Category Archives: Endocrine

Thompson LDR

Endocr Pathol. 2023 Jun;34(2):234-246.

Criteria overlap for separating between malignant follicular epithelial cell-derived thyroid gland neoplasms with high grade features of increased mitoses and tumor necrosis but lacking anaplastic histology. Patterns of growth, nuclear features, tumor necrosis, and various mitotic index cutoffs are suggested, but a reproducible Ki-67-based labeling index has not been established. Forty-one cases diagnosed as poorly differentiated thyroid carcinoma (PDTC) or high grade differentiated follicular cell-derived thyroid carcinoma (HGDFCDTC) were reviewed, with histologic features, mitotic figure counts, and Ki-67 labeling index reviewed on cases within Southern California Permanente Medical Group from 2010 to 2021 to establish any potential outcome differences. There were 17 HGDFCDTC (nine papillary thyroid carcinoma; eight oncocytic follicular thyroid carcinoma), median age 64 years, affecting nine females and eight males. Tumors were large (median, 6.0 cm), usually unifocal (n = 13), with only one tumor lacking invasion. Tumor necrosis was present in all; median mitotic count was 5/2 mm2 (median Ki-67 labeling index 8.3%). Three patients had metastatic disease at presentation, with additional metastases in four patients (41.2% developed metastases); 11 were without evidence of disease (median 21.2 months); with the remaining six patients alive (n = 4) or dead (n = 2) with metastatic disease (median 25.8 months). Criteria associated with an increased risk of developing metastatic disease: widely invasive tumors; age ≥ 55 years; male; advanced tumor size and stage; extrathyroidal extension; but not increased mitotic rate or higher labeling index. There were 24 PDTC, median age 57.5 years, affecting 13 females and 11 males. Tumors were large (median, 6.9 cm), with 50% part of multifocal disease, with three tumors lacking invasion. Insular/trabecular/solid architecture was seen in all tumors; tumor necrosis was present in 23; and median mitotic count was 6/2 mm2 (median Ki-67 labeling index 6.9%). Five patients had metastatic disease at presentation, with additional metastases in 3 patients (29.2% developed metastases); 16 were without evidence of disease (median, 48.1 months); with the remaining 8 patients alive (n = 3) or dead (n = 5) with metastatic disease (median, 22.4 months). Criteria associated with an increased risk of developing metastatic disease: widely invasive tumors; male; advanced tumor size and stage; extrathyroidal extension; but not increased mitotic rate or higher labeling index. HGDFCDTC shows tumor necrosis, a median Ki-67 labeling index of 8.3%, with a high percentage (41%) of patients developing metastatic disease. Extent of invasion (non-invasive, minimally invasive, angioinvasive, widely invasive) correlates strongly with developing metastatic disease. PDTC presents at a slightly younger age, with large tumors, often in a background of multifocal tumors, with tumor necrosis nearly always seen, a median Ki-67 labeling index of 6.9%, with 29% of patients developing metastatic disease. Separation between groups is meaningful as early metastatic disease is relatively common, but mitotic counts/labeling indices are not different between the groups nor able to potentially risk stratify development of metastatic disease.

PubMed ID: 37195480

Article Size: 2.5 MB

Czarnywojtek A, Pietrończyk K, Thompson LDR, Triantafyllou A, Florek E, Sawicka-Gutaj N, Ruchała M, Płazinska MT, Nixon IJ, Shaha AR, Zafereo M, Randolph GW, Angelos P, Al Ghuzlan A, Agaimy A, Ferlito A.

Virchows Arch. 2023 Aug;483(2):133-144.

We present a thorough review of the literature on Riedel thyroiditis (RT) with emphasis on aetiology, diagnosis and management, using the PubMed, Sinomed, and China National Knowledge Infrastructure databases. Although the exact aetiology of RT remains obscure, the histopathological features are consistent with a localized form of IgG4-related systemic disease (IgG4-RSD). Nevertheless, IgG4-RSD as a systemic fibroinflammatory disorder per se rarely affects the thyroid in the context of multiorgan manifestations. The initial diagnosis of RT is based on clinical history and imaging, but confirmation by histopathological examination is mandatory. In contrast to the historical surgical approach, glucocorticosteroid therapy is currently considered first line therapy, in line with the RT currently being viewed as a manifestation of, or analogous to, IgG4-RSD. For disease relapse, immunomodulatory agents (azathioprine, methotrexate, rituximab) can be used.

PubMed ID: 37204493

Article Size: 1.6 MB

Liu A, Borges PM, Tay YS, Thompson LDR, Kong MX, Lai J.

Anticancer Res. 2022 Mar;42(3):1481-1485. doi: 10.21873/anticanres.15619.

BACKGROUND: Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a complex disorder. Carriers develop hamartomatous tumors, with an increased risk for developing malignant tumors in multiple organs. Surveillance to facilitate the early detection and treatment of malignancies is extremely important.

CASE REPORT: A 31-year-old male presented with a 10 cm left lobe thyroid gland mass. After fine needle aspiration a left hemithyroidectomy was performed, which demonstrated a minimally invasive follicular thyroid carcinoma (FTC, stage pT3a) and microscopic classical papillary thyroid carcinoma (PTC) in the background of about 50 separate adenomatous nodules (0.2-5 mm). Immunostaining showed loss of PTEN protein in the minimally invasive FTC and in all of the nodules tested, with uninvolved parenchyma serving as an internal control. Kaiser Permanente Northern California (KPNC) Hereditary Cancer Panel, testing for 62 genes, was performed and showed germline mutations in PTEN and RecQ like helicase 4 (RECQL4) genes. Completion thyroidectomy subsequently performed demonstrated about 60 follicular cell-derived adenomatous nodules (0.3-10 mm). Genetic counseling and evaluation documented Cowden syndrome (CS) in the family. Thus, PHTS was confirmed.

CONCLUSION: This report documents synchronous FTC and PTC in a background of multiple follicular adenomatous nodules with a novel RECQL4 mutation in an adult patient with PHTS. As such, documented the loss of PTEN protein in a thyroid gland affected by multiple adenomatous nodules aided in diagnosing PHTS.

PubMed ID: 35220242

Article Size: 1.6 MB

Böhland M, Tharun L, Scherr T, Mikut R, Hagenmeyer V, Thompson LDR, Perner S, Reischl M.

PLoS One. 2021 Sep 22;16(9):e0257635. doi: 10.1371/journal.pone.0257635. eCollection 2021.

When approaching thyroid gland tumor classification, the differentiation between samples with and without “papillary thyroid carcinoma-like” nuclei is a daunting task with high inter-observer variability among pathologists. Thus, there is increasing interest in the use of machine learning approaches to provide pathologists real-time decision support. In this paper, we optimize and quantitatively compare two automated machine learning methods for thyroid gland tumor classification on two datasets to assist pathologists in decision-making regarding these methods and their parameters. The first method is a feature-based classification originating from common image processing and consists of cell nucleus segmentation, feature extraction, and subsequent thyroid gland tumor classification utilizing different classifiers. The second method is a deep learning-based classification which directly classifies the input images with a convolutional neural network without the need for cell nucleus segmentation. On the Tharun and Thompson dataset, the feature-based classification achieves an accuracy of 89.7% (Cohen’s Kappa 0.79), compared to the deep learning-based classification of 89.1% (Cohen’s Kappa 0.78). On the Nikiforov dataset, the feature-based classification achieves an accuracy of 83.5% (Cohen’s Kappa 0.46) compared to the deep learning-based classification 77.4% (Cohen’s Kappa 0.35). Thus, both automated thyroid tumor classification methods can reach the classification level of an expert pathologist. To our knowledge, this is the first study comparing feature-based and deep learning-based classification regarding their ability to classify samples with and without papillary thyroid carcinoma-like nuclei on two large-scale datasets.

PubMed ID: 34550999

Article Size: 3.14 MB

Sanabria A, Zafereo M, Thompson LDR, Hernandez-Prera JC, Kowalski LP, Nixon IJ, Shaha A, Rodrigo JP, Mäkitie A, Vander Poorten V, Suarez C, Zbären P, Rinaldo A, Ferlito A

Surg Oncol. 2021 Mar;36:76-81. doi: 10.1016/j.suronc.2020.12.005. Epub 2020 Dec 8.

Thyroid nodules are a very common clinical condition. The 2015 American Thyroid Association (ATA) guidelines recommend surgical excision for Bethesda IV nodules. The use of intraoperative frozen section (FS) has been recommended as a strategy to tailor the extent of the initial surgery. We critically evaluated the literature that discusses the utility and cost-effectiveness of FS to make an intraoperative decision in patients with thyroid nodules classified as follicular neoplasm. FS should not be recommended as a routine intraoperative test to assess for malignancy in thyroid follicular patterned lesions due to its low performance; the high number of deferred results; the inability to adequately assess histologically defining features; the improvements in risk stratification guiding total thyroidectomy; and the low cost-effectiveness of FS.

PubMed ID: 33316682

Article Size: 4.5 MB

Pantanowitz L, Thompson LDR, Jing X, Rossi ED.

J Am Soc Cytopathol. Sep-Oct 2020;9(5):383-388. doi: 10.1016/j.jasc.2020.06.003. Epub 2020 Jun 18.

Fine-needle aspiration (FNA) has long been considered the first and an important diagnostic tool in the evaluation of thyroid nodules. The advantages of FNA include simplicity, safety, cost-effectiveness, high diagnostic accuracy, and low complication rate. Nevertheless, limitations associated with FNA include a substantial rate of inconclusive results and indeterminate interpretations. Therefore, core needle biopsy (CNB) of the thyroid gland has been proposed as a complementary or even alternate diagnostic method to evaluate thyroid nodules. Although controversial, a growing number of researchers have reported CNB to be an effective and safe sampling method for thyroid nodules, especially for cases with inadequate or indeterminate FNA yields. Skeptics highlight local pain and bleeding risk. Supporters highlight the potential likelihood of overcoming FNA limitations by obtaining a larger amount of tissue and using architecture and cellular details to guide possible ancillary testing. This review evaluates the indications, advantages, and disadvantages of CNB as compared with FNA of the thyroid gland.

PubMed ID: 32665216

Article Size: 1 MB

Miller DL, Thompson LDR, Bishop JA, Rooper LM, Ali SZ.

J Am Soc Cytopathol. Jul-Aug 2020;9(4):221-231. doi: 10.1016/j.jasc.2020.04.008. Epub 2020 Apr 28.

INTRODUCTION: Primary thyroid gland malignant teratomas are extremely rare and can pose diagnostic challenges on fine needle aspiration (FNA) due to their cytomorphologic heterogeneity. Recent next generation sequencing studies have identified recurrent DICER1 hotspot mutations in these tumors, suggesting that malignant teratomas of the thyroid should be considered a distinct pathological entity. Herein, we review the clinico-radiologic and FNA findings in a series of DICER1 mutated malignant teratomas.

METHODS: We performed a retrospective case review of 9 FNAs from 5 patients with a histologically confirmed malignant teratoma of the thyroid gland from 2 large tertiary care pathology practices.

RESULTS: The patients included 4 females and 1 male, with an average age of 43 years (22-65 years). The nodules were centered within the thyroid gland and ranged from 1.7 to 10 cm in diameter. FNAs of primary thyroid teratomas demonstrate marked cellularity, epithelial proliferations, an absence of colloid, and a predominance of immature spindled cells, representing the mesenchymal and neural ectodermal components of these tumors. The FNA interpretations ranged from atypia of undetermined significance to overtly malignant. Three patients died of their disease and 2 are alive with no evidence of disease.

CONCLUSIONS: Malignant thyroid teratoma is a rare entity with cytomorphologic overlap with other highgrade neoplasms of the thyroid. Recent molecular studies have defined recurrent DICER1 mutations in malignant thyroid teratomas and propose these as a distinct clinicopathological entity. The features described here may be helpful in providing a correct prospective interpretation.

PubMed ID: 32448730

Article Size: 3.7 MB

Rooper LM, Bynum JP, Miller KP, Lin MT, Gagan J, Thompson LDR, Bishop JA.

Am J Surg Pathol. 2020 Jun;44(6):826-833. doi: 10.1097/PAS.0000000000001430.

Thyroid gland teratomas are rare tumors that span a wide clinicopathologic spectrum. Although benign and immature teratomas arise in infants and young children and generally have good outcomes, malignant teratomas affect adults and follow an aggressive course. This divergent behavior raises the possibility that benign/immature and malignant teratomas are separate entities rather than different grades of a single tumor. However, the histogenesis and molecular underpinnings of thyroid gland teratomas are poorly understood regardless of grade. In this study, we performed next-generation sequencing on 8 thyroid gland teratomas, including 4 malignant, 3 benign, and 1 immature. We identified DICER1 hotspot mutations in all 4 malignant cases (100%) but not in any benign/immature cases (0%). No clinically significant mutations in other genes were found in either group. We also performed immunohistochemistry to characterize the primitive components of malignant teratomas. Not only did all cases consistently contain immature neural elements (synaptophysin and INSM1 positive), but also spindled cells with rhabdomyoblastic differentiation (desmin and myogenin positive) and bland epithelial proliferations of thyroid follicular origin (TTF-1 and PAX8 positive). Although DICER1 mutations have previously been implicated in multinodular hyperplasia and well-differentiated thyroid carcinomas, these findings demonstrate the first recurrent role for DICER1 in primitive thyroid tumors. The combined neural, rhabdomyoblastic, and homologous epithelial elements highlighted in this series of malignant thyroid gland teratomas parallel the components of DICER1-mutated tumors in other organs. Overall, these molecular findings further expand the differences between benign/immature teratomas and malignant teratomas, supporting the classification of these tumors as separate entities.

PubMed ID: 31917706

Article Size: <1 MB

Thompson LDR.

Ear Nose Throat J. 2021 Sep;100(5_suppl):533S-535S. doi: 10.1177/0145561319890162.

FIRST PARAGRAPH: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a recently recognized indolent neoplasm separated from invasive follicular variant of papillary thyroid carcinoma (FVPTC). NIFTP is a noninvasive, partially to completely encapsulated thyroid follicular neoplasm arranged in almost exclusively follicular architecture, showing papillary carcinoma-like nuclear features in an adequately sampled tumor. In order to qualify for placement in this category, several inclusion and exclusion criteria must be met. Importantly, there can be no invasion at the tumor periphery (ie, usually the capsule) that has been completely sampled for histologic review. There cannot be another recognized pattern of papillary carcinoma, and no more than 30% of the tumor should be solid, trabecular, or insular. There cannot be any tumor necrosis and no increased mitoses of _4 mitoses/2 mm2. Finally, there cannot be any true papillary structures.

PubMed ID: 31760798

Article Size: <1 MB

Whaley RD, Thompson LDR.

Head Neck Pathol. 2020 Sep;14(3):701-706. doi: 10.1007/s12105-019-01099-x. Epub 2019 Nov 28.

Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor of unknown histogenesis generally characterized by the der(17)t(X;17)(p11.2;q25) translocation which results in the ASPSCR1-TFE3 gene fusion. Primary ASPS of the thyroid gland has not yet been reported. During oncology follow-up for breast cancer, a pulmonary nodule and thyroid gland mass were identified in a 71-year-old Korean male. Thyroid ultrasound showed a 5.7 cm left thyroid gland mass. After several fine needle aspirations, a thyroid gland lobectomy was performed after documenting only non-caseating granulomatous inflammation in a biopsy of the lung nodule. A 7.6 cm bulging nodular thyroid gland mass was identified, showing significant destructive invasion. Alveolar nests of large polygonal, eosinophilic, granular neoplastic cells were separated by vascularized stroma. Colloid was absent. Tumor necrosis and increased mitoses were identified. The neoplastic cells were positive with TFE3 and CD68, but negative with pancytokeratin, thyroglobulin, TTF-1, napsin-A, calcitonin, PAX8, CAIX, S100 protein, HMB45, SMA, and desmin. FISH confirmed a TFE3 gene rearrangement. The differential includes several primary thyroid gland epithelial neoplasms, paraganglioma, PEComa, melanoma, crystal storage disease, and metastatic carcinomas, especially Xp11 translocation renal cell carcinoma. The patient has refused additional therapy, but is alive without tumor identified (primary or metastatic).

PubMed ID: 31782115

Article Size: 1.9 MB

Rossi ED, Faquin WC, Baloch Z, Fadda G, Thompson LDR, Larocca LM, Pantanowitz L.

Endocr Pathol. 2019 Jun;30(2):155-162. doi: 10.1007/s12022-019-9574-7.

Advances in our understanding of thyroid lesions, especially those entities with an indolent behavior, has led clinicians to question the most appropriate surgical management of such thyroid nodules. Several studies have shown that the non-invasive encapsulated follicular variant of papillary thyroid carcinomas (NI-EFVPC) exhibits poor histopathologic diagnostic reproducibility and have been over-treated as conventional thyroid cancer. In 2015, an international thyroid working group re-evaluated NI-EFVPC and its diagnostic criteria. The new terminology of Bnoninvasive follicular thyroid neoplasm with papillary-like nuclear features^ (NIFTP) was accordingly introduced to replace NI-EFVPC. The literature has emphasized that NIFTPs are biologically similar to follicular adenomas lacking lymph node metastases and/or recurrence. While the definition of NIFTP is based on specific morphological parameters, recent studies have questioned whether the criterion allowing less than 1% of true papillae should be revised to a total absence of papillae. The motivation for this revision is the rare finding, in some studies, of lymph nodes with metastatic NIFTP. This review evaluates the existing published series of NIFTP cases, clinical consequences of NIFTP, and emerging changes in the diagnostic criteria for NIFTP. The introduction of NIFTP has resulted in significant impact on the clinical management of thyroid nodules. Recent revisions in the morphological criteria for NIFTP emphasize the need to adhere to very stringent histomorphologic criteria when making a diagnosis of NIFTP. The adoption of NIFTP terminology instead of NI-EFVPC is associated with conservative lobectomy without radioactive iodine treatment in the majority of cases.

PubMed ID: 30953289

Article Size: 3.8 MB

Turk AT, Asa SL, Baloch ZW, Faquin WC, Fellegara G, Ghossein RA, Giordano TJ, LiVolsi VA, Lloyd R, Mete O, Rosai J, Suster S, Thompson LDR, Wenig BM.

Thyroid. 2019 May;29(5):619-624. doi: 10.1089/thy.2018.0286. Epub 2019 Apr 27.

Background: Extrathyroidal extension (ETE) by papillary and follicular thyroid carcinoma can be associated with increased risk of tumor recurrence and mortality. In the seventh edition of its Cancer Staging Manual, the American Joint Committee on Cancer (AJCC) defined minimal ETE as the involvement of skeletal muscle (i.e., strap muscles) or perithyroidal soft tissue. The eighth edition of the AJCC Cancer Staging Manual has changed the criteria so that only grossly evident (macroscopic) ETE involving strap muscles (not microscopic ETE involving perithyroidal soft tissue) affects tumor staging. Summary: Concordance of identifying microscopic ETE (as well as extranodal extension by carcinoma metastatic to lymph nodes) was previously evaluated among 11 expert endocrine pathologists. The overall agreement rate was slight when rendering a diagnosis of ETE. Concordance was highest when pathologists assessed the spatial relationship of carcinoma to skeletal muscle. This article discusses the significance of these findings. It also reviews relevant anatomic and developmental considerations related to the boundaries of the thyroid. Conclusions: The results of the concordance study provide additional rationale supporting stringent criteria for diagnosing ETE, as proposed by the eighth edition of the AJCC Cancer Staging Manual. It is expected that these rigid morphologic criteria will potentially reduce interobserver variability and enhance consistency in the diagnosis and staging of thyroid carcinoma.

PubMed ID: 30913992

Article Size: 14.3 MB

Cohen DS, Tongson-Ignacio JE, Lolachi CM, Ghaderi VS, Jahan-Parwar B, Thompson LDR.

Otolaryngol Head Neck Surg. 2019 Apr 23:194599819842859. doi: 10.1177/0194599819842859. [Epub ahead of print]

OBJECTIVES: To recognize that thyroid nodules with atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS; Bethesda III) have different risks of malignancy based on genetic mutation and to consider molecular testing of nodules with AUS/FLUS to help avoid unnecessary morbidity or cost.

STUDY DESIGN: Retrospective cohort study.

SETTING: Multiple locations within Southern California Permanente Medical Group.

SUBJECTS AND METHODS: Patients included those with indeterminate thyroid nodules and AUS/FLUS on 2 separate fine-needle aspirations with positive ThyGenX testing from 2014 to 2017 who underwent thyroid surgery. Patients were classified as having benign or malignant disease. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features was considered benign.

RESULTS: A total of 231 patients had repeat AUS/FLUS with positive molecular testing and surgery. The most frequent type of malignancy was papillary carcinoma, followed by follicular carcinoma. The overall prevalence of malignancy in nodules with mutations was 74.0%, although there was considerable variation: BRAF = 100%, RET = 100%, PAX8-PPARγ = 84.6%, HRAS = 70.7%, HRAS = 63.4%, and KRAS = 33%-a statistically significant finding ( P < .001).

CONCLUSIONS: Not all molecular mutations in thyroid nodules with AUS/FLUS have a high risk of malignancy. Of note, patients with BRAF and RET mutations in our population had a 100% risk of malignancy. Patients with PAX, HRAS, or NRAS mutations had a high risk of malignancy, while patients with KRAS mutations had a lower risk of malignancy. Further studies are needed to determine if the presence of certain molecular mutations can help personalize care and aid in the decision for thyroid surgery.

PubMed ID: 31013183

Article Size: <1 MB

Thompson LDR, Wei C, Rooper LM, Lau SK.

Head Neck Pathol. 2019 Dec;13(4):597-605. doi: 10.1007/s12105-019-01012-6. Epub 2019 Feb 13.

Solitary fibrous tumors of the thyroid gland are exceptionally rare. In order to further characterize the clinical and pathologic features of solitary fibrous tumor arising at this anatomic site, three cases of thyroid gland solitary fibrous tumor were analyzed in conjunction with 35 cases compiled from the English literature. Thyroid gland solitary fibrous tumors showed an equal sex distribution with a mean age at presentation of 54.4 years (range, 28-88 years). The patients typically presented with an asymptomatic, slow growing neck mass. Microscopically, the tumors were characterized by cytologically bland spindle cells with patternless growth, hypocellular and hypercellular areas, variable amounts of collagen, and ectatic, branching blood vessels. Two previous reported tumors were considered to be histologically malignant on the basis of increased mitotic activity, profound pleomorphism and tumor necrosis. Immunohistochemically, the tumor cells are variably positive with CD34, bcl-2, and CD99. STAT6 immunohistochemistry, performed on the current cases, demonstrated a strong, diffuse nuclear expression in all tumors. Among 26 patients with available follow up data (mean 47.3 months), one developed local recurrence and distant metastasis. Solitary fibrous tumors occurring in the thyroid gland are uncommon, but can be reliably diagnosed based on the presence of characteristic morphologic features as well as immunohistochemical expression of STAT6 and CD34. The majority of thyroid gland solitary fibrous tumors have exhibited an indolent clinical course, however experience is limited. The rare potential for aggressive clinical behavior requires clinical surveillance.

PubMed ID: 30758754

Article Size: 2.6 MB

Alves VAF, Kakudo K, LiVolsi V, Lloyd RV, Nikiforov YE, Nosé V, Papotti M, Thompson LDR.

Clinics (Sao Paulo). 2018 May 21;73:e576.

FIRST PARAGRAPH: Over the past decade, improvements in imaging technologies along with greater access to medical care have resulted in the discovery of neoplasms in a much earlier stage. This has contributed to a reduction in cancer mortality. However, an unintended consequence of early detection has been detection of lesions which present at an earlier pathologic stage of development, requiring modification of diagnostic criteria, as well as determining a more appropriate risk stratification to inform management.

PubMed ID: 29791602

Article Size: <1 MB

Kakudo K, El-Naggar AK, Hodak SP, Khanafshar E, Nikiforov YE, Nosé V, Thompson LDR.

Pathol Int. 2018 Jun;68(6):327-333.

In 2016, a new morphological thyroid tumor entity, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), was introduced to replace a group of lowrisk tumors known as noninvasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). Since then, there have been more than 60 publications with a keyword of NIFTP according to a PubMed literature survey on October 28, 2017. These publications cover many aspects on this new tumor entity, cytological diagnosis, ultrasound features, molecular genotyping, clinical management and long-term outcome of NIFTP patients. They supported an indolent nature of NIFTP even in large size (>4 cm) tumors. Under ultrasound examination, NIFTPs are usually in low-suspicion nodules while invasive EFVPTC in intermediate-suspicious nodules and infiltrative FVPTCs in high-suspicion nodules. In FNA cytology, the majority of NIFTP are classified in indeterminate (atypia of uncertain significance/follicular lesion of uncertain significance, follicular neoplasm/suspicious for follicular neoplasm or suspicious for malignancy) categories. The new 4th edition of the World Health Organization (WHO) Classification of Tumours of Endocrine Organs including thyroid tumors was published in 2017 and it incorporated a new chapter on borderline tumors of follicular cell origin. These included hyalinizing trabecular tumor, uncertain malignant potential (UMP), and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). UMP and NIFTP were incorporated as subchapters in a new chapter of other encapsulated follicular-patterned thyroid tumors (Table 1). Their behavior codes were set as /1 (unspecified, borderline, or uncertain behavior), and not /0 (benign tumors), /2 (carcinoma in situ and grade III intraepithelial neoplasia), or /3 (malignant tumors).

This editorial was written by seven authors, on behalf of all authors of the NIFTP working group, to refine diagnostic criteria for NIFTP in order to improve concordance in the diagnosis and to address several issues with the diagnosis of NIFTP raised in recent publications.

PubMed ID: 29675873

Article Size: <1 MB

Thompson LDR, Poller DN, Kakudo K, Burchette R, Nikiforov YE, Seethala RR.

Endocr Pathol. 2018 Sep;29(3):242-249.

The aim of the study was to assess interobserver variation in reporting nuclear features of encapsulated follicular variant of papillary thyroid carcinoma, newly reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), based on a proposed standardized scoring system. An education module was individually reviewed as a pre-evaluation teaching guide of the specific features of classical papillary carcinoma, the specific inclusion and exclusion features for the diagnosis of NIFTP, and a catalog of the standardized scoring system of the nuclear features of papillary carcinoma used to reach this diagnosis. Participants subsequently reviewed 30 cases of thyroid lesions previously scored by members of the Endocrine Pathology Society Working Group for the Re-evaluation of the Encapsulated Follicular Variant of Papillary Thyroid Carcinoma. There was one uninvolved reference image to demonstrate fixation, processing, and cell size and one image from each case for scoring, with results recorded for each participant. The location of training (country and program), years as a practicing pathologist, and approximate number of thyroid gland surgical cases diagnosed per year were recorded. The degree of agreement between participants was assessed by kappa statistics, using the individual criteria and the average composite scores of the Working Group as a point of comparison. Using the Nuclear Standardized Scoring System, the interobserver agreement for final diagnosis score was generally excellent: unweighted and weighted kappa values between individual observers ranging from 0.242 to 0.930 (average 0.626). There was significant agreement between observers in reaching an interpretation of the presence or absence of nuclear features to diagnose NIFTP (score 0–1 versus score of 2–3), with California pathologists, 0.63 (median 0.66, SD 0.15); Japanese pathologists, 0.64 (median 0.66, SD 0.16); and UK pathologists, 0.60 (median 0.57, SD 014) compared to the expert panel, 0.70 (median 0.73, SD 0.19). The use of the nuclear scoring system to evaluate the nuclear features of papillary thyroid carcinoma as applied to reach the diagnosis of NIFTP shows a good to substantial interobserver agreement, suggesting that consensus can be reached in diagnosing the nuclear features required for this newly reclassified neoplasm.

PubMed ID: 29508145

Article Size: 2 MB

 

Hernandez-Prera J, Machado R, Asa SL, Baloch ZW, Faquin WC, Ghossein R Md, LiVolsi VA, Lloyd RV, Mete O, Nikiforov YE, Seethala R, Suster S, Thompson LDR, Turk A, Sadow PM, Urken ML, Wenig BM.

Thyroid. 2017 Dec;27(12):1498-1504.

BACKGROUND: Tall cell variant (TCV) is widely believed to be a more aggressive subtype of papillary thyroid carcinoma (PTC). Despite the significance of TCV with respect to risk stratification and therapeutic decision making, its diagnosis is subject to interobserver variability. We aim to determine the level of agreement among expert pathologists in the identification and reporting of TCV.

METHODS: 17 surgical resections for thyroid cancer containing the diagnostic term “tall cell” in their pathology reports and 22 cases diagnosed as classical PTC were selected. Cases were digitalized and 14 expert pathologists reviewed the scanned slides blinded to the original interpretation. Each pathologist designated each case as TCV or not and answered multiple questions about diagnostic histopathologic features of TCV.

RESULTS: The overall strength of agreement for identifying TCV was fair (Fleiss kappa 0.34) and the proportion of observed agreement was 0.70. Fifteen out of twenty-two (68%) cases originally diagnosed as PTC classical variant were re-classified as TCV by at least one expert pathologist. It was noted that four different definitions for TCV were used by the participants based on various combinations of cell height to width (H:W) ratio and the percentage of tumor cells showing that specific ratio. All pathologists agreed that the diagnosis of TCV does not rely solely on a specific H:W ratio.

CONCLUSIONS: Pathologic reporting of TCV varies among pathologists. This disagreement is a result of the lack of unanimous diagnostic criteria and variation in individual pathologists’ interpretations. These discrepancies lead to over- and under-diagnosis of TCV, which has significant implications in patient management. It is imperative to understand this variability in diagnosis TCV as it relates to risk stratification and interpretation of clinical studies related to this histologic subtype of PTC. Further studies are needed to reach consensus on the diagnostic criteria of TCV.

PubMed ID: 29020884

Article Size: <1 MB

 

Seethala RR, Baloch ZW, Barletta JA, Khanafshar E, Mete O, Sadow PM, LiVolsi VA, Nikiforov YE, Tallini G, Thompson LD.

Mod Pathol. 2018 Jan;31(1):39-55.

The rising incidence of papillary thyroid carcinoma is linked in part to inclusion of noninvasive follicular variant of papillary thyroid carcinoma. Despite its designation as carcinoma, noninvasive follicular variant of papillary thyroid carcinoma appears to be exceptionally indolent, often over treated by current treatment practices. Additionally, criteria for diagnosis have historically been subjective and challenging. Recently, an international multidisciplinary collaborative group performed a clinicopathologic survey of such cases with extended follow-up and concluded based on the outcome data that a revision in nomenclature was warranted, proposing ‘Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP).’ This monograph is a synopsis and guide for pathologists on NIFTP and focuses on histologic features, including inclusion and exclusion criteria used to define NIFTP, as well as grossing guidelines, reporting practices, and potential diagnostic limitations.

PubMed ID: 29052599

Article Size: 1.5 MB

 

Thompson LD.

Ear Nose Throat J. 2017 Feb;96(2):54-55.

FIRST PARAGRAPH: Embryologically, the thyroglossal duct develops as the thyroid anlage descends from the foramen cecum at the base of the tongue to its final resting point in the pretracheal inferior midline neck. The duct usually involutes, but persistence may give rise to a clinical cyst. Thyroglossal duct remnant cysts (TGDCs) are one of the most common neck lesions seen clinically, showing a bimodal age distribution in the first and fifth decades, and identified in approximately 2.2/100,000 population at risk each year. While there is an equal sex distribution, males tend to predominate in pediatric patients while females predominate among adults.

PubMed ID: 28231361

Article Size: <1 MB

Thompson LD, Herrera HB, Lau SK.

Head Neck Pathol. 2017 Dec;11(4):442-449.

Thyroglossal duct cyst (TGDC) carcinomas are rarely encountered in the pediatric population. The clinical behavior of these tumors in the pediatric setting is unclear and management is not well defined. Two cases of pediatric thyroglossal duct cyst carcinoma were identified in a review of all thyroglossal duct cysts diagnosed over a ten year period. These two cases were analyzed along with 57 cases of thyroglossal duct cyst carcinoma affecting patients less than 21 years of age compiled from the English literature. Fifty-nine patients (36 females, 23 males) aged 6–20 years (mean 15.0 years) were identified. All presented with an anterior midline neck mass, which was typically mobile and non-tender. The average tumor size was 2.6 cm. Histologically, all tumors were papillary thyroid carcinomas arising in a background of a thyroglossal duct cyst. The tumors exhibited a papillary, follicular, or mixed architecture with classical papillary thyroid carcinoma nuclear features. Soft tissue extension was present in 16 cases. All patients were managed surgically with a Sistrunk procedure, with additional thyroidectomy performed in 29 patients, combined with a lymph node dissection (n = 15), or a Sistrunk and lymph node dissection (n = 5). All patients were stage I at presentation, with 11 showing lymph node metastases. Postoperative radioactive iodine was employed in 20 patients. A papillary carcinoma of the thyroid gland was reported in four of the patients who had concurrent/subsequent thyroidectomies. Recurrences were reported in four patients, with distant metastases in one patient, who died of disease (13 months). Follow up data was available for 45 patients, with an overall mean follow-up of 54.5 months. All patients were alive, with the exception of one who died with disease. TGDC carcinomas in pediatric patients is associated with a good overall prognosis, best managed by Sistrunk procedure alone, with selected lymph node dissection if clinically indicated.

PubMed ID: 28293858

Article Size: 1.5 MB

 

Chiosea S, Asa SL, Berman MA, Carty SE, Currence L, Hodak S, Nikiforov YE, Richardson MS, Seethala RR, Sholl LM, Thompson LD, Wenig BM, Worden F; Members of the Cancer Biomarker Reporting Committee, College of American Pathologists.

Arch Pathol Lab Med. 2017 Apr;141(4):559-563.

The College of American Pathologists offers these templates to assist pathologists in providing clinically useful and relevant information when reporting results of biomarker testing. The College regards the reporting elements in the templates as important elements of the biomarker test report, but the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice.

The College developed these templates as educational tools to assist pathologists in the useful reporting of relevant information. It did not issue them for use in litigation, reimbursement, or other contexts. Nevertheless, the College recognizes that the templates might be used by hospitals, attorneys, payers, and others. The College cautions that use of the templates other than for their intended educational purpose may involve additional considerations that are beyond the scope of this document.

Completion of the template is the responsibility of the laboratory performing the biomarker testing and/or providing the interpretation. When both testing and interpretation are performed elsewhere (e.g., a reference laboratory), synoptic reporting of the results by the laboratory submitting the tissue for testing is also encouraged to ensure that all information is included in the patient’s medical record and thus readily available to the treating clinical team.

PubMed ID: 27681332

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Thompson LD, Herrera HB, Lau SK.

Head Neck Pathol. 2017 Jun;11(2):175-185.

Carcinomas arising from thyroglossal duct remnant cysts (TGDCs) are rare, without well-defined management and staging criteria. All TGDCs (n = 685) diagnosed between 2005 and 2015 were retrospectively reviewed, with 22 carcinomas identified (3.2 % incidence). Twenty-two patients (17 females, 5 males), aged 12-64 years (mean 39.9 years; median 39 years) were identified. An anterior, superior midline neck mass was the presenting symptom in all patients. A cancer diagnosis [all papillary thyroid carcinoma (PTC)] was made after the Sistrunk procedure (SP), with a Bethesda Category V or VI classification preoperatively by fine needle aspiration in 5 of 12 cases tested. A SP was performed in all patients, with total thyroidectomy concurrently (n = 4) or subsequently (n = 12). A selected neck dissection was performed in 5 patients, with metastases found in 3. Of the patients who had a thyroidectomy, synchronous PTC was identified in 6 (thus, 6 of 22 patients had synchronous thyroid gland primaries). This supports an origin from extra-thyroidal remnants (cyst origin) rather than metastatic tumor from a thyroid gland primary. Follow-up radioactive iodine therapy was performed in 13 patients. Metastatic disease to local lymph nodes 57 months after presentation was seen in 1 patient, with all others alive and disease free (mean 3.8 years; range 0.4-10.8 years). The TGDCs ranged from 0.8 to 5 cm (mean 2.3 cm), while the PTCs ranged from 0.1 to 3.8 cm (mean 1.4 cm). All of the tumors were classical PTC, showing a sclerotic and infiltrative pattern, with a capsule present in 11. Lymphovascular invasion was detected in 11; margins were positive in 6. Using currently defined criteria, the patients were separated into AJCC stage group I (n = 21) or II (n = 1). However, if extension into the adipose tissue (n = 11), skeletal muscle (n = 10), or perineural/perivascular tissues (n = 10) were used to stage the patients, interpreted to represent the equivalent of “extrathyroidal extension” (n = 13) as defined for thyroid gland primaries, there would be 15 group I and 7 group III cases. All seven group III patients were ≥45 years. Three of four patients with lymph node metastasis also showed soft tissue extension. In conclusion, TGDC carcinomas (TGDCCa) are uncommon, with all classical PTC. For “microcarcinomas” (≤1 cm), conservative management can be used for patients <45 years (i.e., Sistrunk procedure only); for >1 cm tumors, and due to the high incidence of concurrent papillary carcinoma and higher stage at presentation in older patients, completion thyroidectomy is recommended for patients ≥45 years. Thus, even though a good prognosis can be expected for PTC developing in TGDCs, staging is advocated to more appropriately match therapeutic interventions.

PubMed ID: 27704385

Article Size: 2.5 MB

 

Du E, Wenig BM, Su HK, Rowe ME, Haser GC, Asa SL, Baloch Z, Faquin WC, Fellegara G, Giordano T, Ghossein R, LiVolsi VA, Lloyd R, Mete O, Ozbek U, Rosai J, Suster S, Thompson LD, Turk AT, Urken ML.

Thyroid. 2016 Jun;26(6):816-9.

Background: Extranodal extension (ENE) in lymph node metastases has been shown to worsen the prognosis of papillary thyroid cancer (PTC). Despite the clinical significance of ENE, there are no stringent criteria for its microscopic diagnosis, and its identification is subject to inter-observer variability. The objective of this study was to determine the level of agreement among expert pathologists in the identification of ENE in PTC cases.

Methods: Eleven expert pathologists from the United States, Italy, and Canada were asked to review 61 scanned slides of representative permanent sections of PTC specimens from Mount Sinai Beth Israel Medical Center in New York. Each slide was evaluated for the presence of ENE. The pathologists were also asked to report the criteria they use to identify ENE.

Results: The overall strength of agreement in identifying ENE was only fair (j = 0.35), and the proportion of observed agreement was 0.68. The proportions of observed agreement for the identification of perinodal structures (fat, nerve, skeletal, and thick-walled vessel involvement) ranged from 0.61 to 0.997.

Conclusions: Overall agreement for the identification of ENE is poor. The lack of agreement results from both variation in pathologists’ identification of features and disagreement on the histologic criteria for ENE. This lack of concordance may help explain some of the discordant information regarding prognosis in clinical studies when this feature is identified.

PubMed ID: 27089928

Article Size: <1 MB

 

Thompson, LDR.

Diagnostic Histopathology 2016.

The most common papillary thyroid carcinoma (PTC) variant is the follicular variant, representing w30% of all PTCs. The tumour is most common in middle aged (4th e 5th decades) women, who usually present with a single dominant nodule (about 3 cm). By definition, follicular architecture must be the dominant finding, while demonstrating the nuclear features of PTC. Papillary structures are <1% of volume, while necrosis, increased mitoses (>3/10 high power fields) and psammoma bodies are absent. The tumour category is divided into “encapsulated/well demarcated” and “invasive” types. The nuclear features include enlarged, elongated and overlapping nuclei; membrane irregularities (irregular contours, grooves and pseudoinclusions); chromatin clearing, margination and glassy nuclei. When the tumour is encapsulated/well demarcated without invasion, demonstrating the other inclusion and exclusion criteria, the new name of “Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features” (NIFTP) is used, a tumour that requires no additional treatment.

PubMed ID: n/a

Article Size: 8.4 MB

Thompson LD, Herrera HB, Lau SK.

Head Neck Pathol. 2016 Dec;10(4):465-474. Epub 2016 May 9.

The clinical features of thyroglossal duct remnant cysts (TGDC) have been well described, however the histopathologic aspects of these lesions have not been addressed in a detailed manner. In particular, there has been no large community practice based series evaluating TGDC histologically compared with management outcomes. A retrospective review of all TGDC diagnosed between 2005 and 2015 was performed. Six hundred eighty-five patients were identified (344 males; 341 females). Age at presentation was bimodal (first and fifth decades) and ranged from 0.8 to 87 years (mean 31.3 years). Males predominate in children (150:111); females in adults (230:194). Patients presented most frequently with a mobile midline neck mass in an infrahyoid location. An associated skin fistula (n = 67) was twice as common in pediatric as adult patients. The average cyst size was 2.4 cm (range 0.4-9.9 cm) by imaging studies and 2.6 cm (range 0.2-8.5 cm) by pathologic examination; pediatric patients had smaller cysts (mean 2.1 cm) than adults (mean 2.8 cm). Histologically, 257 (38 %) TGDC were lined by respiratory epithelium alone, 68 (10 %) squamous epithelium alone, 347 (51 %) exhibited both respiratory and squamous epithelium, and 13 (1 %) had no identifiable epithelial lining. Four hundred eighty-four (71 %) TGDC had associated thyroid gland tissue present within the cyst wall (n = 282), skeletal muscle (n = 71), adipose tissue (n = 34), or a combination of these sites (n = 97). The hyoid bone was identified in 647 (grossly and/or histologically), and absent in 38. Surgical management consisted of Sistrunk procedure (n = 647), cystectomy (n = 31), or thyroidectomy/thyroid lobectomy (n = 7). Treatment related complications were observed in 6 patients, which included vocal cord damage, seroma, and hematoma. Recurrences developed in 20 (3 %) patients, 14 of whom were managed initially by cystectomy. Papillary thyroid carcinoma was identified in 22 (3.2 %) TGDC. In summary, TGDC show a bimodal peak in the 1st and 5th decades, commonly presenting as a midline cervical lesion below the hyoid bone, associated with a skin fistula in 10 %. Histologically TGDC are most commonly lined by a combination of respiratory and squamous epithelium. Thyroid gland tissue is identified in 71 % of cases (0.45 cm mean size), although not limited to the cyst wall, but present in the surrounding soft tissues. Rare TGDC may harbor malignancy (3.2 %). TGDC are most effectively managed by Sistrunk procedure rather than excision, which carries low rates of complications (1 %) and recurrence (3 %).

PubMed ID: 27161104

Article Size: 2.7 MB

 

Thompson, LD.

Mod Pathol. 2016 Jul;29(7):698-707.

Encapsulated follicular variant of papillary thyroid carcinoma is a common thyroid gland cancer, with a highly indolent behavior. Recently, reclassification as a non-malignant neoplasm has been proposed. There is no comprehensive, community hospital based longitudinal evaluation of encapsulated follicular variant of papillary thyroid carcinoma. Ninety-four cases of encapsulated follicular variant of papillary thyroid carcinoma were identified in a review of all thyroid gland surgeries performed in 2002 within the Southern California Permanente Medical Group. All histology slides were reviewed and follow-up obtained. Seventy-five women and nineteen men, aged 20-80 years (mean 45.6 years), had a single (n=61), multiple (same lobe; n=20), or bilateral (n=13) tumor(s), ranging in size from 0.7 to 9.5 cm in diameter (mean 3.3 cm). Histologically, all cases demonstrated a well-formed tumor capsule, with capsular and/or lymphovascular invasion in 17 and no invasion in 77 cases. Lymph node metastases were not identified. The tumors had a follicular architecture, without necrosis or 43 mitoses/10 high-power fields (HPFs). Classical papillary thyroid carcinoma nuclear features were seen in at least three HPFs per 3mm of tumor diameter, including enlarged, elongated, crowded, and overlapping nuclei, irregular nuclear contours, nuclear grooves, and nuclear chromatin clearing. Lobectomy alone (n=41), thyroidectomy alone (n=34), or completion thyroidectomy (n=19) was the initial treatment combined with post-op radioablative iodine in 25 patients. All patients were without evidence of disease after a median follow-up of 11.8 years. Encapsulated follicular variant of papillary thyroid carcinoma showed benign behavior, supporting conservative surgery alone and reclassification of these tumors to Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP).

PubMed ID: 27102347

Article Size: <1 MB

 

Nikiforov YE, Seethala RR, Tallini G, Baloch ZW, Basolo F, Thompson LD, Barletta JA, Wenig BM, Al Ghuzlan A, Kakudo K, Giordano TJ, Alves VA, Khanafshar E, Asa SL, El-Naggar AK, Gooding WE, Hodak SP, Lloyd RV, Maytal G, Mete O, Nikiforova MN, Nosé V, Papotti M, Poller DN, Sadow PM, Tischler AS, Tuttle RM, Wall KB, LiVolsi VA, Randolph GW, Ghossein RA.

JAMA Oncol. 2016 Aug 1;2(8):1023-9.

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.

PubMed ID: 27078145

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Su HK, Wenig BM, Haser GC, Rowe ME, Asa SL, Baloch Z, Du E, Faquin WC, Fellegara G, Giordano T, Ghossein R, LiVolsi VA, Lloyd R, Mete O, Ozbek U, Rosai J, Suster S, Thompson LD, Turk AT, Urken ML.

Thyroid. 2016 Apr;26(4):512-7.

BACKGROUND: Extrathyroidal extension (ETE) is a significant prognostic factor in papillary thyroid carcinoma (PTC). Minimal extrathyroidal extension (mETE) is characterized by involvement of the sternothyroid muscle or perithyroid soft tissue, and is generally identified by light microscope examination. Patients with mETE, identified pathologically, are automatically upstaged to pT3. However, the prognostic implications of mETE have been a source of controversy in the literature. Moreover, there is also controversy surrounding the identification of mETE on pathological specimens. The objective of this study was to determine the level of agreement among expert pathologists in the identification of mETE in PTC cases.

METHODS: Eleven expert pathologists from the United States, Italy, and Canada were asked to perform a review of 69 scanned slides of representative permanent sections of PTC specimens. Each slide was evaluated for the presence of mETE. The pathologists were also asked to list the criteria they use to identify mETE.

RESULTS: The overall strength of agreement for identifying mETE was slight (κ = 0.14). Inter-pathologist agreement was best for perithyroidal skeletal muscle involvement (κ = 0.46, moderate agreement) and worst for invasion around thick-walled vascular structures (κ = 0.02, slight agreement). In addition, there was disagreement over the constellation of histologic features that are diagnostic for mETE, which affected overall agreement for diagnosing mETE.

CONCLUSIONS: Overall agreement for the identification of mETE is poor. Disagreement is a result of both variation in individual pathologists’ interpretations of specimens and disagreement on the histologic criteria for mETE. Thus, the utility of mETE in staging and treatment of PTC is brought into question. The lack of concordance may explain the apparent lack of agreement regarding the prognostic significance of this pathologic feature.

PubMed ID: 26953223

Article Size: <1 MB

 

Thompson LDR.

Ear Nose Throat J. 2007 Nov;86(11):666-7.

FIRST PARAGRAPH: Widely known by its eponym Graves’ disease, diffuse hyperplasia of the thyroid gland is an autoimmune condition in which excess thyroid hormone production is unchecked by the normal feedback loop between the thyroid and the pituitary gland. The immune-system abnormality is mediated by antibodies to the thyrotropin receptor found on follicular epithelial cells. When the most specific antibody, known as thyroid-stimulating immunoglobulin (TSI), is bound to the thyrotropin receptor, the TSI mimics the action of pituitary thyrotropin and stimulates the follicular epithelium to produce hormone. The clinical effect of this autoimmune process is (1) thyrotoxicosis accompanied by diffuse thyroid enlargement and an infiltrative ophthalmopathy and (2) a spectrum of the systemic effects of excessive thyroid hormone production.

PubMed ID: 18225623

Article Size: <1 MB

College of American Pathologists (CAP)

Protocol applies to all carcinomas of the thyroid gland. Lymphomas, sarcomas and metastases are not included.

Based on AJCC/UICC TNM, 7th edition
Protocol web posting date: October 2009
Protocol effective date: January 2010

Article Size: 1 MB

Thompson LD.

Ear Nose Throat J. 2015 Mar;94(3):100-102.

FIRST PARAGRAPH: Thyroid gland follicular carcinoma is a malignant epithelial neoplasm of follicular cell differentiation that exhibits capsular and/or lymphovascular invasion while lacking the nuclear features of thyroid papillary carcinoma. While rarely inherited, follicular carcinoma will develop in about 20% of patients with Cowden syndrome, related specifically to PTEN germline mutations. Previous radiation exposure and iodine deficiency are known environmental etiologic factors.

PubMed ID: 25738712

Article Size: <1 MB

Thompson LD.

Ear Nose Throat J. 2010 Jul;89(7):301-2.

FIRST PARAGRAPH: Medullary thyroid carcinoma (MTC) is a malignant epithelial tumor of the thyroid gland that exhibits C-cell differentiation. C cells arise from the ultimobranchial body, which is derived from the fourth pharyngeal pouch, and they are found in the upper and middle areas of the thyroid lobes. These cells produce calcitonin, a hormone involved in calcium homeostasis. While a number (20%) of MTCs are associated with the autosomal-dominant inherited multiple endocrine neoplasia (MEN) syndromes (specifically MEN2A and MEN2B), most (80%) cases are sporadic. Germline or somatic mutations of the RET gene are characteristic of this tumor. They usually involve an activating point mutation of 10q11.2. Specifically, codon 634 in exon 11 is most common in MEN2A, while codon 918 in exon 16 is most common in MEN2B.

PubMed ID: 20628986

Article Size: <1 MB

Thompson LD.

Ear Nose Throat J. 2011 Sep;90(9):416-7.

FIRST PARAGRAPH: Hyalinizing trabecular ade-noma (HTA) is a very rare tumor (<1% of all primary thyroid gland tumors) of thyroid follicular cell origin with a trabecular pattern of growth and marked intratrabecular hyalinization. For all intents and purposes, this is a benign tumor, although there is a case report of pulmonary metastasis with invasion, suggesting the term tumor be used instead of adenoma. A few cases have occurred following radiation exposure, and there may be a relationship to thyroid papillary carcinoma, as there have been reports of RET/PTC rearrangements.

PubMed ID: 21938699

Article Size: <1 MB