-
Cancer Discovery Jan 2022Developing strategies to inflame tumors is critical for increasing response to immunotherapy. Here, we report that low-dose radiotherapy (LDRT) of murine tumors promotes...
Developing strategies to inflame tumors is critical for increasing response to immunotherapy. Here, we report that low-dose radiotherapy (LDRT) of murine tumors promotes T-cell infiltration and enables responsiveness to combinatorial immunotherapy in an IFN-dependent manner. Treatment efficacy relied upon mobilizing both adaptive and innate immunity and depended on both cytotoxic CD4 and CD8 T cells. LDRT elicited predominantly CD4 cells with features of exhausted effector cytotoxic cells, with a subset expressing NKG2D and exhibiting proliferative capacity, as well as a unique subset of activated dendritic cells expressing the NKG2D ligand RAE1. We translated these findings to a phase I clinical trial administering LDRT, low-dose cyclophosphamide, and immune checkpoint blockade to patients with immune-desert tumors. In responsive patients, the combinatorial treatment triggered T-cell infiltration, predominantly of CD4 cells with Th1 signatures. Our data support the rational combination of LDRT with immunotherapy for effectively treating low T cell-infiltrated tumors. SIGNIFICANCE: Low-dose radiation reprogrammed the tumor microenvironment of tumors with scarce immune infiltration and together with immunotherapy induced simultaneous mobilization of innate and adaptive immunity, predominantly CD4 effector T cells, to achieve tumor control dependent on NKG2D. The combination induced important responses in patients with metastatic immune-cold tumors..
Topics: Adaptive Immunity; Adenocarcinoma, Papillary; Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Disease Models, Animal; Female; Humans; Lymphocytes, Tumor-Infiltrating; Mice; Mice, Inbred C57BL; Ovarian Neoplasms; Radiotherapy Dosage; Tumor Microenvironment
PubMed: 34479871
DOI: 10.1158/2159-8290.CD-21-0003 -
Modern Pathology : An Official Journal... Apr 2011Follicular thyroid carcinoma is being diagnosed less and less frequently despite the increasing incidence of well-differentiated thyroid carcinomas everywhere. This... (Review)
Review
Follicular thyroid carcinoma is being diagnosed less and less frequently despite the increasing incidence of well-differentiated thyroid carcinomas everywhere. This review will discuss the reasons underlying such an observation focusing on the evolution of the morphological and immunohistochemical diagnostic criteria of follicular thyroid tumors. It will address the differential diagnosis between follicular carcinoma and three tumor types--follicular adenoma, follicular variant of papillary carcinoma and poorly differentiated carcinoma--as well as the problems raised by the newly described categories of follicular tumors: follicular tumor of uncertain malignant potential, well-differentiated tumor of uncertain malignant potential and well-differentiated carcinoma, not otherwise specified. Finally, the prognostic and therapeutic significance of some promising molecular biomarkers will be discussed within the frame of the aforementioned histopathological classification.
Topics: Adenocarcinoma, Follicular; Adenocarcinoma, Papillary; Adenoma; Adenoma, Oxyphilic; Biomarkers, Tumor; Diagnosis, Differential; Humans; Neoplasm Invasiveness; Thyroid Neoplasms
PubMed: 21455197
DOI: 10.1038/modpathol.2010.133 -
Dermatology Online Journal Apr 2018A male in his twenties presented with a tender finger nodule that had been present for 3 months. Histopathological examination revealed a dermis with nodules of...
A male in his twenties presented with a tender finger nodule that had been present for 3 months. Histopathological examination revealed a dermis with nodules of necrotic, athypical epithelaia cells with high nuclear to cytoplasmic ratios. Glandular formation was present with lumens lined by columnar epithelium, consistent with digital papillary adenocarcinoma. Digital papilary adenocarcinoma is a rare malignant adnexal tumor arising from sweat glands and requires further work-up.
Topics: Adenocarcinoma, Papillary; Adult; Fingers; Humans; Male; Sweat Gland Neoplasms
PubMed: 29906012
DOI: No ID Found -
Ear, Nose, & Throat Journal Dec 2017
Topics: Adenocarcinoma, Papillary; Humans; Nasopharyngeal Neoplasms
PubMed: 29236265
DOI: 10.1177/014556131709601203 -
Modern Pathology : An Official Journal... Apr 2011The past two decades have seen numerous developments in the understanding of the origins and biology of papillary thyroid carcinoma. Advances in molecular biology,... (Review)
Review
The past two decades have seen numerous developments in the understanding of the origins and biology of papillary thyroid carcinoma. Advances in molecular biology, clinicopathologic studies of new entities, facility with fine-needle aspiration biopsy, and new radiologic imaging techniques have allowed for earlier diagnosis of these tumors. However, these advances have also caused controversies in cytologic and histopathologic diagnoses as well as therapy decisions. This paper will focus on several pathologic aspects of papillary carcinoma, which impact on its biology and prognosis.
Topics: Adenocarcinoma, Follicular; Adenocarcinoma, Papillary; Cell Nucleus; Early Detection of Cancer; Female; Humans; Male; Neoplasms, Radiation-Induced; Prognosis; Thyroid Neoplasms
PubMed: 21455196
DOI: 10.1038/modpathol.2010.129 -
The Journal of Veterinary Medical... Mar 2022Dogs with ovarian papillary adenocarcinoma occasionally present with ascites and/or pleural effusion. These aspirated fluids often contain a large number of cells, and...
Dogs with ovarian papillary adenocarcinoma occasionally present with ascites and/or pleural effusion. These aspirated fluids often contain a large number of cells, and distinction between neoplastic cells and activated mesothelial cells can be difficult. In this study, 7 cases of canine ovarian papillary adenocarcinoma, including 3 with ascites and pleural effusion, were immunohistochemically examined. Ovarian tumor cells were positive for cytokeratin CAM5.2 (CAM5.2), Wilms' tumor 1 (WT-1) and progesterone receptor (PR) in all 7 cases. A metastatic lesion of the mediastinum in one case was also positive for CAM5.2, WT-1 and PR. Immunohistochemistry on cell blocks obtained from ascites and/or pleural effusion of 2 cases revealed the presence of PR-positive epithelial cells. Whereas, activated mesothelial cells in ascites or pleural effusion collected from dogs without neoplastic lesions were negative for PR. In addition, surface epithelium and subsurface epithelial structures (SES) of normal canine ovaries, that are considered to be the cell of origin for ovarian papillary adenocarcinoma, were also positive for CAM5.2, WT-1 and PR. These results indicate that, together with CAM5.2, WT-1 and PR is a useful diagnostic marker for canine ovarian papillary adenocarcinoma. Expression of PR may be associated with progesterone-dependent nature of canine ovarian papillary adenocarcinoma.
Topics: Adenocarcinoma, Papillary; Animals; Biomarkers, Tumor; Diagnosis, Differential; Dog Diseases; Dogs; Immunohistochemistry; Kidney Neoplasms; Ovarian Neoplasms; Pleural Effusion, Malignant
PubMed: 35110458
DOI: 10.1292/jvms.21-0633 -
Diagnostic and Interventional Imaging May 2013Thyroid nodules are very common, while thyroid cancer is rare and has a very good prognosis. Thyroid nodule ultrasound characterization performed by experienced... (Comparative Study)
Comparative Study Review
Thyroid nodules are very common, while thyroid cancer is rare and has a very good prognosis. Thyroid nodule ultrasound characterization performed by experienced clinicians allows the selection of the tumours to be punctured and guiding fine needle aspiration (FNA). FNA provide cytology information able to differentiate benign tumours from cancer in approximately 80% of cases. However, it remains difficult to identify thyroid cancers with ultrasound imaging, as demonstrated by the very low rate of cancers detected in all of the carried out FNA (approximately 5%). As a majority of thyroid cancers are hard, the stiffness evaluation has become part of nodular characterization. Since 2005, elastography has been used for the evaluation of thyroid nodules; quasi-static elastography was the first technique available and used, at first, an external pressure induced by the probe, which was then replaced by carotid internal excitation allowing improvement in sensitivity. Semi-quantitative analysis allows comparison of tissue elasticities between tissue with elasticity anomalies and normal tissue and provides therefore useful analytic information. Shear wave elastography (SWE) provides a map of the elasticity in a region and allows stiffness quantification of lesions in kilopascals in order to reinforce the predictive value of malignancy. A tumour whose stiffness is greater than 65kPa or for which the stiffness ratio is greater than 3.7 compared to surrounding healthy tissue is highly suspicious. SWE may enable the detection of malignant follicular tumours that currently escape detection by the ultrasound-guided ultrasound/aspiration cytology couple. Lymph node metastasis of papillary thyroid cancer can also be detected by elastography due to its increased stiffness.
Topics: Adenocarcinoma, Follicular; Adenocarcinoma, Papillary; Biopsy, Fine-Needle; Carcinoma, Medullary; Diagnosis, Differential; Elasticity Imaging Techniques; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Lymphatic Metastasis; Sensitivity and Specificity; Thyroid Gland; Thyroid Neoplasms; Thyroid Nodule; Ultrasonography, Interventional
PubMed: 23623210
DOI: 10.1016/j.diii.2013.01.023 -
The American Journal of Surgical... Oct 2023Recurrent oncogenic drivers have been identified in a variety of sweat gland tumors. Recently, integration of human papillomavirus type 42 (HPV42) has been reported in...
Recurrent oncogenic drivers have been identified in a variety of sweat gland tumors. Recently, integration of human papillomavirus type 42 (HPV42) has been reported in digital papillary adenocarcinoma (DPA). The main objectives of the present study were (i) to provide an overview of the prevalence of previously identified oncogenic drivers in acral sweat gland tumors and (ii) to genetically characterize tumors in which no recurrent genetic alteration has been identified yet. Cases of acral sweat gland tumors were identified from the database of the French network CARADERM. After histologic review, the presence of previously identified genetic alterations was investigated in the entire cohort (n=79) using a combination of immunohistochemistry and targeted DNA and RNA sequencing. Tumor entities with no recurrent genetic alterations were submitted to whole-transcriptome sequencing. CRTC1::MAML2 fusion was identified in cases of hidradenoma and hidradenocarcinoma (n=9/12 and n=9/12). A p.V600E mutation of BRAF was observed in all cases of tubular adenoma (n=4). YAP1:MAML2 and YAP1::NUTM1 fusions were observed in poroid tumors (n=15/25). ETV6::NTRK3 and TRPS1::PLAG1 fusion transcripts were identified in secretory carcinoma (n=1/1) and cutaneous mixed tumors (n=3/4), respectively. The HPV42 genome was detected in most cases of DPA (n=10/11) and in 1 adnexal adenocarcinoma not otherwise specified. Finally, whole-transcriptome analysis revealed BRD3::NUTM1 or NSD3::NUTM1 fusions in 2 cases of NUT adnexal carcinoma and NCOA4::RET and CCDC6::RET fusion transcripts in 2 cystadenoma/hidrocystoma-like tumors. Our study confirms distinctive cytogenetic abnormalities in a wide number of acral adnexal neoplasms and supports the use of molecular analysis as a valuable aid in the diagnosis of these rare and often difficult to diagnose group of neoplasms.
Topics: Humans; Sweat Gland Neoplasms; Skin Neoplasms; Carcinoma; Acrospiroma; Transcription Factors; Adenocarcinoma, Papillary; Repressor Proteins
PubMed: 37505808
DOI: 10.1097/PAS.0000000000002098 -
Medicine Jun 2019Endoscopic submucosal dissection (ESD) has increasingly been used to treat early gastric cancer (EGC); however, its efficacy in treating papillary adenocarcinoma-type...
Endoscopic submucosal dissection (ESD) has increasingly been used to treat early gastric cancer (EGC); however, its efficacy in treating papillary adenocarcinoma-type EGC remains unknown.We sought to identify risk factors for lymph node (LN) metastasis in papillary adenocarcinoma-type EGC and evaluate the clinical outcome after ESD.This study retrospectively reviewed the medical records of patients who were diagnosed with EGC in our hospital from January 2009 to December 2016. In total, 85 patients had papillary adenocarcinoma-type EGC, of whom 52 and 33 underwent surgical treatment and ESD, respectively. This study analyzed the LN metastasis risk factors and clinical outcomes between these 2 groups and with those of an existing ESD indication group.LN metastasis occurred in 13 (25.0%) of 52 patients who underwent surgery. Multivariate analysis indicated that lymphovascular invasion was an independent risk factor (odds ratio: 20.624; 95% confidence interval: 19.628-21.497; P = .001). Of 33 patients who underwent ESD, 21 (63.6%) had an absolute indication and 12 (36.4%) had an expanded indication. All 3 (9.1%) patients with non-curative resection underwent additional surgery. The clinical outcomes were compared to those of 926 patients who underwent ESD of non-papillary adenocarcinoma-type EGC. There were no significant differences in curative resection rate (P = .327), procedure-related complication (P = .853), local recurrence (P = 1.000), or overall survival (P = 1.000).ESD of papillary adenocarcinoma-type EGC showed an acceptable outcome in comparison to an existing ESD indication group. However, these patients exhibit a relatively higher risk of LN metastasis.
Topics: Adenocarcinoma, Papillary; Aged; Endoscopic Mucosal Resection; Female; Gastrectomy; Humans; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Republic of Korea; Retrospective Studies; Risk Factors; Stomach Neoplasms
PubMed: 31232966
DOI: 10.1097/MD.0000000000016134 -
Pathologica Mar 2019
Topics: Adenocarcinoma; Female; Humans; Thyroid Cancer, Papillary; beta Catenin
PubMed: 31217615
DOI: 10.32074/1591-951X-66-18