Minimally Invasive Follicular Carcinoma: Minimally Invasive Follicular Carcinoma: A Cytological and Histological ChallengeA Cytological and Histological Challenge

David Poller, Queen Alexandra Hospital,Portsmouth, UKDavid Poller, Queen Alexandra Hospital,Portsmouth, UK

22 year old female euthyroid, T4 11.3 (N 7.0-20), 22 year old female euthyroid, T4 11.3 (N 7.0-20), TSH 0.81 (N 0.35-5.0), Ab –veTSH 0.81 (N 0.35-5.0), Ab –ve

MNG, ultrasound guided FNA of a large 29mm solid MNG, ultrasound guided FNA of a large 29mm solid nodule in left lobenodule in left lobe

CytologyCytology

US guided FNA, 4 slides, air dried pap & US guided FNA, 4 slides, air dried pap & giemsa giemsa without without rapid on site assessmentrapid on site assessment

Moderate cellularity, virtually no colloid, Moderate cellularity, virtually no colloid, some cell clusters 3 dimensional with some cell clusters 3 dimensional with some nuclear features suggestive of some nuclear features suggestive of papillary carcinoma; Thy4 ~Bethesda V,papillary carcinoma; Thy4 ~Bethesda V,

Multidisciplinary team decision->left Multidisciplinary team decision->left thyroid lobectomythyroid lobectomy

DiagnosisDiagnosis

Thy4 = Bethesda Class V Thy4 = Bethesda Class V

suspicious neoplasm, cannot exclude FVPCsuspicious neoplasm, cannot exclude FVPC

Left thyroid lobectomy = 20gLeft thyroid lobectomy = 20g

Minimally invasive well differentiatedMinimally invasive well differentiated

follicular carcinomafollicular carcinoma, a 42mm pT3 well, a 42mm pT3 well

differentiated follicular carcinoma, foci ofdifferentiated follicular carcinoma, foci of

vascular invasion-> completionvascular invasion-> completion

thyroidectomythyroidectomy

Minimally Invasive Follicular CarcinomaMinimally Invasive Follicular Carcinoma

Requires assessment of whole lesion with capsule & Requires assessment of whole lesion with capsule & surrounding thyroidsurrounding thyroid

WHO 2004 definition = transcapsular invasion or WHO 2004 definition = transcapsular invasion or vascular invasionvascular invasion

What is Invasion??What is Invasion??‘..Our review of the anatomy of the thyroid gland con-firms that this structure has no defined anatomical fibrous capsule..’

‘..We suggest that the criteria for diagnosing angioinvasion in thyroid carcinomas as well as in other endocrine tumors are inconsistent. ..’

.

4000 carcinoma cases, very rigid criteria 118 cases with tumour invading vessel wall & thrombus adherent to intravascular tumour, 35% developed distant metastases at mean 5.3y follow up

Minimal InvasionMinimal Invasion

‘..The importance of the study is the confirmation that diagnostic reproducibility of minimally invasive FTC is low and that this has clinical implications, and also implications for the design of studies into the treatment and outcome of FTC’

Garcia-Rostan & Sobrinho-Simões Diagn Histopathol 2011; 17: 119.

Other SystemsOther Systems

VeracyteVeracyte: Alexander et al NEJM 2012 mRNA needle washings, 265 : Alexander et al NEJM 2012 mRNA needle washings, 265 nodules, high negative predictive value, 8% misclassified as benign, nodules, high negative predictive value, 8% misclassified as benign, BUT low +ve predictive value for malignancy, 48% of benign BUT low +ve predictive value for malignancy, 48% of benign nodules classified as suspicious, cost US$ 3200 per testnodules classified as suspicious, cost US$ 3200 per test

Assuragen miRInformAssuragen miRInform: Braf, Ret/Ptc, Ras, Pax8/PPAR: Braf, Ret/Ptc, Ras, Pax8/PPARspecificity specificity 98%, sensitivity 60% Hodak & Rosenthal Thyroid 2013, cost US 98%, sensitivity 60% Hodak & Rosenthal Thyroid 2013, cost US $650 per test$650 per test

FinallyFinally

The criteria for maligancy in follicular lesions are not precise and The criteria for maligancy in follicular lesions are not precise and some follicular thyroid lesions with genotypes of follicular some follicular thyroid lesions with genotypes of follicular carcinomas may well be ‘in situ’ lesions that do not demonstrate carcinomas may well be ‘in situ’ lesions that do not demonstrate invasion using conventional morphological criteriainvasion using conventional morphological criteria

If you want to diagnose thyroid nodules you need representative If you want to diagnose thyroid nodules you need representative cells from the lesion(s)cells from the lesion(s)

But in many cases Class I and Class III aspirate rates are high; eg But in many cases Class I and Class III aspirate rates are high; eg Class 1 up to 15%+ and Class III up to 20%, often because of poorly Class 1 up to 15%+ and Class III up to 20%, often because of poorly prepared slides lacking cells prepared slides lacking cells

Rapid On Site Assessment is EssentialRapid On Site Assessment is Essential