department of internal medicine and gastroenterology university of bologna l. bolondi, l. rasciti...

Department of Internal Department of Internal Medicine and Medicine and

GastroenterologyGastroenterologyUniversity of BolognaUniversity of Bologna

L. Bolondi, L. RascitiL. Bolondi, L. Rasciti

CLINICAL AND SONOGRAFIC APPROACH TO CLINICAL AND SONOGRAFIC APPROACH TO THE THYROID NODULETHE THYROID NODULE

Caso clinico

• Donna di 56 anni, sposata con 3 figli, in menopausa da 5 anni.

• Si accorge, guardandosi allo specchio, di lieve asimmetria della circonferenza del collo (modica tumefazione a sin);

• Il medico palpa una formazione nodulare, di consistenza parenchimatosa, non dolente, verosimilmente riferibile al lobo tiroideo sin. Non rileva linfoadenopatie.

Caso clinico

• Funzione tiroidea (FT3, FT4, TSH) nella norma

• Autoanticorpi (anti TG, antimicrosomiali) nella norma

• Emocromocitometrico, GOT, GPT, Azotemia, Glicemia, Protidemia totale ed elettroforesi, VES, Es; urine nella norma

• Viene inviata per esame ecografico

NODULO ISOECOGENO CON AREA LIQUIDA

INTERNA.

AL DOPPLER SEGNI DI VASCOLARIZZAZIONE

PERIFERICA

Key concepts

• Thyroid nodules are the most common endocrine disorder, they can be detected in an otherwise normal gland, especially in iodine-deficient areas. The frequency of thyroid nodules increases throughout life.

• Single nodules are about four times more common in women than in men.

CLINICAL AND SONOGRAFIC APPROACH TO THE THYROID NODULECLINICAL AND SONOGRAFIC APPROACH TO THE THYROID NODULE

Key concepts

• Nodules are 10 times more frequent, in comparison to palpation, when the gland is examined at autopsy, during surgery, or by ultrasonography.


Prevalence of palpable thyroid nodules detected at autopsy or by ultrasonography (solid circle) or by palpation (open square) in subjects without radiation exposure or known thyroid disease.

E. Mazzaferri, NEJM 1993

TIROIDE NORMALE

NORMAL THYROID: Right lobe

TIROIDE: VASCOLARIZZAZIONE

ARTERIA TIROIDEA SUPERIORE

Small (<5mm) non palpable thyroid

nodule in the left lobe

(occasional finding)

Key concepts

• Less than 1% of thyroid nodules detected at US prove to be malignant.

• Less than 5% of solitary nodules detected at US are malignant.

• A significant number of elderly patients have clinically silent thyroid cancers: up to 35% of thyroid glands at autopsy contain tiny (<1.0 cm), clinically unimportant papillary carcinomas.

• Among nodules removed surgically, an estimated 42 to 77 % are non-neoplastic colloid nodules, 15 to 40 % are adenomas, and 8 to 17 % are carcinomas.


Benign Nodulesa) Hyperplastic (colloid) nodule within goiterb) Follicular Adenoma

i. Colloid variantii. Hurthle cell variant

c) Papillary Adenoma (suspect for malignancy)

d) Teratoma


CLASSIFICATION OF THYROID NODULES

• Hyperplastic and Colloid Hyperplastic and Colloid (adenomatous) nodules(adenomatous) nodules are the dominant type of nodules, and can be single or multiple.

• Most are hypofunctioning and incompletely encapsulated. Cytologic studies usually reveal abundant colloid and benign follicular cells, but hemorrhagic nodules or highly cellular aspirates may be difficult to differentiate from follicular cancer.


• A diagnosis of a follicular or Hürthle cell tumor requires further evaluation and management, since the cytologic features of benign follicular or Hürthle cell tumors and low-grade follicular or Hürthle cell cancer are similar.

• Benign from malignant nodules can only be distinguished by the presence or absence of capsular or vascular invasion on histologic examination of surgical specimens.

• Follicular and Hürthle cell tumors have respectively a malignancy rate of 10% to 20%, that cannot generally be assessed adequately at FNAB .


Malignant Nodulesa) Papillary Carcinoma (75-85%)

i. Pure papillaryii. Mixed papillary and follicular carcinoma

b) Follicular Carcinoma (20-25%)i. Malignant adenomaii. Hurthle cell carcinoma or oxyphil

carcinomaiii. Clear-cell carcinoma

c) Medullary Carcinoma (5%)d) Anaplastic Carcinoma (<5%)e) Lymphomaf) Metastatic tumor


Nodules with sonographic apparence of cysts

• Fifteen to 25 percent of all thyroid nodules are cystic.

• High-resolution ultrasound has shown that most of the nodules initially considered to be cystic are complex lesions (solid-cystic).

• Up to 15 percent are necrotic papillary

cancers, and about 30 percent are hemorrhagic adenomas.


NODULE WITH CYSTIC APPEARANCE

HAEMORRHAGIC CYST

Dectection of thyroid nodules

• By chance during routine physical examination

• By chance during US of the neck performed for other problem (i.e. carotid arteries, lymphnodes etc.)

• In symptomatic patiens: local paintendernessswellingdysphagiadysphoniahoarseness


Clinical challenge: to identify which Clinical challenge: to identify which nodules nodules are malignant are malignant

• History and physical examinationHistory and physical examination• Laboratory evaluationLaboratory evaluation• Radionuclide scanningRadionuclide scanning• UltrasonographyUltrasonography• FNA biopsyFNA biopsy• UG-FNA biopsyUG-FNA biopsy


Clinical elements for differential diagnosis

Benign• Family history of benign

thyroid nodule or goiter or autoimmune thyroid disease.

• Symptoms of hypothyroidism or hyperthyroidism.

• Pain or tenderness associated with the nodule.

These factors do not exclude the presence of

thyroid cancer.

Malignant• A family history of

medullary or papillary

thyroid cancer or of familial polyposis (Gardner's syndrome).

• Age—the young (<20 years old) and the old (>70 years old) have the highest incidence of thyroid cancer.

• Rapid tumor growth.



Benign• Soft, smooth, mobile

nodule.

• Multinodular goiter without a dominant nodule.

These factors do not exclude the presence of thyroid cancer.

Malignant• Gender—the proportion

of nodules that are malignant in males is double that in females.

• Nodule plus dysphagia or hoarseness.

• Firm, hard, irregular, and fixed nodule.

• Presence of cervical lymphadenopathy.



Malignant

• History of external neck irradiation during childhood or adolescence (this factor also increases the incidence of nonmalignant thyroid nodular disease) or exposure to nuclear fallout.


Benign

Laboratory evaluation

• In patients with a thyroid nodule, a sensitive thyroid stimulating hormone (TSH) assay should be done, at a minimum, to determine the presence of hyperthyroidism or hypothyroidism.

• Serum calcitonin should be measured when medullary thyroid carcinoma or MEN II is suspected.


Radionuclide scanning

• Aim: to identify hyperfunctioning nodules that are almost always benign.

Limits: lack of differentiating criteria for hypofunctioning nodules

Not all patients with thyroid nodules require nuclear imaging.


Ultrasonography

• Widespread use of ultrasound for examining any neck pathology has resulted in frequent recognition of thyroid nodules, that are too small to be palpated on clinical examination.

• Usually, such nodules are < 1cm in largest diameter, they are typically asymptomatic, and are not associated with lymph nodes or other suggestions of malignancy.

• Often incidentally found, such nodules produce a problem because of the difficulty in achieving a specific diagnosis, which is desired by the patient.


Ultrasonography

• In a recent metanalysis (Ann Intern Med, 126:226-31, 1997.), the risk for malignancy in US incidentalomas ranged betwen 0.45% and 13%.

• Large malignant nodules have been reported to be missed by palpation. The greatest size of malignant non palpable nodules was 2.1 cm.

• The existence of these nodules, detected by US exploration, suggests that a simple follow-up neck palpation, may not be the safest management strategy.


Ultrasonography

• Currently no ultrasound criteria can distinguish benign from malignant thyroid nodules. However some features are suggestive for malignancy:

a)Microcalcification

b)Irregular or microlobulated margin

c) Hypoechogenicity

d)Intranodular blood flow pattern


NODULO ISOECOGENO CON AREA LIQUIDA

INTERNA.

AL DOPPLER SEGNI DI VASCOLARIZZAZIONE

PERIFERICA

HYPERPLASTIC THYROID NODULE

TIROIDE: NODULO IPERPLASTICO

TIROIDE: NODULO PARZIALMENTE CISTICO

CON CALCIFICAZIONI

MEDULLARY CARCINOMA

PAPILLARY CARCINOMA

Intranodular Vascularization

FOLLICULAR CARCINOMA

MORBO DI BASEDOW

TIROIDITE

FNA biopsy

• FNAB has become the initial test, after clinical and/or US examination, because it is safe and inexpensive and leads to a better selection of patients for surgery.

• FNAB is now believed to be the most effective method available for distinguishing between benign and malignant thyroid nodules.

• In this setting the FNAB sensitivity varies from 68 to 98% (mean, 83%) and specificity varies from 72 to 100% (mean, 92%).


FNA biopsy

• Provided that an adequate specimen is obtained, three cytologic results are possible: benign, malignant, and indeterminate (or suspicious) findings.

• A major problem diminishing the potential benefit of FNAB is the unskilled physician performing the biopsy or the inexperienced cytopathologist interpreting the specimens.

• Even in skilled hands, however, approximately 10% of biopsy findings are nondiagnostic.


FNA biopsy

• Repeated FNAB may be appropriate under several circumstances as follows: (1) when the lesion continues to enlarge; (2) when new clinical features develop that suggest possible malignancy; (3) when the previous cytologic diagnosis was indeterminate, or (4) when there is insufficient material for cytologic diagnosis.

• Routine repetitive FNAB of lesions that were previously shown to be benign is rarely indicated.


UG-FNA biopsy

• Ultrasound-guided FNAB (UG-FNAB) has emerged as an alternative to conventional FNAB for the diagnostic evaluation of nonpalpable nodules and for the repeat evaluation of nodules with previous nondiagnostic FNAB.

• It is also an excellent method for the evaluation of complex nodules by precisely positioning the needle in the solid portion of these nodules.


FNAB OF SOLID THYROID NODULE

The arrow points to the needle

UG-FNA biopsy

• In the literature, the sensitivity and specificity of UG-FNAB amounted to 79% and 85%, respectively.

• UG-FNAB is possible for lesions smaller than 1 cm in size, but considering the probable benign nature of most of such lesions, a common alternative course is "observe" such lesions periodically.

• Due to the high prevalence of US thyroid nodules, a systematic UG-FNAB performed on all nonpalpable

nodules is not advisable.


DIAGNOSTIC

FNAB

FOLLICULAR LESION

TREATMENT

ULTRASONOGRAPHY

SUSPICIOUS

CANCER

PALPABLE THYROID NODULE

HOT NODULE

INCREASED RISK

SINGLE NODULE 1 cmor

DOMINANT NODULE

NOT PALPABLE THYROID NODULE

UG-FNAB

FOLLOW UPUS and LAB

NO

NO

YESNO

YES

YES

INCREASED RISKYES

NO

NO

YES

BENIGN

COLD NODULE

NO

YES

CYSTNO YES

INCREASED RISK

NO YES

SURGERY

YES

TSH < 0.03

YES

NO

TSH < 0.03TSH > 4.5

NO


US SIGNS FOR MALIGNANCY

YES

NO

GOZZO COLLOIDOCISTICO TIROIDEO

IPERPLASIA NODULARE

TIROIDE: CA PAPILLIFERO

Nodules with sonographic apparence of cysts

• Both benign and malignant lesions may yield bloody fluid; clear, amber fluid usually indicates a benign lesion.

• Cystic lesions often yield insufficient numbers of cells for diagnosis.


TIROIDE: CISTI EMORRAGICA

TIROIDE: VASCOLARIZZAZIONE

TIROIDITE DI HASHIMOTO

META TIROIDEE DI CA LARINGE

TIROIDE: NODULO IPERPLASTICO

Benign Nodules• Hyperplastic nodules (within goitre)• Follicular Adenoma

• Colloid variant• Hurthle cell variant

• Papillary Adenoma (suspect for malignancy)

• Teratoma


• Papillary carcinomaPapillary carcinoma is usually recognizable in specimens obtained by fine-needle aspiration biopsy. The smears tend to be cellular, and the cells have large nuclei with a pale ground-glass appearance.

• Follicular carcinomaFollicular carcinoma is a tumor most reliably identified by invasion of the capsule or of vessels by malignant cells in surgical specimens (difficult diagnosis at fine-needle aspiration biopsy).

• MedullaryMedullary and and Anaplastic carcinomasAnaplastic carcinomas and Lymphomas Lymphomas (a particular risk in patients with Hashimoto's disease) can ordinarily be identified by fine-needle aspiration biopsy.




• Follicular and Hürthle cell tumors, diagnosed by using FNAB, have respectively a malignancy rate of 10% to 20%, that cannot generally be assesed at FNAB .


• Macrofollicular adenomas have no malignat potential

• Although macrofollicular colloid adenomas have no malignant potential, about 5 percent of microfollicular adenomas, 5 percent of Hurthle-cell adenomas, and 25 percent of embryonal adenomas are follicular cancers.




• Follicular and Hürthle cell tumors, diagnosed by using FNAB, have respectively a malignancy rate of 10% to 20%, that cannot generally be assesed at FNAB .


• Colloid (adenomatous) nodulesColloid (adenomatous) nodules are the dominant type of nodules, and can be single or multiple.

• Most are hypofunctioning and incompletely encapsulated. Cytologic studies usually reveal abundant colloid and benign follicular cells, but hemorrhagic nodules or highly cellular aspirates may be difficult to differentiate from follicular cancer.


• Follicular adenomasFollicular adenomas, which are thought to be monoclonal tumors, tend to be single lesions with well-developed fibrous capsules and a uniform histologic structure distinct from the normal surrounding thyroid. They are classified according to the size or presence of follicles and the degree of cellularity.

• Although macrofollicular colloid adenomas have no malignant potential, about 5 percent of microfollicular adenomas, 5 percent of Hurthle-cell adenomas, and 25 percent of embryonal adenomas are follicular cancers.


department of internal medicine and gastroenterology university of bologna l. bolondi, l. rasciti...

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