Seven years of Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): Rate of Acceptance and Variation of Diagnostic Approaches Across Different Continents.

CONTEXT: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a new entity replacing the diagnosis of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC). Significant variability in the incidence of NIFTP diagnosed in different world regions has been reported. OBJECTIVE: To investigate the rate of adoption of NIFTP, change in practice patterns, and uniformity in applying diagnostic criteria among pathologists practicing in different regions. METHODS: Two surveys distributed to pathologists of the International Endocrine Pathology Discussion Group with multiple-choice questions on NIFTP adoption into pathology practice and whole slide images of 5 tumors to collect information on nuclear score and diagnosis. Forty-eight endocrine pathologists, including 24 from North America, 8 from Europe, and 16 from Asia/Oceania completed the first survey and 38 the second survey. RESULTS: A 94% adoption rate of NIFTP by the pathologists was found. Yet, the frequency of rendering NIFTP diagnosis was significantly higher in North America than in other regions (P = .009). While the highest concordance was found in diagnosing lesions with mildly or well-developed PTC-like nuclei, there was significant variability in nuclear scoring and diagnosing NIFTP for tumors with moderate nuclear changes (nuclear score 2) (case 2, P < .05). Pathologists practicing in North America and Europe showed a tendency for lower thresholds for PTC-like nuclei and NIFTP than those practicing in Asia/Oceania. CONCLUSION: Despite a high adoption rate of NIFTP across geographic regions, NIFTP is diagnosed more often by pathologists in North America. Significant differences remain in diagnosing intermediate PTC-like nuclei and respectively NIFTP, with more conservative nuclear scoring in Asia/Oceania, which may explain the geographic differences in NIFTP incidence.

Performance of a multigene genomic classifier and clinical parameters in predicting malignancy in a Southeast Asian cohort of patients with cytologically indeterminate thyroid nodules.

BACKGROUND: Most thyroid nodules are benign. It is important to determine the likelihood of malignancy in such nodules to avoid unnecessary surgery. The primary objective of this study was to characterize the genetic landscape and the performance of a multigene genomic classifier in fine-needle aspiration (FNA) biopsies of cytologically indeterminate thyroid nodules in a Southeast Asian cohort. The secondary objective was to assess the predictive contribution of clinical characteristics to thyroid malignancy. METHODS: This prospective, multicenter, blinded study included 132 patients with 134 nodules. Molecular testing (MT) with ThyroSeq v3 was performed on clinical or ex-vivo FNA samples. Centralized pathology review also was performed. RESULTS: Of 134 nodules, consisting of 61% Bethesda category III, 20% category IV, and 19% category V cytology, and 56% were histologically malignant. ThyroSeq yielded negative results in 37.3% of all FNA samples and in 42% of Bethesda category III-IV cytology nodules. Most positive samples had RAS-like (41.7%), followed by BRAF-like (22.6%), and high-risk (17.9%) alterations. Compared with North American patients, the authors observed a higher proportion of RAS-like mutations, specifically NRAS, in Bethesda categories III and IV and more BRAF-like mutations in Bethesda category III. The test had sensitivity, specificity, negative predictive value, and positive predictive value of 89.6%, 73.7%, 84.0%, and 82.1%, respectively. The risk of malignancy was predicted by positive MT and high-suspicion ultrasound characteristics according to American Thyroid Association criteria. CONCLUSIONS: Even in the current Southeast Asian cohort with nodules that had a high pretest cancer probability, MT could lead to potential avoidance of diagnostic surgery in 42% of patients with Bethesda category III-IV nodules. MT positivity was a stronger predictor of malignancy than clinical parameters.

Neoplasms in Struma Ovarii: A Review.

Struma ovarii is a well-known ovarian teratoma made up of benign thyroid tissue. These lesions demonstrate variable, normal architecture and normal thyroid immunohistochemical staining with positivity for TTF1, PAX8, and thyroglobulin. Though most are benign, some of these lesions can also present with a malignant component. Within this article, we review the most common diagnostic malignancies including papillary thyroid carcinoma, strumal carcinoid, highly differentiated follicular thyroid carcinoma, and other thyroid carcinomas. We additionally review the use of TTF1 staining to assist in differentiating these lesions from surrounding gynecologic epithelium, which is imperative in making such diagnoses. In highlighting these entities, we hope to provide practicing pathologists with an effective and concise review of these lesions to assist in more challenging cases of struma ovarii.

The Cooperative Human Tissue Network of the National Cancer Institute: Supporting Cancer Research for 35 Years.

The Cooperative Human Tissue Network was created by the NCI in 1987 to support a coordinated national effort to collect and distribute high quality, pathologist-validated human tissues for cancer research. Since then, the network has expanded to provide different types of tissue samples, blood and body fluid samples, immunohistologic and molecular sample preparations, tissue microarrays, and clinical datasets inclusive of biomarkers and molecular testing. From inception through the end of 2021, the network has distributed 1,375,041 biospecimens. It served 889 active investigators in 2021. The network has also taken steps to begin to optimize the representation of diverse communities among the distributed biospecimens. In this article, the authors review the 35-year history of this network, describe changes to the program over the last 15 years, and provide operational and scientific highlights from each of the divisions. Readers will learn how to engage with the network and about the continued evolution of the program for the future.

Brain metastases of papillary thyroid carcinoma origin are derived from aggressive histologic variants and demonstrate similar adverse morphology in the metastatic lesion.

BACKGROUND: Distant metastases of papillary thyroid carcinoma are exceedingly rare. We analyzed all cases of brain metastases of papillary thyroid cancer at our institution and performed a literature review over the past ten years to identify histologic and molecular features of primary and metastatic tumors. METHODS: Following institutional review board approval, the entire pathology archives at our institution were searched for cases of papillary thyroid carcinoma metastatic to brain. Patient demographics, histologic features of both primary and metastatic tumors, molecular information, and clinical outcomes were investigated. RESULTS: We identified 8 cases of metastatic papillary thyroid carcinoma to brain. The average age at time of diagnosis of metastases was 56.3 years (range: 30-85). Average time from diagnosis of primary thyroid cancer to brain metastasis was 9.3 years (range: 0-24 years). All primary thyroid carcinomas demonstrated aggressive sub-types which were correspondingly seen in brain metastases. Next-generation sequencing revealed the most common mutations were identified in BRAFV600E, NRAS, and AKT1 with one tumor harboring a TERT promoter mutation. Six out of eight patients were deceased at the time of study with an average survival time of 2.3 years (range: 0.17-7 years) following diagnosis of brain metastasis. CONCLUSIONS: Based on our study, it is highly unlikely that a low-risk variant of papillary thyroid carcinoma will metastasize to the brain. Therefore, careful and accurate reporting of the papillary thyroid carcinoma subtype in primary thyroid tumors is warranted. Certain molecular signatures are associated with more aggressive behavior and worse patient outcomes and next-generation sequencing should be performed on metastatic lesions.

Insights Obtained from the Nontumorous Glandular Tissue in Patients with Endocrine Tumors.

The pathology of neoplasia tends to focus on the tumor that requires characterization, grading, and staging. However, nontumorous tissue surrounding the lesion can also provide information, particularly about pathogenetic mechanisms. In endocrine tissues, this takes the form of precursor lesions that characterize several genetic predisposition syndromes. In addition, because of the unique functional aspects of endocrine neoplasia, the nontumorous tissue provides evidence of hormone excess, with hyperplasia and/or atrophy and other involutional changes allowing the pathologist to confirm both hormone function by the tumor and the effects of medical therapies. In this article, we review the various clinically relevant features that should be assessed and reported to enhance clinical management of patients with endocrine neoplasms. For example, in thyroid there may be inflammatory thyroiditis or goiter of various etiologies; there may be C-cell hyperplasia either as a preneoplastic lesion in patients with genetic predisposition to medullary thyroid carcinoma or as a reactive phenomenon. Drug-induced changes can be seen in thyroid and adrenal cortex. In neuroendocrine tissues, the nontumorous tissues may show precursor lesions such as endocrine cell hyperplasia/dysplasia; there may be related or unrelated hyperplastic or neoplastic lesions. Some tissues, such as pituitary corticotrophs and adrenal cortex, develop changes that reflect feedback suppression by hormone excess that can serve as biomarkers of tumor functionality and provide enhanced clinicopathologic correlates.

Update on Sinonasal Tract Malignancies.

CONTEXT.­: Sinonasal tract malignancies are rare cancers with frequent morphologic overlap. Given the similar histologic profiles seen in many of these entities, they often present a diagnostic challenge to the practicing pathologist. OBJECTIVE.­: To provide a streamlined algorithm using histologic clues, immunohistochemical profiles, and molecular assays to aid in diagnosis of these lesions. DATA SOURCES.­: Sources were the World Health Organization Tumor Classification, literature review, and institutional experience. CONCLUSIONS.­: Although many sinonasal tract malignancies show similar histology, distinct immunohistochemical and molecular profiles can help parse out differences, thereby facilitating diagnosis for the pathologist.

The Thyroid Pathologist Meets Therapeutic Pharmacology.

The effects of many pharmacological agents on thyroid function are well known. Direct influences on measurements of thyroid function tests are also described. However, certain classes of drugs produce morphological changes in the gland. This review focuses on the significance of the following drug classes for the thyroid pathologist: iodine, antithyroid drugs, psychotropic drugs, antibiotics, cardiotropic drugs, antidiabetic drugs, and immunomodulatory agents. Radioactive iodine initially induces mild histologic changes; however, the long-term effects include marked follicular atrophy, fibrosis, and nuclear atypia-changes that vary depending on the pre-therapy condition of the gland. Some psychotropic drugs have been associated with a spectrum of inflammatory changes throughout the gland. The tetracycline class of antibiotics, namely minocycline, can lead to a grossly black thyroid gland with pigment seen in both colloid and follicular epithelial cells while variably present within thyroid nodules. The surgical pathologist most commonly sees an amiodarone-affected gland removed for hyperthyroidism, and the histologic findings again depend on the pre-therapy condition of the gland. While GLP-1 receptor agonists carry an FDA black box warning for patients with a personal or family history of multiple endocrine neoplasia or medullary thyroid carcinoma, the C cell hyperplasia originally noted in rats has not borne out in human studies. Finally, thyroiditis and hypothyroidism are well known complications of checkpoint inhibitor therapy, and rare cases of severe thyroiditis requiring urgent thyroidectomy have been reported with unique histologic findings. In this review, we describe the histologic findings for these drugs and more, in many cases including their functional consequences.

Diagnostic Accuracy of Fine-Needle Biopsy in the Detection of Thyroid Malignancy: A Systematic Review and Meta-analysis.

Importance: Fine-needle biopsy (FNB) became a critical part of thyroid nodule evaluation in the 1970s. It is not clear how diagnostic accuracy of FNB has changed over time. Objective: To conduct a systematic review and meta-analysis estimating the accuracy of thyroid FNB for diagnosis of malignancy in adults with a newly diagnosed thyroid nodule and to characterize changes in accuracy over time. Data Sources: PubMed, SCOPUS, and Cochrane Central Register of Controlled Trials were searched from 1975 to 2020 using search terms related to FNB accuracy in the thyroid. Study Selection: English-language reports of cohort studies or randomized trials of adult patients undergoing thyroid FNB with sample size of 20 or greater and using a reference standard of surgical histopathology or clinical follow-up were included. Articles that examined only patients with known thyroid disease or focused on accuracy of novel adjuncts, such as molecular tests, were excluded. Two investigators screened each article and resolved conflicts by consensus. A total of 36 of 1023 studies met selection criteria. Data Extraction and Synthesis: The MOOSE guidelines were used for data abstraction and assessing data quality and validity. Two investigators abstracted data using a standard form. Studies were grouped into epochs by median data collection year (1975 to 1990, 1990 to 2000, 2000 to 2010, and 2010 to 2020). Data were pooled using a bivariate mixed-effects model. Main Outcomes and Measures: The primary outcome was accuracy of FNB for diagnosis of malignancy. Accuracy was hypothesized to increase in later time periods, a hypothesis formulated prior to data collection. Results: Of 16 597 included patients, 12 974 (79.2%) were female, and the mean (SD) age was 47.3 (12.9) years. The sensitivity of FNB was 85.6% (95% CI, 79.9-89.5), the specificity was 71.4% (95% CI, 61.1-79.8), the positive likelihood ratio was 3.0 (95% CI, 2.3-4.1), and the negative likelihood ratio was 0.2 (95% CI, 0.2-0.3). The area under the receiver operating characteristic curve was 86.1%. Epoch was not significantly associated with accuracy. None of the available covariates could explain observed heterogeneity. Conclusions and Relevance: Accuracy of thyroid FNB has not significantly changed over time. Important developments in technique, preparation, and interpretation may have occurred too heterogeneously to capture a consistent uptrend over time. FNB remains a reliable test for thyroid cancer diagnosis.

Surgical Aspects of Primary Hyperparathyroidism.

Parathyroidectomy (PTX) is the treatment of choice for symptomatic primary hyperparathyroidism (PHPT). It is also the treatment of choice in asymptomatic PHPT with evidence for target organ involvement. This review updates surgical aspects of PHPT and proposes the following definitions based on international expert consensus: selective PTX (and reasons for conversion to an extended procedure), bilateral neck exploration for non-localized or multigland disease, subtotal PTX, total PTX with immediate or delayed autotransplantation, and transcervical thymectomy and extended en bloc PTX for parathyroid carcinoma. The systematic literature reviews discussed covered (i) the use of intraoperative PTH (ioPTH) for localized single-gland disease and (ii) the management of low BMD after PTX. Updates based on prospective observational studies are presented concerning PTX for multigland disease and hereditary PHPT syndromes, histopathology, intraoperative adjuncts, localization techniques, perioperative management, "reoperative" surgery and volume/outcome data. Postoperative complications are few and uncommon (<3%) in centers performing over 40 PTXs per year. This review is the first global consensus about surgery in PHPT and reflects the current practice in leading endocrine surgery units worldwide. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Molecular identification of an ETV6-RET fusion in a secretory carcinoma associated with a pleomorphic adenoma.

Pleomorphic adenoma (PA) is the most common neoplasm of the salivary glands. Although several carcinomas have been reported to arise from PA, only 1 case of salivary gland secretory carcinoma (SC) ex pleomorphic adenoma has been previously reported. SC is a newly described salivary gland tumor harboring an ETV6-NTRK3 translocation, which is classically observed in secretory carcinoma of the breast, although other translocations have recently been observed. We report the first case of the molecular identification of a rare ETV6-RET translocation in an SC arising from a PA in the submandibular salivary gland (SC ex PA). Our results add to the diversity of tumors that are associated with PA and contribute to the molecular characterization of SC, which will have implications on its diagnosis, prognosis, and treatment.

Preoperative Identification of Medullary Thyroid Carcinoma (MTC): Clinical Validation of the Afirma MTC RNA-Sequencing Classifier.

Background: Cytopathological evaluation of thyroid fine-needle aspiration biopsy (FNAB) specimens can fail to raise preoperative suspicion of medullary thyroid carcinoma (MTC). The Afirma RNA-sequencing MTC classifier identifies MTC among FNA samples that are cytologically indeterminate, suspicious, or malignant (Bethesda categories III-VI). In this study we report the development and clinical performance of this MTC classifier. Methods: Algorithm training was performed with a set of 483 FNAB specimens (21 MTC and 462 non-MTC). A support vector machine classifier was developed using 108 differentially expressed genes, which includes the 5 genes in the prior Afirma microarray-based MTC cassette. Results: The final MTC classifier was blindly tested on 211 preoperative FNAB specimens with subsequent surgical pathology, including 21 MTC and 190 non-MTC specimens from benign and malignant thyroid nodules independent from those used in training. The classifier had 100% sensitivity (21/21 MTC FNAB specimens correctly called positive; 95% confidence interval [CI] = 83.9-100%) and 100% specificity (190/190 non-MTC FNAs correctly called negative; CI = 98.1-100%). All positive samples had pathological confirmation of MTC, while all negative samples were negative for MTC on surgical pathology. Conclusions: The RNA-sequencing MTC classifier accurately identified MTC from preoperative thyroid nodule FNAB specimens in an independent validation cohort. This identification may facilitate an MTC-specific preoperative evaluation and resulting treatment.

A benchmark for oncologic outcomes and model for lethal recurrence risk after transoral robotic resection of HPV-related oropharyngeal cancers.

OBJECTIVES: Increasing use of transoral robotic surgery (TORS) is likely to impact outcomes for HPV+ oropharyngeal squamous cell carcinomas (OPSCCs). We aimed to describe oncologic outcomes for a large HPV+ OPSCC cohort after TORS and develop a risk prediction model for recurrence under this treatment paradigm. MATERIALS AND METHODS: 634 HPV+ OPSCC patients receiving TORS-based therapy at a single institution were reviewed retrospectively to describe survival across the entire cohort and for patients suffering recurrence. Risks for distant metastatic recurrence (DMR) and locoregional recurrence (LRR) were modeled using multivariate logistic regression analyses of case-control sub-cohorts. RESULTS: 5-year overall and recurrence-free survival were 91.2% and 86.1%, respectively. 5-year overall survival was 52.5% following DMR and 83.3% after isolated LRR (P = .01). In case-control analyses, positive surgical margins were associated with DMR (adjusted OR 5.8, CI 2.1-16.0, P = .001), but not isolated LRR, and increased DMR risk 4.2 fold in patients with early clinical stage disease. By contrast, LRR was associated with not receiving recommended adjuvant therapy (OR 13.4, CI 6.3-28.5, P < .001). CONCLUSIONS: This study sets a benchmark for oncologic outcomes from HPV+ OPSCC after TORS-based therapy. Under this treatment paradigm, margins are relevant for assessing lethal recurrence risk during clinical trial design and post-treatment surveillance.

Overview of the 2022 WHO Classification of Thyroid Neoplasms.

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 mm2). 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.

A Cyst-ematic Analysis of the Adrenal Gland: A Compilation of Primary Cystic Lesions From Our Institution and Review of the Literature.

OBJECTIVES: Although primary adrenal lesions and metastases are most commonly encountered, de novo cysts of the adrenal gland can occasionally occur. METHODS: We analyzed the pathology archives at the Hospital of the University of Pennsylvania for diagnoses of cystic lesions of the adrenal gland between 1998 and 2020. Patient demographics and clinical information were extracted, and pathology slides and stains, as appropriate, were analyzed. The literature between 1998 and 2020 was also searched for large case series involving cystic adrenal lesions. RESULTS: We found 18 cystic lesions of the adrenal gland in our archives, categorized as pseudocysts (7), endothelial cysts (5), mesothelial cysts (2), mature teratoma (1), cystic adrenal cortical adenoma (1), cystic pheochromocytoma (1), and cystic metastasis (1). The mean age at time of diagnosis was 52.3 years, and the mean size of the cysts was 6.0 cm. There was a slight female predilection, and cysts were more likely to be found on the left side. All lesions were incidental findings. The cystic metastasis was clear cell renal cell carcinoma. Our findings were also compared with those found in the literature published within the same timeframe. CONCLUSIONS: Adrenal cysts are rare entities. Our findings are concordant with other large studies and provide additional cases to the existing literature. In addition, our literature search expands the possible differential diagnoses for cystic lesions arising in the adrenal gland.

TP53 Mutation and Extraneural Metastasis of Glioblastoma: Insights From an Institutional Experience and Comprehensive Literature Review.

Extraneural metastases of glioblastoma (GBM), although rare, are becoming an increasingly recognized occurrence. Currently, the biological mechanism underlying this rare occurrence is not understood. To explore the potential genomic drivers of extraneural metastasis in GBM, we present the molecular features of 4 extraneural metastatic GBMs, along with a comprehensive review and analysis of previously reported cases that had available molecular characterization. In addition to our 4 cases, 42 patients from 35 publications are reviewed. To compare the molecular profiles between GBM cases with extraneural metastasis and the general GBM population, genomic data from GBM samples in The Cancer Genome Atlas (TCGA) database were also analyzed. We found that 64.5% (20/31) of the cases with extraneural metastasis that were tested for TP53 changes had at least 1 TP53 pathogenic variant detected in either 1 or both primary and metastatic tumors. In contrast, TP53 mutation was significantly less frequent in the unselected GBM from TCGA (22.6%, 56/248) (P=0.000). In addition, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation was more common in unselected TCGA GBM cases (48.6%, 170/350) than in cases with extraneural metastasis (31.8%, 7/22), although not statistically significant. Although isocitrate dehydrogenase (IDH) mutation is a rare occurrence in high-grade astrocytomas, IDH-mutant grade 4 astrocytomas are at least as likely to metastasize as IDH wild-type GBMs; 3 metastatic cases definitively harbored an IDH1 (p.R132H) mutation in our analysis. Our findings not only provide potential biomarkers for earlier screening of extraneural metastasis, but could also suggest clues to understanding biological mechanisms underlying GBM metastasis, and for the development of therapeutic modalities.

Papillary thyroid microcarcinomas: does subtyping predict aggressive clinical behavior?

The most common malignant neoplasm affecting the thyroid gland is papillary thyroid carcinoma (PTC). PTC can demonstrate a number of morphologic variants including, but not limited to, classic, follicular, and tall cell. Each of these morphologic subtypes carry distinct clinical characteristics such that certain variants, like tall cell, behave more aggressively than others. PTCs measuring less than or equal to 1.0 cm are classified as microcarcinomas. Although these lesions are thought to be clinically indolent, we hypothesized that, like their larger counterparts, certain histologic variants may lead to worse patient outcomes. To test our hypothesis, we analyzed our pathology archives between the years 2009 and 2020 for papillary thyroid microcarcinomas and assessed whether different morphologic features correlated with more aggressive clinical behavior. Our findings suggest that certain variants exhibit features that portend a more worrisome clinical course and thus papillary thyroid microcarcinomas should be subtyped to help predict patient outcome.