Pathology of Endocrine Glands - II

Thyroid

Jaroslava Dušková Inst. Pathol. 1st Med. Fac. Charles Univ. Prague

https://www1.lf1.cuni.cz/~jdusk/

Endocrine Pancreas

Thyroid Gland History I.

China (2nd mill.b.C.) description of goitre

(Charvát 1935)

Vitruvius (16.a.C.) goitre in the Alpine region

Warton (1656) „ Adenographia“ the term glandula thyreoidea

Luschka (1860) mechanical support of the laryngeal structures

Thyroid Gland History II.

Basedow (1840) hyperthyreosis

Köstl (1855 - Wien): Der endemische Kretinismus als Gegenstand

der öffentlichen Fürsorge (habilit. thesis)

Gull (1873) hypothyreosis

Murray (1883) Therapy with bovine thyroid extracts

Thyroid Gland History III

Hashimoto (1912) struma lymphomatosa

Kendall (1914): Tyroxine discovery

Aron a Loebe (1929) TSH discovery

Adams a Purves (1952) LATS discovery

Thyroid Gland - embryology and fetal endocrinology

mouth epithelium, end of the 1st iu. month ductus thyreoglosus

lateral pharynx ultimobranchial bodies C- cells. parathyroid glands

fetal secretion starts at 12 weeks effect on GROWTH effect on DIFFERENTIATION

Thyroid Gland - anatomy

Weight in adults 15-20g

over 60g (7g in a neonate) strumalobus dexter

isthmus et lobus pyramidalis

lobus sinister

aberant, accesory, ectopic gland (polyclonality should help to tell from ca)

Thyroid Gland - physiology and regulations

hypothalamohypophysothyreoidal axis (TRH,TSH)

enzymes - deiodases autoregulation influenced by iodine

intake immune system

Morphological Thyroid Investigation

Clinic

scintigraphy SONOGRAPHY CT

Pathology

(biopsy) FNAB histology

Main Tasks in the Thyroid Cytology

reduction of the unnecessary surgery

diagnosis of subclinical inflammation

EARLY DIAGNOSIS of NEOPLASMS

Thyroid Cytology - getting sample

needle 0.6-0.8mm min. 2 punctions

aspirationnonaspiration

cyst: evacuate and aspirate with the second punction the periphery

fluid: whole volume for cytology

Thyroid Cytology- processing

Fixation– air dried – etanol / spray

(cytospin)

CYTOBLOCK

Staining: MGG HE polychrom all histo. imunocyto

TGB,calcitonin, parathormon

Regressive changes of thyroid gland

dystrophy: amyloid deposits, calcification atrophy: due to the lack of TSH

stimmulation, postinflammatory

necrosis: only in hyperplastic or neoplastic goitre

ThyreoiditisNON-SPECIFIC purulent non-specific granulomatose de Quervain lymphocytic (Hashimoto)

hypertrophic atrofic focal

invasive sclerosing Riedel

SPECIFIC tbc syfilis sarcoidosis

Non-Specific Granulomatose Thyreoiditis de Quervain (1904)

Synonyma: „Giant cell“ „Subacute non-purulent“

Clin.features: Oedema, pain, eufunction, may be also silent

Histol. features: disperse granulomas with giant cells

Course: spontaneous healing by 2-4 weeks

Thyreoiditis lymphoplasmocellularis Hashimoto - HT

Hashimoto, H.:Zur Kenntniss der lymphomatösen Veränderung der Schilddrüse

(struma lymphomatosa)

Arch.f. klin. Chir. 97, 1912, 219

Original HT Description

Macro - diff. parenchymatose goitre firm, elastic, gray-yellow

Micro - diffuselymfoplasmocellularlymph. foliculesONCOCYTES

Etiopathogenesis of HT

Etiology: unclear - viri ?

Pathogenesis: dysregulation of T lymphocytes IL-1 expression Fas molecules on the

surface of thyreocytes (they have FasL) apoptosis

activation

Activity: CD 44 proteoglycan influencing migration and lymphocyte proliferation, and metastasizing

Course of HT

a) progressive oncocytic transformation

loss of thyreocytes, transformation to a lymph- node-with-ca- meta image

hyperfunction folowed by

hypofunction

Course of HT

b) regressive loss of parenchyma, fibrosis hypofunction

Course of HT

c) neoplasia carcinoma lymphoma (mostly B - MALT)

Thyroid Malignant Lymphomas

2% thyroid primary malignancies mostly women with HT clinically rapid growth, often hypothyreosis mostly B (MALT),

features of lymphoepithelial lesion both LG and HG diff. dg. HT clinical and cytology suspicion

dg. excision

Chronic Sclerosing Thyreoiditis Riedel (1910) Synonyma: „Invasive Fibrotising“

„ Iron hard (eisenharte) goitre“

Clin.features: slight assym. edema fixation to surrounding structures eu- or hypofunction tracheal stenosis recurrens paresis

Histol. features: tissue destruction fibrotisation fixation to surrounding structures involment of the neck vessels

Course: Stabilisation, possible progression

Thyreoidal Syndromes

hypothyreosis– inborn – cretinism

endemic, sporadic

– acquired – myxedema hyperthyreosis - thyreotoxicosis

Hypothyreosis CRETINISMUS

disturbances of growth & differentiation

BRAIN

LUNG

BONE

Acquired Hypothyreosis - MYXEDEMA

decreased metabolism – bradycardia, low blood pressure, water

retention, obstipation intolerance of cold lowered lipolysis

– weight increase

– hyperlipemia ATHEROSCLEROSIS

Thyreoidal Syndromes

hypothyreosis– inborn – cretinism

endemic, sporadic

– acquired – myxedema hyperthyreosis - thyreotoxicosis

Hyperthyreosis increased metabolism tachycardia, high blood pressure,

fibrilation,– hypercalciuria, diarrhoe

intolerance of warm increased lipolysis, glycogenolysis

– weight decrease– hyperglycemia, diabetes

muscle weekness, insomnia, exophtalmus, pretibial myxedema

Processing of Thyroid Resecate

orientation division

– lobus dx.– isthmus (+lobus pyramidalis)– lobus sin.

cutting in cca 3mm thick lamellae– revision and extensive/complete blocking

of the encapsulated nodules periphery– any suspicious focus for histology

Folicular Neoplasia (proliferating microfollicular lesion)

Histological diagnosis

– microfollicular adenoma

– follicular carcinoma

Cytological features

highly cellular smears– few colloid– microfollicular

formations– thyreocytes regular,

small or slightly enlarged

– bare nuclei– regressive changes:

mostly absent

Oncocytic Tumours

adenoma– architecture follicular, trabecular– cellular atypiae without predictive value

for biological behaviour– more risk in case of solid architecture

EXCLUDE

ANGIOINVASION, CAPSULOINVASION

Oncocytic Tumours

carcinoma– oncopapillary (may lack ground glass nuclei !)

– oncofollicular

must exhibit

ANGIOINVASION and/or

CAPSULOINVASION (all capsule thickness with extracapsular expansion)

Papillary Carcinoma

Histological variants - WHO

microcarcinoma encapsulated follicular diff. sclerosing oxyphil cell

Histological variantsadditional

tall cell

columnar cell macrofollicular with desmopl.stroma hyal. trabecular ca

Papillary CarcinomaCytological featuresgeneral

highly cellular smears few colloid waxy colloid, may be

absent

architecture phragments of papillae groups trabecular microfollicular syncytial formations squamous

metaplasia psammomata

NUCLEI

enlarged non - circular overlapping grooves pseudoinclusions

Medullary Carcinoma

origin fom C-cells

clinical forms :

(parafollicular)

sporadic familiar

– MEN 2a

– MEN 2b

Medullary Carcinoma familiar forms

MEN 2a medullary ca parathyr. adenoma pheochromocytoma

MEN 2b MEDULLARY CA marphanoid habitus mucous neuromas pheochromocytoma parathyr. adenoma -

Medullary carcinomaC-cells (parafollicular)

sporadic familiar

MEN 2a MEN 2b

Medullary carcinoma

Histological diagnosis

Calcitonin + amyloid +- argyrophilia +

Medullary Carcinoma

Histological diagnosis

architecture may mimic any otherthyroid ca!!! (WHO)

Calcitonine + amyloid +- argyrophilia +

Medullary Carcinoma

Cytological types

large cell

small cell

fusocellular

plasmocytoid

highly malignant neoplasm of the old age with rapid progression origin:

non diagnosed differentiated ca hyperplastic goitre chronic inflammation without preceeding goitre

Undifferentiated Carcinoma(anaplastic)

Undifferentiated Carcinoma

Histological variants (often combined)

fusocellular small cell (?) exclude lymphoma! giant cell (monstrous cells) squamous metaplasia composed

lmsa, rmsa,osa, chsa, hae, MFH,

classify as carcinoma!

Other Types of PrimaryThyroid Carcinomas

epidermoid mucoepidermoid mixed follicular and mucoepidermoid

Metastases into Thyroid

kidney lung breast other

Islets of Langerhans (1869)

adults 100 000 -1000 000 cell types:

B - insulin

A - glucagon

D – somatostatin

PP – pancreatic polypeptide

D – vasoactive intestinal polypeptide

Islets of Langerhans -

regressive changes

fibrosis (postinflamm.) - DM I mucoviscidosis – DM 10x frequency hyalinosis, amyloidosis

Islets of Langerhans - progressive changes hyperplasia –diabetic embryopathy nesidioblastosis

- tumours– nesidioma ( event. in MEN I)

(insulinoma, glucagonoma, somatostatinoma,VIPoma, PP-oma, G cells -gastrinoma, EC – serotonin - carcinoid

– neuroendocrine carcinoma

Islets of Langerhans - syndromes

hyperfunction – hypoglycemia (weekness , sweating, tremor,

coma)– Zollinger-Ellison, Werner Morrison, glucagonoma

hypofunction – insulin hyperglycemia – acute : polydipsia, ketoacidosis, coma, liver

steatosis , brain edema

– chronic: diabetes mellitus: microangiopathy, macroangiopathy, neuropathy, retinopathy,embryopathy