cancer de tiroides

Cáncer de )roides

Alejandro Román-González Medicina Interna- Hospital San Vicente Fundación

Fellow Endocrinología Clínica y Metabolismo Universidad de Antioquia

@alejoromanmd [email protected]

endocrinologiaalejoroman.blogspot.com

Cáncer de )roides

Diferenciado

•  Papilar •  Folicular

Mal diferenciado

• Anaplasico •  Pob. diferenciado

Otros

• Medular •  Linfoma • Metástasis

Nódulo )roideo

•  Riesgo de cáncer es del 5%

•  Debe conocerse la función )roidea

•  Correlacionar con hallazgos ecográficos

Román-‐González A et al. Iatreia 2013: Vol. 26 (2): 197-‐206, abril-‐junio 2013

EcograHa )roidea de alta resolución

Med Clin N Am 96 (2012) 329–349

Características ecográficas para predecir malignidad Característica ecográfica Sensibilidad, % Especificidad, % VPP, % VPN, %

Microcalcificaciones 26.1-59.1 85.8-95 24.3-70.7 41.8-94.2

Hipoecogenicidad 26.5-87.1 43.4-94.3 11.4-68.4 73.5-93.8

Márgenes irregulares, ausencia del halo

17.4-77.5 38.9-85 9.3-60 38.9-97.8

Sólido 69-75 52.5-55.9 15.6-27 88-92.1

↑ flujo intranodular 54.3-74.2 78.6-80.8 24-41.9 85.7-97.4

Más alto que ancho 32.7 92.5 66.7 74.8

Risk of Thyroid Cancer Based on Thyroid Ultrasound Imaging Characteris)cs: Results of a Popula)on-‐Based

Study

Smith-‐Bindman R et al. JAMA Intern Med. Published online August 26, 2013

•  18 por 1000 •  Una sola caracterís)ca

Riesgo bajo

•  2 caracterís)cas suges)vas •  Microcalcificaciones •  Sólido o mayor de 2 cms

Moderado

•  960 por 1000 •  Nódulo sólido, mayor de 2 cms y con microcalcificaciones

Alto

IATREIA Vol 26(2) abril-junio 2013

201

Hallazgos en la citologíaEl reporte de la biopsia por aspirado con aguja fina (ACAF) se debe clasificar de la siguiente manera (37,38): Diagnóstico o satisfactorio: mínimo seis grupos celulares con al menos 10 células foliculares tiroideas cada uno; No diagnóstico o no satisfactorio.

Diagnóstico y criterios morfológicos según Bethesda (38)

Comprende seis categorías: 1. Benigno; 2. Atípico/Indeterminado (ASCUS, atypical squamous cell of undetermined significance); 3. Patrón folicular (Neoplasia/Lesión). 4. Sospechoso de malignidad; 5. Maligno; 6. Insatisfactorio.

Benigno

Bajo este término se agrupan las lesiones con bajo riesgo de neoplasia tiroidea. Para disminuir la tasa de falsos negativos (que normalmente es del 5%), se recomienda el seguimiento clínico con exploración ecográfica y nueva punción si hay crecimiento significativo de la lesión. Se exponen a continuación brevemente los criterios morfológicos de las lesiones que componen el grupo.

Bocio coloide o nodular: abundante coloide. Placas de células foliculares pequeñas, benignas (ausencia de las características nucleares del carcinoma papilar). Macrofolículos, macrófagos, metaplasia oncocítica.

Bocio tirotóxico-hiperfuncional: fondo hemático sin coloide. Celularidad moderada. Grupos dispersos de pequeño tamaño. Núcleos redondos y agrandados (anisocariosis) con nucléolo único. Vacuolización citoplasmática marginal en llamarada.

Tiroiditis linfocítica crónica: mezcla de células linfoides maduras y células foliculares grandes con frecuente cambio oncocítico. Ausencia de coloide. Células gigantes ocasionales.

Tiroiditis subaguda o de células gigantes: fondo inflamatorio mixto linfo-monocitario. Granulomas epitelioides. Células gigantes multinucleadas. Cambios epiteliales regresivos (degeneración gránulo-vacuolar). Ausencia de coloide.

Atípico/Indeterminado (células atípicas de significado indeterminado, ASCUS)

No se puede excluir la presencia de una neoplasia con base en los datos citológicos. Bethesda recomienda en estos casos (38), si se puede, informar si el cuadro citológico sugiere un proceso hiperplásico o uno neoplásico.

En este grupo, más que en otros, es fundamental analizar conjuntamente la citología, la clínica y la radiología (triple test), así como repetir la punción siempre que se considere necesario. En 80% a 96% de los ASCUS se aclara el diagnóstico después de repetir la punción. El promedio de lesiones malignas de los ASCUS es de 5% a 10%, por lo que inicialmente no

Tabla 1. Recomendaciones para el aspirado (estudio citológico)

Características Límite de tamaño para hacer la biopsiaHistoria de alto riesgo con características ecográficas de riesgo o sin ellas Más de 5 mmAdenopatías cervicales TodosMicrocalcificaciones 1 cm o másNódulo sólido hipoecoico Más de 1 cmNódulo sólido isoecoico o hiperecoico* 1-1,5 cm o másNódulo mixto sólido-quístico con ecografía de riesgo* 1,5 cm o másNódulo mixto sólido-quístico sin ecografía de riesgo* 2,0 cm o másNódulo espongiforme* 2,0 cm o másNódulo quístico* No requiere

*Estos criterios no están incluidos en la última guía de la ATA de 2009; según ésta, se debe hacer estudio citológico de todos los nódulos mayores de un centímetro. La única excepción son los nódulos espongiformes que se estudian si son mayores de dos centímetros (alto valor predictivo positivo para lesiones benignas)

*Estos criterios no están incluidos en la úl)ma guía de la ATA de 2009; según ésta, se debe hacer estudio citológico de todos los nódulos mayores de un cen`metro. La única excepción son los nódulos espongiformes que se estudian si son mayores de dos cen`metros (alto valor predic)vo posi)vo para lesiones benignas)

Nódulo )roideo, enfoque y manejo. Revisión de la literatura


¿Que hacer luego de BACAF?

•  Insuficiente •  Benigno •  Lesión/a)pia de significado incierto •  Neoplasia Folicular •  Sospechoso de malignidad

•  Maligno


Neoplasia folicular. Observar o tratar.

•  Cáncer en 20-‐30%

•  Conducta estándar: hemi)roidectomía

•  Obje)vo: diferencia cáncer de neoplasia

•  Riesgo quirúrgico

Final Pathology Findings Ajer Immediate or Delayed Surgery in Pa)ents with Cytologically Benign or

Follicular Thyroid Nodules

Manejo quirúrgico si: •  Sospecha ecográfica de malignidad •  Tamaño > 4 cms •  Tg > 100 ng/ml •  Compromiso tráquea o esófago •  Expansión el medias)no •  Nódulos autónomos •  Problema esté)co

World J Surg (2011) 35:558–562

Final Pathology Findings Ajer Immediate or Delayed Surgery in Pa)ents with Cytologically Benign or

Follicular Thyroid Nodules

World J Surg (2011) 35:558–562

stage II in 4 and stage III in 33. Of 125 nodules that

underwent late resection, 8 (6.4%) were pathologically

diagnosed as thyroid carcinoma: 3 papillary carcinomas(all were follicular variants of papillary carcinoma) and 5

follicular carcinomas, with pathological stage II in 6 and

stage III in 2.Table 4 indicates the relationship between pathological

diagnoses and clinical characteristics of 445 patients. There

was no significant difference in age, tumor size, or serumthyroglobulin between benign and malignant thyroid nod-

ules. However, there were significant differences in ultr-

asonographic classification and cytological findingsbetween benign and malignant nodules.

Discussion

Ultrasonography-guided FNAB is the most effectivediagnostic method for the evaluation of nodular thyroid

lesions [1–5]. Unfortunately, even nodules that are benign

cytologically can be diagnosed as malignant tumor

histopathologically after surgery [1, 2, 5–9]. However,

15–20% of cytological follicular neoplasms have been

shown to be malignant histologically [10]. We consider itunnecessary to perform surgery in all cases of benign or

follicular neoplasm; in fact, it is important to select those

patients that require surgical resection. Therefore, at ourinstitution, almost all benign or follicular tumors warrant

observation without surgery, and our criteria for surgical

indication are as described above.Overall, 45 (10.1%) of 445 patients with nodules diag-

nosed as benign or follicular tumors cytologically who

underwent immediate or late surgery in our study had amalignancy, excluding incidental occult papillary carci-

noma. The mean size of nodules was larger and the level of

serum thyroglobulin was significantly higher in patientsundergoing immediate surgery as compared to those

undergoing late surgery, according to our criteria for sur-

gical indication. In addition, nodules resected in immediatesurgery were graded in significantly higher ultrasono-

graphic classes than those resected in late surgery.

Regardless of the absence of significant differences inFNAB diagnosis between late and immediate surgery, the

frequency of malignancy in late surgery was lower than

that in immediate surgery (6.4 versus 11.6%). Late thy-roidectomy never has an adverse outcome in view of Stage

Grouping as compared with that of immediate surgery.

Therefore, we considered that our criteria for surgicalindication in cytologically diagnosed benign or follicular

thyroid nodules are appropriate.

Whether nodule size should be used as a separate cri-terion for recommending surgical therapy or determining

Table 2 Clinical characteristics of patients at initial diagnosis

Immediate surgery (n = 320) Late surgery (n = 125) p Value

Age (years)a 45.4 ± 13.3 (19–69) 46.6 ± 14.5 (11–74) 0.834

Gender (male/female)a 28/292 7/118 0.361

Tumor size (mm)a 46.3 ± 18.0 (10.0–109.0) 36.6 ± 13.7 (11.0–93.0) \0.001

Serum thyrogloblin (ng/ml)a 779 ± 1,599 (10–8,000) 258 ± 595 (1–4,604) \0.001

Ultrasonographic classificationb

Class 2 152 103 \0.001

Class 3 138 20

Class 4 30 2

FNAB diagnosisc

Benign 259 107 0.247

Indeterminate 61 18

Periods from initial biopsy to surgery (months)a 4.8 ± 2.8 (1.4–8.2) 73.8 ± 54.2 (18.3–258.0) \0.001

Data were means ± SD or numbers

Values in parentheses were interquartile rangesa p values for t-testb p values for Fisher’s exact test: class 2 versus classes 3–4c p values for chi-square test

Table 3 Pathological relationship between immediate and late sur-gical treatment

Total Benign Malignant

PC FC Total

Immediate surgery 320 283 10 27 37 (11.6%)

Late surgery 125 117 3 5 8 (6.4%)

Total 445 400 13 32 45 (10.1%)

PC papillary carcinoma; FC follicular carcinoma

560 World J Surg (2011) 35:558–562

123

Clinical Presenta)on of Pa)ents with a Thyroid Follicular Neoplasm: Are there Preopera)ve Predictors

of Malignancy? •  Malignidad – Masculino – Historia familiar –  Radiación

•  Benignidad –  > 45 años – Hiper)roidismo –  Síntomas –  > 4 cms –  Bocio mul)nodular

Najafian A et a. Ann Surg Oncol 2015

Fisher’s exact test was used to compare differences

between the follicular lesion and neoplasm groups withregard to the incidence of surgery, rate of malignancy, and

pathologic and demographic parameters. Chi-square anal-

ysis was used to compare the size of nodules betweengroups. P values of B0.05 were considered significant.

Evaluation of each pathologist’s reporting pattern and

correlation between the cytopathology diagnosis and thehistologic diagnosis from biopsy of surgical specimens

were also compared to determine the utility of the patho-logic classification follicular neoplasm.

RESULTS

During the 17-year period of interest, 540 thyroid nod-

ules in 540 patients were classified as indeterminate for

malignancy on FNA biopsy, that is, 410 (75.9%) lesionswere categorized as follicular lesions and 130 (24.1%) as

follicular neoplasms (Fig. 1). Surgical resection and his-

tologic evaluation of the index nodule was performed in297 (55.0%) of the initial 540 patients: 199 (48.5%) with

follicular lesions and 98 (75.4%) with follicular neoplasms

(P = 0.007) (Table 2). Histologic evidence of differentiatedthyroid cancer was found in 35 (11.8%) of the 297 thyroid

specimens: 14 (7.0%) of 199 follicular lesions and 21

(21.4%) of 98 follicular neoplasms (P = 0.0005) (Table 2).The 35 carcinomas included 27 follicular carcinomas (18

with a cytologic diagnosis of neoplasm; 9 diagnosed as

lesion) and 8 papillary thyroid carcinomas (3 classified asneoplasm; 5 classified as lesion) (Fig. 1). Follicular nod-

ules of uncertain malignant potential were also identified in

six cases (three as neoplasm; three as lesion). Over time,the rate of follicular carcinoma by year was constant (most

often two per year throughout the study). Similarly, the rate

of papillary thyroid carcinoma averaged 0–1 per year.

Patient sex and age, and nodule size were comparablebetween groups of patients diagnosed with follicular lesion

and follicular neoplasm; this was true in the subgroup of

patients who underwent surgical resection as well(Table 3). In the group of patients with a cytopathologic

diagnosis of follicular neoplasm who underwent surgery,

malignant thyroid nodules were more likely to be largerthan benign nodules (mean, 3.4 cm versus 2.6 cm; P =

0.03). The incidence of malignancy in follicular neoplasms

increased with nodule size, from 11.8% for nodules 1.1–2.0 cm to 27.6% for nodules 2.1–3.0 cm, 25.0% for nod-

ules 3.1–4.0 cm, and 37.5% for nodules [4.0 cm

(Table 4). In the follicular lesion group who underwentsurgery, benign lesions were larger than malignant ones,

with mean diameters of 2.8 and 2.3 cm, respectively,

although the difference was not significant (P = 0.15).Other characteristics, including patient age and sex, were

similar between subgroups of patients with benign and

malignant nodules in both the follicular lesion and follic-ular neoplasm groups.

During the study period, 22 pathologists rendered the

cytologic diagnoses in these 540 patients. The meannumber of reports completed by each pathologist was 24.5

(median 20, range 1–95). Fourteen of the 22 pathologists

gave a diagnosis of indeterminate thyroid nodule from anFNA biopsy ten or more times (that is, they had a high

volume of such diagnoses). These 22 pathologists com-

pleted an average of 36.6 reports each, which accounted for513 (95.0%) of the indeterminate diagnoses in this study.

The other eight pathologists completed the remaining 27

(5.0%) reports, averaging 3.4 reports each (low volume).The frequency of using the terms follicular lesion and

follicular neoplasm varied between pathologists. For the 16

540 thyroidfine-needle aspirations

410 lesions75.9%

130 neoplasms24.1%

199 surgery48.5%

211 observation51.5%

32 observation24.6%

98 surgery75.4%

185 benign93.0%

14 malignant7.0%

21 malignant21.4%

77 benign78.6%

9 follicularcarcinomas

5 papillarycarcinomas

18 follicularcarcinomas

3 papillarycarcinomas

FIG. 1 Flow chart showing classification of thyroid fine-needleaspirations (FNA) biopsies, clinical triage, and histologic diagnosis onsurgical specimens

TABLE 2 Classification of thyroid fine-needle aspiration (FNA)biopsies as lesion versus neoplasm with incidence of surgery andsurgical pathologic diagnosis

Triaged Thyroid FNA biopsy diagnosis P value

Lesion (N = 410) Neoplasm (N = 130)

Surgerya 199 (48.5%) 98 (75.4%)

No surgeryb 211 (51.5%) 32 (24.6%) P = 0.007

Surgical specimen diagnosis

Benignc 185 (93.0%) 77 (78.6%)

Malignantd 14 (7.0%) 21 (21.4%) P = 0.0005

a Surgical intervention (hemi- or total thyroidectomy) performed atour institutionb No surgical intervention at our institution by the time of this studyc Benign includes adenoma, hyperplasia, and lesions of uncertainmalignant potentiald Malignant includes malignancy in nodule that had undergone FNAbiopsy; diagnoses included follicular and papillary carcinomas(incidental microcarcinomas were excluded)

Correlating Indeterminate Thyroid FNAs 3149

Ann Surg Oncol (2009) 16:3146–3153

Caso clínico

•  Paciente de 50 años, mujer, nódulo )roideo de 2.5 cms, sólido, BACAF sospechoso de malignidad. Su conducta es:

A. Escribir a [email protected] B. Remisión a cirugía para manejo quirúrgico C. Repe)r ACAF D. Observación E. A y B son correctas.

Carcinoma Papilar de Tiroides

•  Neoplasia endocrina más frecuente

•  Más común 80%

•  Más en mujeres

•  Más mortalidad en hombres

•  Mortalidad estable

•  Aumento de la incidencia •  Causa

Pregunta de examen •  ¿Cuales son las caracterís)cas microscópicas del carcinoma papilar?

•  Hendiduras nucleares •  Pseudoinclusiones intranucleares •  Croma)na pálida •  Células epiteliales con nucleos sobrepuestos, aumentadas de tamaño

•  Grupos papilares •  Coloide en ¨chicle¨ •  Cuerpos de psammoma •  Células gigantes

Variantes

•  Folicular •  Oncoci)ca •  Células claras •  Cribiforme o morular •  Macro-‐folicular •  Sólida •  Células altas •  Columnar •  Esclerosante difusa •  Warthin

Agresivos Células altas Columnar

Esclerosante difuso Folicular

Aumento en incidencia

JAMA Otolaryngol Head Neck Surg. 2014;():. doi:10.1001/jamaoto.2014.1!

Epidemiología

JAMA Otolaryngol Head Neck Surg. 2014;():. doi:10.1001/jamaoto.2014.1!

Fisiopatología y factores de riesgo

ME65CH09-Udelsman ARI 13 December 2013 17:53

INTRODUCTIONThe normal thyroid gland is composed histo-logically of two main parenchymal cell types.Follicular cells line the colloid follicles, concen-trate iodine, and produce thyroid hormones.These cells give rise to both well-differentiatedcancers (i.e., papillary and follicular) andanaplastic thyroid cancer. The second celltype, the C or parafollicular cell, produces thehormone calcitonin and is the cell of origin formedullary thyroid carcinoma (MTC).

Epidemiology and PathogenesisThe diagnosis of thyroid cancer, specificallypapillary thyroid cancer (PTC), has increasedrapidly, with a 240% increased incidence overthe past three decades (1). Although the ma-jority of newly diagnosed thyroid cancers aresmall PTCs, increased incidences have beenexhibited for all sizes and stages of PTC in bothgenders and in all ethnic groups (2). PTC is themost common endocrine malignancy, account-ing for 96.0% of total new endocrine cancersand 66.8% of deaths due to endocrine cancers(3). Per cancer statistics, 60,200 new casesof thyroid cancer will be diagnosed in 2013,with 1,850 deaths due to the disease (3). Thediscrepancy between the total number of casesof thyroid cancer and deaths reflects the rela-

Table 1 Summary of most common currently known genetic alterations identified in nonfamilial thyroid cancer derivedfrom follicular cellsa

Genetic alteration Well-differentiated thyroid cancer

Intermediate/poorlydifferentiatedthyroid cancer Anaplastic thyroid cancer

PTC FTCRET/PTC rearrangement 13–25% 0% 0–13% 0%BRAF mutation 29–69% 0% 0–13% 0–12%NTRK1 rearrangement 5–13% Unknown Unknown UnknownRAS mutation 0–21% 40–53% 18–27% 20–60%PPARG rearrangement 0% 25–63% 0% 0%CTNNB1 mutation 0% 0% 0–25% 66%TP53 mutation 0–5% 0–9% 17–38% 67–88%

aAbbreviations: BRAF, B-type Raf kinase; CTNNB1, β-catenin; FTC, follicular thyroid carcinoma; NTRK1, neurotrophic tyrosine kinase receptor,type 1; PPARG, peroxisome-proliferator-activated-receptor-γ; PTC, papillary thyroid cancer; RET, rearranged in transformation.

tively indolent nature and excellent long-termsurvival associated with thyroid malignancies.

Radiation exposure to the thyroid gland inchildhood, age, female sex, and family historyare risk factors that increase the incidence ofwell-differentiated thyroid cancer. Exposure ofradiation to the thyroid may occur either fromexternal sources or from ingestion of radioac-tive material. Within the first decade after theChernobyl accident, some regions of Belarusshowed a 100-fold increase in thyroid cancer inindividuals below the age of 15 at the time ofexposure (4), reflecting the importance of ageat exposure in the development of radiation-associated thyroid cancer (5).

Epidemiological studies have demonstrateda four- to ten-fold increased risk of well-differentiated thyroid cancer in first-degreerelatives of subjects with this neoplasia (6).In contrast to the well-described molec-ular pathology associated with MTC, themolecular and clinical genetics of follicularcell–derived thyroid cancer are less clear.Well-differentiated thyroid cancer can both beinherited in an autosomal dominant fashion asthe main feature in some syndromes and havean increased incidence in other tumor suscep-tibility syndromes (7). Table 1 summarizesthe most common known genetic alterationsidentified in nonfamilial thyroid cancer derivedfrom follicular cells.

126 Carling · Udelsman

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Annu. Rev. Med. 2014. 65:125–37

Desenlaces

•  60850 casos nuevos al año •  Muertes 1850 (3% anual) •  Recurrencia loco-‐regional •  Micro vs macro-‐metástasis regionales •  2-‐3% metástasis distantes

“Si me da cáncer que sea de )roides”

Remover el tumor

• Cirugía

Yodo radioac)vo

• Depende

Supresión de TSH

• Factor trófico

ME65CH09-Udelsman ARI 13 December 2013 17:53

Hyoid bone

Commoncarotid artery

Superior hornof thymus

ThymusRecurrent laryngeal nerve

External branch of superior laryngeal nerve

VIVI

VIIVII

IIBIIBIBIBIIAIIA IAIA

IIIIIIVAVA VIVI

VBVBIVIV

VIIVII

a b

Figure 1The thyroid gland and lymphatic node basins. (a) Schematic representation of the lymphatic node basins of theneck. The lateral neck lymph node compartments (levels II–V) and the central neck compartment (level VI).(b) Schematic illustration of the anatomical borders of the central neck compartment (level VI). The superiormargin is at the level of the hyoid bone, the inferior margin is at the level of the brachiocephalic vessels,and the lateral margins are at the medial aspect of the common carotid arteries. The central neck (level VI)contains the precricoid (Delphian), pretracheal, paratracheal, and perithyroidal nodes, including those alongthe recurrent laryngeal nerves and the external branch of the superior laryngeal nerve. The parathyroidglands are also normally located in the central neck. Reprinted with permission from Reference 34.

patients older than 45 years; and selected pa-tients with stage I disease, especially those withlarger tumors (>1.5 cm), multifocality, residualdisease, nodal metastasis, vascular invasion,and intermediately differentiated histology (5).

The dosing of 131I for ablation is controver-sial. Low-dose ablation with less than 30 mCi isoften administered on an outpatient basis. Thisapproach should be reserved for low-risk youngpatients who may benefit from an overall lowerradiation exposure and who accept the fact thatseveral low radioiodine doses may be necessarybefore successful ablation. Higher ablativedoses ranging from 100 to 200 mCi should beused preferentially for older high-risk patients,particularly those with an incomplete resectionof the primary tumor, an invasive primarytumor, tumors of intermediate differentiation,or metastases. Dosimetry can be employed

with the goal of deriving the dose of 131I thatwill deliver no more than 200 cGy to theblood, with no more than 120 mCi retained at48 h or 80 mCi in the presence of pulmonarymetastases. Recently, two studies showed thatlow-dose radioactive iodine ablation is likelysufficient for the vast majority of patients with“low-risk” differentiated thyroid cancer (34,35).

To optimize uptake by both normal residualthyroid and thyroid cancer, the traditionalpractice has been to render patients hypothy-roid with a goal of increasing their serumlevels of TSH. To accomplish this, thyroidreplacement after thyroidectomy is oftenperformed by administering triiodothyronine(T3), which has a much shorter half-life thanthat of thyroxine (T4), and discontinuing it twoweeks before treatment. In response to this

www.annualreviews.org • Thyroid Cancer 131

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Manejo quirúrgico inicial

•  Guias 2009: )roidectomia total •  Hemi)roidectomia: tumor < 1 cm •  Guías nuevas: •  Hemi)roidectomia si el tumor es < 4 cms con histología favorables •  Menos cirugías de completación •  Menos vaciamientos centrales

Román-‐González A et al. Qué podemos esperar de las guías ATA 2014 en el manejo de cáncer temprano de )roides. Some)do a Revista Colombiana de Endocrinología 2015.

Yodo radioac)vo •  Yodo radioac)vo

–  Estadio III/IV –  Estadio II en > 45 años –  Estadio I casos seleccionados

•  Ventajas del I •  Dosis más bajas (30 mCi) •  Rh TSH •  Dieta baja en yodo •  Tiroglobulina pre yodo

Román-‐González A et al. Qué podemos esperar de las guías ATA 2014 en el manejo de cáncer temprano de )roides. Some)do a Revista Colombiana de Endocrinología 2015.

Estadificación

Riesgo bajo Riesgo intermedio Riesgo alto

Sin metástasis Invasión microscópica en tejido blando peri

)roideo

Invasión macroscópica

Resección macroscópica Metástasis linfá)ca Resección incompleta

Sin invasión loco regional Histología agresiva Metástasis a distancia

Histología no agresiva

Invasión vascular

Sin captación de I131

Supresión con levo)roxina

– TSH factor trófico para el tejido )roideo Células neoplásicas

– Supresión depende del riesgo del paciente – Por favor no ajuste la dosis si no sabe el riesgo – Pacientes de alto riesgo o con enfermedad persistente TSH <0,1 mUI/L

–  Libres de enfermedad 5 años (bajo riesgo) 0.1 a 0.5 luego 0,3-‐2,0 mUI/L

Estadifación dinámica Respuesta excelente

Respuesta Indeterminada (buena)

Respuesta incompleta

Tg supresión < 0.2 ng/ml Detectable, pero < 1 ng/mL

> 1 ng/mL

Tg es)mulada < 1 ng/ml < 10 ng/mL > 10 ng/mL Tendencia Tg baja En descenso Estable o en ascenso

An)-‐Tg Ausente Nega)vo o en descenso Posi)vo o en ascenso E. fisico Normal Normal Enfermedad palpable Imagen Nega)va Clinicamente

insignificante Posi)va

Estimado de Bajo riesgo

Estimado Enfermedad estable

Estimado Riesgo en ascenso

Seguimiento

Bajo Intermedio Alto Tg suprimida 3-‐6 meses 3-‐6 meses

3-‐6 meses

Tg es)mulada 6-‐12 meses 6-‐12 meses

Depende de la TG

EcograHa 6-‐12 meses

6-‐12 meses

6-‐12 meses

TSH 0.1-‐0.5mU/L

< 0.1mU/L

<0.1mU/L

Bajo Intermedio Alto Tg suprimida 6 meses 6 meses

6 meses

Tg es)mulada No es necesaria 12-‐18 meses Cuando ?

No es necesaria

EcograHa 12 meses

12 meses

6-‐12 meses

TSH 0.3-‐2mU/L

< 0.1mU/L

<0.1mU/L

Seguimiento

Excelente Bioquímica incompleta

Estructural incompleta

indeterminada

Tg suprimida

12 meses 6-‐12 meses

3-‐6 meses

12 meses

Tg es)mulada

No Cada 2 -‐3 años si la Tg <0.6

No es necesaria

Puede reclasificar al paciente

EcograHa 3-‐5 años

1-‐5 años

1-‐5 años

6-‐12 meses por 5 años

TSH 0.5-‐2mU/L < 0.1mU/L <0.1mU/L 0.1-‐0.5 mU/L

Seguimiento

¿Se puede hacer observación en cáncer de )roides?

Muchos de los microcarcinomas de bajo riesgo no crecen o lo hacen lentamente. Una cirugía para estos casos sería sobretratamiento. No es tarde hacer una cirugía si se encuentra crecimiento o compromiso ganglionar durante el seguimiento ac)vo. En contraste de los Carcinomas de )roides clínicos, los MC en adultos mayores tendrán menor probabilidad de progresión que en jóvenes.

Ito Y. NonoperaTve management of low-‐risk differenTated thyroid carcinoma. Curr Opin Oncol 2015, 27:15–20

Clasificación de los microcarcinomas

1.  Causando síntomas clínicos (Clínicamente sintomá)co)

2.  Descubierto a par)r de una metástasis ganglionar o a distancia

3.  Hallado incidentalmente luego de cirugía por una condición benigna

4.  Detectado por estudios de imágenes (incidental)

5.  Revelado durante la autopsia (latente)

Differences in the Recurrence and Mortality Outcomes Rates of Incidental and Nonincidental Papillary Thyroid Microcarcinoma: A Systema)c Review and Meta-‐Analysis of 21 329 Person-‐Years

of Follow-‐up

PTMC was 3% (95% CI, 2–5%). There was a clear dif-ference between the two groups: recurrence in the incidentalgroup(0.5%;4/854;95%CI,0–1%)wassignificantly lowerthan the nonincidental group (7.9%; 173/2669; 95% CI,5–11%). The conditional odds ratio (OR) for recurrence inthe nonincidental group was 14.7 (95% CI, 5.6–54.8, P !.001) compared with the incidental group.

All four recurrences in the incidental group involvedlymph nodes. In the nonincidental group, lymph nodeswere involved in 80% of recurrences (122/153) (Figure 2).Thyroid recurrences were noted in 23 cases (15%, 23/153), of which six were in the contralateral thyroid lobe.It was not possible to ascertain from the data whether the

contralateral lobe recurrences weretrue recurrences or second primariesdue to multifocal disease. Distant me-tastases were recorded in 21 recurrentcases (13.7%), of which 14 were re-portedinthesamestudybySugitanietal(17).

Significant heterogeneity was de-tected due to the nature of poolingretrospective cohort data (I2 "84.2%, P ! .001). To explore theheterogeneity within the noninci-dental group, a sensitivity analysiswas performed by removing twostudies that seemed to include sub-jects who were substantially morelikely to suffer recurrence (17, 26).Even after excluding these studies,the recurrence in the nonincidentalgroup (4%; 95% CI, 2–5%), re-mained significantly higher than forthe incidental group (0.1%), with an

OR " 9.2 (95% CI, 3.5–34.42; P ! .001).

MortalityAll studies reported all-cause mortality, with an overall

incidence of 0.1% (95% CI, 0.0–0.4%). None of the stud-ies of subjects with incidental PTMC reported any deathsamong 854 patients. There were deaths reported in onlythree studies of nonincidental cases, with 17 deaths among2669 subjects. Although there were statistically significantdifferences found in mortality between the groups (P ".02), the absolute numerical differences were small.

Sensitivity analysisFurther sensitivity analyses were carried out on the two

primary outcomes by including those studies with at least50 subjects, and resulted in similar findings to the previousanalyses (plots available from the authors).

Secondary outcomes

Characteristics of subjects with incidental and non-incidental PTMCAverage size of lesion (mm). Only seven studies reporteddata on the variability of the average lesion size (Figure3A). The overall pooled estimate of lesion size for all sub-jects combined was 5.7 mm (95% CI, 4.9–6.5). The av-erage lesion size for the incidental PTMC group was 4.6mm (95% CI, 4.0–5.2) and the average lesion size for thenonincidental group was 6.9 mm (95% CI, 6.4–7.5). Sub-group analysis suggested there was a clear difference inaverage lesion size between the two groups (P ! .001), but

StudyIncidental PTMC

Wada N, 2003Dietlein M,2005Lo CY, 2006Roti E,2006Schonberger J, 2007Sakorafas GH, 2007Gülben K, 2008Pazaitou-Panayiotou K, 2008Lin JD,2008Besic N, 2009Pisanu A, 2009Xu YN, 2010Summary (I-squared = 0%, p = 0.999)

Non - incidental PTMCWada N, 2003Roti E,2006Lo CY, 2006Schonberger J, 2007Cappelli C, 2007Pazaitou-Panayiotou K, 2008Lin JD, 2008Besic N, 2009Pisanu A, 2009Abboud B, 2010Sugitani I, 2010Xu YN, 2010Ito Y, 2010Moon HJ,2011Summary (I-squared = 89.6%, p < 0.001)

Recurrenceproportion

1/1550/200/750/520/540/271/810/30

2/1260/107

0/730/54

4/854

6/2594/191

13/1103/13

48/1023/102

20/2097/147

3/760/12

21/561/123

32/105912/288

173/2669

0.0060.0000.0000.0000.0000.0000.0120.0000.0160.0000.0000.0000.000

0.0230.0210.1180.2310.4710.1250.0960.0480.0390.0000.3750.0080.0300.0420.079

lower0.0000.0000.0000.0000.0000.0000.0000.0000.0020.0000.0000.0000.000

0.0080.0060.0640.0500.3700.0270.0590.0190.0080.0000.2490.0000.0210.0220.049

95% CIsupper0.0350.1680.0480.0680.0660.1280.0670.1160.0560.0340.0490.0660.011

0.0500.0530.1940.5380.5720.3240.1440.0960.1110.2650.5150.0440.0420.0720.109

wgts%

20.5 0.9

11.0 5.4 5.8 1.6 5.7 1.9 8.7

22.210.5 5.8100

10.210.1 7.1 1.3 4.8 2.9 8.8 9.1 8.1 3.4 3.4

10.110.610.0100

0 0.1 0.2 0.3 0.4 0.5

Recurrence Proportion

Figure 1. Forest plot for incidence of recurrence for nonincidental and incidental PTMCsubjects, using random effects meta-analysis (21). Confidence intervals for proportions werecalculated using an exact method for the binomial distribution.

7/1226/32

11/112/21

33/36/7

33/34848/48

1/36/13

44/45/6

22/211/111/1

0 10 20 30 40 50Number of recurrences

Summary 122/153Moon HJ,2011

Ito Y, 2010Xu YN, 2010

Sugitani I, 2010Pisanu A, 2009Besic N, 2009

Pazaitou K, 2008Cappelli C, 2007

Schonberger J, 2007Lo CY, 2006Roti E,2006

Wada N, 2003 Non-Incidental

6Summary 4/4

Lin JD,2008Gülben K, 2008Wada N, 2003

Incidental

Proportion of recurrences involving lymph nodes

Subjects with recurrence in lymph nodesSubjects with recurrence in other locations

Figure 2. Total number and sites of recurrences (lymph nodes vsother sites) for incidental (upper) and nonincidental (lower) PTMCsubgroups. In total, there were 4/854 (0.5%) and 122/2460 (5.0%)recurrences in the incidental and nonincidental subgroups respectively(P ! .001).

2838 Mehanna et al Incidental and Nonincidental PTMC J Clin Endocrinol Metab, August 2014, 99(8):2834–2843

The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 28 January 2015. at 18:29 For personal use only. No other uses without permission. . All rights reserved.

J Clin Endocrinol Metab 99: 2834 –2843, 2014

1 a 2 veces por año

Crecimiento ≥3 mm

Aparición De Ganglios

(TG en aspirado)

TomograHa cuando el nódulo tenía ecos fuertes posteriores

Observación en micro-‐carcinoma

Ito Y. NonoperaTve management of low-‐risk differenTated thyroid carcinoma. Curr Opin Oncol 2015, 27:15–20

Progresión=crecimiento de 2 mm. N=162. 70% estable

Metástasis ganglionares: 1.2%

Ito Yet al. An observa)on trial without surgical treatment in pa)ents with papillary microcarcinoma of the thyroid. Thyroid 2003; 13:381–388.

Segundo reporte Crecimiento (progresión) del nódulo a 5 años: 6.7%

Aparición de nuevos ganglios cervicales: 1.7%

Ito Y et al. A therapeu)c strategy for incidentally detected papillary microcarcinoma of the thyroid. Nat Clin Pract Endocrin Metab 2007; 3:240–248.

Incidencia de crecimiento del tumor a 10 años: 8.0% N=1235 pacientes

Ito Y et al. Pa)ent age is significantly related to the progression of papillary microcarcinoma of the thyroid under observa)on. Thyroid 2014; 24:27–34.

230 pacientes Crecimiento del tamaño 7.3% Metástasis ganglionares 1.3%

No se demostraron datos longitudinales.

Sugitani I et al. Three dis)nctly different kinds of papillary thyroid microcarcinoma should be recognized: our treatment strategies and

outcomes. World J Surg 2010; 34:1222–1231.

Sugitani I, Fujimoto Y, Yamada K. Associa)on between serum thyrotropin concentra)on and growth of asymptoma)c papillary thyroid microcarcinoma.

World J Surg 2014; 38:673–678.

322 pacientes Seguimiento entre 2 y 22 años de observación

Aumento del tamaño en 16 de 322: 5% Compromiso ganglionar: 3 de 322:1%

Haugen et al. ATA guidelines 2014, Thyroid 2014 (in press)

Observación de microcarcinomas: Recomendación 12

•  Pacientes con tumores de muy bajo riesgo •  Alto riesgo quirurgico •  Expecta)va de vida corta •  Comorbilidades medicas o quirurgicas a corregir antes de cirugía

La frase más peligrosa en el lenguaje es “siempre lo hemos hecho así”

Grace Hopper Valverde, Vivae imagines par)um corporis humani, 1566

cancer de tiroides

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