Thyroid Pathology PDF

THYROID PATHOLOGY  Thyroid gland : Anatomy ▪ Thyroid gland is a bilobed organ in the lower half of anterior neck, which is composed of two bulky lateral lobes joined by a thin isthmus ▪ Shape of adult thyroid resembles a butterfly or a capital H, with each lobe having pointed upp...

THYROID PATHOLOGY  Thyroid gland : Anatomy ▪ Thyroid gland is a bilobed organ in the lower half of anterior neck, which is composed of two bulky lateral lobes joined by a thin isthmus ▪ Shape of adult thyroid resembles a butterfly or a capital H, with each lobe having pointed upper and blunted lower poles ▪ Practical implications for pathologists: - Grossing of surgical thyroid specimens, which are submitted as a single lobe (lobectomy), lobe with isthmus (hemithyroidectomy) or the whole gland (total thyroidectomy); other procedures are subtotal thyroidectomy and neck dissection - Evaluation of the organ on autopsy - Thyroid FNA by interventional cytopathologist, often combined with ultrasound ▪ Historical aspects: - English name for thyroid gland is derived from the Greek thyreoeidos (Thyreos = shield, eidos = form); German word Schilddrüse means "shield gland" - Leonardo Da Vinci (1452 - 1519) is credited as the first to draw thyroid gland as an anatomical organ - The gland was named thyroid by Thomas Wharton (1614 - 1673) because of its proximity to the thyroid cartilage Pyramidal lobe (lobe of Lalouette) is a vestige of the inferior portion of thyroglossal duct : - Narrow conical shaped projection of thyroid tissue extending upward from isthmus to hyoid bone and lying on the surface of thyroid cartilage - Present in approximately half of all thyroid glands, reported range 30% - 75% - Mean length 24 mm, with half of pyramidal lobes exceeding 20 mm - More frequently attached to the left side of the isthmus and even to the left lobe itself - Usually appears as fibrous tract, but in pathologic conditions becomes prominent or cystic - Thyroid tissue in pyramidal lobe is usually not active, hence is not visible on scintigraphy - Pyramidal lobe can be a source of recurrent disease if it is left behind during thyroid surgery  produce coloide Gland is composed of thyroid follicles with a single layer of cuboidal to low columnar epithelium Lumen contains colloid, which is scalloped and pale in follicles with active secretory activity Thyroid gland: and densely eosinophilic in inactive follicles. Stroma contains C cells, formerly called parafollicular cells (actually are intrafollicular), derived from neural crest Histology C cells represent 0.1% of gland and produce calcitonin C cells have pale / clear cytoplasm, oval nuclei, difficult to identify with H&E, use calcitonin stain Thyroid gland: Physiology  Sanderson's polsters: collections of small follicles projecting into 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 marcador del pulmon marcadores Follicular cells: thyroglobulin , TTF1, low molecular weight keratin Colloid: thyroglobulin C cells: calcitonin, neuron specific enolase, chromogranin A, synaptophysin, C cells are NEGATIVE for thyroglobulin Thyroglobulin Thyroglossal duct (TGD) cyst thyroides bara por el conducto tyroglosso que se atrofia despues si no se atrofie = cyst Definition / general The most common developmental anomaly of thyroid gland, and the most common congenital neck mass Midline neck developmental anomaly due to persistence and cystic dilation of thyroglossal duct Gross description Cysts are unilocular or multilocular with rounded, smooth external surfaces Cystic content includes clear mucinous or viscous fluid / gel having a broad range of color (clear, yellowish tan, reddish brown and grayish white) and degree of opacity; infected cysts contain purulent exudate Microscopic (histologic) description Type of epithelial lining varies: Ciliated pseudostratified columnar (respiratory), squamous epithelium and cuboidal epithelium Very often the cyst is denuded of epithelium, at least focally, which reflects epithelial damage by inflammation Secondary inflammation is common Thyroid follicles in the cyst / duct wall epithelio differente de la glandula Hashimoto thyroiditis 80% = mujer inflammacion Definition / general Autoimmune disease with goiter, aumenta los anticuerpos aue ataca a la thyroid elevated circulating antithyroid peroxidase and antithyroglobulin antibodies First described by Hakaru Hashimoto in 1912 Epidemiology 90 - 95% in women, usually 45 - 65 years old; clusters in families More common in Whites than Blacks Clinical features Adults present with painless, gradual thyroid failure due to autoimmune destruction  puntos violetas = cellulas inflamatorias Gross description Diffuse symmetric enlargement of thyroid gland Cut surface resembles lymph nodes with tannish yellow color Occasionally gland is nodular or asymmetric No necrosis or calcification Microscopic (histologic) description Extensive lymphocytic infiltrate with germinal center formation Atrophic follicles with abundant Hürthle cells ofltalmo Graves disease vocio = hyperplasiado del Definition / general thyroide Named after Robert J. Graves (1796-1853) Commonly seen in middle aged women Also called diffuse toxic goiter, autoimmune hyperthyroidism, Basedow disease (in Europe) hashimoto = hypothyroidismo Autoimmune disease characterized by hyperthyroidism due to circulating autoantibodies against thyrotropin (TSH receptor) that activates the receptor, leading to increased thyroid hormone synthesis and secretion and growth of the thyroid gland Associated with diffuse goiter, infiltrative ophthalmopathy and less commonly infiltrative dermopathy, including pretibial myxedema and thyroid acropachy (extremity swelling, clubbing of fingers and toes due to periosteal new bone formation) Presence of thyrotropin receptor antibody in the serum and orbitopathy on clinical examination distinguishes Graves disease from other causes of hyperthyroidism Gross description Diffuse and symmetrically enlarged thyroid gland with beefy red cut surface Microscopic (histologic) description Hyperplastic thyroid follicles with papillary infoldings Tall follicular cells with papillae usually lacking fibrovascular cores Colloid shows peripheral scalloping  vocio Multinodular goiter Definition / general Most common disease of thyroid gland Nodular enlargement with distorted outer surface May cause compression of trachea , esophagus or blood vessels and may grow behind sternum or clavicle (plunging goiter) Majority asymptomatic and euthyroid 90% of those affected are women Iodine deficiency is most common cause worldwide Serum thyroid stimulating hormone (TSH) concentration is inversely proportional to the size of the goiter Gross description Multinodular goiters are asymmetric, large, up to 2 kg, cystic and hemorrhagic with brown gelatinous colloid nodules with focal calcification Microscopic (histologic) description Variable sized dilated follicles with flattened hyperplastic epithelium Nodules may be present but without thick capsule Secondary changes may be seen, including foci of fresh or old hemorrhage, rupture of follicles with granulomatous response, fibrosis, calcification and even osseous metaplasia Some of the cystically dilated follicles may show papillary projections (Sanderson polsters) that may mimic papillary carcinoma; however, they lack the nuclear features of papillary carcinoma  Follicular adenoma proliferation benigna nodulo hyperplasiado no tumoral = nodulo frio Definition / general Benign tumor that shows evidence of follicular differentiation but lacks evidence of capsular and vascular invasion and lacks papillary carcinoma nuclear features Clinical features / diagnosis: Presents with long standing solitary thyroid nodule Patient is usually euthyroid Radiology description Usually "cold" nodule Gross description Solitary, encapsulated, variable size (1 - 10 cm) Solid, fleshy, tan to light brown  capsula = va a islar para quedarse en este lugar no metastasia Microscopic (histologic) description Completely enveloped by thin fibrous capsule Architecturally and cytologically different from surrounding gland; surrounding thyroid tissue shows signs of compression Closely packed follicles, trabeculae or solid sheets Patterns: Normofollicular (simple) Macrofollicular (colloid): large colloid filled follicles with flattened epithelium Microfollicular (fetal): small follicles Trabecular / solid (embryonal): cords / trabeculae with few follicles Cuboidal to low columnar cells, pale staining with round inconspicuous nucleoli Commonly secondary changes of hemorrhage, hemosiderin deposition, sclerosis, edema, necrosis and cystic changes No capsular or vascular invasion after thorough sampling (at least 10 blocks), no / rare mitotic figures, no papillary nuclear features Follicular carcinoma mas freq Definition / general Thyroid carcinoma with follicular differentiation but no papillary nuclear features Comprises 6 - 10% of thyroid carcinomas Usually solitary "cold" nodule on radionuclide scan Extensive sampling of capsule is recommended Three types: Minimally invasive follicular carcinoma With capsular invasion only Encapsulated angioinvasive: Tumors with limited vascular invasion (< 4) have a better prognosis than those with extensive vascular invasion Widely invasive: Extensive invasion of thyroid and extrathyroidal soft tissue Gross description Tan to brown solid cut surface, can have cystic changes and hemorrhage Minimally invasive: usually single encapsulated nodule, with thickened and irregular capsule Widely invasive: extensive permeation of capsule or no capsule All capsule with adjacent tissue needs to be submitted for histological evaluation Microscopic (histologic) description proliferacion de celulas foliculares Trabecular or solid pattern of follicles (small, normal sized or large - microfollicular, normofollicular or macrofollicular respectively) No nuclear features of papillary thyroid carcinoma Invasion of adjacent thyroid parenchyma, capsule (complete penetration) or blood vessels (in or beyond the capsule) Capsular invasion: capsule is typically thickened and irregular, needs penetration through the capsule (full thickness), may have reactive pseudocapsule around the invasion Edge Vascular invasion: vessel within or beyond capsule, tumor covered with endothelium, attached to the wall or with thrombus May have nuclear atypia, focal spindled areas, mitotic figures (< 3/10HPF) rompe la capsula maligna  cuboideas cytop nucleus proeminente Oncocytic (Hürthle cell) tumors celulas neurales Definition / general Follicular neoplasm with more than 75% oncocytic tumor cells Oncocytic appearance is due to accumulation of dysfunctional mitocondria Synonym: oncocytic cell is also called Hürthle, Askanazy and oxyphilic cells Malignant if capsular and / or vascular invasión Tumor size, nuclear atypia, multinucleation, pleomorphism, mitoses or histologic pattern of the lesion are not determinants of malignancy Hematogenous metastases, 30% to lymph node (in contrast, rare in follicular carcinoma) Papillary carcinoma. General hace papilla = mas freq Definition / general 75 - 80% of thyroid carcinomas Occult tumors in 6% at autopsy (1 to 10 mm), 46% multicentric, 14% with nodal metastases Epidemiology Usually women (70%) of reproductive age Clinical features Usually presents as painless nodule or mass in neck or cervical node; usually cold on scan Usually diagnosed by FNA At presentation, 67% in thyroid only, 13% in thyroid and cervical nodes, 20% in nodes only Nodal involvement is often not clinically nodulo en el thyroide apparent due to small size and similar consistency; nodal metastases may undergo cystic change and resemble branchial cleft cysts Gross description Solid, white, firm, often multifocal (20%), encapsulated (10%) or infiltrative Variable cysts, fibrosis, calcification Microscopic (histologic) description Complex, branching, randomly oriented papillae with fibrovascular cores associated with follicles Usually dense fibrosis Papillae lined by cuboidal cells, nuclei are overlapping with finely dispersed optically clear chromatin (also called ground glass, Orphan Annie nuclei, not seen in cytology or frozen section material, micronucleoli, eosinophilic intranuclear inclusions (represent cytoplasmic invaginations) and nuclear longitudinal grooves (represent folding of redundant nuclear membrane, but nonspecific. forma papilla Psammoma bodies: In 50% of tumors in papillary stalk in mas freq , forma papilas, cuerpos sammoma fibrous stroma between tumor cells Due to tumor cell necrosis Fairly specific but may also be seen in metastases Note: presence of psammoma body in neck or within cervical lymph node means papillary thyroid carcinoma must be ruled out cuerpos de Sammoma = carcinoma papilar del thyroides carcinoma papilar del thyroides nucleos grandes Papillary carcinoma punction del cyste = extraer liquido Cytology Cellular aspirate with monolayer sheets of cells, often with 3 dimensional papillary architecture Often psammoma bodies Cells have dense squamoid cytoplasm, enlarged overlapping nuclei with irregular contours, intranuclear inclusions and grooves (don't see ground glass nuclei), architectura papilar nucleo muy grande ; menos cytoP Bethesda systems for cytology Diagnostic categories Poorly differentiated thyroid carcinoma muy maligno peor diagnostico Definition / general Malignant follicular cell neoplasm with limited evidence of follicular cell differentiation Intermediate clinical behavior between well differentiated (papillary and follicular carcinoma) and anaplastic carcinoma Terminology Insular carcinoma Solid type follicular carcinoma Clinical features Large solitary thyroid mass. Patient may have a history of recent growth in a longstanding uninodular or multinodular thyroid Intermediate behavior between well differentiated and anaplastic carcinoma Has nodal and hematogenous metastases and 3 year survival of 38% Extends to perithyroidal soft tissue in 60 - 70% cases Vascular invasion in 60 - 90% cases Regional lymph node metastasis in 15 - 65% Distant metastasis in 40 - 70% Gross description Large (median size: 5 cm), grayish white, some show soft pale areas of necrosis Microscopic (histologic) description Prototypical type insular carcinoma: solid nests composed of small uniform cell with round hyperchromatic nuclei or convoluted nuclei, increased mitotic figures, necrosis mucho mas concentrada carcinoma solide pobremente diferenciada  se puede diffferenciar en todas cosas = porrly differentiated too Anaplastic carcinoma menos freq Definition / general Undifferentiated (high grade) carcinoma of thyroid gland 2 - 5% of thyroid cancers but 40% of thyroid cancer deaths Rapidly enlarging, bulky neck mass invades adjacent structures causing hoarseness, dysphagia, dyspnea Pathophysiology May arise as anaplastic transformation of differentiated thyroid carcinoma (papillary, follicular or Hürthle cell carcinoma Gross description Infiltrative large solid tumor with necrosis and hemorrhage  anaplasica = todos tipos de cellulares Microscopic (histologic) description Three patterns (can be singly or in any combination): ✓ Sarcomatoid: malignant spindle cells resembling high grade pleomorphic sarcoma ✓ Giant cell: highly pleomorphic tumor cells with some tumor giant cells, may have cavernous blood filled sinuses resembling aneurysmal bone cyst ✓ Epithelial: squamoid / squamous tumor nests with occasional focal keratinization Necrosis Vascular invasion with obliteration of the lumen Increased mitotic figures Heterologous differentiation: neoplastic bone and cartilage Microscopic appearance of anaplastic thyroid carcinoma is highly variable. Frequently encountered patterns include squamoid (a), giant cell (b), and spindle cell ( (c). Medullary carcinoma tumores neuroendocrino = marcadores neuronales no de thyroides Definition / general Neuroendocrine tumor derived from C cells (formerly called parafollicular cells), which secrete calcitonin 1 - 2% of thyroid carcinomas Either sporadic (nonhereditary) or familial (hereditary) Sporadic: 70%, age 40 - 60, solitary Familial: 30%, younger patients (mean age 35) Due to MEN 2A or 2B syndromes, familial medullary thyroid carcinoma (FMTC) syndrome, von Hippel-Lindau disease or neurofibromatosis Caused by gain of function germline mutations in the RET gene Usually bilateral, multicentric with C cell hyperplasia Usually discovered by screening test for serum calcitonin or peripheral blood RET oncogene mutational analysis Gross description ▪ Sporadic: typically presents as a single circumscribed but nonencapsulated, gray-tan mass ▪ Familial: generally bilateral / multiple foci Microscopic (histologic) description Wide variety of morphology, can mimic any other thyroid malignancy Round, plasmacytoid, polygonal or spindle cells in nests, cords or follicles; often mixtures of these cells Round nuclei with finely stippled to coarsely clumped chromatin and indistinct nucleoli, occasional nuclear pseudoinclusion Eosinophilic to amphophilic granular cytoplasm due to secretory granules Generally low mitotic figures Stroma has amyloid deposits from calcitonin, prominent vascularity with glomeruloid configuration or long cords of vessels,coarse calcifications, occasional psammoma-like bodies ❑ IHQ: Chromogranine, calcitonin, synaptophisin… Chromogranine Secondary tumors / metastases Definition / general Tumors arising in thyroid by direct extension from adjacent structures or by vascular spread from nonthyroidal sites Despite being highly vascularized, the thyroid is a rare site for distant metastases The frequency of metastasis in routine practice is < 0.2% of thyroid malignancies Direct extension common from tumors of larynx, pharynx, trachea, esophagus and neck - usually are squamous cell carcinoma Primary sites for distant metastases to thyroid are kidney (34%), lung (15%), gastrointestinal tract (14%) and breast (14%)  mas freq mas benigno 2 nd mas freq immunohistoquimia and marcadores neurales neunorales