Pulmonary valve spindle-cell lipoma: A case report.

Primary cardiac tumours are rare and most of them are benign. Myxomas, fibroelastomas and lipomas are common in adults. Primary valvular cardiac tumours are even more rare and affect all four valves in a similar proportion. Valvular lipomas are very rare. In the pulmonary valve there is only one described. Lipomas can be spindle-cell varieties. But of these, there is only one described in a valve, and it is placed in the aortic valve. Pulmonary valve lipomas can produce obstruction to the right ventricular outflow tract as well as pulmonary valve regurgitation, or pulmonary embolism. Symptoms may be dyspnoea, angina, arrhythmias, or syncope. We aim to illustrate with this case report how we came into this very rare pathology, so we present a 54-year-old woman with a giant spindle-cell lipoma located in the anterior pulmonary leaflet and severe dyspnoea. Total resection of the tumour was performed and restoration of valve function was obtained by means of bicuspidization of the remaining pulmonary leaflets. She had a good recovery after surgery and no complication during the postoperative evolution, being discharged from hospital after 7 days from surgery, with echocardiographic control showing good biventricular function, absence of tumour or obstruction, and minimal pulmonary valve regurgitation.

Intussusceptive angiogenesis facilitated by microthrombosis has an important example in angiolipoma. An ultrastructural and immunohistochemical study.

The microvasculature of angiolipoma frequently presents thrombi. Our objectives are to assess whether intussusceptive angiogenesis (IA) participates in vasculature formation in non-infiltrating angiolipoma and, if so, to explore how thrombi are involved in the IA process. For this purpose, we studied angiolipoma specimens (n: 52), using immunohistochemistry, and confocal and electron microscopy. The results showed the presence of folds and pillars, hallmarks of IA, dividing the vessel lumen. Folds showed a cover formed by reoriented endothelial cells from the vessel wall, or from newly formed folds, and a core initially formed by thrombus fragments (clot components as transitional core), which was replaced by extracellular matrix and invaginating pericytes establishing numerous peg-and-socket junctions with endothelial cells (mature core). A condensed plasmatic electron-dense material surrounded and connected folds and pillars with each other and with the vascular wall, which suggests a clot role in fold/pillar arrangement. In conclusion, we contribute to IA participation in capillary network formation in angiolipoma and the immunohistochemical and ultrastructural events by which microthrombosis facilitates IA. Therefore, in addition to the histogenesis of angiolipoma, we provide an easily obtainable substrate for future studies on clot component action in IA, of clinical and therapeutic interest.

Ultrastructural Study of Platelet Behavior and Interrelationship in Sprouting and Intussusceptive Angiogenesis during Arterial Intimal Thickening Formation.

Platelets in atherosclerosis, bypass stenosis, and restenosis have been extensively assessed. However, a sequential ultrastructural study of platelets in angiogenesis during the early phases of these lesions has received less attention. Our objective was the study of platelets in angiogenesis and vessel regression during intimal thickening (IT) formation, a precursor process of these occlusive vascular diseases. For this purpose, we used an experimental model of rat occluded arteries and procedures for ultrastructural observation. The results show (a) the absence of platelet adhesion in the de-endothelialized occluded arterial segment isolated from the circulation, (b) that intraarterial myriad platelets contributed from neovessels originated by sprouting angiogenesis from the periarterial microvasculature, (c) the association of platelets with blood components (fibrin, neutrophils, macrophages, and eosinophils) and non-polarized endothelial cells (ECs) forming aggregates (spheroids) in the arterial lumen, (d) the establishment of peg-and-socket junctions between platelets and polarized Ecs during intussusceptive angiogenesis originated from the EC aggregates, with the initial formation of IT, and (e) the aggregation of platelets in regressing neovessels ('transitory paracrine organoid') and IT increases. In conclusion, in sprouting and intussusceptive angiogenesis and vessel regression during IT formation, we contribute sequential ultrastructural findings on platelet behavior and relationships, which can be the basis for further studies using other procedures.

Adrenal lipoma: A case report and literature review.

The study reports a case of a 57-year-old female patient with incidental right adrenal lipoma (LA). The tumor was detected by ultrasound (US) and confirmed by computed tomography (CT). Due to the size of the mass, it was decided to perform a laparoscopic adrenalectomy. During the differential microscopic diagnosis, were considered adrenal lipomatous tumors, myelolipoma, angiomyolipoma and teratomas, among others. In all these neoplasms, LA is a rare tumor, with only 24 cases reported in the anglo-saxon literature revised. It is a benign adrenal gland tumor with generally asymptomatic and non-functioning nature.

Telocytes/CD34+ Stromal Cells in Pathologically Affected White Adipose Tissue.

We studied telocytes/CD34+ stromal cells (TCs/CD34+SCs) in pathologically affected white adipose tissue after briefly examining them in normal fat. To this aim, we reviewed pathological processes, including original contributions, in which TCs/CD34+SCs are conserved, increased, and lost, or acquire a specific arrangement. The pathologic processes in which TCs/CD34+SCs are studied in adipose tissue include inflammation and repair through granulation tissue, iatrogenic insulin-amyloid type amyloidosis, non-adipose tissue components (nerve fascicles and fibres in neuromas and hyperplastic neurogenic processes) and tumours (signet ring carcinoma with Krukenberg tumour and colon carcinoma) growing in adipose tissue, adipose tissue tumours (spindle cell lipoma, dendritic fibromyxolipoma, pleomorphic lipoma, infiltrating angiolipoma of skeletal muscle and elastofibrolipoma), lipomatous hypertrophy of the interatrial septum, nevus lipomatosus cutaneous superficialis of Hoffman-Zurhelle and irradiated adipose tissue of the perirectal and thymic regions. Two highly interesting issues emerged: (1) whether the loss of CD34 expression in TCs/CD34+SCs is by changes in marker expression or the disappearance of these cells (the findings suggest the first possibility) and (2) whether in some invasive and metastatic malignant tumours, TCs/CD34+SCs that completely surround neoplastic cells act as nurse and/or isolating cells. Further studies are required on adipose tissue TCs/CD34+SCs, mainly in lipomatosis and obesity.

Presence/Absence and Specific Location of Resident CD34+ Stromal Cells/Telocytes Condition Stromal Cell Development in Repair and Tumors.

CD34+ stromal cells/telocytes (CD34+SCs/TCs) can have a role as mesenchymal precursor cells. Our objective is to assess whether the myofibroblastic stromal cell response in repair and in desmoplastic reactions in tumors depend on the presence or absence of resident CD34+SCs/TCs in specific regions/layers of an organ and on the location of their possible subpopulations. For this purpose, using conventional and immunohistochemical procedures, we studied specimens of (a) acute cholecystitis, with early repair phenomena (n: 6), (b) surgically resected segments of colon tattooed with India ink during previous endoscopic removal of malignant polyps, with macrophage infiltration and stromal cell reaction (n: 8) and (c) infiltrative adenocarcinomas of colon, with desmoplastic reaction (n: 8). The results demonstrated (a) stromal myofibroblastic reaction during repair and tumor desmoplasia in most regions in which resident CD34+SCs/TCs are present, (b) absence of stromal myofibroblastic reaction during repair in the mucosa of both organs in which resident CD34+SCs/TCs are absent and (c) permanence of CD34+SCs/TCs as such, without myofibroblastic response, in smooth muscle fascicles, nerves, and Meissner and Auerbach plexuses, in which the CD34+SCs/TCs mainly undergo reactive phenomena. Therefore, the development of activated αSMA+ myofibroblasts in these conditions requires the presence of resident CD34+SCs/TCs and depends on their location. In conclusion, the facts support the hypotheses that CD34+SCs/TCs participate in the origin of myofibroblasts during repair and tumor stroma formation, and that there is a heterogeneous population of resident CD34+SCs/TCs with different roles.

Pathological findings in very low risk prostate cancer in surgical specimens. / Hallazgos patológicos en el cáncer de próstata de muy bajo riesgo en piezas de prostatectomía radical.

OBJECTIVE: Perform a detailed anatomopathological analysis of consecutive surgical specimens in men with clinically very low risk prostate cancer according to National Comprehensive Cancer Network (NCCN) criteria.MATERIALS AND METHODS: The study included 799 prostate cancer patients who under went radical prostatectomy between January 2005 and December 2013. We identified 81 consecutive patients with clinically very low risk prostate cancer. The slides of the patients who fulfilled the inclusion criteria were re-reviewed. The parameters studied were: pathological stage, histological grade by Gleason score (GSS), margins involvement, tumor percentage (PT), and number of apparently independent tumor foci (FT). RESULTS: The patients had organ-confined tumors in almost all of them (pT2: 97.5%). Most of the cancers studied were bilateral (pT2c: 67.9%), multifocal (FT≥2:88.8%), with a low tumor percentage (PTand with a low Gleason Score (GSS≤6: 91,3%). Non-confined disease: 2.5%, all cases extra-prostatic extension (pT3a). GSS>6: 8,6%, all cases GSS7 (3+4). CONCLUSIONS: The NCCN criteria for very low risk prostate cancer help to make a good selection of non-aggressive tumors and are a useful tool for including patients in an active surveillance program.

OBJETIVO: Realizar un análisis patológic odetallado de las piezas de prostatectomía radical en pacientes diagnosticados con cáncer de próstata de muy bajo riesgo según los criterios de la NCCN. MATERIAL Y MÉTODOS: El estudio incluye 799 pacientes con cáncer de próstata a los que se realizó una prostatectomía radical entre 2005 y 2013. 81 pacientes con cáncer de próstata clínicamente de muy bajo riesgo fueron identificados. Las laminillas de los pacientes identificados fueron revisadas. Los parámetros estudiados fueron: estadio patológico, grado de Gleason, márgenes quirúrgicos, % de tumor, y el numero de focos tumorales aparentemente independientes. RESULTADOS: La gran mayoría de pacientes presentaron tumores órgano-confinados (pT2: 97,5%). El 68% de los canceres fue bilateral (pT2c), multifocal (mas de2 focos 88%), con un porcentaje tumoral de menos del 10% en el 80% de los casos y mas del 90% con Gleason 6. La enfermedad no órgano-confinada se evidencio en 2,5% pT3a. CONCLUSIONES: Los criterios de NCCN para muy bajo riesgo nos ayudan a clasificar pacientes con tumores poco agresivos y son una buena herramienta para seleccionar pacientes para programas de vigilancia activa.

Hallazgos patológicos en el cáncer de próstata de muy bajo riesgo en piezas de prostatectomía radical / Pathological findings in very low risk prostate cancer in surgical specimens

OBJETIVO: Realizar un análisis patológico detallado de las piezas de prostatectomía radical en pacientes diagnosticados con cáncer de próstata de muy bajo riesgo según los criterios de la NCCN. MATERIAL Y MÉTODOS: El estudio incluye 799 pacientes con cáncer de próstata a los que se realizó una prostatectomía radical entre 2005 y 2013. 81 pacientes con cáncer de próstata clínicamente de muy bajo riesgo fueron identificados. Las laminillas de los pacientes identificados fueron revisadas. Los parámetros estudiados fueron: estadio patológico, grado de Gleason, márgenes quirúrgicos, % de tumor, y el numero de focos tumorales aparentemente independientes. RESULTADOS: La gran mayoría de pacientes presentaron tumores órgano-confinados (pT2: 97,5%). El 68% de los canceres fue bilateral (pT2c), multifocal (mas de 2 focos 88%), con un porcentaje tumoral de menos del 10% en el 80% de los casos y mas del 90% con Gleason 6. La enfermedad no órgano-confinada se evidencio en 2,5% pT3a. CONCLUSIONES: Los criterios de NCCN para muy bajo riesgo nos ayudan a clasificar pacientes con tumores poco agresivos y son una buena herramienta para seleccionar pacientes para programas de vigilancia activa

OBJECTIVE: Perform a detailed anatomopathological analysis of consecutive surgical specimens in men with clinically very low risk prostate cancer according to National Comprehensive Cancer Network (NCCN) criteria. MATERIALS AND METHODS: The study included 799 prostate cancer patients who underwent radical prostatectomy between January 2005 and December 2013. We identified 81 consecutive patients with clinically very low risk prostate cancer. The slides of the patients who fulfilled the inclusion criteria were re-reviewed. The parameters studied were: pathological stage, histological grade by Gleason score (GSS), margins involvement, tumor percentage (PT), and number of apparently independent tumor foci (FT). RESULTS: The patients had organ-confined tumors in almost all of them (pT2: 97.5%). Most of the cancers studied were bilateral (pT2c: 67.9%), multifocal (FT≥2: 88.8%), with a low tumor percentage (PT<10%: 80.2%) and with a low Gleason Score (GSS≤6: 91,3%). Non-confined disease: 2.5%, all cases extra-prostatic extension (pT3a). GSS>6: 8,6%, all cases GSS7(3+4). CONCLUSIONS: The NCCN criteria for very low risk prostate cancer help to make a good selection of non-aggressive tumors and are a useful tool for including patients in an active surveillance program

Participation of Intussusceptive Angiogenesis in the Morphogenesis of Lobular Capillary Hemangioma.

In lobular capillary hemangioma (LCH), misnamed pyogenic granuloma, only sprouting angiogenesis (SA) has been considered. We assess the occurrence of intussusceptive angiogenesis (IA) in LCH and whether IA determines the specific and other focal patterns in the lesion. For this purpose, we study specimens of 120 cases of LCH, using semithin sections (in 10), immunohistochemistry, and confocal microscopy (in 20). In addition to SA, the results in LCH showed (1) intussusceptive phenomena, including pillars/folds and associated vessel loops, which encircled interstitial tissue structures (ITSs). (2) Two types of evolved loops depending on interendothelial contacts from opposite walls: (a) numerous interendothelial contacts, alternating with capillary-sized lumens (main capillary pattern of the lesion) and (b) few interendothelial contacts, wide open lumens, and intravascular transport of pillars/folds, which were arranged linearly, forming septa (focal sinusoidal-like pattern) or were irregularly grouped (focal intravascular papillary endothelial hyperplasia, IPEH-like pattern). In conclusion, we demonstrate that IA participates in synergistic interaction with SA in LCH development and that the prevalence of specific intussusceptive phenomena determines the predominant capillary pattern and associated sinusoidal hemangioma-like and IPEH-like patterns in the lesion, which suggest a role of IA as conditioner of vessel tumour/pseudo-tumour morphology.

Intussusceptive lymphangiogenesis in vascular transformation of lymph node sinuses.

Numerous lymphatic anastomosing channels in the lymph nodes are the most demonstrative finding of the rare lesion termed "vascular transformation of lymph node sinuses" (VTS). The mechanism of lymphatic vessel formation in VTS has not been studied. Vessel intussusception contributes to vascular expansion, and intraluminal pillars/posts, interstitial tissue structures or larger pillars (ITSs) and folds are the hallmarks of this process in blood vessels. The aim of this work is to assess whether these hallmarks of intussusception occur in VTS lymphatic vessels, indicating intussusceptive lymphangiogenesis. For this purpose, specimens of five cases of VTS were used for serial histological sections, immunohistochemistry and immunofluorescence in confocal microscopy, which enabled us to demonstrate the 3D image that defines the pillars. The studies showed a) meshworks of lymphatic vessels, which form complex loops, resembling sinuses of lymph nodes, b) presence of intralymphatic pillars, ITSs and folds, with a cover of lymphatic endothelial cells expressing podoplanin and a varying-sized connective core (e.g. collagen), and c) increase of vessel meshwork and linear arrangement, splitting and fusion of ITSs, pillars and folds, with remodelling and segmentation. In conclusion, the development of lymphatic vessel loops, ITSs, pillars and folds with segmentation in VTS supports intussusceptive lymphangiogenesis. This mechanism of intussusception is of interest because it participates in VTS histogenesis, contributes to general knowledge of intussusceptive lymphangiogenesis, which has received less attention than intussusception in blood vessels, and provides a basis for further studies in other lymphatic conditions.

Extracellular multivesicular bodies in tissues affected by inflammation/repair and tumors.

Extracellular vesicles (EVs) are a heterogeneous population involved in intercellular communication. Little attention has been paid to a peculiar EV type with the appearance of a multivesicular body: extracellular multivesicular body (EMVB), also termed matrix vesicle cluster/multivesicular cargo. The aim of this work is to assess the ultrastructural characteristics, participation, and tissue location of EMVBs in inflammation/repair and tumors (with physiopathological processes involving intense intercellular communication), for which representative specimens were used. The results showed several forms of EMVBs: a) mature EMVBs, made up of clusters of vesicles surrounded by a plasma membrane, b) pre-EMVBs, with protruding grouped vesicles under the cell membrane, and c) post-EMVBs, releasing their vesicles. In tissues with inflammation/repair, EMVBs were observed in vessel lumens, interstitial spaces of vessel walls (between endothelial cells, pericytes, and smooth muscle cells) and between inflammatory and stromal cells. In tumors, such as basal cell carcinoma, craniopharyngioma, syringocystoadenoma, fibrous histiocytoma, alveolar rhabdomyosarcoma, lymphomas, neuroblastoma, astrocytomas, meningiomas, and hydatiform mole, EMVBs were present in tumor gland lumens and between tumor cells. In conclusion, in numerous physiopathological processes, we contribute EMVB ultrastructural characteristics (including different forms of mature, pre- and post-EMVBs, suggesting a more efficient EV transport), location and relationship with different types of cells. Further studies are required to assess the role of EMVBs in these physiopathological conditions.

Localized amyloidosis of the epididymis: a previously unreported phenomenon.

BACKGROUND: Localized amyloidosis has not been documented in the epididymis; we report this phenomenon for the first time. CASE PRESENTATION: The first aim of this work is to report three cases of localized epididymal amyloidosis. Two cases were clinically detected as epididymal nodules, and a third after reviewing 120 epididymides obtained with neighbouring pathological processes. Amyloid deposits showed Congo red positivity, with yellow-green birefringence, and immunohistochemical expression for light chains kappa and lambda, transthyretin, amyloid P and cytokeratin AE1 AE3. No immunoreactivity for amyloid A was seen. Amyloid deposit location was intraluminal, with partial or total loss of the epididymal epithelium and subsequent passage to the interstitium, forming large masses. No amyloid deposits were observed around blood vessels. A secondary objective was to explore in normal epididymis the amyloid tested in epididymal amyloidosis. In normal epididymides, expression of amyloid P and transthyretin was detected in the apical surface of epithelial cells. Amyloid P also showed strong expression in spermatozoa. CONCLUSION: We contribute the existence of localized epididymal amyloidosis, which presents a distinctive, initial intratubular location, where there is a unique proteome and where functional amyloids act during sperm maturation.

Ultrastructure and histogenesis of the acral calcified angioleiomyoma.

We studied the ultrastructure, immunohistochemistry, and histogenesis of the acral calcified angioleiomyoma, observing three concentric zones: (a) pseudocapsular, thin, with spindle-shaped stromal cells (SCs), presenting scarce organelles and expressing CD34, (b) muscular, forming a ring, with smooth muscle cells of heterogenous phenotype (mainly in quantity and thickness of filaments, and in expression of h-caldesmon, αSMA, and desmin), and (c) central, extensive, calcified (spicular and/or star-shaped calcium deposits around collagen fibers), with pericytic involutive vasculature. The intratumoral vessels were thick (several layers of perivascular cells, with a continuum of phenotypes, resembling myopericytoma vessels) and thin (slit-like channels), without adventitial SCs or elastic material. The extratumoral vessels showed adventitial SCs (which contribute to form the tumor pseudocapsule), hyperplasia of the media and intima layers, and/or occlusion of the lumen by a wide, homogenous fibrotic central zone. Histogenetically, the collagenous matrix may act as a mineralization substrate and the calcifying modified pericytes as inductors; intratumoral vessels may originate from the peritumoral vessels or from the vessel where the tumor develops; and extratumoral vessel modifications, mimicking tumor features, concur with a minor repetitive trauma pathogenesis.

MTHFR C677T polymorphism and anatomopathological characteristics with prognostic significance in sporadic colorectal cancer.

Methylenetetrahydrofolate reductase (MTHFR) plays a key role in folate metabolism, and folate is implicated in carcinogenesis due to its role in DNA methylation, repair and synthesis. The MTHFR C677T polymorphism is associated with decreased risk of CRC and increased sensitivity to 5-FU treatment. The present study addressed the relationship between this polymorphism and histopathological and immunohistochemical characteristics of prognostic significance in 50 patients from the Canary Islands. No differences were found between the MTHFR C677T genotypes with respect to tumor budding, tumor necrosis, desmoplastic fibrosis and tumoral eosinophilia. No significant differences were found in Ki-67, bcl-2 (cytoplasmic and nuclear), CD31, CD3+ T lymphocytes (both stromal and intraepithelial) and peritumoral CD20+ B lymphocytes. In carriers of the MTHFR CC variant, tumor margins were infiltrative more frequently (68.7%) than in CT+TT carriers (33.3%, p=0.03). In addition, wild-type CC genotype showed stromal CD20+ B lymphocytes (68.8%) more often than CT+TT carriers (33.3%, p=0.03). Both parameters indicate a better tumor prognosis when the MTHFR 677T variant is present.

Clinicopathological analysis of factors related to colorectal tumor perforation: influence of angiogenesis.

Colorectal tumor perforation is a life-threatening complication of this disease. However, little is known about the anatomopathological factors or pathophysiologic mechanisms involved. Pathological and immunohistochemical analysis of factors related with tumoral neo-angiogenesis, which could influence tumor perforation are assessed in this study. A retrospective study of patients with perforated colon tumors (Group P) and T4a nonperforated (controls) was conducted between 2001 and 2010. Histological variables (differentiation, vascular invasion, and location) and immunohistochemical (CD31, Growth Endothelial Vascular Factor (VEGF) and p53) related with tumor angiogenesis were analyzed. Of 2189 patients, 100 (4.56%) met the inclusion criteria. Of these, 49 patients had nonperforated (2.23%) and 51 had perforated tumors (2.32%). The P group had lower number of right-sided tumors (7/51, 13.7%) compared with controls (13/49, 36.7%) (P = .01). The high-grade tumors (undifferentiated) represented only 3.9% of the perforated tumors; the remaining 96.1% were well differentiated (P = .01). No differences between groups in the frequency of TP53 mutation or VEGF and CD31 expression were found. In the P group, only 2 (3.9%) had vascular invasion (P = .01). Of the 12 tumors with vascular invasion, only 2 were perforated (16.6%). The median number of metastatic lymph-nodes in P Group was 0 versus 3 in controls (Z = -4.2; P < .01). Pathological analysis of variables that indirectly measure the presence of tumor angiogenesis (differentiation, vascular invasion, and the number of metastatic lymph nodes) shows a relationship between this and the perforation, location, and tumor differentiation. We could not directly validate our hypothesis, by immunohistochemistry of TP53, VEGF, and CD31, that perforated tumors exhibit less angiogenesis.

CD34-positive fibroblasts in Reinke's edema.

OBJECTIVES/HYPOTHESIS: To elucidate whether and to what extent CD34+ fibroblasts (so-called CD34+ fibrocytes, CD34+ dendritic cells, and CD34+ stromal cells) occur in normal human vocal folds and in Reinke's edema. STUDY DESIGN: Histological study. METHODS: Conventional, immunohistochemical, and ultrastructural procedures were performed in histological blocks of 18 selected cases of Reinke's edema (with typical findings including acellular edematous spaces in the subepithelial connective tissue of vocal folds, and disarrangement of elastic, collagen, and reticular fibers). For control purposes, four normal vocal folds were analyzed. RESULTS: In normal vocal folds, most stromal cells were spindle-shaped CD34+ fibroblasts. In Reinke's edema, increased density and changes in the morphology and size of this subpopulation of fibroblasts were demonstrated in the connective tissue surrounding the edematous spaces, particularly in their borders, where together with some macrophages they formed boundaries, mimicking the walls of distended lymphatic vessels when conventional stains were used. These activated CD34+ fibroblasts acquired a dendritic morphology (with long, moniliform, often bifurcated, overlapping multipolar processes), and their cytoplasmic organelles were increased in number. In addition to CD34, they expressed vimentin, CD10 and CD99, but no α-smooth muscle actin (α-SMA), CD31, CD117, CD68, h-caldesmon, desmin, or S-100 protein. CONCLUSIONS: CD34+ fibroblasts are a major cell component in the stroma of vocal folds in Reinke's edema, and their activation, with increased density and morphologic changes around the edematous spaces, occurs without immunophenotypic transformation toward myofibroblasts (no expression of α-SMA). The mechanisms by which these cells act in Reinke's edema require further study.

Metastatic lymphs nodes and lymph node ratio as predictive factors of survival in perforated and non-perforated T4 colorectal tumors.

AIMS: Recently it has been hypothesized that perforation of colorectal cancer (CRC) itself is not a predictor of poor prognosis. The aim of this study was to analyze the prognostic impact, of the spontaneous perforation of the tumour, metastatic lymph nodes and lymph node ratio (LNR) after potentially curative surgery. METHODS: Retrospective analysis of oncologic outcomes of patients with T4a CRC grouped by perforated and non-perforated tumours. Between 2001 and 2010, 100 patients were included. Oncologic outcomes, disease-free survival and global survival were analyzed. RESULTS: Forty-nine patients had a non-perforated cancer and 51 presented a perforated neoplasm. Perforated cancers had a lower mean number of lymph nodes (1.16 vs. 4.14, P < 0.001), lower LNR (0.13 vs. 0.33, P = 0.001), better TNM-stage (P < 0.001), and lower metastases during follows-up (P = 0.02). The perforated-group had higher survival (P = 0.017) and higher metastasis-free time (P = 0.03). LNR cutoffs (<0.05, 0.05-0.4, and >0.4) had significant differences in overall survival (log-rank < 0.001). The predictive value of LNR and metastatic lymph nodes in mortality was similar. CONCLUSIONS: In our experience, perforated cancers had higher survival rates and metastasis-free interval that non-perforated cancers, probably by a lower number of metastatic lymph nodes, smaller LNR and better TNM stage. Moreover the predictive value, in mortality rate, of metastatic lymph nodes and LNR was similar.

Impact of the MTHFR C677T polymorphism on colorectal cancer in a population with low genetic variability.

PURPOSES: Methylenetetrahydrofolate reductase (MTHFR) plays a key role in folate metabolism, and folate is implicated in carcinogenesis by its role in DNA methylation, repair, and synthesis. We analyzed the impact of MTHFR C677T polymorphism in colorectal cancer in a region of the Tenerife Island whose population has a history of genetic isolation and a low genetic variability. This allows analyzing the effects of the polymorphism that are not due to interactions with different genetic variants. METHODS: Genomic DNA of 50 Spanish sporadic colorectal cancer (CRC) patients and 103 controls was analyzed by PCR/RFLP and sequencing. RESULTS: The T allele is more frequent in controls than in patients (P < 0.01). The variant (T) carriers displayed significant odds ratio values for the CT heterozygotes (P = 0.026) and even when grouping heterozygote (CT) and homozygotes (TT) (P = 0.015). Patients carriers of the variant T (CT y TT) show a higher survival rate after chemotherapy than the CC homozygotes (log rank; P = 0.001). CONCLUSIONS: The MTHRF C677T variant has a protective effect on CRC development in a population with low allelic variability and an optimal intake of folic acid. Moreover, patients carrying the variant (T) show a better prognosis after 5-fluorouracil/folinic acid-based chemotherapy.

Correlación entre los depósitos de hemosiderina en biopsias de médula ósea y marcadores séricos de hierro corporal: validación de un método semicuantitativo de evaluación de la tinción de Perls / Correlation between haemosiderin deposits in bone marrow biopsies and serum markers for stored body iron: evaluation of a semiquantitative assessment method using Perls’ staining

Hemos realizado una evaluación semicuantitativa de la cantidad de pigmento hemosiderínico, en biopsias de médula ósea mediante tinción de Perls, en un total de 75 pacientes a los que se realizó esta prueba por diferentes motivos. Coincidentes en el tiempo, se han determinado a estos mismos pacientes los valores séricos de ferritina e índice de saturación de la transferrina. En el análisis de los resultados hemos observado que existe correlación estadísticamente significativa entre la intensidad de los depósitos medulares de pigmento hemosiderínico y los niveles de ferritina e índice de saturación de la transferrina. Esta observación es sugestiva de que, a pesar de las limitaciones de la tinción de Perls como técnica de rutina en biopsias de médula ósea, cuando los depósitos de pigmento hemosiderínico son detectables e intensos, el procedimiento, al menos en ciertos casos, nos da una idea de la sobrecarga férrica de los pacientes. De este modo, en algunas situaciones la detección de dicho pigmento en las biopsias de médula ósea podría complementar otros exámenes hematológicos(AU)

A semiquantitative assessment of the amount of haemosiderin pigment in bone marrow biopsies was made using Perls’ staining in a total of 75 patients with different diagnoses. Simultaneously, the serum ferritin and transferrin saturation index were measured. It was found that there is a statistically significant correlation between the intensity of the deposits of haemosiderin pigment and the serum parameters analyzed. Thus, despite the limitations of Perls’ staining as a technique for routine bone marrow biopsies, it can provide an indication of iron overload when the deposits are detectable and intense. Therefore, the detection of pigment in bone marrow biopsies could complement other haematological tests in some cases(AU)

Myopericytoma and arterial intimal thickening: the relationship between myopericytes and myointimal cells.

BACKGROUND: Myopericytomas with intravascular growth have been reported and have been occasionally documented as intraarterial. In a retrospective study, we assessed intraarterial growth in myopericytomas, co-existence with arterial intimal thickening (IT) and the relationship between the two. METHODS: This retrospective study was undertaken using 11 myopericytomas evaluated in serial microscopical sections. The results in light microscopy, electron microscopy and immunohistochemistry [including α-smooth muscle actin (SMA), desmin and h-caldesmon] were evaluated. RESULTS: In four myopericytomas, we found intraarterial growth, with large areas of disrupted arterial wall and attachment of veins and venules, exhibiting angiogenic phenomena. Arterial IT was present and partially incorporated within the tumor (simulating medium-sized vessels). The neointimal (myointimal) cells shared morphological and immunohistochemical phenotype with the myopericytoma myoid cells, including α-SMA positivity and desmin negativity. Four of the remaining myopericytomas showed structures similar to arterial IT within the tumor. CONCLUSIONS: The findings shown here, including the association between myopericytomas and arterial IT, the incorporation of the latter into the tumor and the similar phenotype of their respective myoid and myointimal cells, support a close relationship between these processes. Histogenically, the pericytes of the penetrating neovasculature originating from the attached venules and veins may contribute to both lesions.