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Inactivating alterations in the SWItch/Sucrose NonFermentable (SWI/SNF) Chromatin Remodeling Complex subunits have been described in multiple tumor types. Recent studies focused on SMARC subunits of this complex to understand their relationship with tumor characteristics and therapeutic opportunities. To date, pancreatic cancer with these alterations has not been well studied, although isolated cases of undifferentiated carcinomas have been reported. Herein, we screened 59 pancreatic undifferentiated carcinomas for alterations in SWI/SNF complex-related (SMARCB1 [BAF47/INI1], SMARCA4 [BRG1], SMARCA2 [BRM]) proteins and/or genes using immunohistochemistry and/or next-generation sequencing. Cases with alterations in SWI/SNF complex-related proteins/genes were compared with cases without alterations, as well as with 96 conventional pancreatic ductal adenocarcinomas (PDAC). In all tumor groups, mismatch repair and PD-L1 protein expression were also evaluated. Thirty of 59 (51%) undifferentiated carcinomas had a loss of SWI/SNF complex-related protein expression or gene alteration. Twenty-seven of 30 (90%) SWI-/SNF-deficient undifferentiated carcinomas had rhabdoid morphology (vs 9/29 [31%] SWI-/SNF-retained undifferentiated carcinomas; P < .001) and all expressed cytokeratin, at least focally. Immunohistochemically, SMARCB1 protein expression was absent in 16/30 (53%) cases, SMARCA2 in 4/30 (13%), and SMARCA4 in 4/30 (13%); both SMARCB1 and SMARCA2 protein expressions were absent in 1/30 (3%). Five of 8 (62.5%) SWI-/SNF-deficient undifferentiated carcinomas that displayed loss of SMARCB1 protein expression by immunohistochemistry were found to have corresponding SMARCB1 deletions by next-generation sequencing. Analysis of canonical driver mutations for PDAC in these cases showed KRAS (2/5) and TP53 (2/5) abnormalities. Median combined positive score for PD-L1 (E1L3N) was significantly higher in the undifferentiated carcinomas with/without SWI/SNF deficiency compared with the conventional PDACs (P < .001). SWI-/SNF-deficient undifferentiated carcinomas were larger (P < .001) and occurred in younger patients (P < .001). Patients with SWI-/SNF-deficient undifferentiated carcinoma had worse overall survival compared with patients with SWI-/SNF-retained undifferentiated carcinoma (P = .004) and PDAC (P < .001). Our findings demonstrate that SWI-/SNF-deficient pancreatic undifferentiated carcinomas are frequently characterized by rhabdoid morphology, exhibit highly aggressive behavior, and have a negative prognostic impact. The ones with SMARCB1 deletions appear to be frequently KRAS wild type. Innovative developmental therapeutic strategies targeting this genomic basis of the SWI/SNF complex and the therapeutic implications of EZH2 inhibition (NCT03213665), SMARCA2 degrader (NCT05639751), or immunotherapy are currently under investigation.
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Gastrointestinal (GI) tract involvement by Langerhans cell histiocytosis (LCH) is rare and its clinicopathologic characteristics have only been described in case reports and small series. We reviewed hematoxylin and eosin and CD1a, S100, and Langerin immunohistochemical-stained slides from 47 patients with well-documented demographic and clinical findings. Our cases included 8 children and 39 adults, with a mean follow-up of 63 months. All pediatric patients had concurrent multisystem LCH, presented with GI symptoms, and showed nonpolypoid lesions. Seven (88%) showed multifocal GI disease, including 5 with multiple GI organ involvement. All sampled lesions from children exhibited infiltrative growth. More than half had died of the disease or manifested persistent LCH at last follow-up. Twenty-five of 39 (64%) adults had LCH involving only the GI tract (single system), with the remaining 14 (36%) exhibiting multisystem disease. Adult single-system GI LCH was typically encountered incidentally on screening/surveillance endoscopy (72%). Most exhibited isolated colorectal involvement (88%) as a solitary polyp (92%), with a well-demarcated/noninfiltrative growth pattern (70%), and excellent prognosis (100%). In comparison, adult patients with multisystem LCH more frequently presented with GI symptoms (92%, P < .001), noncolorectal GI site involvement (50%, P = .02), multifocal GI lesions (43%, P = .005), nonpolypoid lesions (71%, P < .001), infiltrative histologic growth pattern (78%, P = .04), and persistent disease (57%, P < .001). Adult patients with multisystem LCH appear to exhibit similar clinicopathologic features to those of pediatric patients. These results demonstrated that adults with single-system LCH involving the GI tract have an excellent prognosis, whereas multisystem LCH occurring at any age carries an unfavorable prognosis. High-risk features of GI LCH include pediatric age, GI symptomatology, noncolorectal GI involvement, multifocal GI disease, nonpolypoid lesions, and infiltrative growth pattern.
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The assessment of the expression of programmed cell death ligand-1 (PD-L1) using immunohistochemistry (IHC) has been controversial since its introduction. The methods of assessment and the range of assays and platforms contribute to confusion. Perhaps the most challenging aspect of PD-L1 IHC is the combined positive score (CPS) method of interpretation of IHC results. Although the CPS method is prescribed for more indications than any other PD-L1 scoring system, its reproducibility has never been rigorously assessed. In this study, we collected a series of 108 gastric or gastroesophageal junction cancer cases, stained them using the Food and Drug Administration-approved 22C3 assay, scanned them, and then circulated them to 14 pathologists at 13 institutions for the assessment of interpretative concordance for the CPS system. We found that higher cut points (10 or 20) performed better than a CPS of <1 or >1. We used the Observers Needed to Evaluate Subjective Tests algorithm to assess how the CPS system might perform in the real-world setting and found that the cut points of <1 or >1 showed an overall percent agreement of only 30% among the pathologist raters, with a plateau occurring at 8 raters. The raters performed better at higher cut points. However, the best cut point of <20 versus that of >20 was still disappointing, with a plateau at an overall percent agreement of 70% (at 7 raters). Although there is no ground truth for CPS, we compared the score with quantitative messenger RNA measurement and showed no relationship between the score (at any cut point) and messenger RNA amount. In summary, we showed that CPS shows high subjective variability among pathologist readers and is likely to perform poorly in the real-world setting. This system may be the root cause of the poor specificity and relatively low predictive value of IHC companion diagnostic tests for PD-1 axis therapies that use the CPS system.
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Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Apoptose , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Junção Esofagogástrica/patologia , Imuno-Histoquímica , Ligantes , Patologistas , Reprodutibilidade dos Testes , Neoplasias Gástricas/diagnósticoRESUMO
Most pancreatic neuroendocrine neoplasms are slow-growing, and the patients may survive for many years, even after distant metastasis. The tumors usually display characteristic organoid growth patterns with typical neuroendocrine morphology. A smaller portion of the tumors follows a more precipitous clinical course. The classification has evolved from morphologic patterns to the current World Health Organization classification, with better-defined grading and prognostic criteria. Recent advances in molecular pathology have further improved our understanding of the pathogenesis of these tumors. Various issues and challenges remain, including the correct recognition of a neuroendocrine neoplasm, accurate classification and grading of the tumor, and differentiation from mimickers. This review focuses on the practical aspects during the workup of pancreatic neuroendocrine neoplasms and attempts to provide a general framework to help achieve an accurate diagnosis, classification, and grading.
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Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/patologia , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Prognóstico , Organização Mundial da Saúde , Gradação de TumoresRESUMO
BACKGROUND: Type I gastric neuroendocrine tumors (GNETs) are typically managed either expectantly or endoscopically. In contrast, locoregional surgery has been recommended for patients with type III GNETs because of the risk of metastasis. This study aimed to identify predictors of outcome independent of type in a contemporary cohort of GNET patients. METHODS: A single-institution retrospective cohort study of 121 patients with a pathologic diagnosis of primary GNET between January 2009 and June 2019 was performed. GNETs were designated as type 1 (n = 74) if atrophic gastritis was present, or as type III (n = 47) in the absence of atrophic gastritis. Demographic, clinical, and histopathologic factors were examined using Kaplan-Meier and multivariable Cox regression to assess the impact of various factors on recurrence and overall survival. RESULTS: Median follow-up for the entire cohort was 62.7 months. While there was no difference in OS in patients with different GNET types (p = 0.10), higher tumor grade (p = 0.02) and presence of nodal or distant metastases (p = 0.02) predicted worse survival on multivariable analysis. Among type III GNET patients, those with small (< 0.5 cm), grade 1 lesions ("low-risk") were less likely to develop metastases (0% versus 33%, p < 0.01) and more likely to survive (100% versus 67%, p < 0.01) at 5 years. CONCLUSIONS: Size and tumor grade predict recurrence and survival in patients with GNETs irrespective of type. Small, low-grade type III GNETs are associated with minimal risk of progression and may be managed accordingly.
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Tumores Neuroendócrinos , Neoplasias Gástricas , Humanos , Recidiva Local de Neoplasia , Tumores Neuroendócrinos/cirurgia , Estudos Retrospectivos , Neoplasias Gástricas/cirurgiaRESUMO
Challenges exist with standardized colorectal cancer reporting despite adoption of the American Joint Committee on Cancer-Staging Manual 8th edition. We performed this study to gauge current practice patterns among a diverse group of surgical pathologists. A web-based questionnaire depicting problematic issues and images related to colorectal carcinoma staging was circulated among 118 surgical pathologists and their responses were correlated with their geographic location (North America vs. Europe vs. others), nature of practice (academic vs. community), the sign-out model (gastrointestinal subspecialty vs. general surgical pathology), and years of professional experience. We found that a substantial number of practicing pathologists ignore recommended-staging criteria in specific settings, particularly with respect to assessment of advanced T stage. Tumors that communicated with the serosa through inflammatory foci were staged as pT3 (49%) or pT4a (51%) by nearly equal numbers of pathologists regardless of level of experience, the sign-out model, or geographic location. Only 65% assigned T stage and margin status based on extent of viable tumor in the neoadjuvant setting. One-third of pathologists, particularly those in Europe (p = 0.015), classified acellular mucin deposits as N1 disease when detected in treatment-naive cases. Nearly 50% of pathologists classified isolated tumor cells (i.e., deposits <0.2 mm) in lymph nodes as metastatic disease (i.e., pN1, p = 0.02). Our results suggest that pathologists ignore recommendations that are based on insufficient data and apply individualized criteria when faced with situations that are not addressed in the American Joint Committee on Cancer Staging Manual 8th edition. These variations in practice limit the ability to compare outcome data across different institutions and draw attention to areas that require further study.
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Neoplasias Colorretais/patologia , Estadiamento de Neoplasias/normas , Patologistas/normas , Patologia Cirúrgica/normas , Humanos , Inquéritos e QuestionáriosRESUMO
AIMS: CDH1 germline mutation is associated with high penetrance of hereditary diffuse gastric cancer (HDGC). Due to the lack of endoscopically identifiable lesions, routine surveillance is ineffective in the early detection of gastric cancer, and risk-reduction gastrectomy is often recommended. Many academic pathology departments elect to submit the entire gastrectomy specimen for histological examination, which is associated with significantly increased cost, technical and professional time, and turnaround time. METHODS: We present our experience with 5 completely submitted and 2 representatively submitted prophylactic total gastrectomy cases in HDGC patients. RESULTS: Multifocal intramucosal signet ring cell carcinoma was identified in all cases except one, in which only in situ carcinoma was identified. The tumoral foci (2 to 35 per case; average 14.4) were concentrated in proximal stomach. No submucosal invasion or nodal metastases was seen in any case. The final stage was either stage 0 (pTisN0cM0) or stage 1a (pT1aN0cM0). CONCLUSIONS: Our findings are in line with that reported in the literature. Considering that deeply invasive carcinoma is very rare in this situation, and no further treatment is indicated for the vast majority of those patients, complete submission and pathologic examination of the entire stomach provides little additional value for routine clinical management. We propose a two-step approach with targeted submission of the proximal stomach, and subsequent entire submission of the remaining stomach if no intramucosal carcinoma is identified during the initial targeted examination.
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Antígenos CD/genética , Caderinas/genética , Mutação em Linhagem Germinativa/genética , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Gástricas/patologia , Adulto , Carcinoma in Situ/patologia , Carcinoma in Situ/ultraestrutura , Carcinoma de Células em Anel de Sinete/patologia , Carcinoma de Células em Anel de Sinete/ultraestrutura , Feminino , Gastrectomia/métodos , Predisposição Genética para Doença , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Síndromes Neoplásicas Hereditárias/patologia , Estudos Retrospectivos , Comportamento de Redução do Risco , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/ultraestrutura , Estados Unidos/epidemiologiaRESUMO
Although axillary lymphadenopathy is a common clinical encounter, systemic evaluation of non-sentinel lymph node biopsy is sparse. We reviewed our institution's 15-year experience to delineate the spectrum of diagnoses in non-sentinel axillary lymph nodes. 1165 non-sentinel axillary lymph node biopsies were retrieved and the diagnosis and relevant clinical information was reviewed. This spectrum of diagnoses was further stratified by gender, age, and oncologic history. The spectrum of diagnoses included: breast carcinoma (27.6%), lymphoma (29.2%), melanoma (3.5%), other carcinoma (2.9%), sarcoma (0.4%), and benign changes (36.3%). The most common diagnoses in men were lymphoma (61.8%) and benign changes (23.6%); while in women they were benign change (41.2%), breast carcinoma (37.8%) and lymphoma (16.7%). Besides benign changes, lymphoma and breast carcinoma were most common in women younger and older than 30 years, respectively. In patients with a history of malignancy, the most common diagnoses were metastasis from the known tumor and benign change; while in patients with a negative oncologic history and female patients without a history of breast cancer, the diagnosis was generally either lymphoma or benign change. Anaplastic large cell lymphoma was rare but may be mistaken as metastatic carcinoma thus a high index of suspicion is warranted. Thus through retrospective review of a large cohort of non-sentinel axillary lymph node biopsies, we described the spectrum of pathological entities based on the gender, age, and clinical history, which could provide valuable information for further work-up of axillary lymph node biopsy.
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Axila , Excisão de Linfonodo , Linfadenopatia/diagnóstico , Linfadenopatia/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
We aimed to report autopsy findings in patients with acute myeloid leukemia (AML) and non-Hodgkin lymphoma (NHL) in the modern era, and also to focus on lung pathology in the subgroup of patients with acute respiratory failure (ARF) of unknown etiology, which is associated with especially high mortality rates. Charts and autopsy reports of 107 patients (59 AML and 48 NHL) autopsied between 2003 and 2018 were reviewed. More than 50% of patients had missed major diagnoses found at autopsy with 95% of lungs displaying abnormal findings. Malignant infiltration in at least one organ was observed in about 70% of patients with either no complete remission or relapse at the time of death (n = 92) versus 20% in patients without signs of active malignancy (n = 15) (p = 0.001). In patients with ARF of unknown etiology (n = 59), the proportion of malignant lung infiltration was 27% and equilibrated with bacterial pneumonias (29%), fungal pneumonias represented 8%, and isolated alveolar damage or pulmonary edema were the only findings in 32% of patients. Overall, 85% of patients with ARF of unknown etiology had either relapsed or not achieved remission at time of death and 80% of patients with malignant lung infiltration had ARF of unknown etiology. Ninety percent of malignant infiltration and fungal infections were observed in patients with no complete remission or relapse. Autopsy remains valuable in AML and NHL patients; besides infections, malignant infiltration is a significant contributor to ARF of unknown etiology and is rarely diagnosed ante mortem.
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Leucemia Mieloide Aguda/patologia , Pulmão/patologia , Linfoma não Hodgkin/patologia , Insuficiência Respiratória/patologia , Doença Aguda , Adulto , Idoso , Autopsia , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/etiologia , Estudos RetrospectivosRESUMO
CONTEXT: Core biopsy (CB) is a main tool for diagnosis of liver mass lesions. When CB is performed with fine needle aspiration (FNA), the CB may be interpreted by a cytopathologist or gastrointestinal pathologist. OBJECTIVE: This study compares interpretation of liver mass biopsy between cytopathologist and gastrointestinal pathologist in the era of subspecialty practice. DESIGN: 349 liver mass lesions with FNA and CB performed during a 5-year period were retrieved. All cases were initially interpreted by a cytopathologist and retrospectively reviewed by a gastrointestinal pathologist. RESULTS: The overall agreement was 95.1% (332/349 cases). There was agreement on 57/65 non-neoplastic cases (87.7%) with 8 (12.3%) discordant cases including 4 steatosis (steatohepatitis missed in 3 cases, 1 re-interpreted as focal nodular hyperplasia [FNH]); 3 inflammation (1 necrotizing granulomatous inflammation, 1 massive necrosis instead of fibrosing cholestatic hepatitis, and 1 hepatocellular carcinoma [HCC] was missed); and 1 initially deemed normal re-interpreted as FNH. There was agreement on 275/284 neoplastic cases (96.8%), with 9 (3.2%) discordant cases including: 2 initially interpreted as HCC (1 metastatic adrenal cortical carcinoma, 1 cholangiocarcinoma); 3 adenocarcinomas (2 further defined as prostatic primary, 1 well-differentiated neuroendocrine tumor [WDNET]); 2 metastatic carcinomas (1 tumor-induced fibrosis instead of cirrhosis, 1 LCNEC re-interpreted as WDNET); 1 poorly differentiated carcinoma (re-interpreted as LCNEC); and 1 sarcomatoid carcinoma (re-interpreted as leiomyosarcoma). CONCLUSION: Cytopathologist and gastrointestinal pathologist are highly concordant in the interpretation of neoplastic liver mass CB. Consultation may improve accuracy in certain non-neoplastic biopsies and neuroendocrine neoplasms.
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Adenocarcinoma/patologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia com Agulha de Grande Calibre , Feminino , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Patologistas , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The expression profile of immunohistochemical markers of origin in poorly differentiated neuroendocrine carcinoma (PDNEC) is not well studied. MATERIALS AND METHODS: Seventy-four PDNECs from gastroenteropancreatic (GEP) organs and the lung, including 48 large cell NEC (LCNEC) and 26 small cell carcinomas (SmCC), were subject to immunohistochemical staining for CDX2, TTF1 and ISL1. The staining intensity (1 to 3) and percentage of positive tumor cells [0 (negative), 1 (<50%) and 2 (≥50%)] were assessed. The multiplicative index (maximum 6) was calculated and the average total score (aTS) was determined for each primary site and histologic subtype. RESULTS: In the 38 GEP and 36 lung PDNECs, CDX2, TTF1 and ISL1 staining was observed in 71% (aTS 2.8), 16% (aTS 0.4), 63% (aTS 1.9), and 22% (aTS 0.6), 72% (aTS 2.9) and 92% (aTS 3.8), respectively. GEP PDNECs showed a higher aTS for CDX2 and lower aTS for TTF1 and ISL1, compared to that of lung PDNECs (Student's t-test, pâ¯<â¯0.001). SmCC had a higher aTS for TTF1 and ISL1 (pâ¯<â¯0.001) and lower aTS for CDX2 (pâ¯<â¯0.002) than that of LCNEC. CONCLUSIONS: CDX2 and TTF1 demonstrate potential utility in suggesting the primary site of PDNEC. In addition, CDX2 may be useful in supporting the diagnosis of LCNEC in cases with overlapping or borderline morphology. Utility of ISL1 as an adjunctive diagnostic marker of SmCC remains to be studied.
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Biomarcadores Tumorais/análise , Fator de Transcrição CDX2/biossíntese , Carcinoma Neuroendócrino/diagnóstico , Proteínas de Ligação a DNA/biossíntese , Proteínas com Homeodomínio LIM/biossíntese , Fatores de Transcrição/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Neuroendócrino/patologia , Feminino , Humanos , Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologiaRESUMO
We previously found loss of forkhead box A1 (FOXA1) expression to be associated with aggressive urothelial carcinoma of the bladder, as well as increased tumor proliferation and invasion. These initial findings were substantiated by The Cancer Genome Atlas, which identified FOXA1 mutations in a subset of bladder cancers. However, the prognostic significance of FOXA1 inactivation and the effect of FOXA1 loss on urothelial differentiation remain unknown. Application of a univariate analysis (log-rank) and a multivariate Cox proportional hazards regression model revealed that loss of FOXA1 expression is an independent predictor of decreased overall survival. An ubiquitin Cre-driven system ablating Foxa1 expression in urothelium of adult mice resulted in sex-specific histologic alterations, with male mice developing urothelial hyperplasia and female mice developing keratinizing squamous metaplasia. Microarray analysis confirmed these findings and revealed a significant increase in cytokeratin 14 expression in the urothelium of the female Foxa1 knockout mouse and an increase in the expression of a number of genes normally associated with keratinocyte differentiation. IHC confirmed increased cytokeratin 14 expression in female bladders and additionally revealed enrichment of cytokeratin 14-positive basal cells in the hyperplastic urothelial mucosa in male Foxa1 knockout mice. Analysis of human tumor specimens confirmed a significant relationship between loss of FOXA1 and increased cytokeratin 14 expression.
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Carcinoma de Células de Transição/patologia , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia , Idoso , Animais , Biomarcadores Tumorais/metabolismo , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/mortalidade , Diferenciação Celular/fisiologia , Modelos Animais de Doenças , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Queratina-14 , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Modelos de Riscos Proporcionais , Caracteres Sexuais , Análise Serial de Tecidos , Transcriptoma , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
Autoimmune pancreatitis (AIP) is a rare cause of chronic pancreatitis that poses a diagnostic challenge to the clinician in that it mimics pancreatic cancer and presents with painless obstructive jaundice. In this review, we discuss the two types of AIP: type 1, known as lymphoplasmacytic sclerosing pancreatitis and type 2, known as idiopathic duct centric pancreatitis. Type 1 AIP is considered as a pancreatic manifestation of immunoglobulin G4-related disease. The etiopathogenesis of AIP, particularly type 2 AIP, is largely unknown. Both types of AIP have unique pancreatic histological features; however, the radiological and clinical features may mimic those of pancreatic cancer. The most commonly used diagnostic criteria, including the Japan Pancreas Society criteria, the Mayo Clinic HISORt (histology, imaging serology, other organ involvement, and response to therapy) criteria, and the International Association of Pancreatology's international consensus diagnostic criteria, that help to differentiate AIP from pancreatic cancer are reviewed in this article. The treatment of choice for induction of remission for AIP is steroid therapy. Relapses are more common in type 1 AIP. In selected patients, immunomodulators such as azathioprine and rituximab are used to maintain remission.
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Doenças Autoimunes/diagnóstico , Pancreatite/diagnóstico , Algoritmos , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Diagnóstico Diferencial , Humanos , Fatores Imunológicos/uso terapêutico , Neoplasias Pancreáticas/diagnóstico , Pancreatite/tratamento farmacológico , Pancreatite/imunologia , Pancreatite/patologia , Prognóstico , Indução de Remissão , Rituximab/uso terapêuticoRESUMO
AIMS: Current guidelines offer limited strategies for managing recurrent/persistent oesophageal adenocarcinoma (EAC). Salvage endoscopic mucosal/submucosal resection (ER) shows promise in oesophageal squamous cell carcinoma, however its success in EAC is limited. We aimed to elucidate histological characteristics influencing salvage ER success in patients with low-stage, pretreated EAC. METHODS: We retrospectively reviewed 272 EAC tumours postoesophagectomy from five US centres and collected clinicopathological data including discontinuous growth (DG), defined as separate tumour foci ≥2 mm from the main tumour. We selected 101 patients with low-stage disease and divided them into treatment-naïve (n=70) and neoadjuvant therapy (n=31) groups. We compared the two groups and differences in clinical, histological and outcome characteristics were identified. RESULTS: In the entire cohort (n=272), DGs were identified in 22% of cases. Multivariate analysis revealed DGs as an independent prognostic factor for recurrence and positive oesophagectomy margins. Lymphovascular invasion (LVI) and background intestinal metaplasia predicted DG presence and absence, respectively. Compared with the treatment-naïve low T-stage subgroup, the pretreated subgroup exhibited higher incidence of poorly differentiated carcinoma (16% vs 46%, p=0.007), larger tumours (14 vs 30 mm, p<0.001), higher tumour, node, metastases stage (7% vs 30%, p=0.004), more nodal disease (7% vs 36%, p<0.001) and frequent DGs (1% vs 13%, p=0.030). CONCLUSIONS: In treated low T-stage EACs, DGs may contribute to suboptimal outcomes following salvage ER. Presence of LVI (as a surrogate for DGs) and poor differentiation in the absence of intestinal metaplasia in biopsy samples may serve as histological poor prognosticators in treated patients with EAC being considered for salvage ER.
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The significance of discontinuous growth (DG) of the tumor to include tumor deposits and intramural metastasis in esophageal adenocarcinoma (EAC) is unclear. Esophagectomy specimens from 151 treatment-naïve and 121 treated patients with EAC were reviewed. DG was defined as discrete (≥2 mm away) tumor foci identified at the periphery of the main tumor in the submucosa, muscularis propria, and/or periadventitial tissue. Patients' demographics, clinicopathologic parameters, and oncologic outcomes were compared between tumors with DG versus without DG. DGs were identified in 16% of treatment-naïve and 29% of treated cases ( P =0.01). Age, gender, and tumor location were comparable in DG+ and DG- groups. For the treatment-naïve group, DG+ tumors were larger with higher tumor grade and stage and more frequent extranodal extension, lymphovascular/perineural invasion, and positive margin. Patients with treated tumors presented at higher disease stages with higher rates of recurrence and metastasis compared with treatment-naïve patients. In this group, DG was also associated with TNM stage and more frequent lymphovascular/perineural spread and positive margin, but not with tumor size, grade, or extranodal extension. In multivariate analysis, in all patients adjusted for tumor size, lymphovascular involvement, margin, T and N stage, metastasis, neoadjuvant therapy status, treatment year, and DG, DG was found to be an independent adverse predictor of survival outcomes in EAC. DG in EAC is associated with adverse clinicopathologic features and worse patient outcomes. DG should be considered throughout the entire clinicopathologic evaluation of treatment-naïve and treated tumors as well as in future staging systems.
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Adenocarcinoma , Neoplasias Esofágicas , Humanos , Prognóstico , Relevância Clínica , Extensão Extranodal/patologia , Neoplasias Esofágicas/cirurgia , Adenocarcinoma/patologia , Estudos Retrospectivos , Estadiamento de NeoplasiasRESUMO
The digestive organs contain a large number of neuroendocrine cells as part of the diffuse neuroendocrine system. Neuroendocrine tumors can occur in every digestive organ. It has long been recognized that this is a diverse group of tumors with very different clinical outcomes; however, well-recognized prognostic parameters had been elusive until recently. Over the years, there have been several different classification schemes, each with different strengths and weaknesses. In an effort to standardize the classification and grading criteria for gastroenteropancreatic neuroendocrine tumors, the current World Health Organization classification includes a histologic grade based on proliferative rate (mitotic rate and Ki67 index) and a TNM stage that varies from organ to organ. The prognostic value of both the grade and stage has been validated in multiple studies. However, several issues remain, including the lack of standardized methods to assess proliferative rate, potential discrepancies between the mitotic count and the Ki67 index; intratumoral heterogeneity in proliferative rate; and the need for refinement in proliferative cut-points to define the grades. More studies are needed to further improve the classification of neuroendocrine tumors, thus guiding optimal treatment for these tumors.
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Neoplasias Intestinais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , HumanosRESUMO
Preoperative neoadjuvant therapy followed by resection is the mainstay treatment for locally advanced esophageal adenocarcinoma. We recently observed the histology shift from predominant esophageal adenocarcinoma in the biopsy to neuroendocrine neoplasm with or without adenocarcinoma in the post-treatment resection. The underlying mechanism of this finding is uncertain, and there is limited information in the literature. A total of 11 patients were identified: 10 patients received presurgical chemoradiation and 1 with chemotherapy. All biopsies were diagnosed with adenocarcinoma. When neuroendocrine immunomarkers were retrospectively performed on 5 biopsies, 2 showed focal positivity, although the classic neuroendocrine morphology was not readily appreciated. All resections contained neuroendocrine neoplasm, including 8 of well-differentiated type and 3 of neuroendocrine carcinomas. Two post-treatment esophagectomies consisted of neuroendocrine neoplasm only without residual adenocarcinoma. Upon follow-up, 8 patients died of the disease (median survival = 26 months), and 3 patients were alive after a median follow-up of 14 months. The overall median survival time was better than the reported esophageal neuroendocrine carcinoma (15 months). The 5-year observed survival rate was 11.3%, which was lower than the Surveillance, Epidemiology, and End Results 5-year survival rate of adenocarcinoma (21.8%). We reported a small series of esophageal adenocarcinoma that showed histology shift between biopsy and esophagectomy after neoadjuvant therapy. Our limited data suggest that prognosis of this group is different than the conventional adenocarcinoma. Awareness of this morphological change reminds pathologists to examine the biopsy specimens thoroughly, because recognition of neuroendocrine neoplasm, especially high-grade neuroendocrine component, might potentially affect pre- and post-surgical regimens.
RESUMO
Neuroendocrine tumors (NET) encompass a diverse, heterogeneous group of neoplasms that originate from the secretory cells of the neuroendocrine system. These neoplasms typically express the somatostatin receptor (SSTR), which can be targeted by molecular agents for imaging and therapy. This is particularly advantageous for imaging NETs that are indolent, slow-growing, and less well detected by [18F]FDG and for the detection of occult disease not easily identified by anatomic imaging. Herein, we present a case in which [68Ga]DOTATATE PET/CT was used to diagnose the etiology of biochemical recurrence in NET that was not apparent on MRI. The importance of understanding deviations from the normal biodistribution of the radiotracer is emphasized as key in interpreting nuclear medicine studies and establishing the diagnosis. Imaging the SSTR is of particular interest given the recent FDA approval of [68Cu]DOTATATE as a new and possibly more available molecular radiotracer.
RESUMO
Myofibroblastoma is a rare benign mesenchymal tumor first described in the breast. It is also known as mammary-type myofibroblastoma outside of the breast, more frequently located along the embryonic milk line. Exceptionally, myofibroblastoma can occur at visceral locations. We present a case of myofibroblastoma detected incidentally in the liver. A well-circumscribed mass, grossly measuring 6.2â cm in the liver parenchyma, was found on imaging studies. Histologically, the lesion is characterized by benign spindle cells in a hyalinized collagenous stroma, with positive staining for SMA and ER, focal positivity for CD34, negative for desmin, and loss of RB1. This rare tumor at such an unusual location makes it diagnostically challenging, especially on core biopsy of the lesion. To our knowledge, this is the second case of myofibroblastoma in the liver reported in the English literature and the first such case with a detailed pathology description.