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1.
Anticancer Res ; 40(4): 2133-2139, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234906

RESUMO

BACKGROUND/AIM: Metaplastic breast carcinoma (MBC) is a rare malignancy, which is often triple-negative for the hormone receptors and human epidermal growth factor receptor 2, and thus, does not benefit from targeted therapy. In this study, we examined the expression of methylation and demethylation enzymes by immunostaining MBC and the adjacent normal tissues or triple-negative ductal carcinoma (TNDC), and identified alterations that may be used as therapeutic targets. MATERIALS AND METHODS: We retrospectively studied surgical specimens from 15 patients who underwent surgery for MBC at Kanagawa Cancer Center between 2005 and 2016, and similarly from 14 patients with TNDC. The frequencies of high methylation/demethylation enzyme expression were compared among them. RESULTS: The frequencies of high enhancer of zeste homolog 2 (EZH2) and multiple myeloma SET domain (MMSET) expression were significantly higher in both MBC and TNDC than in normal tissue. CONCLUSION: EZH2 and MMSET may be useful therapeutic targets in MBC.


Assuntos
Neoplasias da Mama/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Histona-Lisina N-Metiltransferase/genética , Metaplasia/genética , Proteínas Repressoras/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Metaplasia/diagnóstico , Metaplasia/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Receptor ErbB-2/genética , Receptores Estrogênicos/genética , Receptores de Progesterona/genética
3.
Virchows Arch ; 476(4): 551-559, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31897816

RESUMO

Lymphocytic gastritis (LG) is an uncommon reaction pattern of gastric injury characterized by intraepithelial lymphocytosis of the surface foveolar epithelium and chronic inflammation in the lamina propria. It most commonly occurs in association with gluten-sensitive enteropathy, Helicobacter pylori gastritis, non-steroidal anti-inflammatory drugs, and microscopic colitis. While the topography of LG has been described in gluten-sensitive enteropathy and H. pylori infection, no definite morphologic features have been used to further subcategorize LG based on possible etiologies. Furthermore, new immunotherapy agents have been associated with lymphocytic infiltrate in the gastrointestinal tract, but their association with LG has not been reported. Cases of LG were collected from our institution in the period between August 2011 and September 2017. The topography of LG and morphologic features such as glandular microabscesses, intestinal metaplasia, lymphoid aggregates, surface vs pit distribution of lymphocytes, and number of intraepithelial lymphocytes per 100 epithelial cells were assessed for each case using the updated Sydney System where applicable. Twenty-seven cases of LG were identified in the recent 6-year period at our institution. Gluten-sensitive enteropathy is the main reported cause of LG followed by NSAID injury. Cases of LG associated with gluten-sensitive enteropathy are antral predominant, those associated with H. pylori are body predominant, and those occurring in the setting of NSAID injury show pangastritis. Glandular microabscesses are observed in all cases of LG associated with H. pylori, and not in the setting of GSE or NSAID injury. In addition, a case of LG associated with melanoma immunotherapy has been identified. Topography and morphology of lymphocytic gastritis may point to the cause of injury, allowing for proper treatment of the underlying disease.


Assuntos
Gastrite/etiologia , Gastrite/patologia , Infecções por Helicobacter/patologia , Linfocitose/patologia , Biópsia/métodos , Doença Celíaca/patologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/diagnóstico , Infecções por Helicobacter/complicações , Helicobacter pylori/patogenicidade , Humanos , Metaplasia/patologia
8.
Arq Bras Cir Dig ; 32(4): e1480, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31859933

RESUMO

BACKGROUND: The presence of intestinal metaplasia in the distal esophagus (Barrett's esophagus) is an important precursor of adenocarcinoma. Knowledge of the risk factors and the process by which the Barrett develops is very important and Helicobacter pylori (HP) can contribute to this development. AIM: To analyze the impact of HP in the gastric mucosa with intestinal metaplasia in the distal esophagus in areas of columnar epithelialization smaller than 10 mm in length and epidemiological data on prevalence. METHOD: A retrospective study in which were included 373 consecutive patients diagnosed with columnar epithelium in the distal esophagus was done. In all, HP was investigated by urease and histology, exclusion and inclusion factors were applied and patients were divided into two groups: the first grouping the ones without histological diagnosis of Barrett's esophagus (235-63%) and the second with it (138-37%). RESULTS: There was no significant difference between HP and non-HP patients in relation to the probability of having intestinal metaplasia (p=0.587). When related to the general group, there was an inverse association between the bacterium and the columnar epithelia in the distal esophagus. Age (p=0.031), gender (p=0.013) and HP (p=0.613) when related together to intestinal metaplasia showed no significant relation. In isolation, when related to age and gender, regardless of HP, results confirmed that patients in more advanced age and women present a higher incidence of intestinal metaplasia. CONCLUSION: There is an inverse relation between HP and the areas of columnar epithelization in the distal esophagus, regardless of the presence or absence of intestinal metaplasia. Age and gender, regardless of HP, showed higher prevalence in women and in older the number of cases with intestinal metaplasia in the distal esophagus.


Assuntos
Esôfago de Barrett/patologia , Epitélio/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori , Adulto , Fatores Etários , Idoso , Esôfago de Barrett/microbiologia , Epitélio/microbiologia , Feminino , Humanos , Masculino , Metaplasia/microbiologia , Metaplasia/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais
10.
World J Gastroenterol ; 25(30): 4105-4124, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31435167

RESUMO

Gastric cancer remains the third leading cause of mortality from cancer worldwide and carries a poor prognosis, due largely to late diagnosis. The importance of the interaction between Helicobacter pylori (H. pylori) infection, the main risk factor, and host-related genetic factors has been studied intensively in recent years. The genetic predisposition for non-hereditary gastric cancer is difficult to assess, as neither the real prevalence of premalignant gastric lesions in various populations nor the environmental risk factors for cancer progression are clearly defined. For non-cardiac intestinal-type cancer, identifying the factors that modulate the progression from inflammation toward cancer is crucial in order to develop preventive strategies. The role of cytokines and their gene variants has been questioned in regard to non-self-limiting H. pylori gastritis and its evolution to gastric atrophy and intestinal metaplasia; the literature now includes various and non-conclusive results on this topic. The influence of the majority of cytokine single nucleotide polymorphisms has been investigated for gastric cancer but not for preneoplastic gastric lesions. Among the investigated gene variants onlyIL10T-819C, IL-8-251, IL-18RAP917997, IL-22 rs1179251, IL1-B-511, IL1-B-3954, IL4R-398 and IL1RN were identified as predictors for premalignant gastric lesions risk. One of the most important limiting factors is the inhomogeneity of the studies (e.g., the lack of data on concomitant H. pylori infection, methods used to assess preneoplastic lesions, and source population). Testing the modifying effect of H. pylori infection upon the relationship between cytokine gene variants and premalignant gastric lesions, or even testing the interaction between H. pylori and cytokine gene variants in multivariable models adjusted for potential covariates, could increase generalizability of results.


Assuntos
Citocinas/genética , Mucosa Gástrica/patologia , Infecções por Helicobacter/epidemiologia , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologia , Atrofia/epidemiologia , Atrofia/etiologia , Atrofia/patologia , Progressão da Doença , Mucosa Gástrica/microbiologia , Predisposição Genética para Doença , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Metaplasia/epidemiologia , Metaplasia/etiologia , Metaplasia/patologia , Polimorfismo de Nucleotídeo Único , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/etiologia , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia
11.
Pathology ; 51(6): 600-604, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31445809

RESUMO

Oncocytic metaplastic lesions of the nasopharynx are rare benign entities which are divided into melanotic and non-melanotic forms. Less than 40 non-melanotic and 30 melanotic cases have been reported in the literature. We present the largest known case series to date of melanotic oncocytic metaplasia and more than 20 cases of non-melanotic oncocytic metaplasia. Clinical, endoscopic, histological and immunohistochemical features were reviewed. Most cases presented in males starting from their late adulthood. Compared to its non-melanotic counterpart, all cases of melanotic oncocytic metaplasia had a smoking history (p=0.041). All cases of melanotic oncocytic metaplasia were negative to melanocytic markers (S100, HMB-45, Melan-A and MiTF). Although no disease-related mortality was recorded, concurrent melanoma and nasopharyngeal carcinoma were seen in two cases.


Assuntos
Melanócitos/patologia , Nasofaringe/patologia , Células Oxífilas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Metaplasia/patologia , Pessoa de Meia-Idade
12.
Acta Gastroenterol Belg ; 82(2): 257-260, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31314185

RESUMO

It has recently been shown that duodenal foveolar gastric metaplasia (FGM) sometimes presents as a polyp. The mechanism by which FGM develops into a polypoid lesion is unknown and it is unclear whether this form of FGM is indistinguishable from other polypoid lesions or whether endoscopists do not recognize it because they are unfamiliar with it. We identified and retrieved archival cases of FGM endoscopically suspicious for adenomatous polyp and examined their pathological, clinical and endoscopic features. Endoscopic features of the 13 identified FGMs presenting as polyps were heterogeneous and overlapping with those of adenomatous polyps. FGM was frequently associated with mucosal and submucosal Brunner's glands, but defining and recognizing hyperplasia of these glands remains difficult. Other pathological features could not explain the development of a polypoid lesion. The endoscopic features of FGM polyps are non-specific, overlapping with those of adenomatous polyps. FGM polyps probably acquire their polypoid aspect due to association with Brunner's gland hyperplasia (BGH), which also arises due to chronic inflammation and damage. Because BGH is ill-defined and difficult to recognize, while FGM is diagnosed easily, this type of polypoid lesions has until now only been recognized based on the presence of FGM, although FGM is most likely a secondary phenomenon and not the primary cause of the polyp.


Assuntos
Glândulas Duodenais/diagnóstico por imagem , Úlcera Duodenal/patologia , Endoscopia do Sistema Digestório , Hamartoma/patologia , Pólipos Intestinais , Metaplasia , Glândulas Duodenais/patologia , Duodenopatias/diagnóstico por imagem , Duodenopatias/patologia , Hamartoma/diagnóstico por imagem , Humanos , Pólipos Intestinais/diagnóstico por imagem , Pólipos Intestinais/patologia , Metaplasia/diagnóstico por imagem , Metaplasia/patologia
13.
Diagn Pathol ; 14(1): 75, 2019 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31299983

RESUMO

BACKGROUND: The bone formation within bladder tumors could be encountered in 3 conditions. These might consist of malignant bone formation in mesenchymal tumors; mixed mesenchymal and epithelial tumors; and epithelial tumors with stromal osseous metaplasia (SOM). This last is relatively rare. According to the English literature, only 12 cases have been reported in primary tumor and 7 in metastatic deposits of bladder primaries. Herein, we presented an additional case. CASE PRESENTATION: An 83-year-old man was admitted 13 years ago for prostatic adenocarcinoma, treated with radical prostatectomy. Biochemical recurrence was detected 2 years after surgery (prostate-specific-antigen (PSA) level: 4.60 ng/mL) and progressively normalized (<1.0 ng/mL) after adjuvant radiotherapy and annual injection of leuprorelin (enantoneR). He was referred after 8 years for hematuria, PSA level having slightly increased (0.60 ng/ml). Cystoscopy showed a nodular growth in the bladder wall, visualized as a calcified tumor on computed tomography (CT) and removed with transurethral resection. Histologically, the tumor consists of a non-muscle-invasive high grade papillary urothelial carcinoma with metaplastic bone within the stroma. Immunohistochemical analysis particularly demonstrated positive expression of respectively CD56 on osteoblasts, and CD68 on osteoclasts. MDM2 and CDK4 were negatives on osteoid and bone tissue. Six courses of Bacillus Calmette-Guerin (BCG) therapy have been administered. Two local recidives have occurred during an 8-month follow-up period after immunotherapy and were treated with six further courses of BCG therapy. At one-month follow-up, the patient was well without remaining symptoms. CONCLUSION: SOM is a rare benign condition whose pathogenesis remains uncompletely defined. Sarcomatoïd carcinoma represents the main differential diagnosis that influences therapeutic procedures. Prognosis depends essentially on the extent of the carcinomatous component .


Assuntos
Carcinoma Papilar/diagnóstico , Metaplasia/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias Urológicas/diagnóstico , Idoso de 80 Anos ou mais , Carcinoma Papilar/patologia , Diagnóstico Diferencial , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Metaplasia/patologia , Prognóstico , Células Estromais/patologia , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias Urológicas/patologia , Urotélio/patologia
14.
Pathol Int ; 69(6): 319-330, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31290583

RESUMO

Barrett's esophagus is considered a precancerous lesion of esophageal adenocarcinoma (EAC). Long-segment Barrett's esophagus, which is generally associated with intestinal metaplasia, has a higher rate of carcinogenesis than short-segment Barrett's esophagus, which is mainly composed of cardiac-type mucosa. However, a large number of cases reportedly develop EAC from the cardiac-type mucosa which has the potential to involve intestinal phenotypes. There is no consensus regarding whether the definition of Barrett's epithelium should include intestinal metaplasia. Basic researches using rodent models have provided information regarding the origins of Barrett's epithelium. Nevertheless, it remains unclear whether differentiated gastric columnar epithelium or stratified esophageal squamous epithelium undergo transdifferentiation into the intestinal-type columnar epithelium, transcommittment into the columnar epithelium, or whether the other pathways exist. Reflux of duodenal fluid including bile acids into the stomach may occur when an individual lies down after eating, which could cause the digestive juices to collect in the fornix of the stomach. N-nitroso-bile acids are produced with nitrites that are secreted from the salivary glands, and bile acids can drive expression of pro-inflammatory cytokines via EGFR or the NF-κB pathway. These steps may contribute significantly to carcinogenesis.


Assuntos
Esôfago de Barrett/patologia , Esôfago/patologia , Refluxo Gastroesofágico/fisiopatologia , Metaplasia/patologia , Esôfago de Barrett/complicações , Carcinogênese/patologia , Humanos , Estômago/patologia
15.
BMC Gastroenterol ; 19(1): 102, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31226941

RESUMO

BACKGROUND: Aryl-hydrocarbon receptor (AhR) is a multiple ligand-activated transcription factor that has important roles in xenobiotic, physiological, or pathological functions. Transgenic mice systemically expressing constitutively-active AhR (CA-AhR) have been created to mimic activated AhR signaling in vivo. However, their detailed histopathological features are unclear. In the present study, we generated CA-AhR-expressing FVB/N mice (FVB-CA-AhR mice) and clarified their phenotypes in detail. METHODS: Male and female FVB-CA-AhR and wild-type mice were histopathologically examined from 6 to 33 weeks of age. RESULTS: Among the systemic organs, only the stomachs in FVB-CA-AhR mice showed pathological changes including cystic structures beneath the serosa; in addition, stomach weights increased with age. Histopathologically, cystic structures and alcian blue-positive metaplasia were observed in the mucosa of the proper gastric glands, and these two histometric parameters were positively correlated. Furthermore, proliferating cells shifted from the isthmus to the base of the glands, and parietal cells decreased. Age-related histopathological changes were clearer in females than in males. Importantly, in FVB-CA-AhR mice, intramucosal cysts developed as extramucosal cysts beneath the serosa, penetrating the lamina muscularis mucosae and the muscularis propria. Their incidence reached 100% in 28-week-old male mice and 33-week-old female mice. Extramucosal cysts contained alcian blue-, Griffonia simplicifolia lectin II-, or trefoil factor 2-positive cells, suggesting a stomach origin for the cysts and spasmolytic polypeptide-expressing metaplasia-like lesions. CONCLUSIONS: Disease onset occurred earlier in FVB-CA-AhR mice than previously reported in C57BL/6-derived CA-AhR mice. Importantly, the histopathological features were partly similar with gastritis cystica profunda in humans and animals. Excessive activation of AhR signaling aggravated abnormalities in the gastric mucosa and were affected by both genetic- and sex-related factors.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Cistos/patologia , Mucosa Gástrica/patologia , Receptores de Hidrocarboneto Arílico/metabolismo , Azul Alciano , Animais , Feminino , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Metaplasia/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fenótipo , Lectinas de Plantas/metabolismo , Transdução de Sinais , Fator Trefoil-2/metabolismo
16.
Diagn Pathol ; 14(1): 61, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31221180

RESUMO

BACKGROUND: Intestinal metaplasia (IM) of the gastric mucosa is classified as complete (Type I) and incomplete IM (Type II and III) subtypes, which showed significantly different risk for developing to gastric adenocarcinoma (GAC). GCRG213, a variant of L1-endonuclease (L1-EN), first identified in our lab, was upregulated in GAC tissue. However, the relationship between GCRG213 and IM subtypes is not clear. Our study explored the association of GCRG213 protein (GCRG213p) with IM subtypes. METHODS: Gastric cancer and/or para-tumor tissue samples were collected from 123 patients who underwent gastrectomy for intestinal type gastric adenocarcinoma. The subtypes of IM were characterized with Alcian blue-periodic acid-Schiff and High Iron Diamine-Alcian blue staining methods. Immunohistochemistry of GCRG213p was performed, and its expression in gastric adenocarcinoma and para-tumor tissue including dysplasia, IM, and normal mucosa were analyzed. RESULTS: GCRG213p was expressed in 48.94% IM, 57.14% dysplasia and 55.32% GAC, respectively. GCRG213p expression was higher in well and moderately differentiated adenocarcinoma (P = 0.037). In IM glands, GCRG213p expressed mainly in the cytoplasm of absorptive enterocytes with defined brush borders, but not in goblet cells. The expression of GCRG213p in type I IM (90.00%) was significantly higher than that in type II (36.36%) and type III (25.00%) (P < 0.001). In normal gastric mucosa, GCRG213p was exclusively positive in the cytoplasm of gastric chief cells. CONCLUSIONS: The expression of GCRG213p in complete IM was significantly higher than in incomplete IM, which implies that GCRG213p may play a role on the developing of IM to adenocarcinoma. GCRG213p was exclusively expressed in chief cells, suggesting that it might be involved in cell differentiation from the chief cells to IM.


Assuntos
Desoxirribonuclease I/metabolismo , Laminas/metabolismo , Metaplasia/patologia , Neoplasias Gástricas/patologia , Estômago/patologia , Mucosa Gástrica/patologia , Humanos , Imuno-Histoquímica/métodos , Mucosa Intestinal/patologia , Metaplasia/metabolismo , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/metabolismo
19.
Indian J Cancer ; 56(2): 124-129, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31062730

RESUMO

BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare disease with incidence of less than 1%. MBC present with a larger tumor size, less number of nodes involved, mostly undifferentiated triple negative tumors. We aimed to determine progression-free and overall survival and reported hospital-based incidence of MBC. MATERIAL AND METHODS: A retrospective closed Cohort study elicited data of 42 patients with MBC from January 2008 to December 2013; followed till August 2016. Kaplan-Meier method was applied to compute overall and progression-free survival analysis. Cox Proportional hazard ratios were computed to assess associations between survival and independent variables. RESULTS: Hospital-based incidence of MBC was 1.92% (42/2187), 95% CI [1.41-2.56]. The median age at tumor diagnosis was 54 years (range, 25-81 years). Thirty-nine (92.9%) patients had Grade III tumor. The most common histopathology was squamous (69%). The median tumor size was 4.5 cm (range, 0.8-17 cm). Nineteen (45.2%) patients had nodal involvement at diagnosis. Four patients (9.5%) had metastatic disease at presentation. Hormone receptors were positive in 19 (45.2%) patients. Her-2 neu receptor was positive in 9 (19%) patients. Sixteen (38.1%) patients had triple negative disease. Neoadjuvant and adjuvant chemotherapy was received by 10 (31.25%) and 19 (45.2%) patients respectively. Both median progression-free and overall survival was 38 months. CONCLUSION: Five-year progression-free and overall survival was 79.5% and 76.3%, respectively. We report better survival outcomes when compared to series described earlier despite our patient population presenting mostly with high grade, large tumors, and half of them exhibiting nodal and hormonal involvement.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Metaplasia/tratamento farmacológico , Prognóstico , Receptor ErbB-2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Estudos de Coortes , Feminino , Humanos , Metaplasia/epidemiologia , Metaplasia/patologia , Metaplasia/terapia , Pessoa de Meia-Idade , Paquistão/epidemiologia , Intervalo Livre de Progressão , Centros de Atenção Terciária , Resultado do Tratamento
20.
Surg Pathol Clin ; 12(2): 315-328, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31097106

RESUMO

In this review, we highlight the benign and premalignant lesions of the endometrium that the pathologist may encounter in daily practice. We begin by detailing our current understanding of excess estrogen in the progression of endometrial neoplasia. We outline the currently accepted terminology to be used when evaluating proliferative endometrial lesions, while highlighting their key features. Attention is then turned to the molecular underpinnings of neoplastic progression and how this can be exploited with immunohistochemical stains when appropriate. Finally, we discuss types of metaplasia and their associations, including so-called papillary proliferations of the endometrium.


Assuntos
Neoplasias do Endométrio/patologia , Lesões Pré-Cancerosas/patologia , Carcinoma in Situ/genética , Carcinoma in Situ/patologia , Progressão da Doença , Hiperplasia Endometrial/genética , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/genética , Endométrio/patologia , Estrogênios/fisiologia , Feminino , Humanos , Metaplasia/patologia , Mutação , Lesões Pré-Cancerosas/genética
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