-
Endocrine Pathology Mar 2022This review summarizes the changes in the 5th edition of the WHO Classification of Endocrine and Neuroendocrine Tumors that relate to the thyroid gland. The new... (Review)
Review
This review summarizes the changes in the 5th edition of the WHO Classification of Endocrine and Neuroendocrine Tumors that relate to the thyroid gland. The new classification has divided thyroid tumors into several new categories that allow for a clearer understanding of the cell of origin, pathologic features (cytopathology and histopathology), molecular classification, and biological behavior. Follicular cell-derived tumors constitute the majority of thyroid neoplasms. In this new classification, they are divided into benign, low-risk, and malignant neoplasms. Benign tumors include not only follicular adenoma but also variants of adenoma that are of diagnostic and clinical significance, including the ones with papillary architecture, which are often hyperfunctional and oncocytic adenomas. For the first time, there is a detailed account of the multifocal hyperplastic/neoplastic lesions that commonly occur in the clinical setting of multinodular goiter; the term thyroid follicular nodular disease (FND) achieved consensus as the best to describe this enigmatic entity. Low-risk follicular cell-derived neoplasms include non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), thyroid tumors of uncertain malignant potential, and hyalinizing trabecular tumor. Malignant follicular cell-derived neoplasms are stratified based on molecular profiles and aggressiveness. Papillary thyroid carcinomas (PTCs), with many morphological subtypes, represent the BRAF-like malignancies, whereas invasive encapsulated follicular variant PTC and follicular thyroid carcinoma represent the RAS-like malignancies. This new classification requires detailed subtyping of papillary microcarcinomas similar to their counterparts that exceed 1.0 cm and recommends not designating them as a subtype of PTC. The criteria of the tall cell subtype of PTC have been revisited. Cribriform-morular thyroid carcinoma is no longer classified as a subtype of PTC. The term "Hürthle cell" is discouraged, since it is a misnomer. Oncocytic carcinoma is discussed as a distinct entity with the clear recognition that it refers to oncocytic follicular cell-derived neoplasms (composed of > 75% oncocytic cells) that lack characteristic nuclear features of PTC (those would be oncocytic PTCs) and high-grade features (necrosis and ≥ 5 mitoses per 2 mm). High-grade follicular cell-derived malignancies now include both the traditional poorly differentiated carcinoma as well as high-grade differentiated thyroid carcinomas, since both are characterized by increased mitotic activity and tumor necrosis without anaplastic histology and clinically behave in a similar manner. Anaplastic thyroid carcinoma remains the most undifferentiated form; squamous cell carcinoma of the thyroid is now considered as a subtype of anaplastic carcinoma. Medullary thyroid carcinomas derived from thyroid C cells retain their distinct section, and there is a separate section for mixed tumors composed of both C cells and any follicular cell-derived malignancy. A grading system for medullary thyroid carcinomas is also introduced based on mitotic count, tumor necrosis, and Ki67 labeling index. A number of unusual neoplasms that occur in the thyroid have been placed into new sections based on their cytogenesis. Mucoepidermoid carcinoma and secretory carcinoma of the salivary gland type are now included in one section classified as "salivary gland-type carcinomas of the thyroid." Thymomas, thymic carcinomas and spindle epithelial tumor with thymus-like elements are classified as "thymic tumors within the thyroid." There remain several tumors whose cell lineage is unclear, and they are listed as such; these include sclerosing mucoepidermoid carcinoma with eosinophilia and cribriform-morular thyroid carcinoma. Another important addition is thyroblastoma, an unusual embryonal tumor associated with DICER1 mutations. As in all the WHO books in the 5th edition, mesenchymal and stromal tumors, hematolymphoid neoplasms, germ cell tumors, and metastatic malignancies are discussed separately. The current classification also emphasizes the value of biomarkers that may aid diagnosis and provide prognostic information.
Topics: Adenocarcinoma, Follicular; Carcinoma, Neuroendocrine; Carcinoma, Papillary; DEAD-box RNA Helicases; Humans; Ribonuclease III; Thyroid Neoplasms; World Health Organization
PubMed: 35288841
DOI: 10.1007/s12022-022-09707-3 -
Endocrine Pathology Mar 2022This review summarizes the changes in the 5th Edition of the WHO Classification of Endocrine and Neuroendocrine Tumors that relate to the pituitary gland. The new... (Review)
Review
This review summarizes the changes in the 5th Edition of the WHO Classification of Endocrine and Neuroendocrine Tumors that relate to the pituitary gland. The new classification clearly distinguishes anterior lobe (adenohypophyseal) from posterior lobe (neurohypophyseal) and hypothalamic tumors. Other tumors arising in the sellar region are also discussed. Anterior lobe tumors include (i) well-differentiated adenohypophyseal tumors that are now classified as pituitary neuroendocrine tumors (PitNETs; formerly known as pituitary adenomas), (ii) pituitary blastoma, and (iii) the two types of craniopharyngioma. The new WHO classification provides detailed histological subtyping of a PitNET based on the tumor cell lineage, cell type, and related characteristics. The routine use of immunohistochemistry for pituitary transcription factors (PIT1, TPIT, SF1, GATA3, and ERα) is endorsed in this classification. The major PIT1, TPIT, and SF1 lineage-defined PitNET types and subtypes feature distinct morphologic, molecular, and clinical differences. The "null cell" tumor, which is a diagnosis of exclusion, is reserved for PitNETs with no evidence of adenohypophyseal lineage differentiation. Unlike the 2017 WHO classification, mammosomatotroph and acidophil stem cell tumors represent distinct PIT1-lineage PitNETs. The diagnostic category of PIT1-positive plurihormonal tumor that was introduced in the 2017 WHO classification is replaced by two clinicopathologically distinct PitNETs: the immature PIT1-lineage tumor (formerly known as silent subtype 3 tumor) and the mature plurihormonal PIT1-lineage tumor. Rare unusual plurihormonal tumors feature multi-lineage differentiation. The importance of recognizing multiple synchronous PitNETs is emphasized to avoid misclassification. The term "metastatic PitNET" is advocated to replace the previous terminology "pituitary carcinoma" in order to avoid confusion with neuroendocrine carcinoma (a poorly differentiated epithelial neuroendocrine neoplasm). Subtypes of PitNETs that are associated with a high risk of adverse biology are emphasized within their cell lineage and cell type as well as based on clinical variables. Posterior lobe tumors, the family of pituicyte tumors, include the traditional pituicytoma, the oncocytic form (spindle cell oncocytoma), the granular cell form (granular cell tumor), and the ependymal type (sellar ependymoma). Although these historical terms are entrenched in the literature, they are nonspecific and confusing, such that oncocytic pituicytoma, granular cell pituicytoma, and ependymal pituicytoma are now proposed as more accurate. Tumors with hypothalamic neuronal differentiation are classified as gangliocytomas or neurocytomas based on large and small cell size, respectively. This classification sets the standard for a high degree of sophistication to allow individualized patient management approaches.
Topics: Adenoma; Craniopharyngioma; Humans; Pituitary Gland; Pituitary Neoplasms; World Health Organization
PubMed: 35291028
DOI: 10.1007/s12022-022-09703-7 -
Head and Neck Pathology Mar 2022The salivary gland section in the 5th edition of the World Health Organization Classification of Head and Neck Tumours features a description and inclusion of several...
The salivary gland section in the 5th edition of the World Health Organization Classification of Head and Neck Tumours features a description and inclusion of several new entities, including sclerosing polycystic adenoma, keratocystoma, intercalated duct adenoma, and striated duct adenoma among the benign neoplasms; and microsecretory adenocarcinoma and sclerosing microcystic adenocarcinoma as the new malignant entities. The new entry also includes mucinous adenocarcinoma subdivided into papillary, colloid, signet ring, and mixed subtypes with recurrent AKT1 E17K mutations across patterns suggesting that mucin-producing salivary adenocarcinomas represent a histologically diverse single entity that may be related to salivary intraductal papillary mucinous neoplasm (IPMN). Importantly, the number of entities in the salivary chapter has been reduced by omitting tumors or lesions if they do not occur exclusively or predominantly in salivary glands, including hemangioma, lipoma, nodular fasciitis and hematolymphoid tumors. They are now discussed in detail elsewhere in the book. Cribriform adenocarcinoma of salivary gland origin (CASG) now represents a distinctive subtype of polymorphous adenocarcinoma (PAC). PAC is defined as a clinically, histologically and molecularly heterogeneous disease group. Whether CASG is a different diagnostic category or a variant of PAC is still controversial. Poorly differentiated carcinomas and oncocytic carcinomas are discussed in the category "Salivary carcinoma not otherwise specified (NOS) and emerging entities". New defining genomic alterations have been characterized in many salivary gland tumors. In particular, they include gene fusions, which have shown to be tightly tumor-type specific, and thus valuable for use in diagnostically challenging cases. The recurrent molecular alterations were included in the definition of mucoepidermoid carcinoma, adenoid cystic carcinoma, secretory carcinoma, polymorphous adenocarcinoma, hyalinizing clear cell carcinoma, mucinous adenocarcinoma, and microsecretory adenocarcinoma.
Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adenoma; Biomarkers, Tumor; Humans; Salivary Gland Neoplasms; Salivary Glands; World Health Organization
PubMed: 35312980
DOI: 10.1007/s12105-022-01420-1 -
Histopathology Sep 2021Pleomorphic adenoma (PA) is the most common salivary gland neoplasm, and its diagnosis is straightforward in the majority of cases. However, not infrequently, PA shows... (Review)
Review
Pleomorphic adenoma (PA) is the most common salivary gland neoplasm, and its diagnosis is straightforward in the majority of cases. However, not infrequently, PA shows unusual and uncommon histological features that can be confused with those of malignancy. The difficulties in diagnosing PA arise from its ability to mimic invasion, show atypical or metaplastic cytomorphology, and show morphological features that overlap with those of established salivary gland carcinomas. In addition, recognising early malignant transformation to carcinoma ex-pleomorphic adenoma continues to be a frequent challenge. This review describes the diagnostic pitfalls of PA, and offers a systematic approach to avoid them by combining classic histopathology with novel immunohistochemical and molecular tests.
Topics: Adenocarcinoma; Adenoma, Pleomorphic; Biomarkers, Tumor; Carcinoma; Cell Transformation, Neoplastic; Diagnosis, Differential; Humans; Metaplasia; Salivary Gland Neoplasms
PubMed: 33368685
DOI: 10.1111/his.14322 -
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 -
La Tunisie Medicale Mar 2018Oncocytic tumors (OT) are rare, representing 3 to 10% of epithelial tumors of the thyroid. It is important to individualize these TO given the relatively high frequency...
BACKGROUND
Oncocytic tumors (OT) are rare, representing 3 to 10% of epithelial tumors of the thyroid. It is important to individualize these TO given the relatively high frequency of carcinomas in this group: 30% against 15% for micro-vesicular lesions of classical cytology and the aggressiveness of malignant OT due to their low iodine uptake.
AIM
The aim of our study was to describe the anatomo-clinical aspects of oncocytic tumors of the thyroid.
METHODS
Our study was retrospective, realized on 99 cases of oncocyte thyroid tumors collected at the Anatomy and Pathology Cytology laboratory of Tunis Charles Nicolle Hospital during a 10-year period (2004-2014).
RESULTS
Our series included: 76 oncocyte adenomas, 13 oncocytic papillary carcinomas, 7 oncocytic carcinomas and 3 tumors of uncertain malignant potential (3%). The correlation of the anatomo-clinical data with the diagnostic categories showed a statistically significant difference concerning the macrovesicular architecture. We found no difference between benign and malignant TO, in relation to age, echogenicity, tumor size, macroscopic appearance, capsule thickness, percentage of oncocyte cells, and the presence of associated lymphocyte thyroiditis.
CONCLUSIONS
In view of the literature data and the findings of our study, it seems that there are no predictive factors for the malignancy of oncocytic tumors at the pre- and peroperative stage, with the exception of papillary-type nuclear atypia for Oncocytic papillary carcinoma.
Topics: Adenoma, Oxyphilic; Adolescent; Adult; Aged; Aged, 80 and over; Cytodiagnosis; Female; Humans; Male; Middle Aged; Retrospective Studies; Thyroid Gland; Thyroid Neoplasms; Tunisia; Ultrasonography; Young Adult
PubMed: 30325491
DOI: No ID Found -
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