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Langenbeck's Archives of Surgery Dec 2021Intraductal papillary mucinous neoplasms (IPMNs) represent a unique opportunity to treat and prevent a curable neoplasm before it has the chance to progress to incurable... (Review)
Review
BACKGROUND
Intraductal papillary mucinous neoplasms (IPMNs) represent a unique opportunity to treat and prevent a curable neoplasm before it has the chance to progress to incurable cancer. This prospect, however, has to be balanced with the real risk of over treating patients with lesions that would, in fact, never progress during the life of the patient.
PURPOSE
Informed clinical decisions in the treatment of IPMNs are first and foremost based on a deep understanding of the pathology of these lesions.
CONCLUSIONS
Here we review the pathology of IPMNs, with an emphasis on the clinical relevance of the important features that characterize these lesions.
Topics: Carcinoma, Pancreatic Ductal; Humans; Pancreatic Neoplasms
PubMed: 34047827
DOI: 10.1007/s00423-021-02201-0 -
Pathology Feb 2018This article reviews the most relevant pathological and molecular features of ovarian tumours that are associated with endometriosis. Endometriosis is a common... (Review)
Review
This article reviews the most relevant pathological and molecular features of ovarian tumours that are associated with endometriosis. Endometriosis is a common condition, affecting 5-15% of all women, and it has been estimated that 0.5-1% of cases are complicated by neoplasia. The most common malignant tumours in this setting are endometrioid adenocarcinoma and clear cell adenocarcinoma, each accounting for approximately 10% of ovarian carcinomas in Western countries. A minority of cases are associated with Lynch syndrome. These carcinomas are often confined to the ovaries at presentation in which case they have relatively favourable outcomes. However, high-stage tumours, particularly clear cell carcinomas, generally have a poor prognosis and this partly reflects relative resistance to current treatment. Histological diagnosis is straightforward in the majority of cases but some variants, for example endometrioid carcinomas with sex cord-like appearances or oxyphil cells, may create diagnostic difficulty. Similarly, clear cell carcinomas can show a range of architectural and cytological patterns that overlap with other tumours, both primary and metastatic, involving the ovaries. Endometriosis-associated borderline tumours are less common, and they often show mixed patterns of differentiation (seromucinous tumours). Atypical endometriosis may represent an intermediate step in neoplastic progression and some of these lesions demonstrate immunohistological and molecular alterations similar to those observed in endometriosis-related tumours. ARID1A mutations are relatively common in all of these tumours, but each has additional characteristic molecular alterations which are likely to be of increasing clinical relevance as targeted therapies are developed. Less is known of the pathogenesis of rarer endometriosis-associated ovarian tumours including endometrioid stromal sarcoma, mesodermal (Müllerian) adenosarcoma, and carcinosarcoma. This article also briefly reviews the issue of synchronous endometrioid carcinomas of the endometrium and the ovary, including the most recent developments on pathogenesis.
Topics: Carcinoma; Endometriosis; Female; Humans; Ovarian Neoplasms
PubMed: 29241974
DOI: 10.1016/j.pathol.2017.10.006 -
Oncology Research and Treatment 2018Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death. Although the treatment modalities are improving, the prognosis of PDAC continues to... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death. Although the treatment modalities are improving, the prognosis of PDAC continues to be poor. Therefore, early detection of PDAC or its precursor lesions may be the best way to improve patient survival. PDACs have several different precursor lesions, including pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), intraductal tubulopapillary neoplasms (ITPNs), intraductal oncocytic papillary neoplasms (IOPNs), and mucinous cystic neoplasms (MCNs). PanINs cannot be identified using imaging modalities, while the other lesions are radiologically detectable. These precursor lesions are categorized based on structural and cytological atypia as low-grade and high-grade lesions. We discuss recent updates regarding histopathological and molecular pathological overviews of PDAC precursor lesions. Better understanding of such lesions may contribute to earlier detection of PDAC or its precursor lesions and improve PDAC patient survival.
Topics: Carcinoma, Pancreatic Ductal; Humans; Mutation; Pancreatic Neoplasms; Proto-Oncogene Proteins p21(ras)
PubMed: 30269131
DOI: 10.1159/000493554 -
Journal of Clinical Pathology Sep 2020
Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Kidney; Kidney Neoplasms; Male; Middle Aged; Succinate Dehydrogenase
PubMed: 32060077
DOI: 10.1136/jclinpath-2019-206260 -
Frontiers in Endocrinology 2021Familial non-medullary thyroid carcinoma (FNMTC) corresponds to 5-10% of all follicular cell-derived carcinoma (FCDTC). Oncocytic thyroid tumors have an increased... (Review)
Review
Familial non-medullary thyroid carcinoma (FNMTC) corresponds to 5-10% of all follicular cell-derived carcinoma (FCDTC). Oncocytic thyroid tumors have an increased incidence in the familial context in comparison with sporadic FCDTC, encompassing benign and malignant tumors in the same family presenting with some extent of cell oxyphilia. This has triggered the interest of our and other groups to clarify the oncocytic change, looking for genetic markers that could explain the emergence of this phenotype in thyroid benign and malignant lesions, focusing on familial aggregation. Despite some advances regarding the identification of the gene associated with retinoic and interferon-induced mortality 19 (GRIM-19), as one of the key candidate genes affected in the "Tumor with Cell Oxyphilia" (TCO) locus, most of the mutations follow a pattern of "private mutations", almost exclusive to one family. Moreover, no causative genetic alterations were identified so far in most families. The incomplete penetrance of the disease, the diverse benign and malignant phenotypes in the affected familial members and the variable syndromic associations create an additional layer of complexity for studying the genetic alterations in oncocytic tumors. In the present review, we summarized the available evidence supporting genomic-based mechanisms for the oncocytic change, particularly in the context of FNMTC. We have also addressed the challenges and gaps in the aforementioned mechanisms, as well as molecular clues that can explain, at least partially, the phenotype of oncocytic tumors and the respective clinico-pathological behavior. Finally, we pointed to areas of further investigation in the field of oncocytic (F)NMTC with translational potential in terms of therapy.
Topics: Animals; Genetic Predisposition to Disease; Genome, Mitochondrial; Humans; Mutation; Oxyphil Cells; Thyroid Neoplasms
PubMed: 34177813
DOI: 10.3389/fendo.2021.691979 -
Head and Neck Pathology Mar 2023Oncocytes are a component of many metaplastic and neoplastic lesions throughout the head and neck area, primarily originating in salivary/seromucinous glands and the... (Review)
Review
BACKGROUND
Oncocytes are a component of many metaplastic and neoplastic lesions throughout the head and neck area, primarily originating in salivary/seromucinous glands and the thyroid gland. In addition, other lesions can contain cells that mimic oncocytes (pseudo-oncocytes); these can be of epithelial or non-epithelial origin.
METHODS
Review article.
RESULTS
Oncocytic metaplasia is common in seromucinous glands throughout the upper aerodigestive tract, most notable in the oral cavity, nasopharynx and larynx. The main oncocytic salivary gland neoplasms are Warthin tumor and oncocytoma. Infarction of Warthin tumor may lead to recognition difficulties. Oncocytic subtypes of mucoepidermoid carcinoma and intraductal carcinoma have morphologic and immunohistochemical features that allow distinction from major oncocytic entities. Oncocytic thyroid tumors include adenoma, carcinoma (follicular, papillary and medullary), along with poorly differentiated tumors. Oncocytic papillary sinonasal and middle ear tumors must be distinguished from low grade adenocarcinomas. Pseudo-oncocytic entities include paraganglioma, Langerhans cell histiocytosis, giant cell tumor, rhabdomyoma, and metastatic tumors.
CONCLUSIONS
Correct diagnosis of oncocytic head and neck lesions requires a knowledge of the spectrum of possible entities, their characteristic sites of occurrence, architecture, histomorphology, and immunohistochemistry. Oncocytic subtypes of several newly described entities are now recognized. Both epithelial and non-epithelial mimics of oncocytes exist. The molecular features of oncocytic tumors can be helpful in their diagnosis and understanding their pathogenesis.
Topics: Humans; Oxyphil Cells; Adenolymphoma; Salivary Gland Neoplasms; Salivary Glands; Adenoma, Oxyphilic
PubMed: 36928735
DOI: 10.1007/s12105-022-01520-y -
International Journal of Surgical... Oct 2022Renal tumors with oncocytic or chromophobe-like morphology can be a common source of diagnostic difficulty. In some series, they constitute the largest group of... (Review)
Review
Renal tumors with oncocytic or chromophobe-like morphology can be a common source of diagnostic difficulty. In some series, they constitute the largest group of unclassified renal cell carcinomas, a term used for neoplasms that do not fit the current classification of renal tumors. We describe the histological, immunohistochemical, and molecular findings of an eosinophilic renal neoplasm which presented with rib and liver metastases, and provide a review of the literature. The possibility of a renal oncocytoma with metastases was initially considered but excluded on the basis of several morphological and immunohistochemical features. Additionally, the tumor did not correspond with other traditional or newly emerging categories of renal neoplasms. It was therefore regarded as an unclassified oncocytic renal neoplasm which demonstrated evidence of malignant potential due to the presence of multiple metastases.
Topics: Adenoma, Oxyphilic; Biomarkers, Tumor; Carcinoma, Renal Cell; Humans; Kidney Neoplasms; Liver Neoplasms; Ribs
PubMed: 35274993
DOI: 10.1177/10668969221084265 -
Mayo Clinic Proceedings Nov 2022
Topics: Humans; Parathyroid Neoplasms; Adenoma, Oxyphilic; Adenoma
PubMed: 36333022
DOI: 10.1016/j.mayocp.2022.09.015 -
Cytopathology : Official Journal of the... May 2020Warthin's tumour (WT) is a benign epithelial salivary tumour, one type of salivary adenoma. Histologically, WT is structured of two components, epithelial tissue that... (Review)
Review
Warthin's tumour (WT) is a benign epithelial salivary tumour, one type of salivary adenoma. Histologically, WT is structured of two components, epithelial tissue that often lines cystic formations and lymphoid tissue in the tumour stroma. FNA is a reliable diagnostic approach in the diagnosis of salivary gland lesions allowing a highly accurate categorization of benign tumour-like lesions, benign tumours and malignant tumours. In the proposed Milan reporting system of salivary gland lesions, WT is categorized in the IVA group of benign neoplasms. Accurate cytological diagnosis is straightforward when three characteristic components are present: oncocytes, either isolated or associated in clusters, lymphocytes and lymphoid cells and often an inflammatory/necrotic-like substance. Also, specific features of scintigraphy and radiological imaging contribute to the diagnosis of WT. WT is categorized according to Seifert G. et al in 4 types, depending on the proportions of the epithelial component and lymphoid stroma. Differential cytopathological and pathohistological diagnosis include other salivary gland lesions with lymphoid, oncocytic epithelial and cystic components. In some cases, such as the metaplastic WT variant, there are additional cytopathological and histological diagnostic difficulties. Moreover, bilateral, multicentric or multiple and infrequently seen extra-salivary localizations of WT are associated with further cytopathological diagnostic difficulties. Also, a rare possibility of malignant transformation of the epithelial or lymphoid component of WT as well as possible association with other primary tumours remains a challenge in accurate cytopathological and histological diagnosis of WT.
Topics: Adenolymphoma; Adenoma; Humans; Lymphocytes; Lymphoid Tissue; Salivary Gland Neoplasms; Salivary Glands
PubMed: 32259367
DOI: 10.1111/cyt.12830 -
Cancer Discovery Aug 2023Oncocytic (Hürthle cell) carcinoma of the thyroid (HCC) is genetically characterized by complex I mitochondrial DNA mutations and widespread chromosomal losses. Here,...
UNLABELLED
Oncocytic (Hürthle cell) carcinoma of the thyroid (HCC) is genetically characterized by complex I mitochondrial DNA mutations and widespread chromosomal losses. Here, we utilize RNA sequencing and metabolomics to identify candidate molecular effectors activated by these genetic drivers. We find glutathione biosynthesis, amino acid metabolism, mitochondrial unfolded protein response, and lipid peroxide scavenging to be increased in HCC. A CRISPR-Cas9 knockout screen in a new HCC model reveals which pathways are key for fitness, and highlights loss of GPX4, a defense against lipid peroxides and ferroptosis, as a strong liability. Rescuing complex I redox activity with the yeast NADH dehydrogenase (NDI1) in HCC cells diminishes ferroptosis sensitivity, while inhibiting complex I in normal thyroid cells augments ferroptosis induction. Our work demonstrates unmitigated lipid peroxide stress to be an HCC vulnerability that is mechanistically coupled to the genetic loss of mitochondrial complex I activity.
SIGNIFICANCE
HCC harbors abundant mitochondria, mitochondrial DNA mutations, and chromosomal losses. Using a CRISPR-Cas9 screen inspired by transcriptomic and metabolomic profiling, we identify molecular effectors essential for cell fitness. We uncover lipid peroxide stress as a vulnerability coupled to mitochondrial complex I loss in HCC. See related article by Frank et al., p. 1884. This article is highlighted in the In This Issue feature, p. 1749.
Topics: Humans; Thyroid Gland; Carcinoma, Hepatocellular; Lipid Peroxides; Fermentation; Oxyphil Cells; Liver Neoplasms; DNA, Mitochondrial
PubMed: 37262067
DOI: 10.1158/2159-8290.CD-22-0976