What are the characteristics of papillary thyroid carcinoma?

Characteristics of Papillary Thyroid Carcinoma

Epidemiology and Incidence

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, representing the majority of all thyroid cancers, with an incidence of 5.7 per 100,000 person-years overall (8.8 per 100,000 in women and 2.7 per 100,000 in men). 1

• The incidence has been escalating globally over recent decades, primarily due to increased detection of micropapillary carcinomas (<1 cm) through improved diagnostic techniques including neck ultrasound and fine needle aspiration cytology 1
• Currently, 60-80% of detected thyroid carcinomas are micropapillary thyroid carcinomas (<1 cm in size) 1
• Among women, incidence rates are highest among Asians (10.96 per 100,000) and lowest among blacks (4.9 per 100,000) 1
• Despite increasing incidence, mortality from thyroid cancer has declined over the last three decades 1

Clinical Presentation

PTC typically presents as a thyroid nodule detected by palpation or more commonly by neck ultrasound, though thyroid nodules are frequent (4-50% prevalence) while thyroid cancer remains rare (only 5% of all thyroid nodules are malignant). 1

• Patients may present with a neck mass and cervical lymphadenopathy 2
• The tumor is often asymptomatic, particularly in micropapillary variants 3

Ultrasound Characteristics

Multiple ultrasound features are associated with malignancy in PTC, and when present simultaneously, the specificity increases significantly. 1

Key suspicious ultrasound features include:

• Hypoechogenicity 1
• Microcalcifications 1
• Absence of peripheral halo 1
• Irregular borders 1
• Solid aspect 1
• Intranodular blood flow 1
• Shape taller than wide 1
• Regional lymphadenopathy 1

Histological and Molecular Features

PTC exhibits distinct histological characteristics and molecular profiles that influence prognosis and treatment decisions. 4

• Histological features indicating poor prognosis include vascular and/or lymphatic invasion, angiogenesis, multifocality, and high cellular proliferation rate 4
• BRAF V600E mutation is present in approximately 57% of aggressive PTC variants 2
• Certain histological variants are associated with more aggressive behavior, including tall cell, columnar cell, diffuse sclerosing, and hobnail variants 4, 2
• The hobnail variant shows prominent apically placed nuclei creating surface bulge, with Ki67 proliferative index ranging from 2-20% (mean 10%) 2

Metastatic Pattern and Behavior

PTC is prone to regional lymph node metastasis, most commonly to central and lateral cervical lymph nodes, with cervical lymph node metastasis occurring in approximately half of patients at presentation. 5, 6

• Lymph node recurrence occurs in 10-14% of patients after initial treatment 5
• Retropharyngeal lymph node metastasis is extremely rare 6
• Distant metastases can occur to liver, lung, bone, brain, muscle, and pancreas, particularly in aggressive variants 2
• Most low-risk micropapillary carcinomas remain indolent, with tumor enlargement detected in only 4.9% at 5 years and 8.0% at 10 years during active surveillance 3
• Novel lymph node metastasis appears in only 1.7% at 5 years and 3.8% at 10 years during active surveillance 3

Prognostic Factors

Despite lymph node metastasis being common, PTC generally has excellent prognosis, particularly in patients under 45 years of age at diagnosis. 4, 5

• Age is a critical prognostic factor: patients ≤45 years have 100% 10-year survival even after lymph node recurrence, while those >45 years have only 41.3% 10-year survival after lymph node recurrence 5
• Clinical factors affecting prognosis include age, sex, and tumor size 4
• Micropapillary thyroid carcinomas (<1 cm) carry excellent long-term prognosis 1
• No patients with low-risk micropapillary carcinoma under active surveillance developed distant metastasis or died of thyroid carcinoma 3
• Aggressive variants with hobnail features show significant mortality, with mean survival of 42.8 months in fatal cases 2

Risk Factors

The only established environmental risk factor for PTC is exposure to ionizing radiation, with risk being greater in younger individuals at time of exposure. 1

• Following the Chernobyl accident in 1986, thyroid cancer incidence in Ukrainian children increased 80-fold from baseline rates of 0.5-1.0 per 1,000 children 1
• The increased incidence was observed as early as 4 years after the accident in children born or conceived around the time of exposure 1

Radioiodine Avidity

A subset of PTCs demonstrate reduced radioiodine avidity, which limits the therapeutic efficacy of radioactive iodine therapy and is associated with specific transcriptomic profiles. 7

• ANO1 expression correlates significantly with iodine avidity (r = 0.54) and serves as a promising biomarker 7
• Thyroid hormone synthesis, PI3K-AKT, and MAPK signaling pathways are key regulators of radioiodine avidity 7
• Early identification of radioiodine-refractory tumors is crucial for personalized treatment strategies 7

Common Pitfalls

• Each individual ultrasound feature has poor predictive value when considered alone; multiple suspicious features must be present simultaneously to increase specificity 1
• Fine needle aspiration cytology has limitations including inadequate samples and inability to distinguish follicular neoplasia 1
• Proper ultrasound technique and experience are essential for accurate monitoring, particularly during active surveillance protocols 3
• Age-based prognostication is critical: lymph node recurrence carries vastly different implications depending on whether the patient is above or below 45 years at primary operation 5