Macroscopically Positive versus Microscopically Positive LN Mets

An important issue in the discussion of PTC nodal metastasis is the segregation of LNs into micrometastasis and macrometastasis (see also Chapter 18, Papillary Thyroid Cancer). Studies of patients with PTC demonstrate that macroscopic cervical nodal metastasis (as determined by detection through preoperative physical exam (PE), ultrasound [US], or intraoperative detection) will occur in 21% to 35% of patients at presentation.^1,2,4 Microscopically positive nodes are far more prevalent, occurring in 23% to 81% of patients with clinically negative preoperative nodal assessments who are operated on prophylactically.^1,6,8–14 Therapeutic nodal dissections target macroscopically positive nodes, whereas prophylactic neck dissections target normal or microscopically positive LNs (see also Chapters 37, Central Neck Dissection: Indications, 38, Central Neck Dissection: Technique, 39, Lateral Neck Dissection: Indications, and 40, Lateral Neck Dissection: Technique).¹⁵

It is important to note that it is macroscopic lymph node metastases that are associated with decreased recurrence-free survival rates as compared to micrometastases.^4,16 In fact, the recurrence rates of microscopically positive nodes is similar to those with pathologically negative nodes as demonstrated in several studies.^7,17 Gemsenjar, in a study of 159 patients with PTC followed for up to 27 years, found that the prognostic significance of nodal positivity resided primarily in clinically macroscopic nodes rather than microscopically positive nodes.⁴ Further, he found significantly higher recurrence in patients with clinically positive nodes compared to those who were clinically negative. A study of patients with primary cancers greater than 1 cm also supports the prognostic significance of radiographically identified nodes (i.e., macroscopically positive). Regardless of tumor size, radiographically (US) identified macroscopic nodes in the lateral neck were associated with significantly worse recurrence-free survival rates (RFS) as compared to pathologically positive, US negative nodes (i.e., nodes that are microscopically positive).¹⁶

The Importance of Radiographic Detection of Macroscopically Positive Nodes Preoperatively

Nodal surgery for macroscopically positive nodes is required in approximately one third of patients presenting with PTC. If this task is not recognized preoperatively then persistence/recurrence of nodal disease is certain. Revision surgery is recognized to be more difficult than primary surgery. Therefore, to save the patient from additional surgery and increased risk, removal of all macroscopic metastatic disease at the time of the initial surgery is preferred. Therefore, it seems reasonable to seek the macroscopically positive nodes radiographically prior to surgery in order to plan an optimal, individualized operation appropriate for the patient’s extent of disease at presentation.

Central Neck Nodes

Despite the commonness of cervical lymph node metastases, there has been controversy on the extent of neck dissection that should be done for PTC. Some surgeons perform prophylactic central neck (pCND) dissection, but this added surgery across all surgical settings will undoubtedly increase complications such as hypoparathyroidism and recurrent laryngeal nerve injury. pCND harvests normal or at best microscopically positive nodes. Given what we know about microscopically positive nodes as stated earlier, it is not surprising that pCND has been shown to have no effect on survival or recurrence.^18,19 The American Thyroid Association (ATA) recommends consideration for central neck dissection only for clinically involved central lymph nodes and may be considered for advanced primary tumors (see Chapters 37, Central Neck Dissection: Indications, and 38, Central Neck Dissection: Technique).²⁰

Intraoperative palpation in detection of nodal disease has also been shown to have low sensitivity and reliability. Moley showed intraoperative palpation was associated with sensitivity of 64% and specificity of 71% in the detection of nodal disease in patients with medullary cancer of the thyroid (MTC).²¹ Other studies have shown experienced surgeons are able to identify less than 50% of grossly positive nodes through intraoperative palpation.^22,23 Therefore, the decision to perform a central neck dissection should not be based on intraoperative palpation, risk factors for nodal disease, or the empiric surgical philosophy of the surgeon or endocrinologist but on objective radiographic data obtained preoperatively for that given patient.

Lateral Neck Nodes

The pattern of spread in PTC in the lateral neck is one that primarily encompasses levels II, III, and IV.²⁴ However, PTC does not uniformly spread to all these levels. Dissection of other levels, such as level V, remains controversial. Lateral neck dissection is generally well tolerated but is not without risk. Risks include shoulder dysfunction (from cranial nerve XI damage), neck pain, damage to cranial nerves (XII, XI, X, VII), chylous leak, damage to great vessels, increased incision size, and hematoma. Prophylactic neck dissection for microscopic disease in the lateral neck has been abandoned.²⁵ The current recommendation is to perform a therapeutic lateral neck lymph node dissection for proved metastatic disease.²⁰ Because the lateral neck is not exposed from a routine thyroidectomy approach, the search for metastatic disease in the lateral neck must be performed prior to entering the operating room (see Chapters 39, Lateral Neck Dissection: Indications, and 40, Lateral Neck Dissection: Technique).

Preoperative Radiographic Evaluation: US and CT

Several techniques to evaluate for lymph node metastases—such as ¹³¹I whole-body scanning, stimulated thyroglobulin measurement, and US—are used after surgery. These can identify lymph nodes not removed at the time of primary surgery; however, ideally all nodes would be identified prior to surgery and removed at the time of the initial surgery. This would eliminate the need for early revision surgery and repeated administration of radioactive iodine. As ¹³¹I whole-body scanning and stimulated thyroglobulin measurements are not useful screening tools in the preoperative period, the methods of preoperative detection of nodal metastases can include physical exam, ultrasound, and axial imaging, including computed tomography (CT) scanning.

Physical Exam

Both endocrinologists and endocrine surgeons routinely perform palpation of the neck. Unfortunately, this has been a historically unreliable detection method for small lymph node metastases. Generally, physical exam detects only large lymph nodes, and even intraoperative palpation will only detect 64% of lymph node metastases.²¹ In our work, neck palpation had a sensitivity of 9% in the central neck and 24% in the lateral neck in the detection of positive papillary nodes.²⁶ Therefore, surgeons must rely on preoperative radiographic studies to reach an accurate assessment of lymph node involvement.