dysregulation in non-alcoholic fatty liver disease.
Background & Aims: In non-alcoholic steatohepatitis (NASH), the function of urea cycle enzymes (UCEs) may be affected, resulting in hyperammonemia and the risk of disease progression. We aimed to determine whether the expression and function of UCEs are altered in an animal model of NASH and in patients with non-alcoholic fatty liver disease (NAFLD), and whether this process is reversible. Methods: Rats were first fed a high-fat, high-cholesterol diet for 10 months to induce NASH, before being switched onto a normal chow diet to recover. In humans, we obtained liver biopsies from 20 patients with steatosis and 15 with NASH. Primary rat hepatocytes were isolated and cultured with free fatty …
Soluble intercellular adhesion molecule-1 (s-ICAM-1/s-CD54) in diffuse large B-cell lymphoma: association with clinical characteristics and outcome
Background: High serum levels of soluble intercellular adhesion molecule-1(s-ICAM-1/s-CD54) have been associated with adverse clinical features and poor outcome in chronic lymphocytic leukemia, Hodgkin’s disease and non-Hodgkin’s lymphoma, but their value in the different subtypes of non-Hodgkin’s lymphoma has not been well addressed. Patients and methods: Our aim was to study the serum levels of s-ICAM-1 in diffuse large B-cell lymphoma (DLBCL) and to correlate them with clinical characteristics and outcome. We analyzed the serum levels of s-ICAM-1 in a series of 55 patients with DLBCL diagnosed in a single institution. s-ICAM-1 levels were quantified by an immunoenzymatic assay. Median ag…
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…
Implicaciones pronósticas del estudio estandarizado de los márgenes de resección en el cáncer de páncreas
Resumen Introduccion La afectacion microscopica de los margenes de reseccion es un factor pronostico fundamental en la cirugia del cancer de pancreas. Sin embargo, su definicion anatomopatologica no esta estandarizada. Este estudio pretende identificar el porcentaje real de pacientes con resecciones R1 al analizar las piezas quirurgicas con un protocolo estandarizado y evaluar sus implicaciones sobre la supervivencia. Pacientes y metodos Serie de 100 pacientes consecutivos intervenidos por adenocarcinoma ductal de pancreas y resecciones macroscopicamente completas, divididos en 2 grupos: pre- y posprotocolo, segun se intervinieran antes o despues de la aplicacion de un protocolo estandariza…
Peripheral T-cell lymphoma associated consecutively with hemophagocytic lymphohistiocytosis and hypereosinophilic syndrome
: Both hemophagocytic lymphohistiocytosis and hypereosinophilic syndrome have been associated with hematologic neoplasms and are respectively related to an overproduction of the cytokines Thelper 1 (Th1) and Th2 by tumor cells or reactive cells. To our knowledge, this is the first time a case of a peripheral T-cell lymphoma consecutively associated with both paraneoplastic conditions has been reported. Importantly, in this case when the lymphoma exclusively involved the bone marrow, severe paraneoplastic systemic damage, a CD8+ suppressor/cytotoxic phenotype and a hypereosinophilia not related to high levels of interleukin (IL)-5 was found. Interestingly, progression of the lymphoma coinci…
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…
Tumor de células de la granulosa extraovárico con mutación FOXL2. Diagnóstico diferencial morfológico e inmunohistoquímico
Extraovarian granulosa cell tumor is a very uncommon tumor and the identification of a recurrent mutation in FOXL2 may be used as another diagnostic tool along with the classical morphological and immunohistochemical findings. Here, we report a new case of extraovarian granulosa cell tumor in a 57 years old female patient presented with a sub-hepatic mass and abdominal pain. Histopathological examination of the excised mass showed features of adult-type granulosa cell tumor with α-inhibin, calretinin, WT1, S100, CD99 and progesterone receptor immunoreactivity. A FOXL2 mutation was detected on molecular biology study. A final diagnosis was an extraovarian adult-type granulosa cell tumor. We …
Neoadjuvant treatment for locally advanced unresectable and borderline resectable pancreatic cancer: oncological outcomes at a single academic centre.
INTRODUCTION: Pancreatic cancer (PC), even in the absence of metastatic disease, has a dismal prognosis. One-third of them are borderline resectable (BRPC) or locally advanced unresectable PC (LAUPC) at diagnosis. There are limited prospective data supporting the best approach on these tumours. Neoadjuvant chemotherapy (ChT) is being increasingly used in this setting. METHODS: This is a retrospective series of consecutive patients staged as BRPC or LAUPC after discussion in the multidisciplinary board (MDB) at an academic centre. All received neoadjuvant ChT, followed by chemoradiation (ChRT) in some cases, and those achieving enough downstaging had a curative-intent surgery. Descriptive da…
Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics
NKX2 homeobox family proteins have a role in cancer development. Here we show that NKX2-3 is overexpressed in tumour cells from a subset of patients with marginal-zone lymphomas, but not with other B-cell malignancies. While Nkx2-3-deficient mice exhibit the absence of marginal-zone B cells, transgenic mice with expression of NKX2-3 in B cells show marginal-zone expansion that leads to the development of tumours, faithfully recapitulating the principal clinical and biological features of human marginal-zone lymphomas. NKX2-3 induces B-cell receptor signalling by phosphorylating Lyn/Syk kinases, which in turn activate multiple integrins (LFA-1, VLA-4), adhesion molecules (ICAM-1, MadCAM-1) a…
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…
Metabolite identification in human liver needle biopsies by high-resolution magic angle spinning1H NMR spectroscopy
High-resolution magic angle spinning (HR-MAS) 1 H NMR spectroscopy of intact human liver needle biopsies has not been previously reported. HR-MAS NMR spectra collected on 17 specimens with tissue amounts between � 0.5 and 12 mg showed very good spectral resolution and signal-to-noise ratios. One-dimensional 1 H spectra revealed many intense signals corresponding to cellular metabolites. In addition, some high molecular weight metabolites, such as glycogen and mobile fatty acids, could be observed in some spectra. Resonance assignments for 22 metabolites were obtained by combining the analysis of three different types of 1D 1 H spectral editing, such as T2 filtering or the nuclear Overhauser…
Does the Artery-first Approach Improve the Rate of R0 Resection in Pancreatoduodenectomy? A Multicenter, Randomized, Controlled Trial
[Objective]: To compare the rates of R0 resection in pancreatoduodenectomy (PD) for pancreatic and periampullary malignant tumors by means of standard (ST-PD) versus artery-first approach (AFA-PD). [Background]: Standardized histological examination of PD specimens has shown that most pancreatic resections thought to be R0 resections are R1. “Artery-first approach” is a surgical technique characterized by meticulous dissection of arterial planes and clearing of retropancreatic tissue in an attempt to achieve a higher rate of R0. To date, studies comparing AFA-PD versus ST-PD are retrospective cohort or case-control studies. [Methods]: A multicenter, randomized, controlled trial was conducte…
Prognostic Implications of the Standardized Study of Resection Margins in Pancreatic Cancers
Abstract Introduction Involvement of surgical resection margins is a fundamental prognostic factor in pancreatic oncological surgery. However, there is a lack of standardized histopathology definition. The aims of this study are to investigate the real rate of R1 resections when surgical specimens are evaluated according to a standardized protocol and to study its survival implications. Patients and methods One hundred consecutive surgically resected patients with pancreatic ductal adenocarcinoma were included in the study. They were further divided into 2 groups: pre-protocol, evaluated before the introduction of the standardized protocol and post-protocol, analyzed with the standardized p…
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 …
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…
HMB-45 Immunostaining and Ultrastructure of Melanocytic Hyperplasia in Pigmented Basal Cell Carcinomas
The pigmented variant of basal cell carcinoma (PBCC) may be clinically misinterpreted as malignant melanoma. Histologically this variant is characterized by the presence of functional melanocytes distributed among epithelial tumor cells, particularly in superficial areas. Our finding of a case of PBCC with numerous atypical HMB-45-positive melanocytes prompted us to analyze the morphologic and immunohistochemical features of 20 consecutive cases of PBCC. Four additional cases with numerous large HMB-45-positive melanocytes, also present in the most invasive tumor nests, were found. Ultrastructural examination was performed in two selected cases. Large melanocytes with immature (stages I an…
Solitary Fibrous Tumor: Integration of Clinical, Morphologic, Immunohistochemical and Molecular Findings in Risk Stratification and Classification May Better Predict Patient outcome
Although solitary fibrous tumors (SFTs) have an unpredictable evolution, some specific clinicopathologic factors have been associated with the final outcome. We retrieved clinical, pathological and molecular data of 97 patients with a histological diagnosis of SFT and Signal transducer and activator of transcription 6 (STAT6) positivity. We retrospectively studied the pathological factors predictive of recurrence/metastasis and compared them with the clinical outcome. A wide immunohistochemical study and molecular analysis to detect NAB2/STAT6 gene fusion, tumor protein-53 (TP53) and/or (telomerase reverse transcriptase) TERT promotor mutation were performed. The risk of metastasis was calc…