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1.
Nihon Shokakibyo Gakkai Zasshi ; 120(1): 80-86, 2023.
Artigo em Japonês | MEDLINE | ID: mdl-36631120

RESUMO

Pancreatic adenosquamous carcinoma is a rare primary pancreas malignant tumor with very poor prognosis, for which there is no standard treatment. The case was of a 71-year-old woman who was admitted to the hospital with jaundice. A pancreatic head tumor was found, and pancreatic adenosquamous carcinoma was diagnosed in EUS-FNA. Despite confirmed distant metastasis, a multidisciplinary treatment centered on chemoradiotherapy gave her a 28-month prognosis.


Assuntos
Carcinoma Adenoescamoso , Neoplasias Pancreáticas , Humanos , Feminino , Idoso , Carcinoma Adenoescamoso/terapia , Carcinoma Adenoescamoso/tratamento farmacológico , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/terapia , Pâncreas , Quimiorradioterapia
2.
J Med Case Rep ; 16(1): 395, 2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36309754

RESUMO

BACKGROUND: Among the total reported cases of pancreatic duct adenocarcinomas, around 1-2.9% are adenosquamous carcinomas of the pancreas. Due to limited data, preoperative diagnosis is a great challenge for physicians, and it is usually set post-operational, based on the pathologist report. We operated on two cases of adenosquamous carcinoma of the pancreas, which we present alongside the operation and treatment planning. CASE REPORT: A 69-year-old Caucasian female and a 63-year-old Caucasian male presented themselves with jaundice in our department. The abdomen computed tomography and magnetic resonance imaging scans revealed lesions of the pancreas. A pancreas-duodenumectomy was performed in both patients, and the post-operational histology analysis revealed adenosquamous carcinoma of the pancreas head. The patients were discharged in good condition and received further chemotherapy treatment after surgery. CONCLUSIONS: Two case reports of adenosquamous carcinoma of the pancreas are described here, which both underwent surgery resection. The limited available literature on this topic substantially limits the knowledge and guidance on treatment. A summarization of the available literature is attempted, alongside a description of possible fields of future research.


Assuntos
Carcinoma Adenoescamoso , Neoplasias Pancreáticas , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Carcinoma Adenoescamoso/diagnóstico por imagem , Carcinoma Adenoescamoso/cirurgia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia , Pâncreas/patologia , Tomografia Computadorizada por Raios X , Abdome
3.
J Biomed Sci ; 29(1): 80, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36224625

RESUMO

BACKGROUND: Human Papillomavirus type 18 (HPV18) is a high-risk HPV that is commonly associated with cervical cancer. HPV18 oncogenes E6 and E7 are associated with the malignant transformation of cells, thus the identification of human leukocyte antigen (HLA)-restricted E6/E7 peptide-specific CD8 + T cell epitopes and the creation of a HPV18 E6/E7 expressing cervicovaginal tumor in HLA-A2 transgenic mice will be significant for vaccine development. METHODS: In the below study, we characterized various human HLA class I-restricted HPV18 E6 and E7-specific CD8 + T cells mediated immune responses in HLA class I transgenic mice using DNA vaccines encoding HPV18E6 and HPV18E7. We then confirmed HLA-restricted E6/E7 specific CD8 + T cell epitopes using splenocytes from vaccinated mice stimulated with HPV18E6/E7 peptides. Furthermore, we used oncogenic DNA plasmids encoding HPV18E7E6(delD70), luciferase, cMyc, and AKT to create a spontaneous cervicovaginal carcinoma model in HLA-A2 transgenic mice. RESULTS: Therapeutic HPV18 E7 DNA vaccination did not elicit any significant CD8 + T cell response in HLA-A1, HLA-24, HLA-B7, HLA-B44 transgenic or wild type C57BL/6 mice, but it did generate a strong HLA-A2 and HLA-A11 restricted HPV18E7-specific CD8 + T cell immune response. We found that a single deletion of aspartic acid (D) at location 70 in HPV18E6 DNA abolishes the presentation of HPV18 E6 peptide (aa67-75) by murine MHC class I. We found that the DNA vaccine with this mutant HPV18 E6 generated E6-specific CD8 + T cells in HLA-A2. HLA-A11, HLA-A24 and HLA-b40 transgenic mice. Of note, HLA-A2 restricted, HPV18 E7 peptide (aa7-15)- and HPV18 E6 peptide (aa97-105)-specific epitopes are endogenously processed by HPV18 positive Hela-AAD (HLA-A*0201/Dd) cells. Finally, we found that injection of DNA plasmids encoding HPV18E7E6(delD70), AKT, cMyc, and SB100 can result in the development of adenosquamous carcinoma in the cervicovaginal tract of HLA-A2 transgenic mice. CONCLUSIONS: We characterized various human HLA class I-restricted HPV18 E6/E7 peptide specific CD8 + T cell epitopes in human HLA class I transgenic mice. We demonstrated that HPV18 positive Hela cells expressing chimeric HLA-A2 (AAD) do present both HLA-A2-restricted HPV18 E7 (aa7-15)- and HPV18 E6 (aa97-105)-specific CD8 + T cell epitopes. A mutant HPV18E6 that had a single deletion at location 70 obliterates the E6 presentation by murine MHC class I and remains oncogenic. The identification of these human MHC restricted HPV antigen specific epitopes as well as the HPV18E6/E7 expressing adenosquamous cell carcinoma model may have significant future translational potential.


Assuntos
Carcinoma Adenoescamoso , Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Vacinas de DNA , Animais , Ácido Aspártico , Linfócitos T CD8-Positivos , Carcinoma Adenoescamoso/complicações , Epitopos de Linfócito T/genética , Feminino , Antígenos HLA-A , Antígeno HLA-A1 , Antígeno HLA-A11 , Antígeno HLA-A2/genética , Antígeno HLA-A24 , Antígeno HLA-B40 , Antígeno HLA-B44 , Antígeno HLA-B7 , Células HeLa , Papillomavirus Humano 18 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/complicações , Peptídeos , Proteínas Proto-Oncogênicas c-akt , Linfócitos T Citotóxicos , Vacinas de DNA/genética
4.
Appl Immunohistochem Mol Morphol ; 30(10): 703-712, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36227108

RESUMO

The pathologic characteristics of squamous cell/adenosquamous carcinomas (SC/ASC) have not been well clarified. As a rare subtype of gallbladder cancer (GBC), no biological markers for diagnosis and prognosis are available. This research evaluated the expression of FOXP1 and FOXO3a in 69 SC/ASC, and 146 adenocarcinoma (AC) samples were analyzed via immunohistochemistry. SC/ASCs were associated with higher rates of lymph node metastasis, invasion, and patients older than 45 years comparing to ACs. FOXP1 and FOXO3a positivity rates were significantly lower in SC/ASC and AC samples from patients with large tumor size, a high TNM stage, lymph node metastasis, invasion, and no history of tumor resection (biopsy only). Positive FOXP1 expression levels were significantly decreased in cases of poorly differentiated AC. The univariate Kaplan-Meier analysis revealed that negative FOXP1 and FOXO3a expression, poor differentiation, large tumor size, high TNM stage, lymph node metastasis, invasion, and an inability to undergo curative resection were all closely associated with decreased overall survival in SC/ASC and AC patients. The multivariate cox regression analysis showed that negative FOXP1 and FOXO3a expression levels were independent predictors of poor prognosis in SC/ASC and AC patients. Our results indicate that negative FOXP1 and FOXO3a expression are closely associated with the pathogenesis, clinicopathologic properties, and prognosis of GBC patients. FOXP1 and FOXO3a may thus be biomarkers of GBC carcinogenesis, progression, and prognosis.


Assuntos
Adenocarcinoma , Carcinoma Adenoescamoso , Carcinoma de Células Escamosas , Neoplasias da Vesícula Biliar , Humanos , Adenocarcinoma/patologia , Biomarcadores Tumorais/metabolismo , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/patologia , Células Epiteliais/metabolismo , Fatores de Transcrição Forkhead , Neoplasias da Vesícula Biliar/patologia , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Proteínas Repressoras , Fatores de Transcrição
5.
Pathologica ; 114(4): 332-338, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36136902

RESUMO

Primary adenosquamous carcinoma of the endometrium with glassy cell features (ASCGCF) is an extremely rare entity and to date, 16 cases of this entity have been reported in the literature. ASC-GCF is an aggressive histological subtype of cervical carcinoma with rapid growth and early metastases; however, very little is known about those originating from the endometrium as they are limited to only a few case reports. Herein, we report a case of primary adenosquamous carcinoma of the endometrium with extensive glassy cell features which posed a major diagnostic challenge by mimicking many entities with its histological diversity.


Assuntos
Carcinoma Adenoescamoso , Carcinoma , Neoplasias do Colo do Útero , Carcinoma Adenoescamoso/diagnóstico , Carcinoma Adenoescamoso/patologia , Endométrio/patologia , Feminino , Humanos , Neoplasias do Colo do Útero/patologia
6.
Pancreatology ; 22(8): 1159-1166, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36150984

RESUMO

BACKGROUND/OBJECTIVES: Pancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). The usual treatment for metastatic or recurrent PASC is systemic chemotherapy in accordance with the PDAC treatment strategy. This study aimed to investigate the efficacy of chemotherapy, especially the benefit of recent combination therapies, in patients with metastatic or recurrent PASC. METHODS: We conducted a multicenter retrospective analysis of 116 patients with metastatic or recurrent PASC treated with first-line chemotherapy between April 2001 and December 2017 at 24 Japanese institutions. RESULTS: Combination chemotherapies included gemcitabine + nab-paclitaxel (GnP, n = 28), fluorouracil/leucovorin + irinotecan + oxaliplatin (FFX, n = 10), gemcitabine + S-1 (GS, n = 10), and others (n = 9). Monotherapies included gemcitabine (n = 51) and S-1 (n = 8). The median overall survival (OS) was 6.5, 7.3, and 4.3 months for the whole cohort, the combination therapy group, and the monotherapy group, respectively. Multivariate analysis indicated that combination therapy showed a better trend in OS than monotherapy (hazard ratio = 0.68; 95% confidence interval, 0.38-1.20). GnP or FFX were selected in 58.7% of patients after FFX was approved in Japan, and revealed a median OS, median progression-free survival, and objective response rate of 7.3 months, 2.8 months, and 26.9% in GnP and 7.2 months, 2.3 months, and 20.0% in FFX respectively. CONCLUSIONS: This study suggests that combination therapy may be more effective than monotherapy. GnP and FFX showed similar and clinically meaningful efficacy for patients with metastatic or recurrent PASC.


Assuntos
Carcinoma Adenoescamoso , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Carcinoma Adenoescamoso/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico
7.
Eur J Cancer ; 175: 19-30, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36087394

RESUMO

BACKGROUND: Primary lung carcinoma is an exceptionally rare childhood tumour, as per definition of the European Cooperative Study Group on Paediatric Rare Tumours (EXPeRT), with an incidence of 0.1-0.2/1,000,000 per year. Little is known about the clinical characteristics of children with primary lung carcinoma, a gap which this joint analysis of the EXPeRT group aimed to fill. PATIENTS AND METHODS: We performed a retrospective case series of children (aged 0-18 years) with primary lung carcinoma, as collected through the EXPeRT databases between 2000 and 2021. We recorded relevant clinical characteristics including treatment and outcome. RESULTS: Thirty-eight patients were identified with a median age of 12.8 years at diagnosis (range: 0-17). Mucoepidermoid carcinoma (MEC) was the most frequent entity (n = 20), followed by adenocarcinoma (n = 12), squamous cell carcinoma (n = 4), adenosquamous carcinoma (n = 1) and small-cell lung cancer (n = 1). Patients with MEC presented rarely with lymph node metastases (2/20 cases). Overall, 19/20 patients achieved long-lasting remission by surgical resection only. Patients with other histologies often presented in advanced stages (14/18 TNM stage IV). With multimodal treatment, 3-year overall survival was 52% ± 13%. While all patients with squamous cell carcinoma died, the 12 patients with adenocarcinoma had a 3-year overall survival of 64% ± 15%. CONCLUSIONS: Primary lung carcinomas rarely occur in children. While the outcome of children with MEC is favourable with surgery alone, patients with other histotypes have a poor prognosis, despite aggressive treatment, highlighting the need to develop new strategies for these children, such as mutation-guided treatment.


Assuntos
Adenocarcinoma , Carcinoma Adenoescamoso , Carcinoma Mucoepidermoide , Carcinoma de Células Escamosas , Adenocarcinoma/patologia , Adolescente , Carcinoma Mucoepidermoide/patologia , Carcinoma de Células Escamosas/patologia , Criança , Humanos , Pulmão/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Síndrome
8.
Front Immunol ; 13: 972298, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052088

RESUMO

Pancreatic adenosquamous carcinoma (ASPC) is a rare subtype of pancreatic cancer with lethal malignancy, and few studies have focused on the heterogeneity of ASPC. Here, we performed a single-cell sequencing procedure on pancreatic tumor tissue from an ASPC patient and a patient with high-grade intraductal papillary mucinous neoplasm (IPMN). Through the combined analysis of single-cell sequencing data from five pancreatic ductal adenocarcinoma (PDAC) patients, one IPMN patient, and one ASPC patient in a public database, we identified 11 main types of cells, including macrophages, B cells, cancer stem cells, ductal cells, fibroblasts, endo/stellate cells, neutrophils, acinar cells, T cells, natural killer (NK) cells, dendritic cells, and mast cells. Then, the different characteristics and differentiation paths of the immune microenvironment among IPMN, ASPC, and PDAC in macrophages, T cells, and cancer-associated fibroblasts (CAFs) were identified through multiple bioinformatics analyses. Two novel special cancer-associated fibroblasts were identified as nCAFs and imCAFs. Then, cancer cells in duct cells were identified using the infercnv software. Two ASPC-specific subgroups of cancer cells with squamous cell features were identified. Finally, the identified specific CAFs and cancer cells were mapped to TCGA-PAAD cohort through the cibersoftx software. All of these identified subgroups were calculated to have a significant prognostic value in pancreatic cancer patients. These findings will promote the clinical application of single-cell sequencing data of pancreatic cancer and deepen our understanding of ASPC.


Assuntos
Adenocarcinoma Mucinoso , Carcinoma Adenoescamoso , Carcinoma Ductal Pancreático , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Adenocarcinoma Mucinoso/patologia , Carcinoma Adenoescamoso/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Humanos , Neoplasias Intraductais Pancreáticas/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Prognóstico , Microambiente Tumoral/genética
9.
Front Immunol ; 13: 944812, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36032124

RESUMO

Lung adenosquamous carcinoma (ASC) is an uncommon histological subtype. We aimed to characterize the tumor immune microenvironment (TIME) in lung ASC and estimate patient response to immune checkpoint inhibitors (ICIs), which have never been systematically investigated. In cohort I, we collected 30 ASCs from a single center for analysis of TIME characteristics, including immuno-phenotyping, tumor mutation burden (TMB), T-cell receptor (TCR) repertoires, tumor-infiltrating lymphocytes (TILs), and immune checkpoint expression. Twenty-two (73.3%) patients were EGFR-positive. The TIME was defined by immune-excluded (60%) and immune-desert phenotype (40%). Strikingly, programmed cell death-ligand 1 (PD-L1) and programmed cell death-1 (PD-1) were predominantly expressed in squamous cell carcinoma components (SCCCs) versus adenocarcinoma components (ACCs), where enhanced CD4+ FOXP3+ regulatory T cell and attenuated CD57+ natural killer cell infiltration were present, consistent with a landscape of fewer innate immune cells, more immunosuppressive cells. SCCCs had higher TMB, higher TCR clonality, and lower TCR diversity than ACC. In cohort III, the efficacy of ICI-based therapy was estimated using a real-world data of 46 ASCs from 11 centers. Majority of 46 patients were driver genes negative and unknown mutation status, 18 (39%) and 18 (39%), respectively. The overall objective response rate of 28%, median progression-free survival of 6.0 months (95% confidence interval [CI] 4.3-7.7), and median overall survival of 24.7 months (95% CI 7.2-42.2) were observed in the ICI-based treatment. This work ascertains suppressive TIME in lung ASC and genetic and immuno-heterogeneity between ACCs and SCCCs. Lung ASC patients have a moderate response to ICI-based immunotherapy.


Assuntos
Adenocarcinoma , Carcinoma Adenoescamoso , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Antígeno B7-H1 , Humanos , Imunoterapia , Pulmão , Receptores de Antígenos de Linfócitos T , Microambiente Tumoral
10.
J Med Virol ; 94(12): 6047-6059, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36000446

RESUMO

The intratumor heterogeneity of human papillomavirus (HPV)-related cervical cancer remains poorly defined. We performed single-cell RNA sequencing on 18 046 individual cells derived from two HPV-related cervical adenosquamous carcinoma samples to analyze the transcriptional heterogeneity of both epithelial and immune constituents, identifying seven epithelial (Epi1-7) and 11 immune subclusters. Based on expression of known cervical cancer markers, Epi1-2 primarily displayed features of adenocarcinoma, whereas Epi3-6 were instead characterized by features of squamous carcinoma. Our analyses also revealed that hypoxia and Kirsten rat sarcoma viral oncogene signaling were highly represented within Epi1; metabolic pathways mediating glycolysis and oxidative phosphorylation were enriched in Epi2-4; while Epi5 was enriched in p53 pathway components and features of epithelial-mesenchymal transition. Moreover, CD8+ FGFBP2+ T cells and FGFBP2+ natural killer cells were found to display high levels of cytotoxic effectors (GZMA, GZMB, GNLY, and PRF1) and low levels of inhibitory markers (PDCD1, TIGIT, and CTLA4), such that tumor infiltration by these populations was positively associated with survival in a cohort of n = 165 patients with HPV-related cervical cancer from The Cancer Genome Atlas database (p = 0.017 and 0.014, respectively). These results shed new light on the intratumor heterogeneity of HPV-related cervical adenosquamous carcinoma, which will help to refine diagnostic and treatment approaches.


Assuntos
Alphapapillomavirus , Carcinoma Adenoescamoso , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Alphapapillomavirus/genética , Antígeno CTLA-4 , Carcinoma Adenoescamoso/complicações , Carcinoma Adenoescamoso/genética , Carcinoma Adenoescamoso/patologia , DNA Viral/genética , Feminino , Humanos , Papillomaviridae/genética , Proteínas Proto-Oncogênicas p21(ras) , RNA , Proteína Supressora de Tumor p53 , Neoplasias do Colo do Útero/patologia
11.
Gynecol Oncol ; 167(1): 28-36, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35970602

RESUMO

OBJECTIVE: To compare survival outcomes of minimally invasive surgery (MIS) and open surgery for radical hysterectomy (RH) in early cervical cancer patients with histologic subtypes of usual-type adenocarcinoma and adenosquamous carcinoma. METHODS: From two centers' cervical cancer cohorts, patients with 2009 FIGO stage IB1-IB2 who underwent RH between 2007 and 2020 were retrospectively identified. Patients with usual-type adenocarcinoma and adenosquamous carcinoma were included in the analysis after pathologic review according to the updated World Health Organization Classification of Tumors. Clinicopathologic characteristics and survival outcomes were compared in terms of open surgery or MIS. RESULTS: This study included 161 patients. No significant differences were noted in overall survival (OS; P = 0.241) and disease-free survival (DFS; P = 0.156) between patients with usual-type adenocarcinoma (n = 136) and those with adenosquamous carcinoma (n = 25). MIS RH group (n = 99) had a significantly smaller tumor size (P < 0.001), lesser pathologic parametrial invasion (P = 0.001), and lesser lymph node metastasis (P < 0.001) than open RH group (n = 62). MIS and open RH groups showed similar OS (P = 0.201) and 3-year DFS rate (87.9% vs. 75.1%; P = 0.184). In multivariate analysis, worse DFS was not associated with MIS (P = 0.589) but was associated with pathologic parametrial invasion (adjusted HR, 3.41; 95% CI, 1.25-9.29; P = 0.016). Consistent results were observed among patients with usual-type adenocarcinoma; MIS was not associated with worse DFS. CONCLUSIONS: Comparable survival outcomes were found for MIS and open RH in early-stage cervical usual-type adenocarcinoma and adenosquamous carcinoma. Although MIS RH was not a poor prognostic factor, pathologic parametrial invasion was significantly associated with worse DFS in cervical usual-type adenocarcinoma and adenosquamous carcinoma.


Assuntos
Adenocarcinoma , Carcinoma Adenoescamoso , Neoplasias do Colo do Útero , Adenocarcinoma/patologia , Carcinoma Adenoescamoso/patologia , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia
13.
Ann Diagn Pathol ; 60: 152029, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36029589

RESUMO

Cytokeratin 10 (CK10) is a type I acidic low molecular weight cytokeratin which is mainly expressed in keratinizing squamous epithelium of the skin. Variable levels of CK10 protein have been described in squamous carcinomas of different sites and in some other epithelial neoplasms. To comprehensively determine the prevalence of CK10 expression in normal and neoplastic tissues, a tissue microarray containing 11,021 samples from 131 different tumor types and subtypes was analyzed by immunohistochemistry. CK10 immunostaining was detectable in 41 (31.3 %) of 131 tumor categories, including 18 (13.7 %) tumor types with at least one strongly positive case. The highest rate of positive staining was found in squamous cell carcinomas from various sites of origin (positive in 18.6 %-66.1 %) and in Warthin tumors of salivary glands (47.8 %), followed by various tumor entities known to potentially exhibit areas with squamous cell differentiation such as teratomas (33.3 %), basal cell carcinomas of the skin (14.3 %), adenosquamous carcinomas of the cervix (11.1 %), and several categories of urothelial neoplasms (3.1 %-16.8 %). In a combined analysis of 956 squamous cell carcinomas from 11 different sites of origin, reduced CK10 staining was linked to high grade (p < 0.0001) and advanced stage (p = 0.0015) but unrelated to HPV infection. However, CK10 staining was not statistically related to grade (p = 0.1509) and recurrence-free (p = 0.5247) or overall survival (p = 0.5082) in 176 cervical squamous cell carcinomas. In the urinary bladder, CK10 staining occurred more commonly in muscle-invasive (17.7 %) than in non-invasive urothelial carcinomas (4.0 %-6.0 %; p < 0.0001). In summary, our data corroborate a role of CK10 as a suitable marker for mature, keratinizing squamous cell differentiation in epithelial tissues. CK10 immunohistochemistry may thus be instrumental for a more objective evaluation of the clinical significance of focal squamous differentiation in cancer.


Assuntos
Carcinoma Adenoescamoso , Carcinoma de Células Escamosas , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Queratinas/análise , Urotélio
14.
Gastroenterol. hepatol. (Ed. impr.) ; 45(7): 543-551, Ago - Sep 2022. graf, ilus, tab
Artigo em Inglês | IBECS | ID: ibc-206913

RESUMO

Introduction: Adenosquamous cancer of the pancreas (ASCP) is an aggressive, infrequent subtype of pancreatic cancer that combines a glandular and squamous component and is associated with poor survival. Methods: Multicenter retrospective observational study carried out at three Spanish hospitals. The study period was: January 2010–August 2020. A descriptive analysis of the data was performed, as well as an analysis of global and disease-free survival using the Kaplan–Meier statistic. Results: Of a total of 668 pancreatic cancers treated surgically, twelve were ASCP (1.8%). Patient mean age was 69.2±7.4 years. Male/female ratio was 1:1. The main symptom was jaundice (seven patients). Correct preoperative diagnosis was obtained in only two patients. Nine pancreatoduodenectomies and three distal pancreatosplenectomies were performed. 25% had major complications. Mean tumor size was 48.6±19.4mm. Nine patients received adjuvant chemotherapy. Median survival time was 5.9 months, and median disease-free survival was 4.6 months. 90% of patients presented recurrence. Ten of the twelve patients in the study (83.3%) died, with disease progression being the cause in eight. Of the two surviving patients, one is disease-free and the other has liver metastases. Conclusion: ASCP is a very rare pancreatic tumor with aggressive behavior. It is rarely diagnosed preoperatively. The best treatment, if feasible, is surgery followed by the standard chemotherapy regimens for pancreatic adenocarcinoma.(AU)


Introducción: El cáncer adenoescamoso de páncreas (CPAS) es un subtipo de cáncer de páncreas agresivo e infrecuente que combina un componente glandular y escamoso, y presenta baja supervivencia. Métodos: Estudio observacional retrospectivo multicéntrico realizado en tres hospitales españoles. El período de estudio fue: enero 2010 - agosto 2020. Se realizó un análisis descriptivo de los datos, así como un análisis de supervivencia global y libre de enfermedad mediante Kaplan-Meier. Resultados: De un total de 668 cánceres de páncreas tratados quirúrgicamente, doce fueron CPAS (1,8%). La edad media de los pacientes fue de 69,2±7,4 años. La proporción hombre /mujer fue de 1: 1. El síntoma principal fue la ictericia (siete pacientes). Se obtuvo un diagnóstico preoperatorio correcto en solo dos pacientes. Se realizaron nueve duodenopancretectomías cefálicas y tres pancreatoesplenectomías distales. El 25% tuvo complicaciones mayores. El tamaño medio del tumor fue de 48,6±19,4mm. Nueve pacientes recibieron quimioterapia adyuvante. La mediana de supervivencia fue de 5,9 meses y la mediana de supervivencia libre de enfermedad fue de 4,6 meses. El 90% de los pacientes presentó recidiva. Diez de los doce pacientes del estudio (83,3%) fallecieron, y la progresión de la enfermedad fue la causa en ocho. De los dos pacientes que sobrevivieron, uno está libre de enfermedad y el otro tiene metástasis hepáticas. Conclusión:El CPAS es un tumor pancreático muy raro y de comportamiento agresivo. Rara vez se diagnostica antes de la operación. El mejor tratamiento, si es posible, es la cirugía seguida de los regímenes de quimioterapia estándar para el adenocarcinoma de páncreas.(AU)


Assuntos
Humanos , Masculino , Feminino , Idoso , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Espanha , Análise de Dados , Estimativa de Kaplan-Meier , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Carcinoma Adenoescamoso , Estudos Retrospectivos , Gastroenterologia , Enteropatias , Doenças Inflamatórias Intestinais
15.
Mod Pathol ; 35(10): 1484-1493, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35871081

RESUMO

Mucoepidermoid carcinoma (MEC) and adenosquamous carcinoma (ASC) have overlapping histopathological appearances and sites of occurrence, which may cause diagnostic difficulty impacting subsequent treatment. We conducted a systematic review of the scientific literature to determine whether molecular alterations were sufficiently different in MEC and ASC to aid in classifying the two entities. We searched Medline, Embase and Web of Science for studies reporting molecular determinations of ASC and/or MEC and screened retrieved records for eligibility. Two independent researchers reviewed included studies, assessed methodological quality and extracted data. Of 8623 identified records, 128 articles were included for analysis: 5 which compared the two tumors in the same investigation using the same methods and 123 which examined the tumors separately. All articles, except one were case series of moderate to poor methodological quality. The 5 publications examining both tumors showed that 52/88 (59%) MEC and 0% of 110 ASC had rearrangement of the MAML2 gene as detected by FISH and/or RT-PCR, but did not investigate other genes. In the entire series MEC had MAML2 gene rearrangement in 1337/2009 (66.6%) of tumors studied. The articles examining tumors separately found that MEC had mutations in EGFR (11/329 cases, 3.3%), KRAS (11/266, 4.1%) and ERBB2 (9/126, 7.1%) compared with ASC that had mutations in EGFR (660/1705, 38.7%), KRAS (143/625, 22.9%) and ERBB2 (6/196, 3.1%). The highest level of recurrent mutations was in pancreatic ASC where (108/126, 85.7%) reported mutations in KRAS. The EGFR mutations in ASC were similar in number and kind to those in lung adenocarcinoma. By standards of systematic review methodology and despite the large number of retrieved studies, we did not find adequate evidence for a distinctive molecular profile of either MEC or ASC that could definitively aid in its classification, especially in histologically difficult cases that are negative for MAML2 rearrangement. The case series included in this review indicate the relevance of MAML2 rearrangement to support the diagnosis of MEC, findings that should be confirmed by additional research with adequate study design.


Assuntos
Carcinoma Adenoescamoso , Carcinoma Mucoepidermoide , Neoplasias das Glândulas Salivares , Carcinoma Adenoescamoso/genética , Carcinoma Adenoescamoso/patologia , Carcinoma Mucoepidermoide/genética , Carcinoma Mucoepidermoide/patologia , Proteínas de Ligação a DNA/genética , Receptores ErbB/genética , Humanos , Hibridização in Situ Fluorescente , Proteínas Nucleares/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias das Glândulas Salivares/patologia , Transativadores/genética , Fatores de Transcrição/genética
16.
BMC Gastroenterol ; 22(1): 346, 2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-35842595

RESUMO

BACKGROUND: Adenosquamous carcinoma (ASC)with concurrent gastric carcinoma with lymphoid stroma (GCLS) are extremely rare tumors. There are only limited cases reported in the literature. Epstein-Barr virus (EBV) infection was found in the concomitant GCLS, but none in the ASC. Here, we report the first case of gastric cancer with EBV infection detected in both ASC and GCLS. CASE PRESENTATION: A 59-year-old man complained of intermittent upper abdominal pain. The gastric endoscopy revealed a type IIc tumor located in the gastric body near the fundus of the stomach. Histological examination of the gastric tumor showed the coexistence of ASC and GCLS. Both components were positive for EBV-encoded RNA (EBER) in situ hybridization. Neoplastic nests of the former were positive for p63, p40 and CK5/6. The glandular components showed positive acid mucus in the Alcian-blue periodic-acid-schiff (AB-PAS) staining. There was significant difference in the expression of epidermal growth factor receptor (EGFR) between adenocarcinoma and squamous carcinoma, but not in other proteins such as human epidermal growth factor receptor 2 (HER2), p53 and mismatch repair proteins. The role of EGFR signaling pathway needs to be further explored in the differentiation of squamous carcinoma in the gastric ASC. Finally, a diagnosis of early EBV associated gastric ASC with concurrent GCLS (pT1bN1) was made. The patient took a single-drug S1 periodically for half a year after the surgery and has been disease free during 8 months of medical follow-up. CONCLUSIONS: This is the first case of EBV associated gastric ASC with concurrent GCLS, and pathologists and clinicians should recognize and pay attention to this type of tumor.


Assuntos
Adenocarcinoma , Carcinoma Adenoescamoso , Carcinoma de Células Escamosas , Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Carcinoma Adenoescamoso/complicações , Carcinoma de Células Escamosas/complicações , Infecções por Vírus Epstein-Barr/complicações , Receptores ErbB , Herpesvirus Humano 4/genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologia
17.
Thorac Cancer ; 13(15): 2275-2278, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35818908

RESUMO

Here, we first report a case of neoadjuvant ceritinib for locally advanced lung adenosquamous carcinoma. In this study, a locally advanced adenosquamous carcinoma (ASC) patient with EML4-ALK fusion who achieved a partial response with neoadjuvant ceritinib treatment after a cycle of neoadjuvant chemotherapy did not show significant efficacy. A complete surgical resection was performed with mild adhesions and a small amount of bleeding intraoperatively. The EML4-ALK fusion was detected by targeted next-generation sequencing (NGS) in both pretreatment biopsy and the postoperative tissue specimens with a dramatic decrease in the allele frequency (26.2% [pre]-2.3% [post]). Pathological examination of the postoperative specimens indicated a diagnosis of ASC but the proportions of adenocarcinoma and squamous cell carcinoma cells in the primary lung tumor and metastatic lymph node site were different, suggesting the various responses to ceritinib. Thus, with the case presented here, we provide the clinical evidence for ALK-positive locally advanced ASC patients benefiting from neoadjuvant ceritinib treatment with a tolerable safety profile, whereas further cohort studies of the efficacy and safety of neoadjuvant ceritinib in such patients are needed.


Assuntos
Antineoplásicos , Carcinoma Adenoescamoso , Neoplasias Pulmonares , Quinase do Linfoma Anaplásico , Antineoplásicos/uso terapêutico , Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma Adenoescamoso/genética , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Terapia Neoadjuvante , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas , Receptores Proteína Tirosina Quinases/uso terapêutico , Sulfonas
18.
Pathol Res Pract ; 236: 153967, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35662040

RESUMO

Colorectal adenosquamous carcinoma (ASC) is exceedingly rare, comprising less than 0.1% of all colorectal malignancies, and is characterized by the admixture of glandular and squamous components. Due to its rarity, immunohistochemical and biological profiles have not been well investigated. The clinico-pathologic features of 29 cases of primary colorectal adenosquamous carcinomas, including four synchronous metastases, as well as the immunohistochemical expression of keratin 20, CDX2, keratin 34ßE12, keratin 5/6, p63, p40, ß-Catenin, Cyclin D1 and mismatch repair protein (MMR) expression in both squamous and glandular components are described. All ASCs showed aggressive clinico-pathologic features; all cases showed at least one aggressive pathologic characteristic (poorly differentiated, vascular invasion, infiltrative growth pattern) and 69% of cases were either stage III or IV. The squamous component was keratin 34ßE12 positive in all cases and keratin 5/6 positive in 27 cases, while only 7 cases showed p63 and/or p40 expression. ß-Catenin and Cyclin D1 showed different expression, with nuclear staining of Cyclin D1 in the squamous component of all cases (both primary and metastatic lesions) and nuclear staining of ß-Catenin predominantly in the glandular component. All but one case showed proficient MMR profile. Sixteen patients (64%) died of their disease with median survival of 10 months. ASC show aggressive clinical outcome and aggressive pathologic characteristics. A peculiar keratin 34ßE12 positive profile in the squamous component is seen differing from squamous cell carcinoma and non-intestinal ASC. The staining patterns for ß-Catenin and Cyclin D1 between components, supports a possible divergent clonal evolution of the neoplasm.


Assuntos
Carcinoma Adenoescamoso , Carcinoma de Células Escamosas , Neoplasias Colorretais , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/patologia , Ciclina D1 , Humanos , Queratina-5 , beta Catenina
19.
Int J Colorectal Dis ; 37(7): 1581-1592, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35678851

RESUMO

BACKGROUND: The relationship between the location of the primary tumor and survival of adenosquamous carcinoma (ASC) remains poorly understood. This study aimed to evaluate the impact of primary tumor location on the survival outcome of patients with ASC. METHODS: Patients with ASC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database with ≥ 150 cases per tumor location. The Kaplan-Meier method was used to generate survival curves and differences among them were compared using the log-rank test. On the other hand, Cox proportional hazards models were used to evaluate factors that had independent predictive effects on cancer-specific survival (CSS). RESULTS: A total of 14,829 eligible patients with ASC were included in this study. Lung and bronchus ASC accounted for 51.1%, followed by the cervix uteri (17.0%), corpus uteri (13.9%), pancreas (4.9%), esophagus (3.1%), gallbladder (2.5%), stomach (2.2%), colon and rectum (2.0%), head and neck (1.8%), and breast ASC (1.3%). The 5-year CSS of breast, cervix uteri, colon and rectum, corpus uteri, esophagus, gallbladder, head and neck, lung and bronchus, pancreas, and stomach ASC was 76.9%, 66.0%, 34.8%, 72.9%, 12.0%, 10.8%, 45.0%, 24.7%, 4.3%, and 17.3%, respectively. COX analysis demonstrated that the primary tumor location was an independent prognostic factor for CSS. Besides, the breast, uterine corpus, and cervix as well as head and neck ASC were significantly associated with better prognosis, while pancreas and gallbladder ASC were significantly associated with poor CSS; stomach and colorectal were roughly the same as ASC prognosis. CONCLUSION: Our study showed that the CSS of patients with ASC depends on the location of the primary tumor. Besides, tumor location is an important factor that should guide the use of chemotherapy and radiation.


Assuntos
Carcinoma Adenoescamoso , Carcinoma Adenoescamoso/epidemiologia , Feminino , Humanos , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais
20.
Jpn J Clin Oncol ; 52(10): 1191-1200, 2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-35726160

RESUMO

OBJECTIVE: Adenosquamous carcinoma is a rare subtype of non-small cell lung cancer characterized by aggressive behavior, with combination of adenocarcinoma and squamous cell carcinoma components. The clinicopathological characteristics and prognosis of resectable adenosquamous carcinoma are incompletely understood and this study aimed to depict those in a large population. METHODS: A total of 805 adenosquamous carcinoma, 7875 squamous cell carcinoma and 23 957 adenocarcinoma patients who underwent lobectomy or sublobectomy were queried from the Surveillance, Epidemiology, and End Results database (2010-17). Clinicopathological characteristics of adenosquamous carcinoma patients were compared with those of squamous cell carcinoma and adenocarcinoma patients. Prognostic factors were identified by univariable and multivariable Cox regression analyses. Propensity score matching was applied to reduce confounding effects. RESULTS: Adenosquamous carcinoma was associated with higher pleural invasion incidence and poorer differentiation compared with squamous cell carcinoma or adenocarcinoma (P values < 0.001). The independent risk factors of cancer-specific survival of adenosquamous carcinoma patients were increasing age, male sex, invading through visceral pleura, poor differentiation and higher stage. Stage IB adenosquamous carcinoma patients whose tumor invaded through visceral pleura had significantly worse survival than those not (P = 0.003). Adenosquamous carcinoma patients had worse survival compared with squamous cell carcinoma (5-year-survival: 64.55 vs. 69.09%, P = 0.003) and adenocarcinoma (5-year-survival: 64.55 vs. 76.79%, P < 0.001) patients before match. And this difference persisted after match. CONCLUSIONS: Resectable adenosquamous carcinoma patients had higher pleural invasion incidence, poorer differentiation and worse survival compared with squamous cell carcinoma and adenocarcinoma patients. Visceral pleural invasion status and differentiation grade were vital prognostic factors of adenosquamous carcinoma patients on the basis of stage.


Assuntos
Adenocarcinoma , Carcinoma Adenoescamoso , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Adenocarcinoma/patologia , Carcinoma Adenoescamoso/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Humanos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Estadiamento de Neoplasias , Prognóstico
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