Cytology of the Cytology of the thyroid glandthyroid gland

A R kA. Ryska

The Fingerland Department of Pathology,Hradec Králové, Czech Republic

StainingStainingStainingStaining

no definite recommendation no definite recommendation 3 optionsp 1. Papanicolaou – excellent nuclear features

x wet fixation neededx wet fixation needed 2. May-Grünwald-Giemsa – drying out at

room temperature, less nuclear details, better cytoplasmic features and otherbetter cytoplasmic features and other structures

3. haematoxylin-eosin

E al ationE al ationEvaluationEvaluation

all smears, whole area (periphery!!!) morphologic features in context – synthesis ofmorphologic features in context synthesis of

information CAVE! - under- or overdiagnosis based on a single CAVE! - under- or overdiagnosis based on a single

morphologic detaill li i th l i ti i t! close clinico-pathologic cooperation is a must!

limitations of the method - FNAC is not supposed to replace histology

second opinion, ancilliary techniquesp , y q

Criteria of aCriteria of adedequacyquacyCriteria of aCriteria of adedequacyquacy

variable at different institutions 5-6 cell groups, 10-15 follicular cells each 5 6 cell groups, 10 15 follicular cells each 10 cell groups, 20 follicular cells each counting of cells = limited evaluation "benign structures only amount of material benign structures only, amount of material

is limited" repeat the aspiration

TheThe BethesdaBethesda s stems stemTheThe BethesdaBethesda systemsystem

unified terminology categories I – VIcategories I VI simplification of the message to a clinician

NonNon diagnostic smearsdiagnostic smearsNonNon--diagnostic smearsdiagnostic smears

missing small nodule abnormal structure of the lesion (cystic abnormal structure of the lesion (cystic,

highly vascularized or regressively changed nodules)

di ti i ti 1 6 21% non-diagnostic aspirations 1,6 - 21% cases

our current series 6,6%

Hyperplastic goiterHyperplastic goiterHyperplastic goiterHyperplastic goiter

any enlargement, variable etiology diffuse goiter (homogenous, no nodular diffuse goiter (homogenous, no nodular

rearrangement) h ld ll l d ff children – virtually always diffuse goiter

variable proliferative activity variable proliferative activity selection of populations with different

f t ti t tifeatures, somatic mutations hyperplastic nodules – nodular goiterype p ast c odu es odu a go te

Colloid goiterColloid goiter difdiffusefuse and nodularand nodularColloid goiter Colloid goiter -- difdiffusefuse and nodularand nodular

variable cellularity of smears abundant colloid, mosaic pattern hyperfunction - anisokaryosis, vacuolization of

cytoplasm, "lace-like margin"cytoplasm, lace like margin macrofollicular – large flat fragments and sheets

non t anspa ent tiss e f agments non-transparent tissue-fragments regressive change – nuclear shrinkage, vacuoles,

granules of hemosiderin siderophages, foamy histiocytes, cholesterol crystalsp g y y y

SubaSubacutecute tthhyroiditiyroiditissSubaSubacutecute tthhyroiditiyroiditiss((de Quervainde Quervain))

viral etiology, heredity (antigen HLA-gy, y ( gB35)f ll i i f i follows acute respiratory infection

may be unilateral (single lobe) may be unilateral (single lobe) solitary nodule!y

CytologicCytologic featuresfeaturesCytologic Cytologic featuresfeatures

moderate cellularity cellular debris, small amounts of colloid, cellular debris, small amounts of colloid,

regressive changes of follicular cellsl h h l d h lymphocytes, neutrophils and macrophages

epitelioid cells - „wavy" nuclei epitelioid cells „wavy nuclei granulomas multinucleated giant cells (reaction to colloid) not specific for subacute thyroiditis !!! not specific for subacute thyroiditis !!!

AutoimmuneAutoimmune thyroiditisthyroiditisAutoimmuneAutoimmune thyroiditisthyroiditis

ThyroiditisThyroiditis Clin.courseClin.course Characteristic featuresCharacteristic featureswith goiter chronic goiter, lymphoid infiltrate, oncocytic

(Hashimoto) chronic transformation of follicular cells, fibrosisatrophic (primary hypothyroidism) chronic atrophy, fibrosishypothyroidism)

juvenile chronic lymphocytic infiltrate

focal lymphocytic self-limited present in 20% of goiters at autopsy

post-partum t i t small goiter, lymphocytic infiltratepost partum transient small goiter, lymphocytic infiltrate

silent transient small goiter, lymphocytic infiltrate

HashimotoHashimoto tthhyroiditiyroiditissHashimotoHashimoto tthhyroiditiyroiditiss

goiter, variable size and character small changes of thyroid size (fast

progression - susp of malignancy)progression susp. of malignancy) clinical symptoms of hypothyroidism US - hypoechoic, inhomogenous

t tstructure

DifDiffusefuse toxictoxic goitergoiterDifDiffusefuse toxic toxic goitergoiter(Graves(Graves--Basedow Basedow diseasedisease))(( ))

most frequent cause of thyroid hyperfunction most frequent cause of thyroid hyperfunction organ specific autoimmune disorder

t tib di i t TSH t autoantibodies against TSH receptor thyroid growth + increased production of T3, T4 indication for FNAC = nodule 40% of GB goitersg Ca in 3,5% of GB goiters probability of malignancy of nodule = 11% probability of malignancy of nodule = 11%

CytologicCytologic featuresfeaturesCytologic Cytologic featuresfeatures

high cellularity minimal amount of colloid minimal amount of colloid follicular cells in small and middle-sized

groups, moderate cohesivity marginal vacuoles at periphery background with small amount of background with small amount of

mature lymphocytes

PapilPapillalarryy ccarcinomarcinomaaPapilPapillalarryy ccarcinomarcinomaa

t f t th id li most frequent thyroid malignancy (65-80%)(65 80%)

derived from follicular cells tumor papillae and/or specific nuclear

f tfeatures F:M = 2-3:1 any age F:M = 2 3:1, any age microCa more frequrent in males !

More aggressive behaviorMore aggressive behavior tall cell PC columnar cell PC diffuse sclerosing PC

Less aggressive encapsulated PC

ill i i papillary microcarcinoma

TypicTypicalal cytologiccytologic features offeatures of PCPCTypicTypicalal cytologic cytologic features of features of PCPC

high cellularity increased N/C ratio/ intranuclear pseudoinclusions – higher frequency

lti l t d i t ll ih t f multinucleated giant cells wihout presence of lymphoid elements

thick colloid (chewing-gum like) intranuclear grooves intranuclear grooves papillary fragments psammoma bodies

FolFollliiccululaarr neoplasmsneoplasmsFolFollliiccululaar r neoplasmsneoplasms Hyperplastic noduleyp p Follicular adenoma

At i l f lli l d (UMP) Atypical follicular adenoma (UMP) Follicular carcinoma

- minimally invasive – without vascular i.- minimally invasive – with vascular i.minimally invasive with vascular i.- widely invasive

Follicular variant of PC Follicular variant of PC Follicular variant of medullary carcinoma Mixed tumors

There are no reliableThere are no reliablecytologic criteriacytologic criteria,

distinguishingdistinguishingbenign and malignantbenign and malignant

follicular tumorsfollicular tumors

FolFollliiccululaarr ccarcinomarcinomaaFolFollliiccululaar r ccarcinomarcinomaa

malignant conterpart of follicular dadenoma

more frequent in elderly and in regions more frequent in elderly and in regionswith iodine defficiency

Evrope 27% USA 10% USA 10%

F lF lllii ll iiFolFollliiccululaar r ccarcinomarcinomaa

invasion transcapsular invasion transcapsular invasion

and/or vascular invasion

minimally invasive FC (without or with a y as e C ( t out o tvascular invasion)

id l i i FC widely invasive FC

BiologicBiologic behaviorbehaviorBiologic Biologic behaviorbehavior

different from PC hematogenous spread, metastases intohematogenous spread, metastases into

bones, brain and lungs ras mutations ras mutations

Cytologic Cytologic features of features of y gy gfolfollliicculularar neoplasianeoplasia

high cellularity low cohesivness of cells

microfollicular formations (rosette like) microfollicular formations (rosette-like) dense colloid in microfollicles absence of colloid in the background nuclear anisomorphy (no prognostic

significance)significance)

Oncocytic (Hürtle cell) tumorsOncocytic (Hürtle cell) tumorsOncocytic (Hürtle cell) tumorsOncocytic (Hürtle cell) tumors

>75% of oncocytes (Askanazy, oxyphillic or Hürthle cells)

abundant mitochondriae

oncocytic adenoma oncocytic carcinoma - follicular - papillary papillary

(oncocytic variant of PC)

Anaplastic (undifferentiated) Anaplastic (undifferentiated) p ( )p ( )carcinomacarcinoma

USA 1,7%, Germany 3,6% M:F = 1,5:1

max 7 decenium max. 7. decenium rapidly growing massp y g g extrathyroidal spread necrosis, calcifications, bone formation

Anaplastic carcinomaAnaplastic carcinomaAnaplastic carcinomaAnaplastic carcinoma large cells, variation of size and shape, large cells, variation of size and shape,

bizzare nuclei, multinucleated cellsi i d i i i mitotic and apoptotic activity

vascular invasion vascular invasion histologic types: squamous

giant-cellspindle cellspindle-cell (sarcomatoid)

frequently mixed features

high cellularity absence of colloid necrotic debris and neutrophills necrotic debris and neutrophills poorly cohesive cell groups large polygonal cells spindle cells spindle cells bi- or multinucleated cells

Medullary thyroid carcinomaMedullary thyroid carcinomaMedullary thyroid carcinoma Medullary thyroid carcinoma (MTC)(MTC)

● relatively rare ( )( )● relatively rare● sporadic

hereditary syndromes (25%) - MEN 2A MEN 2B FMC● hereditary syndromes (25%) - MEN 2A, MEN 2B, FMC

● typical growth pattern x atypical manifestations

l f ll ll● unusual features small cellgiant cellsquamous cellsquamous cellamphicrinemucinouspigmentedpigmentedfollicularoncocytic

moderately to highly cellular smears

poorly cohesive cells, absence of colloid

f t f l id (1/4 ) fragments of amyloid (1/4 cases)

round oval triangular spindle cells round, oval, triangular, spindle cells

Thyroid lymphomasThyroid lymphomasThyroid lymphomasThyroid lymphomas

relatively rare relatively rare 2% of extranodal lymphomas

5% f ll th id li i 5% of all thyroid malignancies max. in 7. decade M:F = 3:1 thyroid enlargement, growth of nodule thyroid enlargement, growth of nodule virtually always in the background of HT non Hodgkin ML 98% B cells non-Hodgkin ML, 98% B cells high-grade transformation from MALT-

l hlymphoma

Secondary neoplasmsSecondary neoplasmsSecondary neoplasmsSecondary neoplasms

rare (autoptic series 24%, bioptical series – significantly less)series significantly less)

direct growth (larynx, hypopharynx, h )esophagus)

hematogenous – tumor generalization hematogenous tumor generalization solitary metastasis, long time span serious diagnostic problem

renal lung breast GIT ca melanoma renal, lung, breast, GIT ca, melanoma