Physical Exam


Laboratory Tests







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Characteristic cytologic features by FNA or after surgical resection; include psammoma bodies, cleaved nuclei with an “orphan-Annie” appearance caused by large nucleoli, and the formation of papillary structures.

PTC tends to be multifocal and to invade locally within the thyroid gland as well as through the thyroid capsule and into adjacent structures in the neck. It has a propensity to spread via the lymphatic system but can metastasize hematogenously as well, particularly to bone and lung. Because of the relatively slow growth of the tumor, a significant burden of pulmonary metastases may accumulate, sometimes with remarkably few symptoms. The prognostic implication of lymph node spread is debated. Lymph node involvement by thyroid cancer can be well tolerated but appears to increase the risk of recurrence and mortality, particularly in older patients. The staging of PTC by the TNM system is outlined in Table 405-12. Most papillary cancers are identified in the early stages (>80% stages I or II) and have an excellent prognosis, with survival curves similar to expected survival(Fig. 405-12). Mortality is markedly increased in stage IV disease, especially in the presence of distant metastases (stage IVC), but this group comprises only about 1% of patients. The treatment of PTC is described below.


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Since the release of the Hib vaccine there has been a dramatic decrease in the incidence as well as a shift in the bacterial etiology. Most cases are now caused by streptococci, staphylococci, nontypeable H influenzae, and Candida albicans. Adults typically have a more indolent course characterized by "severe" sore throat and odynophagia. Direct thermal injury has been reported as a noninfectious cause. On soft tissue lateral neck x-ray, the epiglottis is seen as rounded and blurred (thumbprint sign). Epiglottitis may progress to complete obstruction if not treated. Differential diagnosis includes acute infectious laryngitis, acute laryngotracheobronchitis (croup), acute spasmodic laryngitis, membranous (bacterial) tracheitis, anaphylactic reaction, foreign body aspiration, retropharyngeal abscess, and extrinsic or intrinsic compression of the airway (tumors, trauma, cysts).

There were no clinicopathologic features linked to tumor enlargement except in tumors>or = 7 mm, which tended to enlarge in patients followed for 4 years. To evaluate not only whether observation can continue but also how to dissect the lymph nodes optimally at surgery, US diagnosis for lateral node metastasis is essential because the presence of US-diagnosed lateral metastasis is an even stronger predictive marker for recurrence than the presence of pathologically confirmed node metastasis. The positive predictive value (PPV) was 80.6% for US but reached 100% if fine-needle aspiration biopsy (FNAB) of nodes or FNAB-thyroglobulin measurement is added. Furthermore, carcinomas occupying the upper region of the thyroid more frequently showed US-diagnosed and pathologically confirmed lateral metastasis, and those measuring>or = 7 mm were more likely to show pathologically confirmed lateral metastasis. These findings suggest that, for papillary microcarcinoma: (1) US-diagnosed lateral metastasis is a strong marker predicting a worse relapse-free survival; (2) FNAB of nodes and FNAB-thyroglobulin measurement are useful tools for evaluating lymph node metastasis; and (3) careful US evaluation for lateral metastasis is necessary in patients with a tumor measuring>or = 7 mm or that is located in the upper region of the thyroid both during observation and preoperatively. 1

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Initial staging — In our practice, we use one of the staging systems to estimate disease-specific mortality (usually Tumor Node Metastasis [TNM] (table 1) or Metastases, Age, Completeness of Resection, Invasion, Size [MACIS]) and then an additional clinicopathologic staging system, such as the American Thyroid Association (ATA) system, to estimate the risk of recurrence.

Table 1

ATA risk stratification system to estimate risk of persistent/recurrent disease
Low risk
Papillary thyroid cancer with all of the following present:
No local or distant metastases
All macroscopic tumor has been resected
No invasion of locoregional tissues
Tumor does not have aggressive histology (eg, tall cell, insular, columnar cell carcinoma, Hürthle cell carcinoma, follicular thyroid cancer, hobnail variant)
No vascular invasion
No 131I uptake outside the thyroid bed on the post-treatment scan, if done
Clinical N0 or ≤5 pathologic N1 micrometastases (<0.2 cm in largest dimension)*
Intrathyroidal, encapsulated follicular variant of papillary thyroid cancer*
Intrathyroidal, well-differentiated follicular thyroid cancer with capsular invasion and no or minimal (<4 foci) vascular invasion*
Intrathyroidal, papillary microcarcinoma, unifocal or multifocal, including BRAF V600E mutated (if known)*
Intermediate risk
Any of the following present:
Microscopic invasion into the perithyroidal soft tissues
Cervical lymph node metastases or 131I avid metastatic foci in the neck on the post-treatment scan done after thyroid remnant ablation
Tumor with aggressive histology or vascular invasion (eg, tall cell, insular, columnar cell carcinoma, Hürthle cell carcinoma, follicular thyroid cancer, hobnail variant)
Clinical N1 or >5 pathologic N1 with all involved lymph nodes <3 cm in largest dimension*
Multifocal papillary thyroid microcarcinoma with extrathyroidal extension and BRAF V600E mutated (if known)*
High risk
Any of the following present:
Macroscopic tumor invasion
Incomplete tumor resection with gross residual disease
Distant metastases
Postoperative serum thyroglobulin suggestive of distant metastases
Pathologic N1 with any metastatic lymph node ≥3 in largest dimension*
Follicular thyroid cancer with extensive vascular invasion (>4 foci of vascular invasion)*
131I: iodine-131. RAI: radioactive iodine.
* Proposed modifications, not present in the original 2009 initial risk stratification system.
Reproduced with permission from: Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2016; 26:1. Copyright © 2016 Mary Ann Liebert, Inc.


Formal disease staging is based upon applying the individual TNM descriptors in the AJCC (American Joint Commission on Cancer) staging scheme. Since the AJCC staging system is designed to risk stratify based upon disease-specific mortality and may not accurately predict the risk of recurrence/persistent disease in thyroid cancer, the ATA thyroid cancer management guidelines have proposed a novel clinicopathologic staging system designed to stratify patients as having either a low (papillary thyroid cancer confined to thyroid), intermediate (regional metastases, worrisome histologies, extrathyroidal extension, or vascular invasion), or high risk (gross extrathyroidal extension or distant metastases) of recurrence (See Table 1).

Restaging during follow-up: Dynamic risk stratification — While initial staging systems can be used to guide initial therapeutic and diagnostic follow-up strategy decisions, it is important to recognize that initial risk estimates may need to change as new data are accumulated during follow-up]. In our practice, we restratify patients on each follow-up visit using a reclassification system that emphasizes the response to therapy for each individual patient. As originally conceived, these clinical outcomes described the best response to initial therapy during the first two years of follow-up], but are now being used to describe the clinical status at any point during follow-up.

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