PATHOLOGY of the THYROID

Dr. Mudjiwijono HE, MS, SpPA

Lab. Patologi Anatomi FKUB/RSSA

THYROID PATHOLOGY
1. Inflammation (thyroiditis) 1. Hashimoto thyroiditis 2. Granulomatous (de Quervains) thyroiditis 3. Subacute lymphocytic thyroiditis 2. Hyperplasia 1. Goiter (Diffuse / Multinodular Goiter) 2. Graves disease 3. Neoplasm 1. Benign : Follicular adenoma 2. Malignant : Carcinoma 1. Papillary carcinoma 2. Follicular carcinoma 3. Anaplastic (undifferentiated) carcinoma 4. Medullary carcinoma

THYROIDITIS :
HASHIMOTO THYROIDITIS
Etiology : autoimmune Incidence : > 45 - 65 y.o. Female >> male (10 : 1 to 20 : 1) Macros : - >, diffuse, firm, intact caps, well defined - CS : pale, yellowish gray, vaguely/distinctly nodular Micros : - Lymphocytic infiltration, germinal centers (+) - Plasma cells, histiocytes, multinucleated giant cells (+) - Atrophic follicle, interstitial fibrosis

Clinic :
Thyroid > symmetric, diffuse, pain (-) Initially : mild hyperthyroidism hypothyroidism Sometimes : Very firm, sudden enlargement, severe pressure symptom confused with Ca

SUBACUTE THYROIDITIS
(Granulomatous thyroiditis; De Quervains thyroiditis) Freq : < Hashimoto thyroiditis Incidence : > 40 -50 y.o. Female > male (4 : 1) Etiology : ? (initially with viral inf.) Macros : - >, unilateral / bilateral, rubbery firm - Intact caps, little/no adherence to the surrounding structures - CS : yellowish white

 Micros : - First : PMN infiltration, microabscesses (+) lymphocytes, macrophages, plasma cells, multinucleated giant cells (+) (granulomatous inflammation) late stage : fibrosis (+)
Clinic : - Thyroid >, pain (+) - First : hyperthyroidism : in 2 - 6 weeks (with/without tx ) - T4 dan T3 , TSH - 6 - 8 weeks, thyroid function N

 SUBACUTE LYMPHOCYTIC THYROIDITIS

More common in children Female > male Autoimmun Macros : thyroid N / slight > Micros : - Lymphocytic infiltration, germinal center (+) Clinic : - Pain (-) - Hyperthyroidism (transient) N - Some px : hyperthyroidism hypothyroidism N

HYPERPLASIA
GOITER
The most common thyroid disease Forms : - Diffuse non toxic (simple) goiter - Multinodular goiter - Endemik / Sporadik Etiology and pathogenesis : - Impairment of thyroid hormone synthesis, largely caused by iodine deficiency TSH , hypertrophy and hyperplasia follicular cells thyroid >

Endemic goiter :
* Goiter >10% population * Etiology : 1. Low iodine content in soil, water, food(Andes,Himalaya) 2. Goitrogen (cabbage, cauliflower, radish, cassava)

Sporadic goiter : < endemic goiter

* > female, peak : puberty / young adult * Etiology : - Goitrogen - Genetic

SIMPLE GOITER (Colloid goiter)

Thyroid >, nodule (-) Morphology : * Hyperplastic phase : - Thyroid > diffuse, symmetric, rarely >100 - 150 gm - Follicle ep : columnar, dense papillary projection - Colloid >/<, distended follicles/small and hyperplastic follicles * Involution phase : - Intake iodine / thyroid hormone demand involution follicle > filled with colloid - CS : brownies, translucent - Micros : follicles epithelium flatened /cuboid Clinic : Thyroid >, euthyroid

MULTINODULAR GOITER
Simple goiter repeated hyperplasia and involution multinodular goiter (nodular hyperplasia, adenomatoid goiter, adenomatous hyperplasia) Macros : - Thyroid > asymmetric, multilobulated, >2000 gm - Sometimes : substernal (intrathoracic goiter) - CS : irregular nodule, filled with colloid, brownies and gelatinous - Hemorrhage, fibrosis, calcification, and cystic degeneration

Micros : - Distended follicles flattened epithelium, hyperplastic follicles cuboid epithelium - Follicular hyperplasia (+) - Irregular septae, hemorrhagic area and calcification
Clinic : - Thyroid >, usually euthyroid sometimes toxic multinodular goiter - Airway obstruction, dysphagia, large vascular compression in cervical / upper thoracal (superior vena cava syndrome) - Incidence of malignant degeneration <5%

GRAVES DISEASE
(Basedows disease, Thyrotoxicosis, Diffuse Toxic Goiter, Exophthalmic Goiter) Etiology : - autoimmune (Ab againts TSH receptor) - Thyroid-Stimulating Immunoglobulin (TSI) - Thyrotropin-Binding Inhibitor Immunoglobulin (TBBII) Hyperplasia T3, T4 Macros : - Thyroid >, symmetric , diffuse (mild to moderate) - Succulent, reddish - CS : uniformly gray or red - Long standing cases : friable, dull yellow

 Micros : - Hyperplastic follicles, papillary involding - Lining epithelium : columnar - Colloid : pale, finely vacuolated, rand vacuole - Aggregates of lymphoid tissue, germinal center (+) - Longstanding cases : mild fibrosis Clinic : - > young adult female, muscle weakness, weight loss, exophthalmos, irritability, tachycardia, goiter, appetite , atrial fibrillation (+/-)

BENIGN NEOPLASM :
FOLLICULAR ADENOMA
Etiology : ? - <20% : mutasi gene Macros : - Solitary nodule, spheris, encapsulated, well defined - : 3 cm, sometimes 10 cm - Greyish white - chocolate red - >> : (+) hemorrhages, fibrosis, calcification and cystic degeneration

 Micros : - Uniform follicles, intact caps - Mitosis < - Variant : Hrthle cell adenoma (eosinophilic granules within cytoplasm) Clinic : - Unilateral nodule, pain (-) - Nodule > : dysphagia - Prognosis : very good

THYROID CARCINOMA :

Rare, USA : 1.5% all Ca Usually : young adult and middle age Female > male Follicle epithelium (except medullary ca), majority well-diff. ca Etiology : * Genetic * Environment The most common : exposure to ionizing radiation, esp. at 1st and 2nd decade of life (after Chernobyl disaster at 1986, incidence of papillary ca in children) * Iodine deficiency follicular ca

PAPILLARY CARCINOMA
The most common, USA 85% thyroid ca Present in any age group, > in 25 50 y.o. Macros : - Most cases : solid, whitish, firm, clearly invasive - < 10% : encapsulated - 10% cases : cystic changes - Sometimes : papillary formation are evident to the naked eye Micros : - Papillae : lining by a single/stratified cuboidal cells - Well-differentiated /anaplastic - Nuclei : ground-glass - Intranuclear inclusion / intranuclear groove (+)

 Clinic : - >> asymptomatic, first manifestation : cervical nodal metastases - Hoarse, dysphagia, cough, or dyspnea (+) : late std. - Metastases >> lymphogen, < hematogen (>> lung) Lab : CT Scan/ FNAB Prognosis : - Good, 10 ysr > 95% - 5% - 20% cases : local recurrent - 10% - 15% cases : distant metastases - Prognosis, depend on : - Age (>40 y.o, prognosis <) - Extra-thyroidal extension () - Distant metastases ()

FOLLICULAR CARCINOMA
5% - 15% thyroid ca Female > male (3 : 1) Age > papillary ca, peak : 40 60 y.o. Macros : - Single nodule, encapsulated - CS : solid, fleshy, brownish to reddish grey, sometimes translucent or (+) central fibrosis and calcification Micros : - Uniform epithelial cells, create small follicles, colloid +/- = Follicular adenoma capsular/vascular invasion ca - Variant : Hrthle cell / oncocytic variant

 Clinic :
- Slow growing, pain (-) - Lymphogen metastases < hematogen to the bone, lung, liver, and others Prognosis : - Depend on invasion and staging

ANAPLASTIC CARCINOMA
< 5% thyroid ca Very aggressive, mortality rate 100% Age > other thyroid ca, 65 y.o. Macros : necrotic and hemorrhagic solid tumor mass Micros : (1) large, pleomorphic giant cells (2) spindle cells with a sarcomatous appearance (3) mixed spindle and giant cells Clinic : - Rapid growing, at the time of initial detected : >> extrathyroidal extension / pulmonal metastases - Symptom : dyspnea, dysphagia, hoarseness and cough - Effektive Tx (-), death < 1 yr. after diagnosed

MEDULLARY CARCINOMA

Neuroendocrine Tumor ( parafollicular cell /C cell ), produce calcitonin, serotonin, ACTH, and vasoactive intestinal peptide (VIP) 5% thyroid ca Macros : - Solitary/bilateral, multicentric nodule - > : necrosis and hemorrhage - Solid, firm, nonencapsulated, well circumscribed - CS : grey to yellowish Micros : - Solid proliferation of round to polygonal cells of granular amphophilic cytoplasm - Separated by a highly vascular stroma, hyalinized colagen and amyloid - Pattern of growth : carcinoid like, paraganglioma like, trabecular, glandular or pseudopapillary

 Clinic : - Dysphagia, hoarsenes - Paraneoplastic syndrome - Diarrhoe (caused by VIP) - Cushing syndrome (caused by ACTH) - Calcitonin - CEA (+)

Thank You For Your Attention