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Cancer Treatment Reviews May 2023The new WHO classification of urogenital tumours published in 2022, contains significant revisions upon the previous 2016 version regarding Renal Cell Carcinoma (RCC).... (Review)
Review
The new WHO classification of urogenital tumours published in 2022, contains significant revisions upon the previous 2016 version regarding Renal Cell Carcinoma (RCC). While the most common histotype remains almost untouched, some of the main novelties concerns papillary RCC and oncocytic neoplasms. The main change is the introduction of a new category of molecularly-defined RCC, which includes TFE3-rearranged RCC, TFEB-rearranged, and TFEB-amplified RCC, FH-deficient RCC, SDH-deficient RCC, ALK-rearranged RCC, ELOC (formerly TCEB1)-mutated RCC, SMARCB1 (INI1)-deficient RCC. In this paper we analyze the current knowledge on emerging entities and molecularly-defined RCC to assess whether the current pathological classification offers the oncologist the possibility of selecting more specific and personalized treatments, from both those currently available, as well as those that will soon be available.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; World Health Organization
PubMed: 37060647
DOI: 10.1016/j.ctrv.2023.102558 -
Surgical Pathology Clinics Mar 2021Sialadenoma papilliferum (SP) is a rare, benign salivary gland neoplasm sharing similar histopathologic features and harboring the same genetic alterations, BRAF V600E... (Review)
Review
Sialadenoma papilliferum (SP) is a rare, benign salivary gland neoplasm sharing similar histopathologic features and harboring the same genetic alterations, BRAF V600E or HRAS mutations, with syringocystadenoma papilliferum. SP most commonly occurs in the hard palate and in older adults. Clinically, SP is most likely to be diagnosed as a squamous papilloma. Microscopically, SP shows an exophytic papillary epithelial proliferation and a contiguously endophytic ductal proliferation. Two distinct subtypes are identified: classic SP and oncocytic SP. Conservative surgical treatment seems to be adequate with a low recurrence. SOX10 immunohistochemistry and BRAF analysis may be useful in differential diagnosis.
Topics: Adenoma; Cell Proliferation; Diagnosis, Differential; Epithelial Cells; Humans; Immunohistochemistry; Mutation; Palate, Hard; Prognosis; Proto-Oncogene Proteins B-raf; SOXE Transcription Factors; Salivary Gland Neoplasms; Salivary Glands, Minor
PubMed: 33526222
DOI: 10.1016/j.path.2020.09.006 -
Modern Pathology : An Official Journal... Sep 2022The category of "oncocytic renal tumors'' includes well-recognized entities, such as renal oncocytoma (RO) and eosinophilic variant of chromophobe renal cell carcinoma... (Review)
Review
Do we need an updated classification of oncocytic renal tumors? : Emergence of low-grade oncocytic tumor (LOT) and eosinophilic vacuolated tumor (EVT) as novel renal entities.
The category of "oncocytic renal tumors'' includes well-recognized entities, such as renal oncocytoma (RO) and eosinophilic variant of chromophobe renal cell carcinoma (eo-ChRCC), as well as a group of "gray zone" oncocytic tumors, with overlapping features between RO and eo-ChRCC that create ongoing diagnostic and classification problems. These types of renal tumors were designated in the past as "hybrid oncocytoma-chromophobe tumors". In a recent update, the Genitourinary Pathology Society (GUPS) proposed the term "oncocytic renal neoplasm of low malignant potential, not further classified", for such solitary and sporadic, somewhat heterogeneous, but relatively indolent tumors, with equivocal RO/eo-ChRCC features. GUPS also proposed that the term "hybrid oncocytic tumor" be reserved for tumors found in a hereditary setting, typically arising as bilateral and multifocal ones (as in Birt-Hogg-Dubé syndrome). More recent developments in the "gray zone" of oncocytic renal tumors revealed that potentially distinct entities may have been "hidden" in this group. Recent studies distinguished two new entities: "Eosinophilic Vacuolated Tumor" (EVT) and "Low-grade Oncocytic Tumor" (LOT). The rapidly accumulated evidence on EVT and LOT has validated the initial findings and has expanded the knowledge on these entities. Both are uniformly benign and are typically found in a sporadic setting, but rarely can be found in patients with tuberous sclerosis complex. Both have readily distinguishable morphologic and immunohistochemical features that separate them from similar renal tumors, without a need for detailed molecular studies. These tumors very frequently harbor TSC/MTOR mutations that are however neither specific nor restricted to these two entities. In this review, we outline a proposal for a working framework on how to classify such low-grade oncocytic renal tumors. We believe that such framework will facilitate their handling in practice and will stimulate further discussions and studies to fully elucidate their spectrum.
Topics: Adenoma, Oxyphilic; Biomarkers, Tumor; Carcinoma, Renal Cell; Humans; Kidney; Kidney Neoplasms
PubMed: 35273336
DOI: 10.1038/s41379-022-01057-z -
Frontiers in Endocrinology 2021Hürthle cell lesions have been a diagnostic conundrum in pathology since they were first recognized over a century ago. Controversy as to the name of the cell, the... (Review)
Review
Hürthle cell lesions have been a diagnostic conundrum in pathology since they were first recognized over a century ago. Controversy as to the name of the cell, the origin of the cell, and even which cells in particular may be designated as such still challenge pathologists and confound those treating patients with a diagnosis of "Hürthle cell" anything within the diagnosis, especially if that anything is a sizable mass lesion. The diagnosis of Hürthle cell adenoma (HCA) or Hürthle cell carcinoma (HCC) has typically relied on a judgement call by pathologists as to the presence or absence of capsular and/or vascular invasion of the adjacent thyroid parenchyma, easy to note in widely invasive disease and a somewhat subjective diagnosis for minimally invasive or borderline invasive disease. Diagnostic specificity, which has incorporated a sharp increase in molecular genetic studies of thyroid tumor subtypes and the integration of molecular testing into preoperative management protocols, continues to be challenged by Hürthle cell neoplasia. Here, we provide the improving yet still murky state of what is known about Hürthle cell tumor genetics, clinical management, and based upon what we are learning about the genetics of other thyroid tumors, how to manage expectations, by pathologists, clinicians, and patients, for more actionable, precise classifications of Hürthle cell tumors of the thyroid.
Topics: Adenoma, Oxyphilic; Biopsy; Genome, Mitochondrial; Humans; Mutation; Oxyphil Cells; Thyroid Neoplasms; Thyroidectomy
PubMed: 34177816
DOI: 10.3389/fendo.2021.696386 -
Journal of Translational Medicine Feb 2023Osteosarcoma (OS) is the most frequent and aggressive primary malignant sarcoma among adolescents and chemotherapy has not substantially progressed for decades. New...
BACKGROUND
Osteosarcoma (OS) is the most frequent and aggressive primary malignant sarcoma among adolescents and chemotherapy has not substantially progressed for decades. New insights into OS development and therapeutic strategies are urgently needed.
METHODS
We analyzed integrated single-cell transcriptomes, bulk RNA-seq, and microarray data from Gene Expression Omnibus (GEO) datasets. We also used Weighted Gene Co-expression Network Analysis (WGCNA), Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA), along with Simple ClinVar and Enrichr web servers.
RESULTS
The findings of integrated single-cell analysis showed that OS arises from imperfect osteogenesis during development. Novel abnormalities comprised deficient TGFβ and P53 signal pathways, and cell cycle pathway activation, and a potentially new driver mutation in the interferon induced transmembrane protein 5 (IFITM5) that might function as a pathogenic factor in OS. Osteosarcoma is characterized by oncocyte heterogeneity, especially in immunogenic and adipocyte-like subtypes that respectively promote and hamper OS treatment. Etoposide is a promising chemotherapeutic that provides palliation by affecting the subtype of OS and correcting the abnormal pathways.
CONCLUSION
Various abnormal signal pathways play indispensable roles in OS development. We explored the heterogeneity and underlying mechanisms of OS and generated findings that will assist with OS assessment and selecting optimal therapies.
Topics: Adolescent; Humans; Bone Neoplasms; Osteosarcoma; Signal Transduction; Sarcoma; Gene Expression Profiling; Gene Expression Regulation, Neoplastic
PubMed: 36759884
DOI: 10.1186/s12967-023-03961-7 -
Human Pathology Jun 2023The fifth edition of the World Health Organization (WHO) classification of urinary and male genital organ tumors has been recently published in 2022. The application of... (Review)
Review
The fifth edition of the World Health Organization (WHO) classification of urinary and male genital organ tumors has been recently published in 2022. The application of molecular profiling has made a substantial impact on the classification of urologic tumors. The new WHO classification introduces a group of molecularly well-defined renal tumor subtypes. The significant changes include addition of a category of "other oncocytic tumors" with oncocytoma/chromophobe renal cell carcinoma (chRCC)-like features, elimination of the subcategorization of type 1/2 papillary RCC, and inclusion of eosinophilic solid and cystic RCC as an independent tumor entity. The WHO/ISUP grading now has been recommended for all RCCs. Major nomenclature changes include replacement of histologic "variants" by "subtypes," "clear cell papillary renal cell carcinoma" to "clear cell renal cell tumor," "TCEB1-mutated RCC" to "ELOC-mutated RCC," "hereditary leiomyomatosis and renal cell carcinoma" to "fumarate hydratase-deficient RCC," "RCC-Unclassified" to "RCC-NOS," "primitive neuroectodermal tumor" to "embryonic neuroectodermal tumor," "testicular carcinoid" to "testicular neuroendocrine tumor," and "basal cell carcinoma of the prostate" to "adenoid-cystic (basal-cell) carcinoma of the prostate." Metastatic, hematolymphoid, mesenchymal, melanocytic, soft tissue, and neuroendocrine tumors are collectively discussed in separate chapters. It has been suggested that the morphological classification of urothelial cancer be replaced with a new molecular taxonomic classification system.
Topics: Humans; Male; Carcinoma, Renal Cell; Kidney Neoplasms; Genitalia, Male; Carcinoma, Basal Cell; World Health Organization; Neuroendocrine Tumors; Skin Neoplasms
PubMed: 36084769
DOI: 10.1016/j.humpath.2022.08.006 -
Frontiers in Endocrinology 2021Oncocytes are cells that have abundant eosinophilic cytoplasm due to the accumulation of mitochondria; they are also known as oxyphils. In the thyroid they have been... (Review)
Review
Oncocytes are cells that have abundant eosinophilic cytoplasm due to the accumulation of mitochondria; they are also known as oxyphils. In the thyroid they have been called Hürthle cells but this is a misnomer, since Hürthle described C cells; for this reason, we propose the use of "oncocyte" as a scientific term rather than an incorrect eponym. Oncocytic change occurs in nontumorous thyroid disorders, in benign and malignant tumors of thyroid follicular cells, in tumors composed of thyroid C cells, and intrathyroidal parathyroid proliferations as well as in metastatic lesions. The morphology of primary oncocytic thyroid tumors is similar to that of their non-oncocytic counterparts but also is complicated by the cytologic features of these cells that include both abundant eosinophilic cytoplasm and large cherry red nucleoli. The molecular alterations in oncocytic thyroid tumors echo those of their non-oncocytic counterparts but in addition feature mitochondrial DNA mutations as well as chromosomal gains and losses. In this review we emphasize the importance of recognition of the spectrum of oncocytic thyroid pathology. The cell of origin, morphologic features including architecture, nuclear atypia and invasive growth, as well as high grade features such as mitoses and necrosis, enable accurate classification of these lesions. The molecular alterations underlying the pathological entity are associated with genetic alterations associated with oncocytic change. The arbitrary cut-off of 75% oncocytic change to classify a lesion as an oncocytic variant brings another complexity to the classification scheme of tumors that frequently have mixed oncocytic and non-oncocytic components. This controversial and often confusing area of thyroid pathology requires thoughtful and cautious investigation to clarify accurate diagnosis, prognosis and prediction for patients with oncocytic thyroid lesions.
Topics: Adenoma, Oxyphilic; Humans; Oxyphil Cells; Thyroid Gland; Thyroid Neoplasms
PubMed: 34012422
DOI: 10.3389/fendo.2021.678119 -
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 -
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