Thyroid Gland - Printer Friendly Version
Last revised 25 August 2008
Last major update March 2008
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Table of Contents for Thyroid Gland
Primary references, embryology, normal anatomy, normal histology, normal physiology, cytology, cytodiagnostic groups, FNA tissue effects, crystals, morphologic variations
Congenital/metabolic anomalies: aplasia/hypoplasia, branchial pouch/cleft anomalies, cystic ultimobranchial body remnants, cystinosis, DiGeorge syndrome, heterotopic thyroid tissue, lateral aberrant thyroid, lymph nodes, lymphoepithelial cyst, parasitic nodule, parathyroid tissue, solid cell nests, Tay-Sachs, thymic tissue, thyroglossal duct/cyst
Endocrine abnormalities: amiodarone, hyperthyroidism, hypothyroidism, cretinism, myxedema
Thyroiditis: acute, autoimmune, focal lymphocytic, Hashimoto’s, infectious, palpation, post-operative, post-partum, radiation, Riedel’s, SARS, silent, subacute
Hyperplasia/goiter: amyloid goiter, C cell hyperplasia, dyshormonogenetic goiter, endemic goiter, Graves’ disease, simple and nontoxic multinodular goiter, solitary papillary hyperplastic nodule, toxic multinodular goiter
Miscellaneous non-neoplastic: black/pigmented thyroid, Killian-Jamieson diverticulum, malakoplakia, plasma cell granuloma, sarcoidosis, Teflon
Benign neoplasms: follicular adenoma, granular cell tumor, lymphangioma, paraganglioma, post-operative spindle cell nodule, Rosai-Dorfman disease, solitary fibrous tumor, solitary thyroid nodule
Thyroid cancer: general, WHO classification, children
Papillary thyroid carcinoma: general, cytology, children, variants of papillary carcinoma: columnar, cribriform-morular, diffuse sclerosing, encapsulated, encapsulated follicular, follicular, Hashimoto’s, macrofollicular, microcarcinoma, nodular fasciitis, oncocytic, solid, tall cell, Warthin-like, other: hyalinizing trabecular neoplasm
Other thyroid carcinoma: anaplastic, CASTLE, follicular, Hürthle cell (oncocytic) tumors, insular, medullary, metastases, mucoepidermoid, sclerosing mucoepidermoid with eosinophilia, SETTLE, squamous cell, well differentiated NOS, well differentiated of uncertain malignant potential
Other malignancies: angiosarcoma, hemangiopericytoma, Langerhans cell histiocytosis, lymphoma, neuroblastoma, plasmacytoma, sarcoma, teratoma
Miscellaneous: clear cell change, staging, features to report, grossing, frozen section
Primary references for thyroid gland chapter
AJCC Cancer Staging Manual (6th Ed)
American Journal of Clinical Pathology (AJCP) [free full text and no registration after 1 year]; January 1982 to March 2008
American Journal of Surgical Pathology (AJSP); March 1977 to February 2008
Archives of Pathology and Laboratory Medicine (Archives) [always free full text and no registration]; January 1976 to January 2008
Biomed Central [always free full text and no registration]; 30 August 2000 to 29 January 2008
Human Pathology (Hum Path); March 1970 to March 2008
Modern Pathology (Mod Path) [free full text and no registration after 1 year]; January 1988 to March 2008
Lloyd: Endocrine Diseases (AFIP Atlas of Nontumor Pathology, 2002, Vol 1)
Mills: Histology for Pathologists, 2006 (3rd Ed)
Rosai, J: Ackerman’s Surgical Pathology (9th Ed, 2004)
Sternberg, S: Diagnostic Surgical Pathology (4th Ed, 2004)
Rosai: Tumors of the Thyroid Gland (AFIP Atlas of Tumor Pathology, Series 3, Vol 5, 1993)
Websites: PathologyResources (online AFIP fascicles)
Journal search terms: “thyroid” and each topic below
Please refer to these primary references for more detailed discussions and photographs
Week 3 (day 24) of embryonic life: appears as midline vesicular structure at foramen cecum (base of tongue) from ductlike invagination of ventral pharyngeal endoderm that grows caudally (descends) to become thyroglossal duct in neck; thyroglossal duct then atrophies
Week 7: finishes descent along midline; 2 lateral anlagens develop from 4th-5th branchial pouch, which contains ultimobranchial body; midline and lateral portions of thyroid fuse
Week 9: cords and plates of follicular cells are formed
Week 10: small follicular lumina appear
Week 11-12: colloid secretion appears
Week 14: well developed follicles are lined by follicular cells and contain thyroglobulin containing colloid in lumina
References: Endocr Rev 2004;25:722, eMedicine
Ultimobranchial body development in thyroid gland
Ultimobranchial body is outpouch of 4th pharyngeal pouch that fuses with thyroid diverticulum, giving rise to calcitonin-producing C-cells (Dev Dyn 2006;235:1300)
Forms a small organ in many animals, but is only an embryonic structure in humans
C cells are derived from neural crest, migrate to ultimobranchial bodies
Stages of development:
Stage 1: branchial pouch stage at 5-7 weeks gestation-thick walled stratified epithelial cyst in continuity with primitive pharyngeal cavity; part of branchial pouch complexes IV and V
Stage 2: separation stage at 7-8 weeks-separates into parathyroid and ultimobranchial components
Stage 3: incorporation stage at 8-9 weeks-merges with developing lateral lobes
Stage 4: dissolution stage at 9 weeks to term-ultimobranchial body divides into central thick-walled epithelial cyst (disappears post-natally) and peripheral C cells
Normal anatomy of thyroid gland
Two lateral lobes are connected by a usually thin isthmus, resembling a butterfly
Each lobe has pointed superior and blunted inferior poles
Thyroid gland is anterior to upper trachea and esophagus, just below level of cricoid cartilage
Right lobe may be longer than left
May be lingual/subhyoid (too high) or substernal (too low)
Pyramidal lobe, present in 40-55%, is vestige of thyroglossal duct; narrow projection of thyroid tissue extending upward from isthmus and lying on surface of thyroid cartilage (Surg Radiol Anat 2007;29:21)
Red-brown, normal weight in adults is 15-25g, heavier in women, increases up to 50% during early secretory phase of menstrual cycle
Thyroid has a complete but thin fibrous capsule with septa that divide gland incompletely into lobules
10% of adults have incidental nodules
Parathyroid glands are usually adjacent to posterior surface
Recurrent laryngeal nerves run in cleft between trachea and esophagus, just medial to thyroid lobes
Blood supply: left superior thyroidal artery (branch of external carotid artery) and right and left inferior thyroidal arteries (branches of subclavian artery), regulated by cervical sympathetic ganglia; venous outflow includes internal jugular vein, brachiocephalic vein, sometimes the anterior jugular vein
Regional lymph nodes: Level VI -paralaryngeal, paratracheal, prelaryngeal (Delphian) nodes adjacent to thyroid gland; Level VII - upper mediastinal
References: eMedicine
Normal histology of thyroid gland
Divided into lobules of 20-40 round to oval follicles, each 50-500 microns, with a single layer of cuboidal to low columnar epithelium
Lumen contains colloid, which is scalloped and pale in follicles with active secretory activity, densely eosinophilic in inactive follicles and more flocculent (“like a clump or tuft of wool”) and basophilic in elderly
Stroma contains C cells, formerly called parafollicular cells (actually are intrafollicular), derived from neural crest
C cells represent 0.1% of gland, produce calcitonin, are present in middle and upper thirds of lateral lobes along central axes, are not present in extreme upper and lower poles or in isthmus
Usually 10 C cells per low power field in adults
C cellsare more numerous in neonates, decrease in adults, increase and appear as nodular aggregates after age 60 years
C cells have pale/clear cytoplasm, oval nuclei, difficult to identify with H&E, use calcitonin stain
Sanderson’s polsters: collections of small follicles projecting into the lumen of large actively secreting follicles; may resemble papillary carcinoma
Oncocytes (Hürthle cells, oxyphilic cells, Ashkenazy cells): large cells with abundant deeply eosinophilic granular cytoplasm and numerous mitochondria
Positive stains: follicular cells - thyroglobulin (very specific, weaker staining in oncocytic cells), TTF1, low molecular weight keratin; also EMA, vimentin, T3 (triiodothyronine), T4 (thyroxine), ER beta (not alpha), PgR
Note: thyroglobulin may leak out of follicular cells and create false positivity in adjacent cells
colloid - thyroglobulin, Alcian blue, PAS, T3, T4
C cells - calcitonin, calcitonin gene related peptide (CGRP), nonspecific enolase, low molecular weight keratin, chromogranin A , synaptophysin, CEA, somatostatin; C cells are metachromatic with toluidine blue; C cells are NEGATIVE for thyroglobulin
EM: follicular cells - abundant granular endoplasmic reticulum, well developed Golgi, prominent lysosomes, luminal (apical) microvilli, well developed desmosomes with terminal bars between cells, small mitochondria, may contain lipofuscin; nuclei are round with homogeneous chromatin
C cells – intrafollicular location (separated from thyroid interstitium by follicular basal lamina), numerous dense core neurosecretory granules (type I are 280 nm, moderately electron dense, present in most C cells; type II are 130 nm, more electron dense, rare in C cells)
Normal physiology of thyroid gland
See also Thyroid Gland Physiology in Clinical Chemistry chapter
Purpose of thyroid gland is to produce T4 and T3, which regulate metabolism, increase protein synthesis and increase oxygen consumption in all cells in body; T4 and T3 are also important for growth and development, and maturation of peripheral and central nervous system
Hypothalamus releases thyroid releasing factor (TRF) into hypothalamic-pituitary portal blood circulation, which travels to pituitary, which releases thyroid stimulating hormone (TSH) into blood
Follicular cells normally synthesize thyroglobulin and secrete it into the follicular lumen
Thyroid peroxidase, found in apical membrane of thyroid follicular cells, catalyzes iodination of tyrosine residues on thyroglobulin molecule and coupling of iodotyrosyl residues to form T4 (thyroxine) and T3, which are still bound to thyroglobulin, making them inactive; they are then stored as colloid
In response to TSH, follicular cells pinocytize colloid, release the thyroglobulin, and secrete now active T4 and T3 into bloodstream (drawing)
Body needs 100 mg of iodine per day from diet to synthesis adequate T4; uptake is mediated by human sodium iodide symporter, then oxidized to iodine by iodide peroxidase, which binds to tyrosine
Most T4/T3 is reversibly bound to thyroid binding globulin, which maintains levels within narrow limits
Free T4/T3 enters cells, binds to nuclear receptors, increases protein synthesis and catabolism of carbohydrates and fats (basal metabolic rate)
Decreased serum T4/T3 stimulates release of TRF and TSH via negative feedback regulation; elevated levels have opposite effect
Chronically stimulated (hyperplastic) follicular cells are tall and columnar, may be papillary
C cells secrete calcitonin, which lowers serum calcium by promoting bone absorption of calcium and inhibiting bone resorption by osteoclasts; in humans, has only a minor role in calcium homeostasis
Major role of calcitonin may be to protect skeleton during periods of calcitonin stress, such as growth, pregnancy and lactation
Goitrogens: suppress T4/T3 synthesis by interfering with iodine uptake or other parts of biochemical pathways, causing an increased TSH, which causes goiter (enlargement of thyroid gland); examples include propylthiouracil, which inhibits oxidation of iodide and blocks T4/T3 production; iodides in large doses, which inhibit thyroglobulin proteolysis; vegetables including cabbage, turnips and cassava
References: Endocrinology, An Integrated Approach
Cytology / fine needle aspiration of thyroid gland-general
See also cytology section of specific diagnoses
FNA is most accurate method for rapid diagnosis of thyroid nodules, particularly papillary carcinoma (Cancer 2007;111:306)
FNA is widely accepted as initial step in management of thyroid nodules to distinguish benign from neoplastic, although should be considered a screening test, not a diagnostic test
Main contraindication is bleeding diathesis, as formation of large hematoma at biopsy site may compress trachea
Sensitivity and specificity of FNA are > 90% if specimen adequate, although high false-negative rate exists for detecting thyroid malignancy in males (Am J Surg 2008;195:396)
Recommendations: one repeat FNA following an initially benign FNA diagnosis (AJCP 2006;125:698, Thyroid 2007;17:1061); at least two repeat FNAs following an initially nondiagnostic biopsy (Endocr Pract 2007;13:735); combination of FNA and core needle biopsy is optimal (AJCP 2007;128:370), although core biopsies are not widely performed
Technique: use 25 gauge needle, approach medial to lateral (drawing), make short rapid strokes with only slight changes in direction (CMAJ 2002;167:491); technique without aspiration may be superior (Cancer 1987;59:1201); large needle biopsies obtain more tissue and may cause fewer inadequate specimens (Histopathology 2007;51:249)
Scrapes have equal value to frozen sections in intraoperative management
Ultrafast Pap staining detects Orphan Annie-eyed clear nuclei of papillary thyroid carcinoma
Terminology: recommended to use: (a) standard diagnostic terminology and standard criteria for assessing adequacy (Diagn Cytopathol 2008;36:161), (b) synoptic cytology reporting (ANZ J Surg 2007;77:991); (c) Toyota management process for fewer diagnostic errors (AJCP 2006;126:585)
Limitations: cannot differentiate follicular or Hürthle cell adenomas from carcinoma, which requires surgical excision to detect capsular or vascular invasion; cannot diagnose follicular variant of papillary carcinoma, although cases with features suspicious for papillary carcinoma have higher malignancy rate (72%) than those diagnosed as follicular neoplasm (22%, Cytojournal 2006;3:9)
Adequate specimen: 5 groups of 10 cells each of well preserved follicular epithelium on each of 2 slides
Inadequate specimens: major source of errors (AJCP 2006;125:873); BRAF mutational analysis may be helpful, but often there are inadequate tumor cells (Cytojournal 2006;3:10)
False positives (10%): diagnosis of malignancy often based on only 1 or 2 atypical cytologic features
False negatives (25%): marginally adequate specimens; for papillary thyroid carcinoma, may also be due to nodule heterogeneity (Cancer 2008;114:27)
Lymph nodes: measurement of thyroglobulin in FNA from lymph nodes in patients with history of papillary thyroid carcinoma is useful in detecting recurrent disease, especially if specimen is or likely will be inadequate for evaluation (Cytojournal 2008;5:1)
Cytology / fine needle aspiration of thyroid gland - cytodiagnostic groups
See Table (from Cytojournal 2005;2:12)
1. Benign colloid nodule (solitary colloid nodule, prominent nodule in multinodular goiter, macrofollicular adenoma)
Abundant thick colloid with cracking or bubble pattern and sheets of benign follicular epithelial cells in honeycomb arrangement; may have slightly hyperplastic Hürthle cells
2. Cellular microfollicular lesion (microfollicular adenoma, hyperplastic microfollicular lesion in Hashimoto’s or multinodular goiter, low grade/well differentiated follicular carcinoma)
Very challenging, often reported as indeterminate or suspicious for malignancy
Abundant follicular cells in clusters, acini and small monolayered sheets; cells have scanty, ill-defined cytoplasm and oval nuclei with regular nuclear contours; nucleoli vary from indistinct to prominent, no nuclear features of papillary carcinoma
3. Hürthle cell lesion (adenoma, carcinoma or hyperplastic nodule in Hashimoto’s or multinodular goiter)
Challenging diagnosis
Numerous lymphocytes or thick colloid in the needle aspirate; sheets and clusters of polygonal epithelial cells with abundant granular, eosinophilic or basophilic cytoplasm, oval nuclei with regular nuclear contours and conspicuous or inconspicuous nucleoli; syncytial clusters of Hürthle (oncocytic) cells and abundant naked tumor cell nuclei are suggestive of Hürthle cell carcinoma (Diagn Cytopathol 1999;20:261)
4. Primary malignant tumor (papillary, high grade microfollicular, insular, medullary or anaplastic carcinoma; lymphoma)
5. Cystic lesion (benign colloid nodule, papillary carcinoma, other thyroid neoplasm)
Most are benign, and due to hemorrhagic degeneration of a benign colloid nodule; cytology shows colloid material, benign follicular epithelial cells and hemosiderin laden macrophages; however papillary carcinoma may show similar changes with only rare tumor cells in smear, diagnostic papillary tumor cells are often present in cell block
6. Thyroiditis (acute, Hashimoto’s, subacute)
7. Other (Graves’ disease, metastatic carcinoma)
8. Nondiagnostic
Other classification groupings for cytology of thyroid gland
Probably benign: colloid, histiocytes, normal looking follicular cells; non-diagnostic cases with no Hürthle cell change and no atypia (AJCP 2002;118:518)
Suspicious for malignancy (recommend excision): uniform microfollicular pattern, mitotic activity, predominant oncocytic cytology, nuclear atypia but no history of radiation
Follicular neoplasm: monotonous population of follicular cells in cohesive groups with nuclear overlapping and crowding, in background of scant colloid
Follicular neoplasm with features suspicious for papillary carcinoma: follicular cells in loosely cohesive monolayer sheets and follicular groups, focally with nuclear elongation, chromatin clearing and intranuclear grooves, background is watery and thick colloid
Case reports: diffuse large B cell lymphoma misdiagnosed as anaplastic carcinoma (Cytojournal 2006;3:23)
FNA tissue effects in thyroid gland
Acute changes are hemorrhage, granulation tissue, giant cells, hemosiderin laden macrophages, cholesterol clefts, necrosis, rarely infarction (Diagn Cytopathol 1996;15:211)
Chronic changes are infarction, oncocytes, squamous or spindle metaplasia, fibrosis, calcification, vascular thrombosis (Pathol Res Pract 2007;203:641), rarely tumor implantation along needle tract (Acta Cytol 1990;34:801, Acta Dermatovenerol Alp Panonica Adriat 2006;15:169), rarely papillary endothelial hyperplasia (Archives 1992;116:1040, Archives 1991;115:240)
Colloid often contains birefringent calcium oxalate crystals, particularly in nodular goiter but also other neoplasms, in both histologic sections and fine needle aspirates (Acta Cytol 1999;43:575)
Present in 79% of normal appearing thyroids at autopsy (AJCP 1987;87:443)
Crystals appear to be associated with inactive follicles (AJSP 1993;17:698)
Crystals also present after dialysis (Archives 1979;103:58)
Useful in differentiating thyroid tissue from parathyroid tissue (no crystals) at frozen section (AJSP 2002;26:813)
Morphologic variations of normal thyroid gland
See also parathyroid tissue, thymic tissue
● Adipose metaplasia (mature adipose tissue between follicles or near capsule)
Case report: in nodular goiter (Indian J Pathol Microbiol 2007;50:369)
● Intrathyroidal cartilage, skeletal muscle or salivary gland
● Melanosis of follicular cells in old age (pigment granules also contain colloid-Ultrastruct Pathol 1998;22:401), see also black thyroid
● Calcification associated with vessels in elderly, has no laminations (in contrast to psammoma bodies)
● Squamous metaplasia is rare in normal thyroid, more common in thyroid disorders
Congenital anomalies
Aplasia / hypoplasia of thyroid gland
See also screening-neonatal hypothyroidism in Clinical Chemistry chapter
Definition: total or partial absence of thyroid gland
Most common cause of congenital hypothyroidism
Occurs in 1 per 3-4K live births; rarely is familial (Acta Endocrinol (Copenh) 1981;96:188)
Hemiagenesis or aplasia of one lobe is more common in left lobe, and not associated with functional defects
Molecular: various mutations, including PAX8 (J Clin Endocrinol Metab 2001;86:3962, J Clin Endocrinol Metab 2001;86:234)
References: eMedicine
Branchial pouch / cleft anomalies and thyroid gland
May be cyst, sinus, fistula or cartilage in anterolateral neck
Sites of cysts:
First branchial pouch: preauricular area or beneath posterior half of mandible, may be connected to external auditory canal
Second branchial pouch: anterior to sternocleidomastoid muscle in midneck, may communicate with pharynx
Third/fourth branchial pouch: suprasternal or supraclavicular neck; may be misdiagnosed as bronchogenic cysts; usually left sided and associated with neck infections, treatment is ipsilateral thyroidectomy as lesions pass through thyroid
Clinical branchial cysts may rarely: (a) arise within thyroid gland (Korean J Radiol 2006;7:149), (b) actually be cystic ultimobranchial body remnants, (c) actually be papillary thyroid carcinoma (Kaohsiung J Med Sci 2007;23:634), (d) arise within ectopic thyroid tissue that transforms to papillary carcinoma (Ear Nose Throat J 2006;85:675, World J Surg Oncol 2006;4:24)
Branchial pouch / cleft anomalies rarely are associated with squamous cell carcinoma, but cystic neck masses should be considered to be nodal metastases until proven otherwise (common sites of small primary occult tumors are tonsil, posterior tonsillar pillar, retromolar tongue, nasopharynx)
Cysts derived from branchial cleft have squamous epithelium, cysts derived from branchial pouch have respiratory epithelium, although repeated infections may cause squamous metaplasia (Ann R Coll Surg Engl 2007;89:W12)
Case reports: branchial cleft-like cysts with Hashimoto’s thyroiditis (AJSP 1989;13:45), branchial cyst extending into anterior mediastinum (The Internet Journal of Thoracic and Cardiovascular Surgery 2007; Volume 9, Number 1)
Micro: respiratory or squamous epithelium and lymphoid follicles; cysts may have sebaceous or mucinous glands; may be secondarily infected; occasionally found in thyroid tissue as heterotopic cartilage, thymus or solid cell nests representing ultimobranchial body remnants (see below)
Cytology: may be interpreted as suspicious for carcinoma (Cytopathology 2007;18:184)
DD: papillary carcinoma with cystic change (positive for TTF1, thyroglobulin)
References: Wikipedia #1, #2, eMedicine
Cystic ultimobranchial body remnants and thyroid gland
See also solid cell nests (solid ultimobranchial body remnants), lymphoepithelial cyst
Usually soft tissue of neck near thyroid, occasionally within thyroid
Very common in neonates
Branchial pouch cysts located near thyroid may actually be cystic ultimobranchial body remnants
Micro: cysts lined by flattened multilayered epithelium of squamous cells, occasionally ciliated columnar epithelium; may contain dense eosinophilic material in lumen; may be adjacent to solid cell nests; variable lymphocytes and rare pancreatic tissue
References: AJCP 1994;101:186, Archives 1990;114:1049
Autosomal recessive
Hypothyroidism in 50% (Ann Intern Med 2007;147:242), prevented by oral cysteamine (J Clin Endocrinol Metab 1995;80:3257)
Micro: must fix tissue in absolute alcohol, not formalin, or crystals will be dissolved; intracellular deposits of cysteine; follicular atrophy with fibrosis and decreased colloid; focal papillary hyperplasia with dilated follicles and focal neutrophils
References: eMedicine
DiGeorge syndrome and thyroid gland
Also called 22q11 deletion syndrome, velo-cardio-facial syndrome
Arrested development of third and fourth branchial pouches, causing absence of C cells, thymus and parathyroid glands and conotruncal cardiac defects
Due to del (22) as detected by FISH
References: Hum Path 1987;18:355, eMedicine
Also called ectopic thyroid tissue
Very common
See also parasitic nodule, lymph nodes containing thyroid tissue
Most common site is base of tongue; also larynx, trachea, rarely pericardium
Also found within thyroglossal duct cysts (25-65%, more sections yields higher percentage) and along path of migration of thyroglossal duct from foramen cecum to lower neck
Note: most mediastinal goiters are due to hyperplastic changes that “pull” thyroid tissue, not to ectopic thyroid tissue
Thyroid tissue in ovary (struma ovarii) usually represents teratoma
Heterotopic thyroid has same diseases as thyroid gland
Lingual thyroid: thyroid tissue at base of tongue due to failure of descent; some thyroid remnants at this site in 10% of normals; 70% with grossly evident lingual thyroid have no normal thyroid gland, so surgical excision may cause hypothyroidism; follicular epithelium may grow between skeletal muscle, simulating invasion
Case reports: adrenal gland #1 (Hum Path 1999;30:105), #2 (BMC Urol 2006;6:18), inguinal region (Archives 2005;129:e212), intratracheal (Ear Nose Throat J 2007;86:406), left ventricular outflow tract (Ann Thorac Surg 2000;69:620), parotid gland (Singapore Med J 2004;45:437), with papillary thyroid carcinoma arising in neck branchial cyst (World J Surg Oncol 2006;4:24), supraclavicular (Internet Journal of Surgery 2007. Volume 13, Number 1)
DD: hyperplastic thyroid tissue outside gland in Graves’ disease, mechanical implantation outside gland due to surgery or trauma, teratoma with thyroid component, cystically dilated non-thyroid glands with flattened epithelium and inspissated secretions
Thyroid tissue lateral to the jugular vein, but NOT in lymph nodes, is often a developmental anomaly (heterotopic thyroid tissue)
Thyroid tissue in lateral neck may be due to surgery and trauma, which implant thyroid tissue; usually microscopic size and often surrounded by a fibrous capsule; may also be due to spontaneous separation of thyroid tissue in nodular goiter or Hashimoto’s thyroiditis
Case reports: 35 year old woman with lifelong posterior lateral neck nodule (J Cutan Pathol 2004;31:195)
Lymph nodes (cervical) containing thyroid tissue
May represent heterotopic thyroid tissue or metastatic carcinoma - evaluate with extreme caution
Metastatic carcinoma: primary is usually papillary, but may be occult and require embedding of entire thyroid gland; metastases may replace most of node; primary may also be salivary gland, lung, ovary, thymus
Heterotopic thyroid: usually small aggregate of follicles with no attributes of papillary carcinoma after detailed examination (i.e. no atypical nuclei, no papillary architecture, no psammoma bodies), and limited to capsule/periphery of one or two nodes
May be able to distinguish ectopic thyroid tissue from metastatic tumor by clonal analysis (ectopic tissue is polyclonal, Hum Path 1998;29:187) or genetic fingerprinting (Hum Path 2007;38:378), difficult to distinguish by morphology
Note: macrophages may contain thyroglobulin in lymph nodes draining thyroid tumors (J Clin Pathol 2001;54:314)
Case reports: primary papillary thyroid carcinoma in lateral cervical lymph node (Exp Mol Pathol 2007;82:91)
Lymphoepithelial cyst and thyroid gland
See cystic ultimobranchial body remnants
Rare, benign, <30 cases reported thru 2006
2/3 women
Resembles branchial cleft cyst of lateral neck
Associated with chronic lymphocytic thyroiditis
Case reports: associated with Hashimoto’s thyroiditis (Pathol Res Pract 1997;193:777)
Gross: yellow-tan cyst containing motor oil-type fluid
Micro: epithelial lining of attenuated stratified squamous or focal respiratory-type epithelium, with abundant adjacent lymphoid tissue; lymphoid follicles common in cyst wall; solid cell nests and basaloid squamous nests often found
References: Archives 2003;127:e205, Archives 2003;127:251, Hum Path 1994;25:1238
Parasitic nodule and thyroid gland
Definition: thyroid nodule in neck anatomically separate from thyroid gland
Rosai requires that it be in same fascial plane as thyroid gland, not be associated with lymph nodes, and exhibit a similar histologic appearance as the main gland
Also called sequestered or accessory nodule
Usually multinodular
May include lateral aberrant thyroid or some cases diagnosed as metastatic thyroid carcinoma
May actually be connected to thyroid gland by thin fibrous strand of vascular tissue, or may obtain its vascular supply from surrounding tissue separate from thyroid gland
Case reports: 53 year old woman with Hashimoto’s thyroiditis (Rev Hosp Clin Fac Med Sao Paulo 2000;55:65), 67 year old woman with Graves’ disease (Virchows Arch 1999;434:241)
Gross: 1-4 cm, often fibrovascular pedicle discovered at surgery with careful dissection that connects it to thyroid gland
Micro: normal appearing thyroid tissue with colloid-filled or hyperplastic follicles; similar findings in thyroid gland
DD: displaced thyroid tissue due to prior surgery (may have suture material), nodular hyperplasia with sequestration
Parathyroid tissue within thyroid gland
Intrathyroid parathyroid glands are rare, but parathyroid tissue is not
Parathyroid tissue identified in autopsy study in 22% of fetuses, usually deep, also subcapsular (Pediatr Pathol 1993;13:71)
Parathyroid tissue may undergo same processes as parathyroid glands (Mod Path 1989;2:652)
Case reports: patient with hypercalcemia that corrected post-FNA (Endocr Pract 2008;14:80), intrathyroidal parathyroid carcinoma (Endocr Pract 2007;13:176), intrathyroidal parathyroid cyst (Endocr Pract 2007;13:56)
Solid cell nests of thyroid gland
See also cystic ultimobranchial body remnants
Definition: clusters of epithelial cells (main cells and C cells) dispersed between follicles
Derived from branchial cleft pouch complex; are ultimobranchial body remnants (AJCP 1994;101:186)
Located in posterolateral or posteromedial portion of lateral lobes
Present in 90% of neonatal thyroid glands, 30% of adult thyroids
Usually 0.1 mm
May represent a pool of stem cells in adult thyroid gland (Mod Path 2004;17:819)
CASTLE tumors may arise from solid cell nests (AJSP 2006;30:994)
Micro: small cells in solid structures; low power may show irregular branching shape; composed of main cells and C cells with intermingled cystic structures containing mucin and mixed follicles; may contain ciliated columnar cells; usually surrounded by stroma and demarcated by adjacent thyroid follicles; often adipose tissue or cartilage nearby
main cells - polygonal, elongated or spindle cells with deeply eosinophilic cytoplasm with squamoid features but no intercellular bridges, nuclei are centrally located, oval to fusiform, with uneven nuclear membrane, occasional nuclear grooves, finely granular chromatin
C cells - minor population of cells with clear cytoplasm and centrally located, small compact nuclei; may also contain cells with follicular lumen-like pattern (mixed follicles)
Positive stains: main cells - p63 (Mod Path 2003;16:43), CEA, cytokeratins except CK20; also bcl2, galectin3 (J Clin Pathol 2003;56:142); C cells - calcitonin, calcitonin gene related factor, chromogranin; lumina - PAS+ colloid
Negative stains: CK20, TTF1, thyroglobulin
EM: main cells - desmosomes, intermediate filaments, intracytoplasmic vacuoles and projections; C cells - neurosecretory granules; also ciliated cells, lymphocytes (Ultrastruct Pathol 2000;24:1)
DD: squamous metaplasia, C-cell hyperplasia (uniformly positive for calcitonin, CAM5.2, AE1/AE3, CK7, p63), tangential sections of normal follicles, metastatic squamous carcinoma, papillary microcarcinoma, medullary carcinoma
References: Archives 1990;114:1049, Hum Path 1994;25:684
Tay Sachs disease (amaurotic familial idiocy) and thyroid gland
Associated with severe mental retardation and early death
Due to accumulation of lipofuscin-like pigment in neurons, ganglia and occasionally thyroid gland
Micro: follicular epithelial cells contain yellow pigmented granules with lipofuscin; are autofluorescent
EM: osmophilic deposits in cytoplasm of follicular cells
Thymic tissue within thyroid gland
Small portion of thymic gland derives from fourth branchial pouch, together with upper parathyroid glands and ultimobranchial body, which may be source of thymic tissue within thyroid
Thymic rests present in 1% of adult thyroid glands (Virchows Arch A Pathol Anat Histopathol 1991;418:463), 5% of fetal autopsies (Pediatr Pathol 1993;13:431)
May undergo same disease processes as thymus, including thymoma and thymic carcinoma (AJCP 2007;127:230)
Case reports: 22 year old woman with slowly growing neck mass (Archives 2001;125:842)
Gross images: intrathyroidal thymus gland
Cytology: