Tumori della Tiroide

Il nodulo tiroideo:iter diagnostico

Mauro Maccario

Divisione di Endocrinologia e Malattie del Metabolismo

Università di Torino

Diagnosi differenziale del nodulo tiroideo

• Lesioni tiroidee– gozzo nodulare

– adenoma

– tiroidite di Hashimoto– tiroidite subacuta– cisti del dotto tireoglosso– neoplasie maligne

• Lesioni non tiroidee– linfoadenopatia– adenoma delle

paratiroidi– ascesso cervicale

– igroma cistico– ectopia gh. salivari– aneurisma– laringocele

Tumori maligni della Tiroide

• Derivati dall’epitelio follicolare

Forme differenziate o scarsamente differenziate- Papillare- Follicolare (varianti: Ca a cell. di Hurtle e Insulare)- Carcinoma misto papillare-

follicolare

Forme indifferenziate- Carcinoma anaplastico

• Derivati dalle cellule C parafollicolari

Carcinoma midollare

• Non-epiteliali Linfomi

Sarcomi

Teratomi

• Secondari

Cancro della Tiroide - Epidemiologia

• meno dell’1% dei tumori maligni

(1,5% donne - 0,5% uomini)

• incidenza 5-10 / 100000 (in Piemonte 150-300 nuovi casi /anno)

frequenza simile al mieloma ed al carcinoma dell’esofago della laringe e del collo dell’utero

doppia rispetto al m. di Hodgkin

• 0.4% dei decessi per neoplasia

raro?

guaribile!

Nodulo tiroideo - Epidemiologia

• 4-7 % popolazione U.S.A. ha un nodo palpabile

• aumento di frequenza con l’età• netta prevalenza femminile• 40-50% della popolazione ha un

nodulo dimostrabile all’ETG

• raramente espressione di lesione neoplastica evolutiva

Nodulo tiroideo - percorso diagnostico

Anamnesi

Esami di Laboratorio Imaging

Esame obiettivo

TSH (fT3, fT4,)

AbTPO

Tireoglobulina

Calcitonina

Ecotomografia

Scintigrafia

CT, RMN

Esame citologico su agoaspirato

Screening ?

Popolazioni a rischio Caratteri del nodulo

Incidentaloma

Carcinoma tiroideoScreening in soggetti asintomatici?

• Beneficio della diagnosi precoce– prognosi migliore?

– stadio alla diagnosi nella storia naturale

– storia naturale del tumore occulto

Importanza della diagnosi precoce

Cancer Res 1991 51(4):1234-41Survival and causes of death in thyroid cancer: a population-based study of 2479 cases from Norway.

Akslen LA, Haldorsen T, Thoresen SO, Glattre E

Department of Pathology, Gade Institute, University of Bergen, Norway.

Survival and prognostic factors were studied in 2479 clinically presenting thyroid cancers (TC) reported from the entire Norwegian population from 1970 to 1985. Complete follow-up was obtained (median, 48 months), with information on causes of death. At the end of the observation period, 498 patients were reported to have died of TC, representing 69.7% of all deaths. Among 216 patients dying of other main causes, TC was considered to be a contributing cause of death in 80 cases (11.2%). Multivariate regression analysis of TC deaths showed no significant difference according to sex in any of the histological types. Age had a strong impact on survival, and for papillary carcinomas this effect was apparent after the age of 55 years. Marked differences were observed between various histological types, even between papillary and follicular carcinomas when interactions were included. Furthermore, tumor stage was a strong predictor of TC deaths, and a reduced survival was also found in patients with lymph node metastases. In conclusion, the importance of age, histological type, and tumor stage as major prognostic factors has been documented in this population-based study from Norway.

da: DOH 1999, Cancer in the District of Columbia - 1996

Ca tiroide - Stadio alla diagnosi nella storia naturale

Cancro della tiroideCancro del polmone

Nodulo tiroideoScreening in soggetti asintomatici?

• Beneficio della diagnosi precoce– prognosi migliore?

– stadio alla diagnosi nella storia naturale

– storia naturale del tumore occulto

• Rapporto costo/beneficio– autoscreening, screening periodico presso medico

generale o presso centro specialistico?

– efficacia dello screening

– rapporto nodi benigni / maligni

– modalità di screening (palpazione, ETG, …)

J Clin Ultrasound 1992 Jan;20(1):37-42

Clinical versus ultrasound examination of the thyroid gland in common clinical practice.

Brander A, Viikinkoski P, Tuuhea J, Voutilainen L, Kivisaari LHyvinkaa District Hospital, Finland.

In a prospective series of 72 patients, clinical and ultrasonographic examination of the thyroid gland were compared in detail. Normal-sized lobes were differentiated from enlarged ones both by inspection and by palpation. When lobar size was assessed by palpation, the estimate was most clearly influenced by increase in width. The correlation between two examiners in lobe size assessment was significant. In the classification of thyroid disease as diffuse, solitary, or multinodular, clinical examination and ultrasonography correlated significantly. However, only one third of the clinically solitary nodules proved to be solitary by ultrasound examination. Of 77 separate nodules, 43 escaped detection on clinical examination. Of these 43, 14 nodules exceeded 2 cm in diameter. It is concluded that the use of ultrasonography frequently alters the primary evaluation of thyroid nodularity based on palpation.

Palpazione del collo: sensibilità 44% vs ETG

Of 77 separate nodules, 43 escaped detection on clinical examination. Of these 43, 14 nodules exceeded 2 cm in diameter. It is concluded that the use of ultrasonography frequently alters the primary evaluation of thyroid nodularity based on palpation.

Screening ecograficoRadiology 1991 Dec;181(3):683-7

Thyroid gland: US screening in a random adult population.

Brander A, Viikinkoski P, Nickels J, Kivisaari LHyvinkaa District Hospital, Finland.

High-frequency ultrasound examination of the thyroid was performed in 253 subjects (130 women and 123 men; age range, 19-50 years) that were randomly selected from the population in an area of Finland where goiter is not endemic. Thyroid echo abnormalities were detected in 69 subjects (27.3%). Prevalence of abnormalities increased with age, and women showed more lesions than did men in each of the 3 decades. The abnormality was solitary in 39 subjects (57%), multiple in 15 (22%), and diffuse in 15 (22%). Of the 68 individual nodules, 48 (70%) were smaller than 1 cm in diameter. Anechoic rounded nodules 1-5 mm in diameter were found in 28 subjects. Fine-needle aspiration biopsy was performed in 30 subjects. Cytologic examination revealed no unequivocal malignancies. In eight subjects (3.2%) with a diffuse echo abnormality, cytologic evaluation indicated lymphocytic thyroiditis. It is concluded that the prevalence of small thyroid echo abnormalities in a randomly selected adult population is rather high, a fact that supports use of a conservative approach to these types of findings.

The Canadian Guide to Clinical Preventive Health Care

Give Yourself The Thyroid "Neck Check"It Could Save Your Life

TO TAKE THE THYROID NECK CHECK...

All you will need is:• A glass of water• A hand-held mirror

1. Hold the mirror in your hand, focusing on the area of your neck just below the Adam's apple and immediately above the collarbone. Your thyroid gland is located in this area of your neck.

2. While focusing on this area in the mirror, tip your head back.

3. Take a drink of water and

swallow.

. 4. As you swallow, look at your neck. Check for any bulges or a protrusion in this area when you swallow. Reminder: Don't confuse the Adam's apple with the thyroid gland. The thyroid gland is located further down on your neck, closer to the collarbone. You may want to repeat this process several times.

5. If you do see any bulges or protrusions in this area, see your physician immediately. You may have an enlarged thyroid gland or a thyroid nodule and should be checked to determine whether cancer is present or if treatment for thyroid disease is needed.

The Cancer Related Check-up

Apart from participating in screening that has been recommended as part of a population-based initiative, an individual's periodic encounters with clinicians are viewed by the ACS as having potential for health counseling and a cancer-related check-up. Health counseling may include guidance about smoking cessation, diet, physical activity, and the benefits and risks of undergoing various screening tests. These encounters may include case-finding examinations of the thyroid, testicles, ovaries, lymph nodes, oral region, and skin. Also, self-examination of the skin and breasts can be encouraged, as can the importance of awareness of symptoms of testicular cancer in young men. The ACS recommends a cancer-related check-up every three years for asymptomatic individuals between the ages of 20 and 39, and annually for asymptomatic men and women ages 40 and older

Effectiveness of Early Detection of Thyroid Cancer

The benefits of early detection of thyroid cancer in the general population are not well defined. For all histologic types, 5-year survival is significantly better with earlier stage at diagnosis. A cohort study of mass screening found a significantly higher 7-year cumulative survival rate in patients whose cancer was detected by screening (98%) when compared with those presenting with symptoms (90%). Cancers detected by screening were significantly more likely to have a favorable histology, however, and both lead-time and length biases are likely in this study.

There have been no controlled trials demonstrating that asymptomatic persons detected by screening have a better outcome than those who present with clinical symptoms or signs. In addition, not all cancers detected through screening are likely to present clinically during the patient's lifetime. In autopsy studies in the U.S., the prevalence of occult thyroid carcinoma in adults ranges from 2-13%; in contrast, the annual incidence of thyroid carcinoma is only about 4/100,000 population.

U.S. Preventive Services Task Force - 1996

There have been no controlled trials demonstrating that asymptomatic persons detected by screening have a better outcome than those who present with clinical symptoms or signs. In addition, not all cancers detected through screening are likely to present clinically during the patient's lifetime. In autopsy studies in the U.S., the prevalence of occult thyroid carcinoma in adults ranges from 2-13%; in contrast, the annual incidence of thyroid carcinoma is only about 4/100,000 population.

Incidentaloma tiroideo

Annals of Internal Medicine

REVIEW

Thyroid Incidentalomas: Management Approaches to Nonpalpable Nodules Discovered Incidentally on Thyroid Imaging

Annals of Internal Medicine, 1 February 1997. 126:226-231.

Gerry H. Tan, MD, and Hossein Gharib, MD

Mayo Clinic and Mayo Foundation, Rochester, Minnesota.


G.H. Tan & H. Gharib, Annals of Internal Medicine, 1997. 126:226-231


G.H. Tan & H. Gharib, Annals of Internal Medicine, 1997. 126:226-231

Conclusions: ...

Most of these lesions are benign. For most patients with non-palpable nodules that are incidentally detected by thyroid imaging, simple follow-up neck palpation is sufficient


Anamnesi


Esame obiettivo


Screening ?

Popolazioni a rischio Caratteri del nodulo

Incidentaloma

Anamnesi - Esame obiettivo

CONDIZIONE FAVOREVOLE

• Storia familiare di tiroidite cronica

• Storia familiare di struma• Sintomi di ipo- /

ipertiroidismo• Dolore o tensione

associata al nodulo• nodulo liscio e mobile

• gozzo multinodulare

CONDIZIONE SFAVOREVOLE

• Età < 20 o > 70 anni• Sesso maschile• Disfagia• Storia di radioterapia del

collo• Nodulo duro, fisso,

irregolare

• Adenopatia cervicale

• Storia di cancro della tiroide


Anamnesi


Esame obiettivo


Screening ? Incidentaloma

TSH, fT3, fT4

AbTPO

Tireoglobulina

Calcitonina

Bennedbaek FN, Perrild H, Hegedus L.Diagnosis and treatment of the solitary thyroid nodule. Results of a European survey. Clinical Endocrinol (Oxf) 1999; 50:357-363.

Esami di laboratorio - funzionalità tiroidea

Tests FrequencyTSH 99Free T4 measurement 53Calcitonin 43Thyroid peroxidase (TPO) antibodies 41Free T3 measurement 31Thyroglobulin antibodies 26Total T3 25Total T4 20Sedimentation rate 16Thyroglobulin 14Microsomal antibodies 11Free T4 index 9Tsh-receptor antibodies 6TRH test 4Urinary iodide excretion 4

Case hystory

• 42 y old Caucasian women

• nodule 2x3 cm mobile

• present from 3 months

• no lymphadenopathy

• no family history of thyroid disease

• no previous external irradiation

Esami di laboratorio - funzionalità tiroidea

TSH ultrasensibile

diminuitoaumentato

Scintigrafia Tc99

nodulo captante

nodulonon captante

AbTPO

Nodo sospetto

Nodo tossico(non sospetto)

Tiroidite cronica autoimmune(nodo poco sospetto)

positivo


Esami di laboratorio - Tireoglobulina

Tests FrequencyTSH 99Free T4 measurement 53Calcitonin 43Thyroid peroxidase (TPO) antibodies 41Free T3 measurement 31Thyroglobulin antibodies 26Total T3 25Total T4 20Sedimentation rate 16Thyroglobulin 14Microsomal antibodies 11Free T4 index 9Tsh-receptor antibodies 6TRH test 4Urinary iodide excretion 4

Case hystory







Esami di laboratorio - Tireoglobulina

AACE Clinical Practice Guidelinesfor the Diagnosis

and Management of Thyroid Nodule

Developed byThe American Association of Clinical Endocrinologists

and The American College of Endocrinology

© 1996, AACE

..A baseline serum thyroglobulin levels in the evaluation of solitary thyroid nodule is not a useful or cost-effective test. The value of the thyroglobulin levels lies in serial determinations after thyroid cancer has been diagnosed and the patient has been treated by elimination of most or all of the thyroid gland....


Esami di laboratorio - Calcitonina

Tests FrequencyTSH 99Free T4 measurement 53Calcitonin 43Thyroid peroxidase (TPO) antibodies 41Free T3 measurement 31Thyroglobulin antibodies 26Total T3 25Total T4 20Sedimentation rate 16Thyroglobulin 14Microsomal antibodies 11Free T4 index 9TSH-receptor antibodies 6TRH test 4Urinary iodide excretion 4

Case hystory







Esami di laboratorio - CalcitoninaJ.R. Hahm et al.

Routine Measurement of Serum Calcitonin is Useful for Early Detection of Medullary Thyroid Carcinoma in Patients with Nodular Thyroid Diseases.

Thyroid, 11:73-79, 2001

CT = calcitoninemia

MTC = carcinoma midollare

PTC = carcinoma papillare

FN = lesione follicolare

Esami di laboratorio - Calcitonina

..If the family history is non contributory, routine serum calcitonin measurements are not cost-effective...

..In the absence of suspicion of medullary thyroid cancer or multiple endocrine neoplasia II syndrome, it is neither routinely necessary nor cost effective to determine calcitonin levels in patients with solitary thyroid nodule...

Treatment Guidelines for Patients With Thyroid Nodules and Well-Differentiated Thyroid Cancer Arch Int Med 1996

AACE Clinical Practice Guidelines for the Diagnosis and Management of Thyroid Nodules

1996


Anamnesi


Esame obiettivo


Screening ? Incidentaloma

TSH, fT3, fT4

AbTPO

Tireoglobulina

Calcitonina

Ecotomografia

Scintigrafia

CT, RMN


Imaging - Scintigrafia

Diagnostic procedure FrequencyScintigraphyI 131I123Tc99m

Scintigraphy only

664

1086

8

UltrasonographySizeGrey scaleDoppler

Ultrasonography only

80755733

22Scintigraphy and ultrasonography 58X-ray (chest-trachea) 7

Case hystory







Scintigraphy 66

Scintigraphy and ultrasonography 58

Imaging - Scintigrafia Tc99m / I123

• In paziente ipertiroideo: verifica della presenza di noduli iperfunzionanti (raramente maligni)

• In paziente eutiroideo: verifica dello stato funzionale dei noduli di un gozzo multinodulare

... with the exception of hyperfunctioning nodules, the thyroid scan will not help to differentiate benign from malignant lesions. For this reason, many endocrinologists no longer advocate obtaining thyroid scans as part of the routine initial evaluation of a nodular goiter, and they prefer to perform an

FNAB first.

… Certainly, not all patients with thyroid nodules require nuclear imaging. In many centers, thyroid FNA biopsy has supplanted nuclear thyroid imaging as the initial technical procedure in

Treatment Guidelines for Patients With Thyroid Nodules and Well-Differentiated Thyroid Cancer Arch Int Med 1996

AACE Clinical Practice Guidelines for the Diagnosis and Management of Thyroid Nodules

1996

Imaging - Scintigrafia

evaluating nodules. AACE recommends that the physician use clinical judgment in considering the appropriateness of a thyroid nuclear scan, as it applies to each individual case.

grazie per l’attenzione

Il nodulo tiroideo:iter diagnostico

Health & Medicine

Tumori della Tiroide