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Cells rely on antioxidants to survive. The most abundant antioxidant is glutathione (GSH). The synthesis of GSH is non-redundantly controlled by the glutamate-cysteine ligase catalytic subunit (GCLC). GSH imbalance is implicated in many diseases, but the requirement for GSH in adult tissues is unclear. To interrogate this, we have developed a series of in vivo models to induce Gclc deletion in adult animals. We find that GSH is essential to lipid abundance in vivo. GSH levels are highest in liver tissue, which is also a hub for lipid production. While the loss of GSH does not cause liver failure, it decreases lipogenic enzyme expression, circulating triglyceride levels, and fat stores. Mechanistically, we find that GSH promotes lipid abundance by repressing NRF2, a transcription factor induced by oxidative stress. These studies identify GSH as a fulcrum in the liver's balance of redox buffering and triglyceride production.
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Glutamato-Cisteína Ligase , Glutationa , Fígado , Fator 2 Relacionado a NF-E2 , Triglicerídeos , Animais , Glutationa/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fígado/metabolismo , Glutamato-Cisteína Ligase/metabolismo , Glutamato-Cisteína Ligase/genética , Camundongos , Triglicerídeos/metabolismo , Estresse Oxidativo , Masculino , Metabolismo dos Lipídeos , Camundongos Knockout , Camundongos Endogâmicos C57BL , Oxirredução , Lipogênese/genéticaRESUMO
The SWItch/Sucrose Non-Fermentable (SWI/SNF) complex is a multimeric protein involved in transcription regulation and DNA damage repair. SWI/SNF complex abnormalities are observed in approximately 14-34 % of pancreatic ductal adenocarcinomas (PDACs). Herein, we evaluated the immunohistochemical expression of a subset of the SWI/SNF complex proteins (ARID1A, SMARCA4/BRG1, SMARCA2/BRM, and SMARCB1/INI1) within our PDAC tissue microarray to determine whether SWI/SNF loss is associated with any clinicopathologic features or patient survival in PDAC. In our cohort, 13 of 353 (3.7 %) PDACs showed deficient SWI/SNF complex expression, which included 11 (3.1 %) with ARID1A loss, 1 (0.3 %) with SMARCA4/BRG1 loss, and 1 (0.3 %) with SMARCA2/BRM loss. All cases were SMARCB1/INI1 proficient. The SWI/SNF-deficient PDACs were more frequently identified in older patients with a mean age of 71.6 years (SD = 7.78) compared to the SWI/SNF-proficient PDACs which occurred at a mean age of 65.2 years (SD = 10.95) (P = 0.013). The SWI/SNF-deficient PDACs were associated with higher histologic grade, compared to the SWI/SNF-proficient PDACs (P = 0.029). No other significant clinicopathologic differences were noted between SWI/SNF-deficient and SWI/SNF-proficient PDACs. On follow-up, no significant differences were seen for overall survival and progression-free survival between SWI/SNF-deficient and SWI/SNF-proficient PDACs (both with P > 0.05). In summary, SWI/SNF-deficient PDACs most frequently demonstrate ARID1A loss. SWI/SNF-deficient PDACs are associated with older age and higher histologic grade. No other significant associations among other clinicopathologic parameters were seen in SWI/SNF-deficient PDACs including survival.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Idoso , Montagem e Desmontagem da Cromatina , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/genética , DNA Helicases , Proteínas Nucleares , Fatores de TranscriçãoRESUMO
Undifferentiated carcinomas are highly aggressive tumors with a dismal prognosis. A subset of these tumors has been associated with inactivation or mutations of the Switch/Sucrose Nonfermenting (SWI/SNF) remodeling complex. Our understanding of the relationship between the clinicopathological features and molecular profiling of SWI/SNF-deficient undifferentiated carcinoma is still evolving due to its rarity. We herein present a rare tumor of undifferentiated carcinoma with SMARCB1/INI1 deficiency arising from the colon. The histology revealed a tumor composed of sheets of discohesive, high-grade epithelioid cells with rhabdoid morphology along with anaplastic giant cells. Additionally, there was a significant infiltration of inflammatory cells in the background. Immunohistochemical (IHC) analysis supported the diagnosis of carcinoma with loss of INI1 expression, the tumor was mismatch repair protein proficient. Molecular analysis demonstrated an oncogenic KRAS mutation (p.G12D), whereas it was wild-type BRAF, and wild-type NRAS. The diagnosis of SWI/SNF-deficient undifferentiated carcinoma can be challenging. Correlation with clinical findings, in conjunction with IHC work-up and molecular analysis, is of utmost importance to arrive at the appropriate diagnosis and exclude potential mimics.
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OBJECTIVES: Lobular capillary hemangioma (LCH) rarely involves the gastrointestinal (GI) tract. This study describes clinicopathologic features of LCH in a cohort of GI cases. METHODS: We defined lobular capillary hemangioma as "a proliferation of capillary-sized blood vessels arranged at least focally in a lobular configuration," searched departmental archives for cases, and recorded clinicopathologic findings. RESULTS: We identified 34 GI tract LCHs from 16 men and 10 women; 4 patients had multiple lesions. Mean age was 64 years. Cases arose in the esophagus (n = 7), stomach (n = 3), small bowel (n = 7), and colorectum (n = 17). Twelve patients had anemia or rectal bleeding. No patients had a known genetic syndrome. The lesions manifested as mucosal polyps, with median size of 1.3 cm. Microscopically, 20 lesions were ulcerated, and most involved the mucosa, with 9 extending into the submucosa. Vessel dilation was present in 27 patients, endothelial hobnailing in 13, hemorrhage in 13, and focal reactive stromal atypia in 2. Follow-up information was available for 10 patients, none of whom developed same-site recurrence. Six of the 26 cases (23%) were extradepartmental consultations, including 2 of the multifocal cases. CONCLUSIONS: Gastrointestinal tract LCHs often arise as colorectal polyps. They are typically small but can reach a few centimeters in size and can be multifocal.
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Granuloma Piogênico , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Granuloma Piogênico/patologia , Trato Gastrointestinal/patologia , Mucosa/patologia , Esôfago/patologiaRESUMO
Gallbladder neuroendocrine carcinoma is rare, representing ~4% of all primary malignant gallbladder neoplasms. We report the case of a 75-year-old female who presented for radiologic restaging for lung adenocarcinoma diagnosed elsewhere, demonstrating a hypermetabolic gallbladder mass. With concern for a gallbladder primary, radical cholecystectomy followed. Gross showed a 2-cm polypoid fundic mass; microscopically, tumor cells were arranged in sheets, with organoid features and necrosis, variable cytoplasm, vesicular-granular chromatin, prominent nucleoli, frequent mitoses, and apoptotic figures. Immunohistochemically, synaptophysin, chromogranin, CK7, and TTF-1 were positive; Ki67 was 80%. The combined findings were diagnostic of large-cell neuroendocrine carcinoma. Further investigation including outside slide review with additional stains revealed the lung primary to be classified large-cell neuroendocrine carcinoma, thus the gallbladder tumor representing metastasis. Within 4 months, the patient expired with widespread metastases. To our knowledge, this is the first reported case of metastatic lung large-cell neuroendocrine carcinoma to gallbladder in the English literature.
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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
Cells rely on antioxidants to survive. The most abundant antioxidant is glutathione (GSH). The synthesis of GSH is non-redundantly controlled by the glutamate-cysteine ligase catalytic subunit (GCLC). GSH imbalance is implicated in many diseases, but the requirement for GSH in adult tissues is unclear. To interrogate this, we developed a series of in vivo models to induce Gclc deletion in adult animals. We find that GSH is essential to lipid abundance in vivo. GSH levels are reported to be highest in liver tissue, which is also a hub for lipid production. While the loss of GSH did not cause liver failure, it decreased lipogenic enzyme expression, circulating triglyceride levels, and fat stores. Mechanistically, we found that GSH promotes lipid abundance by repressing NRF2, a transcription factor induced by oxidative stress. These studies identify GSH as a fulcrum in the liver's balance of redox buffering and triglyceride production.
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Activating KRAS mutations and functional loss of members of the SWI/SNF complex, including ARID1A, are found together in the primary liver tumor cholangiocarcinoma (CC). How these mutations cooperate to promote CC has not been established. Using murine models of hepatocyte and biliary-specific lineage tracing, we show that Kras and Arid1a mutations drive the formation of CC and tumor precursors from the biliary compartment, which are accelerated by liver inflammation. Using cultured cells, we find that Arid1a loss causes cellular proliferation, escape from cell-cycle control, senescence, and widespread changes in chromatin structure. Notably, we show that the biliary proliferative response elicited by Kras/Arid1a cooperation and tissue injury in CC is caused by failed engagement of the TGF-ß-Smad4 tumor suppressor pathway. We thus identify an ARID1A-TGF-ß-Smad4 axis as essential in limiting the biliary epithelial response to oncogenic insults, while its loss leads to biliary pre-neoplasia and CC.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Animais , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , Camundongos , Mutação/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
CONTEXT.: High-grade appendiceal mucinous neoplasm (HAMN) is a relatively recently introduced term describing a rare epithelial neoplasm of the appendix that demonstrates pushing-type invasion but high-grade cytologic atypia. It remains understudied. OBJECTIVE.: To describe clinicopathologic features of HAMNs. DESIGN.: We identified 35 HAMNs in a multi-institutional retrospective study. Clinical and histologic features were reviewed in all cases, as well as molecular features in 8 cases. RESULTS.: Patients were 57 years of age on average and most commonly presented with abdominal/pelvic pain. Histologically, 57% of the tumors showed widespread high-grade features. Architectural patterns in high-grade areas included flat, undulating, or villous growth, and occasionally micropapillary, cribriform, or multilayered growth. Thirteen cases had intact serosa, and the remaining 22 perforated the serosa, including 7 with peritoneal acellular mucin beyond appendiceal serosa and 10 with grade 2 pseudomyxoma peritonei. Molecular abnormalities included KRAS mutations in 7 cases and TP53 mutations in 4. No tumor confined to the appendix recurred. Two patients without pseudomyxoma peritonei at initial presentation developed pseudomyxoma on follow-up. Among 11 patients who presented with pseudomyxoma peritonei, 5 died of disease and 3 were alive with disease at last follow-up. CONCLUSIONS.: HAMNs have a similar presentation to low-grade appendiceal mucinous neoplasm, and similar stage-based prognosis. When they spread to the peritoneum, they typically produce grade 2 pseudomyxoma peritonei, which may be associated with a worse prognosis than classical grade 1 pseudomyxoma peritonei.
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Neoplasias do Apêndice , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Humanos , Pseudomixoma Peritoneal/patologia , Estudos Retrospectivos , Neoplasias Peritoneais/patologia , Recidiva Local de Neoplasia , Neoplasias do Apêndice/patologiaRESUMO
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. The need for increased patient survival has not been met for PDAC. The addition of mannose to conventional chemotherapy leads to accumulation of mannose metabolite in cancer cells and increases subsequent cell death. This susceptibility to mannose depends on the levels of phosphomannose isomerase (PMI). The cancer cells with lower levels of PMI are more sensitive to mannose than cells with higher levels. In this study, we investigated the association of PMI expression with clinical and pathological features of PDAC cases. METHODS: PMI antibody immunohistochemistry (AbCam) was performed on tissue microarrays from 235 PDAC by a standard protocol on Ventana automated immunostainer. The PMI intensity was graded (0-3) and the proportion of positivity was scored. Correlation of PMI expression with staging and survival was analyzed. RESULTS: Of the 235 cases, 51.5% (n=121) cases demonstrated grade 2 intensity with 90.1% of these (n=109) showing positivity in ≥70% of tumor cells. Ninety-eight (41.7%) cases exhibited grade 3 intensity with 94.9% (n=93) of these cases showing ≥70% reactivity. Sixteen cases (6.8%) were nonreactive (intensity grade 0-1). Intensity of PMI expression was associated with significantly better prognosis as assessed by median survival in months (M): grade 0-1 intensity group: 11.2 M; grade 2 intensity group: 25.2 M; and grade 3 intensity group: 33.2 M (p=0.03). A minority (6.8%) of PDACs show non-high PMI expression with poorer prognosis. DISCUSSION: Mannose may be a particularly useful adjunct with chemotherapy to treat this aggressive subgroup. PMI expression is also a potential biomarker to predict the prognosis of PDAC.
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Pancreatic cystic lesions are difficult to evaluate amid acute pancreatitis. Without previous pancreatic imaging, it is challenging to discern between pancreatic acute fluid collections and cystic neoplasms. We present a 29-year-old woman with acute pancreatitis and initial cross-sectional imaging suggesting a 2.8-cm cystic lesion in the body/tail of the pancreas. Endoscopic ultrasound completed 5 weeks after index presentation revealed findings worrisome for a cystic neoplasm, but fine-needle aspiration findings suggested lesion to be a pseudocyst (normal carcinoembryonic antigen and cytology, negative mucin stain).
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BACKGROUND: Small cell neuroendocrine carcinoma of the prostate (SCNECP) is a rare, aggressive subtype of prostate carcinoma. Most SCNECP arise from conventional prostate adenocarcinoma (CPAC) treated with androgen deprivation therapy (ADT). CASE PRESENTATIONS: We identified four cases of CPAC treated with ADT, which evolved to SCNECP with liver metastasis. The average interval between the diagnosis of CPAC and SCNECP was 102 months (range: 12 to 168). Histologically, the tumors showed nests of cells with high nuclear:cytoplasmic ratios, granular chromatin, and frequent mitoses. All cases were synaptophysin, chromogranin, and AE1/AE3 positive, with a Ki-67 labeling index ≥70%. NKX3.1 was negative in all but one case and TTF-1 was positive in half. Weak ERG positivity by IHC was seen in one case which also demonstrated the TMPRSS2-ERG gene rearrangement; all other cases were negative for ERG by IHC. Serum prostate specific antigen (PSA) levels were normal to near-normal in all. The median interval between the diagnosis of SCNECP and death was 3.25 months (range: 0.75 to 26). CONCLUSIONS: Our case series highlights the importance of considering a prostate primary, even in the setting of normal PSA levels and loss of prostate markers, when diagnosing neuroendocrine carcinoma in the liver. Further, we emphasize the significance of diagnosing SCNECP that metastasizes to the liver, as it portends a particularly dismal prognosis.
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Carcinoma Neuroendócrino/secundário , Carcinoma de Células Pequenas/secundário , Transformação Celular Neoplásica/patologia , Neoplasias Hepáticas/secundário , Neoplasias da Próstata/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Idoso , Antagonistas de Androgênios/uso terapêutico , Humanos , MasculinoRESUMO
Tumor budding (TB) has been shown to be an adverse prognostic factor in several gastrointestinal malignancies, most notably colorectal carcinoma (CRC). TB has undergone some evaluation in Eastern cohorts of cholangiocarcinoma (CC), and we undertook this study to evaluate whether TB in CC was linked to other clinicopathologic factors or to outcome in a Western cohort. We evaluated 112 cases of CC for age, sex, margin status, location, size, grade, lymphovascular invasion (LVI), perineural invasion (PNI), subtype (large or small duct), staging parameters, recurrence-free survival, disease-specific survival (DSS), and TB. Budding was scored using International Tumor Budding Consensus Conference recommendations for CRC: The highest tumor bud count at the invasive tumor front in a 0.785 mm2 area was recorded and stratified into Bd1 (0-4 buds), Bd2 (5-9 buds), and Bd3 (≥10 buds). Our cohort included 54 (48%) extrahepatic CCs and 58 (52%) intrahepatic CCs. TB was more commonly seen in the settings of higher-grade lesions, males, extrahepatic CC, PNI, LVI, and positive resection margin (all P ≤ 0.021). In multivariate analysis, worse DSS was correlated with budding score Bd2/Bd3 (hazard ratio [HR] 2.6687, 95% confidence interval [CI] 1.585-5.217, P = 0.001) and with nodal disease (HR 2.876, 95% CI 1.585-5.217, P = 0.001). TB is associated with higher-grade disease in CC, and increased TB is associated with poor disease-specific survival. Our findings support the notion that TB may serve as useful information for clinicians with respect to patient prognosis in CC, as in CRC.
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Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Colangiocarcinoma/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
PURPOSE: Although abundant myeloid cell populations in the pancreatic ductal adenocarcinoma (PDAC) microenvironment have been postulated to suppress antitumor immunity, the composition of these populations, their spatial locations, and how they relate to patient outcomes are poorly understood. EXPERIMENTAL DESIGN: To generate spatially resolved tumor and immune cell data at single-cell resolution, we developed two quantitative multiplex immunofluorescence assays to interrogate myeloid cells (CD15, CD14, ARG1, CD33, HLA-DR) and macrophages [CD68, CD163, CD86, IFN regulatory factor 5, MRC1 (CD206)] in the PDAC tumor microenvironment. Spatial point pattern analyses were conducted to assess the degree of colocalization between tumor cells and immune cells. Multivariable-adjusted Cox proportional hazards regression was used to assess associations with patient outcomes. RESULTS: In a multi-institutional cohort of 305 primary PDAC resection specimens, myeloid cells were abundant, enriched within stromal regions, highly heterogeneous across tumors, and differed by somatic genotype. High densities of CD15+ARG1+ immunosuppressive granulocytic cells and M2-polarized macrophages were associated with worse patient survival. Moreover, beyond cell density, closer proximity of M2-polarized macrophages to tumor cells was strongly associated with disease-free survival, revealing the clinical significance and biologic importance of immune cell localization within tumor areas. CONCLUSIONS: A diverse set of myeloid cells are present within the PDAC tumor microenvironment and are distributed heterogeneously across patient tumors. Not only the densities but also the spatial locations of myeloid immune cells are associated with patient outcomes, highlighting the potential role of spatially resolved myeloid cell subtypes as quantitative biomarkers for PDAC prognosis and therapy.
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Carcinoma Ductal Pancreático/imunologia , Células Mieloides/imunologia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Pancreáticas/imunologia , Microambiente Tumoral/imunologia , Idoso , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/prevenção & controle , Pâncreas/imunologia , Pâncreas/patologia , Pâncreas/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
Mesenchymal lesions of the gastrointestinal tract are generally uncommon compared with epithelial derived entities. Angiolipofibroma describes a rare gastrointestinal tract mesenchymal lesion composed of varied amounts of adipose tissue, fibrous tissue, along with admixed blood vessels. Descriptions of this entity are limited to few case reports describing a total of 5 lesions. Angiolipofibroma represents a benign entity that may uncommonly present as a mass lesion concerning for malignancy. The etiology is unclear; however, these may represent a reactive or hamartomatous process. In this article, we sought to further describe this entity and present an additional 11 cases.
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Angiolipoma/patologia , Fibroma/patologia , Neoplasias Intestinais/patologia , Adulto , Idoso , Feminino , Humanos , Pólipos Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Smooth muscle tumors represent the second most common mural mesenchymal neoplasm in the gastrointestinal tract, but established criteria for prognostic assessment of these tumors are lacking. A large cohort of surgically resected intramural gastrointestinal smooth muscle tumors from 31 institutions was analyzed to identify potential prognostic features. Pathologic features were assessed by expert gastrointestinal and/or soft tissue pathologists at each center. Immunohistochemical confirmation was required. A total of 407 cases from the esophagus (n = 97, 24%), stomach (n = 180, 44%), small bowel (n = 74, 18%), and colorectum (n = 56, 14%) were identified. Patients ranged in age from 19 to 92 years (mean 55 years), with a slight female predominance (57%). Mean tumor size was 5.4 cm, with the largest tumor measuring 29 cm. Disease progression following surgery, defined as local recurrence, metastasis, or disease-related death, occurred in 56 patients (14%). Colorectal tumors were most likely to progress, followed by small bowel and gastric tumors. None of the esophageal tumors in this series progressed. Receiver operator characteristic analysis identified optimal cutoffs of 9.8 cm and 3 mitoses/5 mm2 for discriminating between progressive and non-progressive tumors. Histologic features strongly associated with progression by univariate analysis included moderate-to-severe atypia, high cellularity, abnormal differentiation (defined as differentiation not closely resembling that of normal smooth muscle), tumor necrosis, mucosal ulceration, lamina propria involvement, and serosal involvement (P < 0.0001 for all features). Age, sex, and margin status were not significantly associated with progression (P = 0.23, 0.82, and 0.07, respectively). A risk assessment table was created based on tumor site, size, and mitotic count, and Kaplan-Meier plots of progression-free survival for each subgroup revealed progression-based tiers. Based on our findings, it appears that nonesophageal gastrointestinal smooth muscle tumors measuring >10 cm and/or showing ≥3 mitoses/5 mm2 may behave aggressively, and therefore close clinical follow-up is recommended in these cases.
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Neoplasias Gastrointestinais/patologia , Tumor de Músculo Liso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de ProgressãoRESUMO
Worldwide, primary liver cancer is the fourth leading cause of cancer mortality. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Sarcomatoid hepatocellular carcinoma (SHC) is a rare subtype of HCC with conventional HCC admixed with areas with sarcomatoid morphology. SHC is an aggressive, rapidly growing tumor with unfavorable prognosis. Pedunculated SHC is an uncommon presentation of SHC. Due to its rarity, much remains unknown about the etiopathogenesis, molecular underpinnings, and treatment of SHC. We present a case of an exophytic SHC arising in a background of cirrhosis in an older adult. A resection was performed, but the patient subsequently developed multiple additional intrahepatic metastatic lesions necessitating further treatment with chemotherapy.
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GATA3 is a transcription factor involved in the development and differentiation of lymphocytes, breast, and hair follicles. The protein is a useful immunohistochemical (IHC) marker for supporting diagnoses of breast or urothelial carcinoma. This can be especially helpful in metastatic neoplasms to help delineate site of origin. GATA3 is also reportedly positive in a percentage of pancreatic ductal adenocarcinomas (PDACs) and cholangiocarcinomas (CCs), but no study has closely evaluated this relationship with respect to clininopathologic features or patient outcome. Using tissue microarrays, we analyzed 240 PDACs and 60 CCs with GATA3 IHC and compared expression to various clinical and pathologic parameters. Overall, GATA3 positivity was seen in 16% of PDACs and 5% of CCs. GATA3 positivity in PDAC cases was more common in male patients (P=0.013). GATA3-positive PDACs trended toward worse survival on multivariate analysis (P=0.074). The only 3 GATA3-positive CCs were poorly differentiated (P=0.069); low case number precluded multivariate survival analysis for CCs. GATA3 positivity can occur in carcinomas of the pancreatobiliary system, which should be considered during IHC workup of neoplasms of unclear origin. This positivity seems to have minimal relevance to patient outcome.
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Neoplasias dos Ductos Biliares/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Diferenciação Celular , Colangiocarcinoma/metabolismo , Fator de Transcrição GATA3/metabolismo , Neoplasias Pancreáticas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma Ductal Pancreático/mortalidade , Colangiocarcinoma/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Pancreáticas/mortalidadeRESUMO
Hepatic artery thrombosis (HAT) following orthotopic liver transplantation (OLT) can cause hepatic parenchymal necrosis and ischemic cholangiopathy. This study investigates additional histologic features that may suggest HAT in post-OLT liver specimens. For 94 liver specimens (explanted allografts and biopsies) from patients with a clinical or pathologic diagnosis of HAT, we recorded length of time between OLT and procedure, categorizing cases into early HAT (;≤30â¯days since OLT) and late HAT (>30â¯days since OLT). Common histologic findings in HAT included lobular necrosis (60 cases, 64%), portal inflammation (68 cases, 72%), ductular reaction (73 cases, 78%), lobular cholestasis (70 cases, 74%), and bile-tinged macrophages (40 cases, 43%). Ductular cholestasis was seen in 30 cases (32%); 10 of those patients were clinically septic. Bile in veins was seen in 16 (17%) cases and arteritis in 6 (6%) cases. Findings more common in resection than biopsy specimens included lobular necrosis (Pâ¯<â¯.0001), hemorrhage (Pâ¯=â¯.0044), ductular cholestasis (Pâ¯=â¯.0003), and bile-tinged macrophages (Pâ¯<â¯.0001). Lobular necrosis was more common in early HAT (Pâ¯=â¯.0002), and ductular reaction (Pâ¯=â¯.006) and bile in veins (Pâ¯=â¯.03) were more common in late HAT. Histologic changes in HAT vary based on specimen type and whether HAT is early or late. In late HAT, biliary injury might occur after a prolonged period of ischemia, with subsequent bile duct necrosis, bile in veins, and remodeling (eg, ductular reaction). Bile in veins is an unusual finding that may occur in HAT, although it can be seen in bile infarcts from other causes.
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Artéria Hepática/patologia , Falência Hepática/cirurgia , Transplante de Fígado/efeitos adversos , Fígado/patologia , Complicações Pós-Operatórias/patologia , Trombose/patologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Colestase/etiologia , Colestase/patologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Trombose/etiologia , Adulto JovemRESUMO
Vascular abnormalities and lesions of the small bowel and colon are rare. A florid vascular proliferation (FVP) associated with colon obstruction and intussusception has been described and can mimic malignant vascular tumors such as angiosarcoma. In this article, we report a case of colonic FVP associated with colon obstruction, a case of small bowel FVP associated with a Meckel's diverticulum, and a case of small bowel FVP with intussusception. All cases occurred in older adults (mean 73 years of age, range 62-80 years of age). FVP grossly appeared as a mass-like lesion in one small bowel case, while the other cases did not demonstrate a grossly identifiable mass. Histologically, all cases demonstrated a transmural vascular proliferation with plump endothelial cells. No significant cytologic atypia was seen, and mitotic figures were rare. No recurrence was seen in all cases with an average follow-up of 22 months. It is important to be aware of this entity as it appears to be a nonneoplastic reactive process, unlike some of its histologic mimics.