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Endocrinology and Metabolism (Seoul,... Oct 2022The fifth edition of the World Health Organization (WHO) histologic classification of thyroid neoplasms released in 2022 includes newly recognized tumor types, subtypes,... (Review)
Review
The fifth edition of the World Health Organization (WHO) histologic classification of thyroid neoplasms released in 2022 includes newly recognized tumor types, subtypes, and a grading system. Follicular cell-derived neoplasms are categorized into three families (classes): benign tumors, low-risk neoplasms, and malignant neoplasms. The terms "follicular nodular disease" and "differentiated high-grade thyroid carcinoma" are introduced to account for multifocal hyperplastic/neoplastic lesions and differentiated thyroid carcinomas with high-grade features, respectively. The term "Hürthle cells" is replaced with "oncocytic cells." Invasive encapsulated follicular and cribriform morular variants of papillary thyroid carcinoma (PTC) are now redefined as distinct tumor types, given their different genetic alterations and clinicopathologic characteristics from other PTC subtypes. The term "variant" to describe a subclass of tumor has been replaced with the term "subtype." Instead, the term "variant" is reserved to describe genetic alterations. A histologic grading system based on the mitotic count, necrosis, and/or the Ki67 index is used to identify high-grade follicular-cell derived carcinomas and medullary thyroid carcinomas. The 2022 WHO classification introduces the following new categories: "salivary gland-type carcinomas of the thyroid" and "thyroid tumors of uncertain histogenesis." This review summarizes the major changes in the 2022 WHO classification and their clinical relevance.
Topics: Humans; Carcinoma, Papillary; Thyroid Neoplasms; Adenocarcinoma, Follicular; Thyroid Cancer, Papillary; World Health Organization
PubMed: 36193717
DOI: 10.3803/EnM.2022.1553 -
Thyroid : Official Journal of the... Jul 2015Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the... (Review)
Review
BACKGROUND
Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed.
METHODS
A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects ≤18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force.
RESULTS
These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided.
CONCLUSIONS
In response to our charge as an independent task force appointed by the ATA, we developed recommendations based on scientific evidence and expert opinion for the management of thyroid nodules and DTC in children and adolescents. In our opinion, these represent the current optimal care for children and adolescents with these conditions.
Topics: Adenocarcinoma, Follicular; Adenoma, Oxyphilic; Adolescent; Biopsy, Fine-Needle; Carcinoma; Carcinoma, Papillary; Child; Disease Management; Humans; Societies, Medical; Thyroid Cancer, Papillary; Thyroid Gland; Thyroid Neoplasms; Thyroid Nodule; Ultrasonography; United States
PubMed: 25900731
DOI: 10.1089/thy.2014.0460 -
Annals of Oncology : Official Journal... Dec 2019
Topics: Humans; Adenocarcinoma, Follicular; Carcinoma, Neuroendocrine; Follow-Up Studies; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms
PubMed: 31549998
DOI: 10.1093/annonc/mdz400 -
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 -
Nature Reviews. Endocrinology Nov 2016During the past few decades, the incidence of thyroid cancer has increased substantially in many countries, including the USA. The rise in incidence seems to be... (Review)
Review
During the past few decades, the incidence of thyroid cancer has increased substantially in many countries, including the USA. The rise in incidence seems to be attributable both to the growing use of diagnostic imaging and fine-needle aspiration biopsy, which has led to enhanced detection and diagnosis of subclinical thyroid cancers, and environmental factors. The latest American Thyroid Association (ATA) practice guidelines for the management of adult patients with thyroid nodules and differentiated thyroid cancer differ substantially from the previous ATA guidelines published in 2009. Specifically, the problems of overdiagnosis and overtreatment of a disease that is typically indolent, where treatment-related morbidity might not be justified by a survival benefit, now seem to be acknowledged. As few modifiable risk factors for thyroid cancer have been established, the specific environmental factors that have contributed to the rising incidence of thyroid cancer remain speculative. However, the findings of several large, well-designed epidemiological studies have provided new information about exposures (such as obesity) that might influence the development of thyroid cancer. In this Review, we describe the changing incidence of thyroid cancer, suggest potential explanations for these trends, emphasize the implications for patients and highlight ongoing and potential strategies to combat this growing clinical and public health issue.
Topics: Adenocarcinoma, Follicular; Age Distribution; Biopsy, Fine-Needle; Carcinoma; Carcinoma, Neuroendocrine; Carcinoma, Papillary; Humans; Incidence; Medical Overuse; Obesity; Radiation Exposure; Risk Factors; Sex Distribution; Smoking; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Thyroid Nodule; United States
PubMed: 27418023
DOI: 10.1038/nrendo.2016.110 -
American Family Physician Sep 2020Thyroid nodules can be detected by ultrasonography in up to 68% of the general population. They are typically benign and are often discovered incidentally. The primary... (Review)
Review
Thyroid nodules can be detected by ultrasonography in up to 68% of the general population. They are typically benign and are often discovered incidentally. The primary goal of thyroid nodule evaluation is to determine whether it is malignant. After thyroid ultrasonography has been performed, the next step is measurement of serum thyroid-stimulating hormone. If levels are low, a radionuclide thyroid uptake scan is indicated. Hyperfunctioning nodules are rarely malignant and do not require tissue sampling. Nonfunctioning nodules and nodules in a patient with a normal or high thyroid-stimulating hormone level may require fine-needle aspiration based on ultrasound characteristics and size. Nodules with suspicious features and solid hypoechoic nodules 1 cm or larger require aspiration. The Bethesda System (categories 1 through 6) is used to classify samples. Molecular testing can be used to guide treatment when aspiration yields an indeterminate result. Molecular testing detects mutations associated with thyroid cancer and can help inform decisions about surgical excision vs. continued ultrasound monitoring. Treatment of pregnant women with nonfunctioning thyroid nodules and of children with thyroid nodules is similar to that for nonpregnant adults, with the exception of molecular testing, which has not been validated in these populations.
Topics: Adenocarcinoma, Follicular; Antithyroid Agents; Biopsy, Fine-Needle; Carcinoma, Papillary; Humans; Iodine Radioisotopes; Molecular Diagnostic Techniques; Mutation; Predictive Value of Tests; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroid Nodule; Thyroidectomy; Tumor Burden; Ultrasonography; Watchful Waiting
PubMed: 32866364
DOI: No ID Found -
Cancer Discovery Jan 2023The skin is exposed to viral pathogens, but whether they contribute to the oncogenesis of skin cancers has not been systematically explored. Here we investigated 19 skin...
UNLABELLED
The skin is exposed to viral pathogens, but whether they contribute to the oncogenesis of skin cancers has not been systematically explored. Here we investigated 19 skin tumor types by analyzing off-target reads from commonly available next-generation sequencing data for viral pathogens. We identified human papillomavirus 42 (HPV42) in 96% (n = 45/47) of digital papillary adenocarcinoma (DPA), an aggressive cancer occurring on the fingers and toes. We show that HPV42, so far considered a nononcogenic, "low-risk" HPV, recapitulates the molecular hallmarks of oncogenic, "high-risk" HPVs. Using machine learning, we find that HPV-driven transformation elicits a germ cell-like transcriptional program conserved throughout all HPV-driven cancers (DPA, cervical carcinoma, and head and neck cancer). We further show that this germ cell-like transcriptional program, even when reduced to the top two genes (CDKN2A and SYCP2), serves as a fingerprint of oncogenic HPVs with implications for early detection, diagnosis, and therapy of all HPV-driven cancers.
SIGNIFICANCE
We identify HPV42 as a uniform driver of DPA and add a new member to the short list of tumorigenic viruses in humans. We discover that all oncogenic HPVs evoke a germ cell-like transcriptional program with important implications for detecting, diagnosing, and treating all HPV-driven cancers. See related commentary by Starrett et al., p. 17. This article is highlighted in the In This Issue feature, p. 1.
Topics: Female; Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Uterine Cervical Neoplasms; Skin Neoplasms; Bone Neoplasms; Breast Neoplasms; Papillomaviridae; Adenocarcinoma, Clear Cell; Adenocarcinoma, Papillary; Germ Cells
PubMed: 36213965
DOI: 10.1158/2159-8290.CD-22-0489 -
International Journal of Molecular... Jun 2017Differentiated thyroid cancer (DTC) is a rare malignant disease, although its incidence has increased over the last few decades. It derives from follicular thyroid... (Review)
Review
Differentiated thyroid cancer (DTC) is a rare malignant disease, although its incidence has increased over the last few decades. It derives from follicular thyroid cells. Generally speaking, the prognosis is excellent. If treatment according to the current guidelines is given, cases of recurrence or persistence are rare. DTC requires special expertise by the treating physician. In recent years, new therapeutic options for these patients have become available. For this article we performed a systematic literature review with special focus on the guidelines of the American Thyroid Association, the European Association of Nuclear Medicine, and the German Society of Nuclear Medicine. For DTC, surgery and radioiodine therapy followed by levothyroxine substitution remain the established therapeutic procedures. Even metastasized tumors can be cured this way. However, in rare cases of radioiodine-refractory tumors, additional options are to be discussed. These include strict suppression of thyroid-stimulating hormone (also known as thyrotropin, TSH) and external local radiotherapy. Systemic cytostatic chemotherapy does not play a significant role. Recently, multikinase or tyrosine kinase inhibitors have been approved for the treatment of radioiodine-refractory DTC. Although a benefit for overall survival has not been shown yet, these new drugs can slow down tumor progression. However, they are frequently associated with severe side effects and should be reserved for patients with threatening symptoms only.
Topics: Adenocarcinoma; Adenocarcinoma, Follicular; Carcinoma, Papillary; Drug Therapy; Enzyme Inhibitors; Humans; Iodine Radioisotopes; Neoplasm Metastasis; Noonan Syndrome; Prognosis; Protein-Tyrosine Kinases; Radiotherapy; Radiotherapy, Adjuvant; Thyroid Cancer, Papillary; Thyroid Hormones; Thyroid Neoplasms; Thyroid Nodule; Thyrotropin; Thyroxine
PubMed: 28629126
DOI: 10.3390/ijms18061292 -
JAMA Oncology Aug 2016Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are...
IMPORTANCE
Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer.
OBJECTIVE
To evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC.
DESIGN, SETTING, AND PARTICIPANTS
International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature.
MAIN OUTCOMES AND MEASURES
Frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria.
RESULTS
Consensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median [range], 13 [10-26] years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6% (95% CI, 96.3%-99.4%), specificity of 90.1% (95% CI, 86.0%-93.1%), and overall classification accuracy of 94.3% (95% CI, 92.1%-96.0%) for NIFTP.
CONCLUSIONS AND RELEVANCE
Thyroid tumors currently diagnosed as noninvasive EFVPTC have a very low risk of adverse outcome and should be termed NIFTP. This reclassification will affect a large population of patients worldwide and result in a significant reduction in psychological and clinical consequences associated with the diagnosis of cancer.
Topics: Adenocarcinoma, Follicular; Adult; Aged; Aged, 80 and over; Carcinoma; Carcinoma, Papillary; Female; Humans; Male; Medical Overuse; Middle Aged; Neoplasm Invasiveness; Retrospective Studies; Terminology as Topic; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroid Nodule; Young Adult
PubMed: 27078145
DOI: 10.1001/jamaoncol.2016.0386 -
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