Liquid biopsy for gastric cancer: Techniques, applications, and future directions.

After the study of circulating tumor cells in blood through liquid biopsy (LB), this technique has evolved to encompass the analysis of multiple materials originating from the tumor, such as nucleic acids, extracellular vesicles, tumor-educated platelets, and other metabolites. Additionally, research has extended to include the examination of samples other than blood or plasma, such as saliva, gastric juice, urine, or stool. LB techniques are diverse, intricate, and variable. They must be highly sensitive, and pre-analytical, patient, and tumor-related factors significantly influence the detection threshold, diagnostic method selection, and potential results. Consequently, the implementation of LB in clinical practice still faces several challenges. The potential applications of LB range from early cancer detection to guiding targeted therapy or immunotherapy in both early and advanced cancer cases, monitoring treatment response, early identification of relapses, or assessing patient risk. On the other hand, gastric cancer (GC) is a disease often diagnosed at advanced stages. Despite recent advances in molecular understanding, the currently available treatment options have not substantially improved the prognosis for many of these patients. The application of LB in GC could be highly valuable as a non-invasive method for early diagnosis and for enhancing the management and outcomes of these patients. In this comprehensive review, from a pathologist's perspective, we provide an overview of the main options available in LB, delve into the fundamental principles of the most studied techniques, explore the potential utility of LB application in the context of GC, and address the obstacles that need to be overcome in the future to make this innovative technique a game-changer in cancer diagnosis and treatment within clinical practice.

Prognostic role of the number of resected and negative lymph nodes in Spanish patients with gastric cancer.

INTRODUCTION: Lymph node (LN) involvement is one of the most critical prognostic factors in resected gastric cancer (GC). Some analyses, mainly conducted in Asian populations, have found that patients with a higher number of total lymph nodes (NTLN) and/or negative lymph nodes (NNLN) have a better prognosis, although other authors have failed to confirm these results. MATERIALS AND METHODS: Retrospective study including all patients with GC resected in a tertiary hospital in Spain between 2001 and 2019 (n = 315). Clinicopathological features were collected and patients were categorized according to the NTLN and the NNLN. Statistical analyses were performed. RESULTS: Mean NNLN was 17. The NNLN was significantly related to multiple clinicopathological variables, including recurrence and tumor-related death. The classification based on the NNLN (N1: ≥16, N2: 8-15, N3: ≤7) effectively stratified the entire cohort into three distinct prognostic groups and maintained its prognostic value within both the pN0 and pN+ patient subsets. Furthermore, it was an independent prognostic indicator for both overall and disease-free survival. Conversely, the mean NTLN was 21.9. Patients with ≤16 LN retrieved exhibited distinct clinicopathological features compared to those with >16 LN, but no significant differences were observed in terms of recurrence or disease-associated death. The application of alternative cut-off points for NTLN (10, 20, 25, 30, and 40) showed no prognostic significance. CONCLUSIONS: In Spanish patients with resected GC the NNLN hold prognostic significance, while the NTLN does not appear to be prognostically significant. Incorporating the NNLN into GC staging may enhance the accuracy of the TNM system.

Sperm protein antigen 17 and Sperm flagellar 1 cancer testis antigens are expressed in a rare case of ciliated foregut cyst of the common hepatic duct.

INTRODUCTION: Ciliated foregut cysts (CFCs) are frequently described in liver, pancreas and gallbladder and generally considered benign although one case of squamous cell metaplasia and five cases of squamous cell carcinoma arising from a ciliated hepatic foregut cyst have been reported. Here we explore two cancer-testis antigens (CTAs), Sperm protein antigen 17 (SPA17) and Sperm flagellar 1 (SPEF1) expression in a rare case of CFC of the common hepatic duct MATERIALS AND METHODS: 3 µm-thick CFC sections were immunohistochemically treated with antibodies raised against human SPA17 or SPEF1. In silico Protein-Protein Interaction (PPI) network and differential protein expression were also investigated RESULTS: Immunohistochemistry revealed SPA17 and SPEF1 in the cytoplasm of ciliated epithelium. SPA17, but not SPEF1, was also detected in cilia. The PPI networks demonstrated that other CTAs are significantly predicted functional partners with SPA17 and SPEF1. The differential protein expression demonstrated that SPA17 was higher in breast cancer, cholangiocarcinoma, liver hepatocellular carcinoma, uterine corpus endometrial carcinoma, gastric adenocarcinoma, cervical squamous cell carcinoma, bladder urothelial carcinoma. SPEF1 expression was higher in breast cancer, cholangiocarcinoma, uterine corpus endometrial carcinoma and kidney renal papillary cell carcinoma CONCLUSIONS: Our study suggests that further characterization of SPA17 and SPEF1 in patients with CFCs might provide significant insights to understand the mechanisms underlying their potential to malignant transformation.

Clinicopathological differences, risk factors and prognostic scores for western patients with intestinal and diffuse-type gastric cancer.

BACKGROUND: In the molecular era, the Laurén system is still a cost-effective and widely implemented classification for gastric cancer (GC) and it has been recently associated with clinical, histological and molecular features of these tumors. Despite recent advances in the understanding of the molecular biology of GC, there is a need to develop new prognostic tools for patient stratification in clinical practice. Thus, the identification of easily available prognostic factors in patients with intestinal and diffuse-type tumors can significantly improve risk assessment and patient stratification in GC. AIM: To identify clinicopathological differences, risk factors, and to develop cost-effective prognostic scores for patients with intestinal and diffuse-type GC. METHODS: Retrospective study of all patients undergoing surgery for GC at a tertiary referral center from 2001 to 2019. 286 cases met inclusion criteria (intestinal: 190, diffuse: 96). Clinical data and gross findings were collected. All specimens were reviewed by two independent pathologists and a detailed protocol for histologic evaluation was followed. Five tissue microarrays (TMAs) were constructed and sections of the TMA block were immunostained for HERCEPTEST, MSH2, MSH6, MLH1 and PMS2. Statistical analyses were performed and prognostic scores were developed based on hazard ratios. RESULTS: Intestinal and diffuse-type GC showed different epidemiological, clinicopathological and prognostic features. Diffuse tumors were significantly associated with younger age, less symptomatology, flat morphology, deeper invasion, perineural infiltration, advanced stage at diagnosis, administration of adjuvant therapy and poorer prognosis. Intestinal lesions were fungoid or polypoid, showed necrosis, desmoplasia, microsatellite instability and HERCEPTEST positivity and were diagnosed at earlier stages. Tumor depth, desmoplasia, macroscopic type and lymph node involvement were independently related to the Laurén subtype. Furthermore, intestinal and diffuse GC were associated with different risk factors for progression and death. Vascular invasion, perineural infiltration and growth pattern were important prognostic factors in intestinal-type GC. On the contrary, tumor size and necrosis were significant prognosticators in diffuse-type GC. Our recurrence and cancer-specific death scores for patients with intestinal and diffuse-type GC showed an excellent patient stratification into three (diffuse GC) or four (intestinal) prognostic groups. CONCLUSION: Our findings support that Laurén subtypes represent different clinicopathological and biological entities. The development of specific prognostic scores is a useful and cost-effective strategy to improve risk assessment in GC.

Pathologic Lymph Node Staging of Gastric Cancer.

OBJECTIVES: The TNM classification is the main tool for lymph node (LN) staging in gastric cancer (GC). However, alternative LN staging systems have been proposed, and the role of features other than the number of metastatic LNs is being investigated. Our aim is to discuss the main challenges of LN assessment in GC. METHODS: Comprehensive review of the literature on alternative LN staging systems, examined LNs, sentinel LN (SLN) biopsy, LN micrometastases (LNMIs), extracapsular extension (ECE), and tumor deposits (TDs) in GC. RESULTS: Many controversies exist regarding LN assessment in GC. The TNM classification shows excellent prognostic performance, but alternative prognostic methods such as the LN ratio or log odds of positive LNs have demonstrated to be better than the TNM system in terms of prognostic accuracy. The value of SLN biopsy and LNMIs in GC is still unclear, and several challenges concerning their clinical impact and pathologic analysis must be overcome before their introduction in clinical practice. Most authors have identified ECE and TDs as independent prognostic factors for survival in GC. CONCLUSIONS: Further studies should be performed to evaluate the impact of these features on the TNM classification and patient outcomes, as well as to standardize alternative LN staging systems.

Are Borrmann's Types of Advanced Gastric Cancer Distinct Clinicopathological and Molecular Entities? A Western Study.

Most studies on the clinicopathological impact of Borrmann classification for gastric cancer (GC) have been performed in Asian patients with type IV tumors, and immunohistochemical features of Borrmann types have scarcely been analyzed. We assessed the clinicopathological, molecular features and prognostic value of Borrmann types in all patients with advanced GC resected in a Western institution (n = 260). We observed a significant relationship between Borrmann types and age, systemic symptoms, tumor size, Laurén subtype, presence of signet-ring cells, infiltrative growth, high grade, tumor necrosis, HERCEPTEST positivity, microsatellite instability (MSI) and molecular subtypes. Polypoid GC showed systemic symptoms, intestinal-type histology, low grade, expansive growth and HERCEPTEST positivity. Fungating GC occurred in symptomatic older patients. It presented intestinal-type histology, infiltrative growth and necrosis. Ulcerated GC showed smaller size, intestinal-type histology, high grade and infiltrative growth. Most polypoid and ulcerated tumors were stable-p53-not overexpressed or microsatellite unstable. Flat lesions were high-grade diffuse tumors with no MSI, and occurred in younger and less symptomatic patients. No association was found between Borrmann classification and prognosis. According to our results, Borrmann types may represent distinct clinicopathological and biological entities. Further research should be conducted to confirm the role of Borrmann classification in the stratification of patients with advanced GC.

Update, validation and comparison of three different clinicopathological scores for patients with resected gastric cancer: A western experience.

INTRODUCTION: Gastric cancer (GC) is a multifactorial disease. Several prognostic scores have been proposed for refining the prognostic information provided by the TNM classification. Our aim is to validate and compare the prognostic performance of different clinicopathological scores in a western cohort of patients (Marubini, Haraguchi and Kologlu scores). MATERIAL AND METHODS: Retrospective study of all cases of GC resected in a western tertiary center (N = 377). Clinicopathological features were collected, scores were applied and statistical analyses were performed. RESULTS: 315 cases were finally included. According to Marubini, Haraguchi and Kologlu scores, patients were stage I (18.5%, 13.3% and 49%), II (29.3%, 47.2% and 29.5%) and III (52.2%, 39.5% and 21.5%, respectively). All classifications were significantly associated with lymphovascular invasion, perineural infiltration, lymph node involvement, patient progression and death due to GC. All scores showed good patient stratification by Kaplan-Meier analyses, but OS and DFS curves depending on Haraguchi score were less evenly spaced. Kologlu classification showed prognostic superiority over Haraguchi and Marubini classifications by ROC analysis. AUC values for OS and DFS were 0.654 and 0.647 (Marubini), 0.626 and 0.618 (Haraguchi) and 0.724 and 0.709 (Kologlu). Kologlu and Marubini classifications were independent factors for both OS and DFS, but Haraguchi classification was independently associated only with DFS. CONCLUSIONS: Clinicopathological scores can be easily validated and are cost-effective. Kologlu score is the most thorough classification, and it showed the best prognostic performance for both DFS and OS in our study. More studies are needed to validate its value in other populations.

The role of fine-needle aspiration cytology in the diagnosis of soft tissue nodules: Experience in a tertiary center / Utilidad de la punción-aspiración con aguja fina en el diagnóstico de nódulos de partes blandas: nuestra experiencia

INTRODUCTION: Excisional or core needle biopsy is considered the gold standard for diagnosing soft tissue lesions (STL). However, the role of fine-needle aspiration cytology (FNAC) in STL remains controversial. MATERIALS AND METHODS: We have reviewed 234 FNAC of STL diagnosed in our institution with the aim of analyzing the reliability of FNAC in STL. Cytological diagnoses were classified into groups and correlated with histological diagnoses. We have also reviewed the literature and compared our results with those previously reported. RESULTS: The majority of patients were male (53.4%) and mean age was 61 years. Lesions were mainly located in the head and neck region. Inadequate material was obtained in 22.6% of cases and most lesions were inflammatory lesions or benign soft tissue tumors. Carcinoma and benign soft tissue tumor were the most frequent cytological diagnoses. Biopsy was performed in 36.1% of cases, and carcinoma was detected in 33.3% of inflammatory FNACs. General and specific concordances were 65.9% and 47.1%. Diagnostic sensitivity, specificity, negative and positive predictive values were 71.4%, 100%, 85.7% and 93.8%, respectively. CONCLUSIONS: FNAC of STL is a valuable tool for diagnosing benign epithelial cysts, carcinomas, hematolymphoid neoplasms and benign soft tissue tumors. Inflammatory smears may be associated with false-negative cases. The availability of a multidisciplinary team, clinical and imaging features, ROSE and immunohistochemical and molecular techniques is required for improving the role of FNAC of STL

INTRODUCCIÓN: El estudio histológico se considera el gold standard para el diagnóstico de las lesiones de partes blandas (LPB). El valor de la punción-aspiración con aguja fina (PAAF) en las LPB es controvertido. MATERIAL Y MÉTODOS: Revisión de 234 PAAF de LPB diagnosticadas en nuestra institución. Los diagnósticos citológicos se clasificaron en grupos y se correlacionaron con el diagnóstico histológico. Revisamos la literatura y comparamos nuestros resultados con los descritos previamente. RESULTADOS: El 53,4% de pacientes fueron varones, y la edad media fue de 61 años. Las lesiones se localizaban principalmente en cabeza y cuello. En el 22,6% de los casos no se obtuvo material adecuado, y la mayor parte de estos casos fueron lesiones inflamatorias o tumores de partes blandas (TPB) benignos en histología. Los diagnósticos citológicos más frecuentes fueron carcinoma y TPB benigno. Se realizó biopsia en el 36,1% del total de los casos, y se detectó carcinoma en el 33,3%. La concordancia general y específica entre citología e histología fue del 65,9 y 47,1%, respectivamente. La sensibilidad, especificidad, valor predictivo negativo y positivo fueron del 71,4, 100, 85,7 y 93,8%, respectivamente. CONCLUSIONES: La PAAF es una herramienta útil para diagnosticar quistes epiteliales benignos, carcinomas, neoplasias hematopoyéticas y TPB benignos. Las lesiones inflamatorias en citología pueden tener una tasa importante de falsos negativos. La disponibilidad de un equipo multidisciplinar, los datos clínicos y de imagen, rapid on-site evaluation (ROSE) y las herramientas inmunohistoquímicas y moleculares son esenciales para mejorar el papel de la PAAF en el diagnóstico de las LPB

The role of fine-needle aspiration cytology in the diagnosis of soft tissue nodules: Experience in a tertiary center.

INTRODUCTION: Excisional or core needle biopsy is considered the gold standard for diagnosing soft tissue lesions (STL). However, the role of fine-needle aspiration cytology (FNAC) in STL remains controversial. MATERIALS AND METHODS: We have reviewed 234 FNAC of STL diagnosed in our institution with the aim of analyzing the reliability of FNAC in STL. Cytological diagnoses were classified into groups and correlated with histological diagnoses. We have also reviewed the literature and compared our results with those previously reported. RESULTS: The majority of patients were male (53.4%) and mean age was 61 years. Lesions were mainly located in the head and neck region. Inadequate material was obtained in 22.6% of cases and most lesions were inflammatory lesions or benign soft tissue tumors. Carcinoma and benign soft tissue tumor were the most frequent cytological diagnoses. Biopsy was performed in 36.1% of cases, and carcinoma was detected in 33.3% of inflammatory FNACs. General and specific concordances were 65.9% and 47.1%. Diagnostic sensitivity, specificity, negative and positive predictive values were 71.4%, 100%, 85.7% and 93.8%, respectively. CONCLUSIONS: FNAC of STL is a valuable tool for diagnosing benign epithelial cysts, carcinomas, hematolymphoid neoplasms and benign soft tissue tumors. Inflammatory smears may be associated with false-negative cases. The availability of a multidisciplinary team, clinical and imaging features, ROSE and immunohistochemical and molecular techniques is required for improving the role of FNAC of STL.

IKKα Promotes the Progression and Metastasis of Non-Small Cell Lung Cancer Independently of its Subcellular Localization.

Lung cancer is the leading worldwide cause of cancer mortality, however, neither curative treatments nor substantial prolonged survival has been achieved, highlighting the need for investigating new proteins responsible for its development and progression. IKKα is an essential protein for cell survival and differentiation, which expression is enhanced in human non-small cell lung cancer (NSCLC) and correlates with poor patient survival, appearing as a relevant molecule in lung cancer progression. However, there are not conclusive results about its role in this type of cancer. We have recently found that IKKα performs different functions and activates different signaling pathways depending on its nuclear or cytoplasmic localization in tumor epidermal cells. In this work, we have studied the involvement of IKKα in lung cancer progression through the generation of lung cancer cell lines expressing exogenous IKKα either in the nucleus or in the cytoplasm. We demonstrate that IKKα signaling promotes increased cell malignancy of NSCLC cells as well as lung tumor progression and metastasis in either subcellular localization, through activation of common protumoral proteins, such as Erk, p38 and mTor. But, additionally, we found that depending on its subcellular localization, IKKα has non-overlapping roles in the activation of other different pathways known for their key implication in lung cancer progression: while cytoplasmic IKKα increases EGFR and NF-κB activities in lung tumor cells, nuclear IKKα causes lung tumor progression through c-Myc, Smad2/3 and Snail activation. These results suggest that IKKα may be a promising target for intervention in human NSCLC.

Premature aging and cancer development in transgenic mice lacking functional CYLD.

CYLD is a deubiquitinating enzyme known for its role as a tumor suppressor whose mutation leads to skin appendages tumors and other cancers. In this manuscript we report that the tumor suppressor CYLD, similarly to other renowned tumor suppressor genes, protects from premature aging and cancer. We have generated transgenic mice expressing the mutant CYLDC/S protein, lacking its deubiquitinase function, under the control of the keratin 5 promoter, the K5-CYLDC/S mice. These mice express the transgene in different organs, including those considered to be more susceptible to aging, such as skin and thymus. Our results show that K5-CYLDC/S mice exhibit epidermal, hair follicle, and sebaceous gland alterations; and, importantly, they show signs of premature aging from an early age. Typically, 3-month-old K5-CYLDC/S mice exhibit a phenotype characterized by alopecia and kyphosis, and, the histological examination reveals that transgenic mice show signs of accelerated aging in numerous organs such as skin, thymus, pancreas, liver and lung. Additionally, they spontaneously develop tumors of diverse origin. Over-activation of the NF-κB pathway, along with hyperactivation of Akt, JNK and c-Myc, and chronic inflammation, appear as the mechanisms responsible for the premature aging of the K5-CYLDC/S mice.

Metástasis de dermatofibrosarcoma diagnosticada mediante cápsula endoscópica / Metastasis of dermatofibrosarcoma diagnosed by capsule endoscopy

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MUC1 expression in colorectal carcinoma: Clinicopathological correlation and prognostic significance / Expresión de MUC1 en el carcinoma colorectal: correlación clinicopatológica y valor pronóstico

Introduction: MUC1 overexpression has been linked to cancer development and has been associated with a higher stage at diagnosis and presence of lymph node or distant metastases. However, its prognostic significance is still unclear. We aimed to evaluate the relationship between MUC1 expression and prognosis of colorectal carcinoma. Materials and methods: Immunohistochemical expression of MUC1 in 96 colorectal carcinomas with analysis of potential prognostic influence. Results: 55.2% of patients were women and the mean age was 65.9 years. Tumors were more frequently located in rectum or sigmoid colon (60.4% and 21.9%). Most tumors were T3 (60.3%). 36.9% of patients showed lymph node metastases and 30.2% showed distant metastasis at the time of diagnosis. MUC1 was intensely positive in 46% and negative in 37.9% of tumors. Overall, 61% of patients recurred and 40.4% died during follow-up. 58.5% of tumors of surviving patients were intensely positive for MUC1 and 29.5% were negative, as compared with 28.5% (intense positivity) and 51.4% (negativity) in the group of patients who died (p=0.022). 65% of tumors of patients without recurrences showed intense positivity for MUC1 and 23% of them were negative as compared with 33.9% (intense positivity) and 47% (negativity) in the group of patients who recurred (p=0.019). Conclusions: Loss of MUC1 expression was more frequent in cases with disease recurrence or death, as compared with patients with stable disease, in whom intense positivity was more frequently seen. These findings disagree with the majority of previous studies, indicating the need for further investigation

Introducción: La sobreexpresión de MUC1 se ha asociado al desarrollo de cáncer, mayor estadio al diagnóstico y la presencia de metástasis ganglionares o a distancia. Sin embargo, su valor pronóstico es dudoso. Nuestro objetivo es evaluar la relación entre la expresión inmunohistoquímica de MUC1 y el pronóstico del carcinoma colorrectal (CRC). Material y métodos: Expresión inmunohistoquímica de MUC1 en 96 CRC y análisis de su influencia pronóstica. Resultados: El 55,2% de los pacientes eran mujeres, con edad media de 65,9 años. Los tumores se localizaban principalmente en recto o sigma (60,4 y 21,9%). El 60,3% de los CRC fueron estadio T3. El 36,9% de pacientes mostraron metástasis ganglionares y el 30,2% a distancia. MUC1 fue intensamente positivo en el 46% y negativo en el 37,9% de los casos. En el 61% de los pacientes se observaron recurrencias y el 40,4% falleció. Un 58,5% de tumores de pacientes vivos mostró positividad intensa y un 29,5% negatividad para MUC1, en comparación con un 28,5 y 51,4% de positividad intensa y negatividad en los pacientes que murieron (p=0,022). El 65% de los tumores de pacientes sin recurrencias fueron intensamente positivos para MUC1 y el 23% fue negativo, en comparación con un 33,9 y 47% de positividad intensa y negatividad en pacientes con recurrencias (p=0,019). Conclusiones: La pérdida de expresión de MUC1 fue más frecuente en pacientes con recurrencias o fallecidos que en pacientes estables. Estos resultados son contrarios a la mayoría de estudios previos y subrayan la necesidad de realización de más estudios

Factores pronósticos en el adenocarcinoma de ampolla duodenal / Prognostic factors in adenocarcinoma of the ampulla of Vater

Introducción: El adenocarcinoma de ampolla duodenal (ampolla de Vater) parece un tumor de comportamiento menos agresivo que otros de la región pancreatobiliar. Nuestro estudio busca definir factores que condicionan el pronóstico de este tipo de neoplasia. Material y métodos: Revisión retrospectiva de los pacientes operados por adenocarcinoma de ampolla duodenal en un solo centro. Se ha valorado el intervalo libre de progresión y la supervivencia global como variables de resultado. Resultados: Un total de 24 pacientes fueron sometidos a una duodenopancreatectomía cefálica por un adenocarcinoma de ampolla duodenal. Un 54,2% eran mujeres y la edad media fue 72,5 (45-85). El principal tipo histológico fue el intestinal (50%), seguido del biliopancreático (37,5%). El resto fueron mucinosos. Solo el 8,3% de los casos fueron poco diferenciados. Se detectó invasión vascular e infiltración perineural en el 31,8 y 20,8% de los casos, respectivamente. Un 54,1% de los casos no tenían afectación ganglionar al diagnóstico y la mayoría de los tumores eran T1 o T3 (39,1 y 43,5%, respectivamente). Un 34,8% de los pacientes recayeron, sobre todo a nivel ganglionar local (62,5% de las recaídas) y todos ellos fallecieron por el tumor, en su mayoría en el primer año tras el diagnóstico. El estudio multivariable mediante regresión de Cox demostró que el único factor que condicionaba un menor intervalo libre de progresión y supervivencia global de forma independiente era el estadio N. Conclusiones: La afectación ganglionar es el factor más importante como predictor de pronóstico en esta neoplasia

Introduction: Ampullary adenocarcinoma seems less aggressive than other pancreato-biliary neoplasms. The aim of this study is to define determining prognostic factors. Material and methods: Retrospective case series from a large tertiary Hospital including all patients diagnosed with ampullary adenocarcinoma who underwent cephalic pancreatoduodenectomy with curative intent. Outcome variables have been progression free survival and overall survival. Results: 24 patients were included. 54.2% were females and the mean age was 72.5 (45-85). Most cases were of intestinal type (50%), followed by pancreatobiliary (37.5%) and mucinous. Only 8.3% were high histopathological grade. Vessel invasion was detected in 31.8% of the cases and perineural infiltration in 20.8%. A large percentage of cases showed no lymph node involvement at the time of diagnosis (54.1%). Most cases were stage T1 or T3 (39.1 y 43.5%, respectively). 34.8% of the patients recurred, mainly in regional lymph nodes (62.5% of the recurrences) and they all died of tumor, mainly during the first year after diagnosis. Multivariate analysis with Cox regression model revealed that only lymph node involvement was independently associated to a shorter disease free progression interval and overall survival. Conclusions: Lymph node involvement was the most important predictive factor for ampullary adenocarcinoma in this series

MUC1 expression in colorectal carcinoma: Clinicopathological correlation and prognostic significance.

INTRODUCTION: MUC1 overexpression has been linked to cancer development and has been associated with a higher stage at diagnosis and presence of lymph node or distant metastases. However, its prognostic significance is still unclear. We aimed to evaluate the relationship between MUC1 expression and prognosis of colorectal carcinoma. MATERIALS AND METHODS: Immunohistochemical expression of MUC1 in 96 colorectal carcinomas with analysis of potential prognostic influence. RESULTS: 55.2% of patients were women and the mean age was 65.9 years. Tumors were more frequently located in rectum or sigmoid colon (60.4% and 21.9%). Most tumors were T3 (60.3%). 36.9% of patients showed lymph node metastases and 30.2% showed distant metastasis at the time of diagnosis. MUC1 was intensely positive in 46% and negative in 37.9% of tumors. Overall, 61% of patients recurred and 40.4% died during follow-up. 58.5% of tumors of surviving patients were intensely positive for MUC1 and 29.5% were negative, as compared with 28.5% (intense positivity) and 51.4% (negativity) in the group of patients who died (p=0.022). 65% of tumors of patients without recurrences showed intense positivity for MUC1 and 23% of them were negative as compared with 33.9% (intense positivity) and 47% (negativity) in the group of patients who recurred (p=0.019). CONCLUSIONS: Loss of MUC1 expression was more frequent in cases with disease recurrence or death, as compared with patients with stable disease, in whom intense positivity was more frequently seen. These findings disagree with the majority of previous studies, indicating the need for further investigation.

[Prognostic factors in adenocarcinoma of the ampulla of Vater]. / Factores pronósticos en el adenocarcinoma de ampolla duodenal.

INTRODUCTION: Ampullary adenocarcinoma seems less aggressive than other pancreato-biliary neoplasms. The aim of this study is to define determining prognostic factors. MATERIAL AND METHODS: Retrospective case series from a large tertiary Hospital including all patients diagnosed with ampullary adenocarcinoma who underwent cephalic pancreatoduodenectomy with curative intent. Outcome variables have been progression free survival and overall survival. RESULTS: 24 patients were included. 54.2% were females and the mean age was 72.5 (45-85). Most cases were of intestinal type (50%), followed by pancreatobiliary (37.5%) and mucinous. Only 8.3% were high histopathological grade. Vessel invasion was detected in 31.8% of the cases and perineural infiltration in 20.8%. A large percentage of cases showed no lymph node involvement at the time of diagnosis (54.1%). Most cases were stage T1 or T3 (39.1 y 43.5%, respectively). 34.8% of the patients recurred, mainly in regional lymph nodes (62.5% of the recurrences) and they all died of tumor, mainly during the first year after diagnosis. Multivariate analysis with Cox regression model revealed that only lymph node involvement was independently associated to a shorter disease free progression interval and overall survival. CONCLUSIONS: Lymph node involvement was the most important predictive factor for ampullary adenocarcinoma in this series.

Neoplasias de células histiocitarias y dendríticas: revisión de la literatura / Histiocytic and dendritic cell neoplasms: Review of the literature

Las neoplasias de células histiocitarias y dendríticas (NHD) son poco frecuentes y su biología, pronóstico, tratamiento y terminología están aún en estudio. Son lesiones constituidas por células derivadas de células dendríticas o macrófagos y presentan un amplio rango de características clínicas, morfológicas y pronósticas. Su diagnóstico es complejo y requiere la integración de datos clínicos y morfológicos y la realización de un amplio panel inmunohistoquímico. Tras la detección de mutaciones de BRAF en las histiocitosis de células de Langerhans, se están realizando estudios para determinar el significado de otras alteraciones moleculares en las NHD. Realizamos una revisión de la bibliografía publicada sobre las NHD en los últimos 10 años, con especial énfasis en la patología molecular de estas lesiones

Histiocytic and dendritic cell neoplasms (HDN) are rare and their biology, prognosis, treatment and terminology are still under discussion. They are composed of macrophage and dendritic-derived cells and show a wide range of clinical, morphological and prognostic features. Clinicopathological correlation and a broad immunohistochemical panel are required to establish a correct diagnosis. After the detection of BRAF mutations in Langerhans cell histiocytosis, the potential role of other molecular alterations is being studied. We have reviewed the literature published in the last 10 years to provide an overview of NHD, with particular emphasis their molecular features

Tumor miofibroblástico inflamatorio de mama: una entidad poco frecuente / Inflammatory myofibroblastic tumor of the breast: A rare entity

Denominado también seudotumor inflamatorio, el tumor miofibroblástico inflamatorio se considera actualmente una auténtica neoplasia de bajo grado. Aunque su localización más frecuente es el pulmón, se ha descrito en muchas otras, incluida la mama, cuya afectación fue descrita por vez primera por Pettinato et al. en 1998. Presentamos el caso de una mujer de 52 años perimenopáusica que consultó por notar masa de crecimiento lento en la mama derecha. La lesión era bien delimitada en la mamografía, con un aspecto hipoecogénico en la ecografía. Se realizó una biopsia con aguja gruesa y el diagnóstico fue miofibroma con recomendación de exéresis. Tras la resección se observó una lesión fusocelular con llamativa presencia de elementos inflamatorios, cuya morfología y estudio inmunohistoquímico era compatible con tumor miofibroblástico inflamatorio. Tras ampliar los márgenes de resección y con un estudio de extensión negativo (PET-TC), la paciente está siendo seguida en consulta sin signos sugestivos de recidiva tras 8 meses. El tumor miofibroblástico inflamatorio de mama es muy poco frecuente, con menos de 30 casos a nivel mundial. Plantea un extenso diagnóstico diferencial con lesiones benignas y malignas y en ocasiones puede coexistir o anteceder a carcinomas en la mama adyacente. Su comportamiento es de bajo potencial maligno, aunque hay algunos casos que se han comportado de forma agresiva con recidiva precoz y metástasis sistémicas. El tratamiento es quirúrgico y no está indicado tratamiento sistémico, pero sí control clínico a medio plazo. No es posible definir con claridad los factores que determinan el comportamiento biológico de esta lesión, dada su rareza

Also known as inflammatory pseudotumor, inflammatory myofibroblastic tumor is now considered a true low-grade neoplasm. Although the lung is the most common site, it has been described in many other locations, including the breast; the first report of breast involvement was by Pettinato et al. in 1988. We report the case of a 52-year-old perimenopausal woman presenting with a slow-growing mass in her right breast. Mammography revealed a well demarcated lesion which was hypoechoic on ultrasound. A needle biopsy was performed yielding an initial diagnosis of myofibroma and the mass was resected. Histopathology of the 5-cm tumor revealed a fusocellular proliferation with a striking presence of inflammatory cells, morphologically and immunohistochemically concordant with inflammatory myofibroblastic tumor. The patient underwent further surgery to ensure free margins and after a negative extension study (PET-CT) is receiving no further therapy. To date, she has shown no signs of recurrence 8 months postoperatively. Inflammatory myofibroblastic tumor of the breast is very infrequent, with less than 30 reported cases. Differential diagnosis with both benign and malignant entities is extensive and it may precede or coexist with carcinoma of the adjacent breast. Although it is considered a low-malignant potential lesion, there are well documented cases of recurrence and even metastasis. Surgical resection with wide margins is the primary treatment and no systemic therapy is indicated; however, clinical follow-up is mandatory as there are no well-established criteria as yet to predict the biological behavior of this tumor

[Histiocytic and dendritic cell neoplasms: Review of the literature]. / Neoplasias de células histiocitarias y dendríticas: revisión de la literatura.

Histiocytic and dendritic cell neoplasms (HDN) are rare and their biology, prognosis, treatment and terminology are still under discussion. They are composed of macrophage and dendritic-derived cells and show a wide range of clinical, morphological and prognostic features. Clinicopathological correlation and a broad immunohistochemical panel are required to establish a correct diagnosis. After the detection of BRAF mutations in Langerhans cell histiocytosis, the potential role of other molecular alterations is being studied. We have reviewed the literature published in the last 10 years to provide an overview of NHD, with particular emphasis their molecular features.

[Inflammatory myofibroblastic tumor of the breast: A rare entity]. / Tumor miofibroblástico inflamatorio de mama: una entidad poco frecuente.

Also known as inflammatory pseudotumor, inflammatory myofibroblastic tumor is now considered a true low-grade neoplasm. Although the lung is the most common site, it has been described in many other locations, including the breast; the first report of breast involvement was by Pettinato et al. in 1988. We report the case of a 52-year-old perimenopausal woman presenting with a slow-growing mass in her right breast. Mammography revealed a well demarcated lesion which was hypoechoic on ultrasound. A needle biopsy was performed yielding an initial diagnosis of myofibroma and the mass was resected. Histopathology of the 5-cm tumor revealed a fusocellular proliferation with a striking presence of inflammatory cells, morphologically and immunohistochemically concordant with inflammatory myofibroblastic tumor. The patient underwent further surgery to ensure free margins and after a negative extension study (PET-CT) is receiving no further therapy. To date, she has shown no signs of recurrence 8 months postoperatively. Inflammatory myofibroblastic tumor of the breast is very infrequent, with less than 30 reported cases. Differential diagnosis with both benign and malignant entities is extensive and it may precede or coexist with carcinoma of the adjacent breast. Although it is considered a low-malignant potential lesion, there are well documented cases of recurrence and even metastasis. Surgical resection with wide margins is the primary treatment and no systemic therapy is indicated; however, clinical follow-up is mandatory as there are no well-established criteria as yet to predict the biological behavior of this tumor.