RESUMEN
PURPOSE: Granular cell tumours (GCTs) of the pancreas are mostly benign and exceptionally rare, with no unique identifying radiological features. Following a case discussion of a patient with GCT, a comprehensive review of available literature was conducted to identify the common diagnostic features associated with GCT. METHODS: Following a case report identified in our institution, a systematic review was conducted by two authors in accordance with Preferred Reporting Items for Systematic review and Meta-Analysis protocols (PRISMA) guidelines. Databases MEDLINE, EMBASE, Scopus, World of Science, and grey literature were searched on August 2021. Inclusion criteria were histopathology diagnosed granular cell tumour of the pancreas. RESULTS: A 37-year-old male presented with 1 month of abdominal pain and an MRI demonstrating a dilated main pancreatic duct, distal parenchymal atrophy, but no focal lesion. Repeat MRI at 6 months re-demonstrated similar findings and subsequent endoscopic ultrasound was suspicious for main duct IPMN. Following multidisciplinary team discussion, a spleen-preserving distal pancreatectomy was performed. Histopathology demonstrated granular cell tumour with cells diffusely positive for S100 and no malignant transformation. 11 case reports were identified in the literature with diagnosis confirmed on tissue histopathology based on positive immunohistochemical staining for S-100 protein. Eight patients presented with gastrointestinal symptoms with abdominal pain the main presenting complaint (50%). 10 patients underwent CT with portal venous contrast and all underwent endoscopic examination. Imaging findings were similar in five studies for EUS which demonstrated a hypoechoic lesion with homogenous appearance. On non-contrast CT GCT was iso-enhancing, and with portal venous contrast demonstrated hypo-enhancement that gradually enhanced on late phases. Pre-operative diagnosis of pancreatic carcinoma was described in six cases based on imaging and biopsy, resulting in progression to surgical resection. Nine patients were managed surgically and no complications identified on follow-up (6-52 months). CONCLUSION: The currently proposed management pathway includes EUS with biopsy and CT, and surgical resection recommended due to malignancy risk. Improved sample collection with EUS-FNA and microscopic assessment utilising S-100 immunohistochemistry may improve pre-operative diagnosis. Limitations include rare numbers in reported literature and short follow-up not allowing an assessment of GCT's natural history and malignancy risk. Additional cases would expand the current dataset of GCTs of the pancreas, so that surgical resection may be avoided in the future.
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Tumor de Células Granulares , Neoplasias Pancreáticas , Masculino , Humanos , Adulto , Tumor de Células Granulares/diagnóstico por imagen , Tumor de Células Granulares/cirugía , Páncreas , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Endosonografía/métodos , Dolor AbdominalRESUMEN
Glioblastoma, WHO-grade IV glioma, carries a dismal prognosis owing to its infiltrative growth and limited treatment options. Glioblastoma-derived extracellular vesicles (EVs; 30-1000 nm membranous particles) influence the microenvironment to mediate tumor aggressiveness and carry oncogenic cargo across the blood-brain barrier into the circulation. As such, EVs are biomarker reservoirs with enormous potential for assessing glioblastoma tumors in situ. Neurosurgical aspirates are rich sources of EVs, isolated directly from glioma microenvironments. EV proteomes enriched from glioblastoma (n = 15) and glioma grade II-III (n = 7) aspirates are compared and 298 differentially-abundant proteins (p-value < 0.00496) are identified using quantitative LC-MS/MS. Along with previously reported glioblastoma-associated biomarkers, levels of all eight subunits of the key molecular chaperone, T-complex protein 1 Ring complex (TRiC), are higher in glioblastoma-EVs, including CCT2, CCT3, CCT5, CCT6A, CCT7, and TCP1 (p < 0.00496). Analogous increases in TRiC transcript levels and DNA copy numbers are detected in silico; CCT6A has the greatest induction of expression and amplification in glioblastoma and shows a negative association with survival (p = 0.006). CCT6A is co-localized with EGFR at 7p11.2, with a strong tendency for co-amplification (p < 0.001). Immunohistochemistry corroborates the CCT6A proteomics measurements and indicated a potential link between EGFR and CCT6A tissue expression. Putative EV-biomarkers described here should be further assessed in peripheral blood.
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Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Chaperonina con TCP-1/metabolismo , Vesículas Extracelulares/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patología , Chaperonina con TCP-1/química , Cromatografía Liquida , Glioma/metabolismo , Glioma/patología , Humanos , Pronóstico , Proteómica , Espectrometría de Masas en TándemRESUMEN
Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.
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Carcinoma Ductal Pancreático/genética , Reparación de la Incompatibilidad de ADN/genética , Mutación , Neoplasias Pancreáticas/genética , Transcriptoma , Adulto , Anciano , Anciano de 80 o más Años , Análisis Mutacional de ADN , Femenino , Genoma , Humanos , Masculino , Persona de Mediana Edad , Homólogo 1 de la Proteína MutL/genética , Proteína 2 Homóloga a MutS/genética , Proteínas Proto-Oncogénicas p21(ras)/genéticaRESUMEN
AIMS: Mesothelioma is a relatively uncommon but highly malignant neoplasm. Most patients die of disease within 1 year of diagnosis, but some have prolonged survival. Prospective identification of these longer-term survivors may help to guide treatment. We therefore sought to investigate the role of p16 immunohistochemistry (IHC) both alone and in combination with other markers as a potential predictor of prolonged survival in mesothelioma. METHODS AND RESULTS: P16 IHC was performed on unselected pleural mesotheliomas biopsied from 1991 to 2014; 153 of 208 (74%) cases were p16-negative, which correlated significantly with poor overall survival in both univariate (median survival 7.6 versus 13.6 months; P = 0.001) and multivariate analysis [hazard ratio (HR): 1.632; 95% confidence interval (CI): 1.103-2.415; P = 0.014]. Other independent factors associated with prolonged survival included loss of expression of BAP1 and epithelioid morphology. We therefore stratified patients further based on these three independent prognostic variables and demonstrated an unusually prolonged survival in mesotheliomas which were epithelioid, BAP1 IHC negative and p16 IHC positive (12% of cases, median survival 31.7 months, P < 0.0001). CONCLUSIONS: In conclusion, p16 IHC is an independent prognostic biomarker in pleural mesothelioma. When used in combination with BAP1 IHC and morphological subtyping, patients with exceptionally prolonged survival can potentially be identified.
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Biomarcadores de Tumor/análisis , Inhibidor p16 de la Quinasa Dependiente de Ciclina/biosíntesis , Neoplasias Pulmonares/patología , Mesotelioma/patología , Neoplasias Pleurales/patología , Proteínas Supresoras de Tumor/biosíntesis , Ubiquitina Tiolesterasa/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Masculino , Mesotelioma/mortalidad , Mesotelioma Maligno , Persona de Mediana Edad , Fenotipo , Neoplasias Pleurales/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Proteínas Supresoras de Tumor/análisis , Ubiquitina Tiolesterasa/análisisRESUMEN
There is some uncertainty about pathological grading of mucinous colorectal adenocarcinoma, defined as colorectal cancer demonstrating at least 50% mucinous differentiation. Under the WHO 2000 classification mucinous colorectal cancer was considered high grade. However under the current WHO 2010 classification microsatellite unstable/mismatch repair-deficient (MSI/MMRd) mucinous colorectal cancer is considered low grade, whereas microsatellite stable/mismatch repair proficient (MSS/MMRp) tumours are high grade. However there is little empirical evidence for this approach. We therefore compared the long term survival of patients with MSI/MMRd vs MSS/MMRp mucinous colorectal cancer in a large unselected cohort of patients undergoing surgery at our institution from 1998 to 2011. There were 2608 patients in the cohort, of which 264 (10.1%) were mucinous. 95 (36%) of the mucinous tumours were microsatellite unstable. The all-cause 5-year survival of mucinous MSI/MMRd colorectal cancer was similar to that of non-mucinous low-grade colorectal cancer (73 vs 67%, P=0.368), and significantly better than that of both non-mucinous high-grade (73 vs 53%, P<0.001) and mucinous MSS/MMRp colorectal cancer (73 vs 57%, P=0.023). The 5-year survival of mucinous MSS/MMRp colorectal cancer was slightly better than that of non-mucinous high-grade patients (57 vs 53%, P=0.027), but significantly worse than that of non-mucinous low-grade colorectal cancer (57 vs 67%, P=0.018). In multivariate Cox regression analysis, conventional histological grade based on glandular differentiation maintained prognostic significance (P=0.003) whereas MSI/MMRd status just failed to be statistically significant (P=0.062). Our findings support the WHO 2010 approach that as a group mucinous MSS/MMRp colorectal cancers are biologically aggressive. However, grading based exclusively on MSI/MMR status may be overly simplistic as conventional grading based on the degree of glandular differentiation still holds greater prognostic significance in multivariate analysis.
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Adenocarcinoma Mucinoso/patología , Neoplasias Colorrectales/patología , Trastornos por Deficiencias en la Reparación del ADN/mortalidad , Clasificación del Tumor/métodos , Adenocarcinoma Mucinoso/clasificación , Adenocarcinoma Mucinoso/mortalidad , Anciano , Neoplasias Colorrectales/clasificación , Neoplasias Colorrectales/mortalidad , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Análisis de Matrices TisularesAsunto(s)
Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Anticoagulantes/efectos adversos , Exantema/inducido químicamente , Pirazoles/efectos adversos , Piridonas/efectos adversos , Anticoagulantes/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Embolia Pulmonar/tratamiento farmacológico , Pirazoles/uso terapéutico , Piridonas/uso terapéuticoRESUMEN
Although most mesotheliomas present with pleural effusions, it is controversial whether mesothelioma can be diagnosed with confidence in effusion cytology. Therefore, an ancillary marker of malignant mesothelial cells applicable in effusions would be clinically valuable. BRCA-1-associated protein (BAP1) is a tumor suppressor gene, which shows biallelic inactivation in approximately half of all mesotheliomas. We investigated whether loss of BAP1 expression by immunohistochemistry can be used to support a diagnosis of mesothelioma in effusion cytology. Immunohistochemistry for BAP1 was performed on cell blocks and interpreted blinded. 43 of 75 (57%) effusions associated with confirmed mesothelioma showed negative staining with positive internal controls. Of 57 effusions considered to have atypical mesothelial cells in the absence of a definitive diagnosis of mesothelioma, 8 cases demonstrated negative staining for BAP1. On follow-up six of these patients received a definitive diagnosis of mesothelioma in the subsequent 14 months (two were lost to follow-up immediately, and mesothelioma could not be excluded). Only 5 of 100 consecutive benign effusions were interpreted as BAP1 negative. One of these patients died soon after and mesothelioma could not be excluded. On unblinded review the four other patients with apparently negative BAP1 staining but no malignancy lacked convincing positive staining in non-neoplastic cells suggesting that BAP1 immunohistochemistry may have initially been misinterpreted. 47 effusions with adenocarcinoma were BAP1 positive. We conclude that loss of BAP1 expression, while not definitive, can be used to support the diagnosis of mesothelioma in effusion cytology. We caution that interpretation of BAP1 immunohistochemistry on cell block may be difficult and that convincing positive staining in non-neoplastic cells is required before atypical cells are considered negative. We also note that BAP1 loss is not a sensitive test as it occurs in only half of all mesotheliomas and cannot be used to exclude the diagnosis.
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Biomarcadores de Tumor/análisis , Mesotelioma/diagnóstico , Derrame Pleural Maligno/etiología , Neoplasias Pleurales/diagnóstico , Proteínas Supresoras de Tumor/biosíntesis , Ubiquitina Tiolesterasa/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Citodiagnóstico/métodos , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Derrame Pleural Maligno/diagnóstico , Proteínas Supresoras de Tumor/análisis , Ubiquitina Tiolesterasa/análisis , Adulto JovenRESUMEN
AIM: Medullary carcinoma is a recently described subtype of mismatch repair deficient (MMRd) colorectal carcinoma (CRC) which, despite being poorly differentiated by traditional morphological criteria, has been reported to have a good prognosis. We investigated the pathological and clinical features of medullary CRC in an unselected cohort of CRCs undergoing surgical resection. METHODS: All CRCs resected within a single health district database from 1998 to 2012 were categorized prospectively and underwent retrospective review to identify 91 medullary CRCs, with 11 additional cases from 2013 to 2014. Strict criteria were employed to diagnose medullary carcinoma requiring both MMRd and greater than 90 % of the tumor to demonstrate typical morphology, including solid growth. The demographic and pathological features, as well as all-cause survival, were compared with other CRCs, and specifically to other MMRd CRCs. RESULTS: From 1998 to 2012, 91 of 3,295 CRCs (2.8 %) were of the medullary type. Medullary CRC was more likely to arise in females than males (3.3:1; p < 0.0001), the elderly (mean age 77 vs. 71 years; p < 0.001), and the right colon (86 %; p < 0.0001). All medullary CRCs demonstrated MMR deficiency (considered an inclusion criteria) and 86 % were BRAFV600E-mutated (p < 0.0001). Thirty-day mortality after resection was higher in medullary CRC (4.6 vs. 1.7 %; p = 0.049). On univariate analysis, survival was not better than well-differentiated or other MMRd tumors. However, using a multivariate model, a medullary phenotype was protective (hazard ratio of death 0.54, 95 % CI 0.30-0.96; p = 0.037). CONCLUSIONS: Medullary CRC is more common than previously reported, frequently presents with locally advanced disease, and may be associated with higher mortality at 30 days after resection. Despite this, when strict criteria are used for diagnosis, the overall survival is favorable when compared with CRCs with equivalent demographic and pathological characteristics.
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Adenocarcinoma/patología , Carcinoma Medular/patología , Neoplasias Colorrectales/patología , Adenocarcinoma/mortalidad , Anciano , Anciano de 80 o más Años , Carcinoma Medular/mortalidad , Neoplasias Colorrectales/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Although gemcitabine is commonly used as adjuvant therapy for pancreatic adenocarcinoma and pancreaticobiliary-type periampullary cancers, not all patients appear to benefit. This translational study evaluates the potential of a patient-derived subrenal capsule pancreatic cancer xenograft (SRCPCX) model to identify within eight weeks after surgery those tumours which will respond to gemcitabine. METHODS: SRCPCXs from 32 pancreatectomy patients were established in six to ten NOD/SCID mice per patient. After four weeks the mice were randomly assigned to receive gemcitabine or saline for four more weeks. After eight weeks, gemcitabine response in the grafts was evaluated by the percentage of tumour growth inhibition (%TGI), histological morphology and immunohistochemical markers (Ki-67, CK7 and cleaved caspase-3). These were collated into an Overall Response. Survival was assessed by Kaplan-Meier and Cox multivariate analyses. RESULTS: 375 of 450 pieces of tissue from 27 of 31 patients were evaluable. In 90% of patients, histopathological and immunostaining features of saline-treated control grafts were concordant with their original tumours. At follow up, six of 15 patients whose tumours had an Overall Response to gemcitabine died, compared with ten of 12 whose tumours did not respond (P = 0.025, Fisher's exact test). This was associated with improved survival on Kaplan-Meier analysis (P = 0.013). Cox multivariate analysis indicated that Overall Response, stage and grade were independent predictors of survival. CONCLUSION: This SRCPCX model retains major histopathological and immunohistochemical characteristics of the original tumour and when a combination of measures is used, enables early assessment of tumour sensitivity to gemcitabine in pancreatic cancers.
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Quimioradioterapia Adyuvante/métodos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Ensayo de Capsula Subrrenal/métodos , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antibióticos Antineoplásicos/uso terapéutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Pancreatectomía , Neoplasias Pancreáticas/cirugía , Valor Predictivo de las Pruebas , Análisis de Supervivencia , Resultado del Tratamiento , GemcitabinaRESUMEN
Immunohistochemistry has recently been validated for the detection of the BRAFV600E mutation across a range of tumor types. In colorectal carcinoma, the presence of the BRAFV600E mutation can be used to virtually exclude Lynch syndrome in mismatch repair-deficient tumors. In mismatch repair-proficient tumors, BRAFV600E mutation assessed by molecular methods has been proposed as a poor prognostic factor. We investigated whether combined BRAFV600E and mismatch repair status assessment by immunohistochemistry alone can be used as a prognostic marker in the routine clinical setting. We performed immunohistochemistry for BRAFV600E, MLH1, PMS2, MSH2, and MSH6 on 1426 consecutive unselected colorectal carcinomas. Ninety-one (6.4%) carcinomas were mismatch repair-proficient and BRAFV600E mutant, and these tumors demonstrated a significantly worse 5-year survival of 49.7% compared with mismatch repair-proficient BRAF wild type (74.1% of tumors, 65.4% survival), mismatch repair-deficient BRAFV600E mutant (12.9% of tumors, 70.1% survival), and mismatch repair-deficient BRAF wild type (6.6% of tumors, 73.6% survival). The poor survival was confirmed by univariate analysis (P<0.01) but fell away in multivariate analysis (P=0.68) because of the strong effect of tumor stage and age on overall survival. We conclude that in addition to its utility in screening for Lynch syndrome, reflex BRAFV600E and mismatch repair assessment by immunohistochemistry can be used as a powerful predictor of all-cause survival.
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Carcinoma/mortalidad , Neoplasias Colorrectales/mortalidad , Reparación de la Incompatibilidad de ADN , Proteínas Proto-Oncogénicas B-raf/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/genética , Carcinoma/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/metabolismo , Femenino , Humanos , Inmunohistoquímica , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Tasa de Supervivencia , Adulto JovenRESUMEN
The liver is the most frequent and often the only site of distant disease in colorectal cancer and, of all treatment protocols currently in use, resection is the most likely to result in long-term cure. Within the liver, tumour proximity to major vasculature and biliary structures poses a resection challenge, requiring a balance of achieving negative margins while preserving adequate vascular circulation and biliary drainage. The focus on parenchymal sparing resections are important but just as important may be the 'biological' behaviour of the tumour. In colorectal liver metastases (CRLM), biomarkers such as the Kirsten rat sarcoma oncogene homologue (KRAS) gene and histological growth patterns (HGPs) further improve the prognostication after resection. However, to date, the association between the KRAS status and HGPs in CRLM and their impact on resection margins around major vasculature or biliary structures in terms of overall survival and recurrence rates are unclear. The aim of this review was to explore the available evidence for the association between KRAS and HGPs in CRLM and attempt to define their impact on resection margins near major structures.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Conductos Biliares/patología , Neoplasias Colorrectales/patología , Hepatectomía , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/secundario , Márgenes de Escisión , Pronóstico , Proteínas Proto-Oncogénicas p21(ras)/genéticaRESUMEN
BACKGROUND: Juvenile polyposis syndrome (JPS) is a rare hereditary polyposis disease frequently associated with an autosomal-dominant variant of the SMAD4 or BMPR1A gene. It often manifests with symptoms in children and adolescents and is infrequently diagnosed in asymptomatic adults. Establishing the diagnosis is important as patients with JPS have a high risk of developing gastrointestinal cancer and require genetic counselling and close routine follow-up. CASE SUMMARY: We report on the case of a 56-year-old female diagnosed with JPS after genetic testing revealed a rare variant of the BMPR1A gene BMPR1A c.1409T>C (p.Met470Thr). She was initially referred for colonoscopy by her general practitioner after testing positive on a screening faecal immunochemical test and subsequently found to have polyposis throughout the entire colorectum on her index screening colonoscopy. The patient was asymptomatic with a normal physical examination and no related medical or family history. Blood tests revealed only mild iron deficiency without anemia. To date, there has only been one other reported case of JPS with the same genetic variant. Subsequent colonoscopies were organised for complete polyp clearance and the patient was returned for surveillance follow-up. CONCLUSION: JPS patients can present with no prior symptoms or family history. Genetic testing plays an important diagnostic role guiding management.
RESUMEN
BACKGROUND: The majority of cutaneous squamous cell carcinomas (cSCC) have a favourable prognosis. However, a subset of cases follow an aggressive disease course with progression to metastasis and death. Several histopathological parameters are associated with poor outcomes, but lymphovascular invasion (LVI) has not been well studied. OBJECTIVE: To assess the prognostic significance of LVI in cSCC and determine associations between LVI and cSCC. METHODS: A retrospective review of 486 consecutive cases of cSCC over a 5-year period from a single centre was stratified by the presence or absence of LVI. Logistic regression and multivariate survival analysis were used to determine associations of LVI and prognostic significance of LVI, respectively. FINDINGS: LVI was present in 41 cases (9.2%). LVI was significantly associated with increasing depth of invasion, microanatomical tumour location (subcutis vs. dermis), and tumour dimensions (P < 0.05). Univariate survival analysis revealed significantly lower 2-year overall survival rates for patients with LVI (37.1%) compared with those without (66.6%) (95% CI = 60.6-73.3, P < 0.001). LVI was also found to be an independent marker of poor disease-specific survival (HR = 0.232 (95% CI = 0.090-0.600), P = 0.003), poor overall survival (HR 0.338 (95% CI = 0.184-0.623), P < 0.001) and poor disease-free survival (HR 0.461 (95% CI = 0.230-0.923), P = 0.029) through multivariate analysis. CONCLUSIONS: This study confirms that LVI is an independent poor prognosticator in cSCC, with significantly worse survival indices at 2 years. Future systems of risk stratification for cSCC should incorporate LVI.
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Carcinoma de Células Escamosas , Neoplasias Cutáneas , Humanos , Pronóstico , Carcinoma de Células Escamosas/patología , Estadificación de Neoplasias , Metástasis Linfática , Neoplasias Cutáneas/patología , Estudios Retrospectivos , Invasividad Neoplásica/patologíaRESUMEN
Immunoglobulin G4-related disease (IgG4-RD) of the ureter is a rarely reported disease, often mimicking urothelial carcinoma. This paper describes a case of an otherwise healthy patient with a lesion involving the ureter revealed on Computed tomography (CT), avid on fludeoxyglucose positron emission tomography (FDG PET), that prior to surgery was suspicious for urothelial carcinoma, until intra-op frozen section revealed otherwise. Diagnosis of ureteral IgG4-RD should be considered as a differential diagnosis, with serum IgG4 levels obtained.
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Carcinoma de Células Renales/genética , Carcinoma de Células Renales/terapia , Sistemas de Liberación de Medicamentos , Exantema/genética , Indoles/uso terapéutico , Neoplasias Renales/genética , Neoplasias Renales/terapia , Leiomiomatosis/genética , Leiomiomatosis/terapia , Neoplasias Primarias Múltiples/genética , Neoplasias Primarias Múltiples/terapia , Medicina de Precisión , Pirroles/uso terapéutico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/terapia , Segunda Guerra Mundial , Adulto , Alelos , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/patología , Deleción Cromosómica , Terapia Combinada , Fumarato Hidratasa/genética , Asesoramiento Genético , Humanos , Médula Renal/patología , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Leiomiomatosis/diagnóstico , Leiomiomatosis/patología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Escisión del Ganglio Linfático , Metástasis Linfática/patología , Masculino , Técnicas Analíticas Microfluídicas , Reacción en Cadena de la Polimerasa Multiplex , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Primarias Múltiples/patología , Nefrectomía , Nueva Gales del Sur , Análisis de Secuencia por Matrices de Oligonucleótidos , Opsinas de Bastones/genética , Piel/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , SunitinibRESUMEN
There is increasing interest in p53 immunohistochemistry as an adjunct to haematoxylin and eosin (H&E) assessment for dysplasia in oesophageal Barrett's mucosa; however, published information on the patterns of staining remains scant. Here, we present descriptions of normal and aberrant p53 staining in non-neoplastic and dysplastic Barrett's mucosa in endoscopic mucosal resections. A retrospective series of archival endoscopic mucosal resections for biopsy proven dysplasia at our institution were retrieved for this study, comprising 28 sections from 23 patients. p53 immunohistochemistry was performed using an in-house optimised protocol and the staining pattern assessed in H&E confirmed non-neoplastic, dysplastic and neoplastic areas of Barrett's mucosa with regard to individual cell intensity and location of positive cells with respect to gland microanatomy. In non-neoplastic epithelium, normal p53 staining was weak, heterogenous and localised to the crypts. In dysplastic epithelium, p53 over-expression was seen which was of moderate to strong intensity in either a crypt predominant location or diffuse involving crypt and surface epithelium. The crypt predominant pattern was observed more commonly in low grade dysplasia while the diffuse pattern was more commonly seen in high grade dysplasia. In a minority of cases, there was complete loss of p53 staining in dysplastic epithelium and contiguous neoplasia (null phenotype). p53 immuno-expression in non-neoplastic and dysplastic Barrett's mucosa is distinctive when interpreted with regard to cell intensity and gland microanatomy. We propose that these staining patterns may assist in the interpretation of dysplasia in endoscopic biopsies of Barrett's mucosa.
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Esófago de Barrett/metabolismo , Mucosa Esofágica/metabolismo , Neoplasias Esofágicas/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Esófago de Barrett/patología , Resección Endoscópica de la Mucosa , Mucosa Esofágica/patología , Neoplasias Esofágicas/patología , Humanos , Inmunohistoquímica , Estudios RetrospectivosRESUMEN
The gene CDC73 (previously known as HRPT2) encodes the protein parafibromin. Biallelic mutation of CDC73 is strongly associated with malignancy in parathyroid tumors. Heterozygous germline mutations cause hyperparathyroidism jaw tumor syndrome,which is associated with a high life-time risk of parathyroid carcinoma. Therefore loss of parafibromin expression by immunohistochemistry may triage genetic testing for hyperparathyroidism jaw tumor syndrome and be associated with malignant behavior in atypical parathyroid tumors. We share our experience that parafibromin-negative parathyroid tumors show distinctive morphology. We searched our institutional database for parathyroid tumors demonstrating complete loss of nuclear expression of parafibromin with internal positive controls. Forty-three parafibromin-negative tumors from 40 (5.1%) of 789 patients undergoing immunohistochemistry were identified. Thirty-three (77%) were external consultation cases; the estimated incidence in unselected tumors was 0.19%. Sixteen (37.2%) fulfilled World Health Organization 2017 criteria for parathyroid carcinoma and 63% had serum calcium greater than 3mmol/L. One of 27 (3.7%) noninvasive but parafibromin-negative tumors subsequently metastasized. Parafibromin-negative patients were younger (mean, 36 vs. 63 y; P<0.001) and had larger tumors (mean, 3.04 vs. 0.62 g; P<0.001). Not all patients had full testing, but 26 patients had pathogenic CDC73 mutation/deletions confirmed in tumor (n=23) and/or germline (n=16). Parafibromin-negative tumors demonstrated distinctive morphology including extensive sheet-like rather than acinar growth, eosinophilic cytoplasm, nuclear enlargement with distinctive coarse chromatin, perinuclear cytoplasmic clearing, a prominent arborizing vasculature, and, frequently, a thick capsule. Microcystic change was found in 21 (48.8%). In conclusion, there are previously unrecognized morphologic clues to parafibromin loss/CDC73 mutation in parathyroid tumors which, given the association with malignancy and syndromic disease, are important to recognize.
Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias de las Paratiroides/patología , Proteínas Supresoras de Tumor/biosíntesis , Adenoma/complicaciones , Adenoma/diagnóstico , Adolescente , Adulto , Anciano , Femenino , Fibroma/complicaciones , Fibroma/diagnóstico , Humanos , Hiperparatiroidismo/complicaciones , Hiperparatiroidismo/diagnóstico , Neoplasias Maxilomandibulares/complicaciones , Neoplasias Maxilomandibulares/diagnóstico , Masculino , Persona de Mediana Edad , Mutación , Neoplasias de las Paratiroides/diagnóstico , Neoplasias de las Paratiroides/genética , Proteínas Supresoras de Tumor/análisis , Proteínas Supresoras de Tumor/genética , Adulto JovenRESUMEN
Eosinophilic angiocentric fibrosis (EAF) is a rare, benign condition affecting the respiratory mucosa and is generally characterized by a locally destructive growth. We present a case of a lady with a saddle nose deformity that had for many years been treated as granulomatosis with polyangiitis (GPA), of which saddle nose deformity is a classic feature. At the time of surgery, she was found to have subglottic stenosis another classic feature of GPA, however, histology demonstrated EAF. We discuss the difference between the two conditions and highlight the importance of making the correct diagnosis.