Pitfalls in thyroid tumour pathology

This review provides an itemized listing of major diagnostic pitfalls in the field of thyroid tumour pathology, emphasizing the features that the authors have found most useful in their recognition and avoidance.     

Synchronous papillary thyroid carcinoma and follicular thyroid carcinoma: case report and review of literature

Collision tumor is a term denoting two histologically distinct tumor types occuring at the same anatomic site, which is a rare clinical entity. In the thyroid gland, collision tumors are rare. Here we report a case of the synchronous occurrence of follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC). The current case report describes a 40-year-old woman with synchronous FTC and PTC. Pathologists and surgeons should be aware of collision tumors to avoid possible misdiagnosis.     

Subisthmic accessory thyroid gland in man: A case report and a review of thyroid anomalies

Morphological variations of the thyroid gland are common and generally occur superior to the gland, reflecting its developmental origin. In this report we describe an accessory lobe located inferior to both lateral lobes and the isthmus. The accessory lobe was supplied by a branch of the right inferior thyroid artery and its vein drained via the plexus thyroideus impar. A discussion of thyroid anomalies is presented and a system for classifying variations of thyroid anatomy is proposed. Clin. Anat. 10:341–344, 1997. © 1997 Wiley-Liss, Inc.     

Cytokines, thyroid autoantibody synthesis and thyroid cell survival in culture

In autoimmune thyroid disease lymphoid cells infiltrating the thyroid gland occur in conspicuous aggregates or as a diffusely distributed population invading the thyroid follicles. Consequently cytokines secreted by activated T cells or macrophages could influence neighbouring thyroid cells as well as other lymphocytes. We have investigated this possibility using recombinant cytokines. Thyroid cell survival was assessed in terms of mitochondrial dehydrogenase activity in monolayers exposed to tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-1 (IL-1 alpha and beta) and interleukin-2 (IL-2) in the presence or absence of thyroid-stimulating hormone (TSH). Neither TNF-alpha nor IL-2 affected thyroid cell survival, IFN-gamma was usually inhibitory and IL-1 alpha slightly enhanced cell survival in some experiments. However, the effects were small and variable and were not enhanced by potentially synergistic combinations of cytokines, longer periods of exposure, or different culture conditions. In contrast, IFN-gamma, IL-2 and TNF-alpha inhibited the ability of thyroid lymphocytes from patients with Graves' disease and Hashimoto's thyroiditis to synthesize autoantibodies to thyroid peroxidase (TPO) and thyroglobulin (Tg). Comparison of lymphoid populations isolated by digestion and/or mechanical disaggregation indicated that a population of activated B cells, plasma cells and T cells, intimately associated with thyroid cells since they could only be extracted by digestion, was influenced by cytokines. Our studies suggest that in addition to its well-recognized ability to induce MHC class II antigens on thyroid cells, IFN-gamma may inhibit thyroid cell proliferation and TNF-alpha, IFN-gamma and IL-2 may down-regulate thyroid autoantibody synthesis.     

EGF-receptors in human normal and pathological thyroid tissue

Expression of the epidermal growth factor receptor (EGFR) was studied in cryosections from human thyroid tissues. Normal tissue (4 cases), nodular goitre (12), toxic goitre (9), adenoma (9), follicular carcinoma (1), papillary carcinoma (7) and poorly differentiated carcinoma (1) were used for immunohistochemistry. Northern blot analysis was performed in two nodular goitres, three adenomas, two papillary carcinomas, one follicular carcinoma and the adjacent normal tissue in five cases as well as in two cell lines from anaplastic carcinomas. Epidermal growth factor receptor immunoreactivity was detected in all tissues examined. The amount of EGFR mRNA did not differ between normal and abnormal tissues. However, the EGFR staining was weaker in normal thyroid tissue compared to the adjacent neoplastic areas suggesting an upregulation at the posttranslational level in the latter. A strong staining was also seen in hyperfunctioning thyroid glands. The EGFR location was mainly basal or basolateral in all thyroid tissues with normal histology and in toxic diffuse goitre. Pericellular and sometimes cytoplasmatic staining was seen in neoplastic tissues. In nodular goitre the staining was both basal, lateral and apical and varied in intensity. Our data suggest that a non-polarized location of EGFR probably indicates a loss of the normal epithelial cell polarity and could be interpreted as an early sign of dedifferentiation. Furthermore, a role for the EGFR is proposed, not only in the development of thyroid neoplasias but also in goitre formation.     

Incidentally detected liver metastasis of well-differentiated follicular carcinoma of the thyroid, mimicking ectopic thyroid

A case of incidentally detected liver metastasis of follicular carcinoma of the thyroid, histologically mimicking ectopic thyroid, is described. The patient was a 48-year-old woman. A 2-cm mass was incidentally detected in the left lobe of the liver by abdominal computed tomography (CT) scan. Partial liver resection was performed for diagnosis and treatment. Histologically, the liver nodule was composed of small-to-large follicles containing colloid material. The lining epithelium was flat or cuboidal and showed no cellular or nuclear atypia. Immunohistochemical studies for thyroid-specific proteins, thyroglobulin (Tg), triiodothyronine (T3) and thyroxine (T4), suggested that the nodule was of thyroid origin. Therefore, a differential diagnosis of metastasis of well-differentiated thyroid cancer, ectopic thyroid tissue and teratoma was made. The patient had a history of subtotal thyroidectomy performed 8 years ago due to a thyroid tumor. The original surgical specimens of the thyroid tumor were diagnosed as follicular adenoma. Additional sections of the specimen were reviewed and an area of convincing vascular invasion was found that was suggestive of follicular carcinoma. Subsequent whole-body examination failed to find other metastases. It was determined that the liver tumor was metastasized from well-differentiated follicular carcinoma of the thyroid.     

Adenolipoma of the thyroid gland

A rare case of adenolipoma (thyrolipoma) of the thyroid gland is reported. Previously reported cases are reviewed and the pathogenesis of this unusual thyroid lesion is discussed.     

Minimally invasive follicular thyroid carcinoma

Infiltration of the capsule, vascular invasion, and/or neoplastic extension into the adjacent parenchyma are regarded as prerequisites for the diagnosis of follicular carcinoma. In modern practice, most of these tumors fall into the category of follicular carcinoma, minimally invasive (FCMI) characterized by evidence of limited capsular or vascular invasion with an excellent long-term prognosis and a good patient outcome. Notwithstanding the wide acceptance of the diagnostic criteria established by the World Health Organization for the classification of follicular carcinomas in particular, they have been difficult to apply and have led to a great deal of confusion. This confusion is compounded when applied to "low-grade" or "minimally invasive" follicular carcinoma because of the poor reproducibility of the classification and the variable results reported in the literature. Our surgical colleagues face a similar lack of a standardized treatment for low-grade follicular carcinomas, which leads to unnecessary surgical treatment. Standardization of histologic criteria is necessary to promote confidence and uniformity in the therapeutic approach of these tumors. We believe that a FCMI is defined as an encapsulated follicular tumor (not papillary), with only small to medium vessel invasion within or immediately adjacent to the tumor capsule and/or up to full-thickness capsular transgression without accompanying extension into the thyroid parenchyma with intervening fibrosis. By using these criteria, patients can be managed with conservative surgical excision to yield an excellent long-term patient outcome.     

Structure and function of the thyroid gland after thymectomy

Tomsk Medical Institute. (Presented by Academician of the Russian Academy of Medical Sciences N. V. Vasil'ev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 9, pp. 329–332, September, 1992.     

Black thyroid revisited: cytologic diagnosis in fine-needle aspirates is unlikely

We report four patients diagnosed with black discoloration of the thyroid gland at surgery and a fifth patient in which the "black thyroid" was an incidental finding at autopsy. The four patients diagnosed at surgery had prior fine-needle aspirations (FNA), which did not reveal any characteristic pigmentation. One patient presented with cervical lymph node metastases from a papillary microcarcinoma of thyroid. The second patient was diagnosed as a cellular adenomatoid nodule, and suppressive therapy was recommended. She elected to have surgery instead. The third patient underwent surgery because of an oxyphilic cell nodule, in a background of lymphocytic thyroiditis, in which a Hürthle cell neoplasm could not be ruled out. His aspirates were reviewed at two other institutions, and no diagnosis of black thyroid was entertained. The fourth patient had an adenomatoid nodule with cystic change and slightly atypical squamous metaplasia. She decided to have surgery, which revealed a black thyroid. Later, it was discovered that the patients had received minocycline for the treatment of acne. FNA does not seem to be a reliable method to diagnose black thyroid preoperatively. Although this is a striking operative finding, diagnosing it on FNA seems to be unlikely and also inconsequential.     

Occult thyroid carcinoma: a rare case report and review of literature

Occult thyroid carcinoma is very common in the clinic and is generally divided into four groups. Here, we proposed two types of occult thyroid carcinoma as the fifth group. The first type was locoregional lymph node metastases from thyroid carcinoma, and the second type was distant organ metastases from thyroid carcinoma. The unique aspect of the fifth group was that the primary carcinoma of the fifth group was not finally found by pathological examination. To better understand the fifth group, we reported a typical case. Furthermore, we discussed the diagnostic criteria and procedures and the management of the fifth group of occult thyroid carcinoma.     

Value of combined clinical information and thyroid peroxidase antibodies in pregnancy for the prediction of postpartum thyroid dysfunction

PROBLEM: To investigate the utility of thyroid peroxidase antibodies (TPOAb) in early pregnancy combined with clinical information for prediction of postpartum thyroid dysfunction (PPTD) within 1 year postpartum. METHOD OF STUDY: We studied 98 pregnant women by determining their TPOAb levels in early pregnancy, as well as their serum thyrotropin and free thyroid (fT4) levels at 6 and 12 months postpartum. Furthermore, they answered a questionnaire and physical examination was performed by only one examiner. RESULTS: Of the 98 women, 10 were positive TPOAb in early pregnancy. The overall risk of PPTD within 1 year of follow-up was 10.2% (95% CI 4.1-16.3). Risk of PPTD was significantly higher among women with a family history of thyroid disease, TPOAb positive and presenting goiter in early pregnancy. The sensitivity, specificity and positive predictive value of TPOAb in PPTD prediction were 60.0%, 95.5% and 60%. Restricting screening to women with a family history of thyroid disease or presenting goiter increases the positive predictive value from 60% to 82.4%. CONCLUSION: Our results suggest that TPOAb could be used as a screening test for PPTD prediction at least among women who present a high risk of developing PPTD.     

Resolution of chronic urticaria in patients with thyroid autoimmunity

Background: Autoimmune disease has been implicated as a cause of chronic urticaria, and anti-thyroid antibodies have been found in patients with chronic urticaria. Because some patients with chronic urticaria and autoimmune hypothyroidism have had clinical resolution with thyroid hormone replacement, we investigated the effect of thyroid hormone in euthyroid patients with chronic urticaria and thyroid autoimmunity. Methods: Ten euthyroid patients with refractory hives were treated with thyroxine. Seven patients had elevated anti-thyroid antibodies at baseline. Thyroid function and anti-microsomal and anti-thyroglobulin antibody levels were monitored during treatment. If a clinical response was achieved, thyroxine was discontinued and restarted if symptoms recurred. Results: Seven patients with elevated anti-thyroid antibodies reported resolution of symptoms within 4 weeks. Three patients without elevated anti-thyroid antibodies did not respond. Five patients had a recurrence of symptoms after treatment was stopped, which resolved after treatment was restarted. Thyroid-stimulating hormone levels decreased in all patients with a clinical response. No correlation between clinical resolution and anti-thyroid antibody levels was seen. Conclusion: Thyroid autoimmunity in euthyroid patients may be associated with chronic urticaria, and treatment with thyroid suppression can result in clinical remission. (J ALLERGY CLIN IMMUNOL 1995;96:901-5.)     

Papillary thyroid carcinomas

Summary It is generally believed that the histological pattern of papillary thyroid carcinomas has no influence on the course of the disease. However, we were puzzled by the evident differences in the clinical course of these tumours and decided to re-examine all microscopic specimens available at the Institute of Pathology of the University of Zürich. These had been obtained from 169 surgical cases operated on between 1962 and 1977. We classified the material according to precise morphological criteria and matched it with a number of clinical and catamnestic data in order to determine which parameters correspond best with the development of the disease. Although the fate of patients below 50 years of age is slightly more favourable than that of older subjects, age is by no means the most important factor. In fact, the prognosis correlates significantly better with the initial local extension of the primary tumour (occult, intrathyroid or extrathyroid). Furthermore, this parameter is closely related to the histological pattern of our various papillary carcinoma subtypes which we graded according to differentiation. All factors considered, the morphological pattern appears to offer a rewarding approach to the provision of an accurate prognosis.     

Hereditary and familial thyroid tumours

The worldwide incidence of thyroid malignancies has been increasing rapidly. Sensitive imaging modalities and early detection of thyroid lesions have made thyroid cancers the most rapidly increasing cancers in the USA in 2017 (SEER Cancer Facts, 2017). Clinical awareness of potential risk factors, such as inherited thyroid cancers, has allowed earlier recognition of more vulnerable population clusters. Hereditary thyroid neoplasms arising from calcitonin‐producing C cells are known as familial medullary thyroid carcinomas (FMTCs), and include well‐documented syndromes such as multiple endocrine neoplasia IIA or IIB, and pure familial medullary thyroid carcinoma syndrome. Familial thyroid cancers arising from follicular cells are referred to as familial non‐medullary thyroid carcinoma (FNMTC), or familial follicular cell‐derived carcinoma. Clinicopathological correlations have resulted in the further subclassification of FNMTCs into two groups. Among the first group are found syndromes characterised by a predominance of non‐thyroidal tumours, including familial adenomatous polyposis, Cowden syndrome, Werner syndrome, Carney complex, and Pendred syndrome. The second group encompasses a spectrum of familial syndromes characterised by a predominance of non‐medullary thyroid tumours, such as pure familial papillary thyroid carcinoma with or without oxyphilia, familial papillary thyroid carcinoma with papillary renal cell carcinoma, and familial papillary carcinoma with multinodular goitre. Most familial thyroid cancers have been described as being more aggressive than sporadic thyroid cancers, with a predisposition for lymph node metastasis, extrathyroidal invasion, and a younger age of onset. The distinct thyroid pathology in some of these syndromes should alert the pathologist to a possible familial cancer syndrome.     

Arterial supply to the thyroid gland and the relationship between the recurrent laryngeal nerve and the inferior thyroid artery in human fetal cadavers

The aim of this study was to identify the arterial supply to the thyroid gland and the relationship between the inferior thyroid artery (ITA) and the recurrent laryngeal nerve (RLN) in fetal cadavers using anatomical dissection. The anterior necks of 200 fetuses were dissected. The origins of the superior thyroid artery (STA) and the ITA and location of the ITA in relation to the entrance of the thyroid lobe were examined. The relationship between the ITA and the RLN was determined. The origins of the STA were classified as: external carotid artery, common carotid artery (CCA), and the thyrolingual trunk. The origins of the ITA were the thyrocervical trunk and the CCA. The ITA was absent on the left side in two cases. The relationship of the RLN to the ITA fell into seven different types. Type 1: the RLN lay posterior to the artery; right (42.5%), left (65%). Type 2: the RLN lay anterior to the artery; right (40.5%), left (22.5%). Type 3: the RLN lay parallel to the artery; right (11.5%), left (7%). Type 4: the RLN lay between the two branches of the artery; right (1%), left (3.5%). Type 5: The extralaryngeal branch of the RLN was detected before it crossed the ITA; right (4.5%), left (0%). Type 6: the ITA lay between the two branches of the RLN; right (0%), left (0.5%). Type 7: the branches of the RLN lay among the branches of the ITA; right (0%), left (0.5%). The results from this study would be useful in future thyroid surgeries. Clin. Anat. 27:1185–1192, 2014. © 2014 Wiley Periodicals, Inc.