Background:

        -  Thyroid cancer is the most common endocrine malignancy and papillary thyroid cancer
           (PTC) accounts for more than 80% of thyroid cancer.

        -  The incidence of thyroid cancer has risen over the past decades.

        -  Central neck lymph node metastasis (LNM) is common in PTC and preoperative imaging
           studies do not identify all involved lymph nodes in the central neck.

        -  It remains controversial if prophylactic central neck lymph node dissection (pCND) in
           patients with low-risk PTC results in lower rates of persistent/recurrent disease and
           higher complication rates as there has been no randomized controlled trial addressing
           these issues to date.

        -  Serum thyroglobulin (Tg), especially when TSH-stimulated, is a very sensitive and
           specific marker for persistent/recurrent PTC, in the absence of interfering anti-Tg
           antibodies.

        -  Retrospective studies have compared the postoperative TSH-stimulated Tg levels between
           those who underwent pCND and those who did not with conflicting results. A randomized
           trial is needed.

        -  Health-related quality of life (QOL) is a well-accepted tool to measure the outcome of
           cancer treatments. SF-36 v2 questionnaire has been frequently used to evaluate the QOL
           in patients with thyroid cancer. There is no study evaluating the difference in QOL in
           patients with low-risk PTC undergoing total thyroidectomy (TT) with and without pCND.

      Objectives:

      -To determine and compare biochemical cure rates in patients with low-risk PTCs undergoing
      total thyroidectomy (TT) with and without pCND as measured by postoperative TSH-stimulated
      serum thyroglobulin (stim-Tg) at 3 months (prior to RAI treatment).

      Eligibility:

        -  Patients greater than or equal to 18 years who have thyroid nodule(s) greater than or
           equal to 1 cm. but less than or equal to 4 cm. in size with either:

             -  inconclusive thyroid cytology positive for BRAF V600E mutation or RET/PTC
                rearrangement or

             -  cytologically suspicious for or consistent with PTC

        -  Absence of extrathyroidal extension or lymphadenopathy suggesting metastatic PTC on
           physical examination and neck ultrasound.

      Design:

        -  Prospective, single-blinded, randomized controlled clinical trial.

        -  Cytology will be reviewed by Laboratory of Pathology, NCI or a pathology laboratory at
           the enrolling institution. Once patients provide written informed consent, they will
           receive routine history, physical, radiographic (neck ultrasonography (USG), and/or
           other indicated tests) examinations as well as blood tests. Preoperative fine needle
           aspiration for cytology and BRAFV600E mutation will be performed if participant has not
           had either test performed.

        -  Preoperative assessment of QOL using standardized questionnaire (SF-36 v2) will be
           obtained within 30 days prior to surgery

        -  Preoperative vocal cord assessment will be done by flexible laryngoscopy.

        -  Participants will be randomized after clinical staging, including ultrasonography, to
           receive TT and pCND or TT alone and will be blinded from the result of randomization and
           treatment. Patients will remain blinded from treatment assignment for the duration of
           the study except for patients assigned to TT alone but found to have lymph node
           metastases as described below.

        -  If participants in TT alone group are found to have lymph node metastasis at the time of
           the operation by frozen section analysis, a therapeutic CND will be performed.
           Participants will remain in the intention to treat (TT alone) group. TT patients will be
           informed if a therapeutic CND is indicated and as such the blind will be broken for
           these patients prior to study completion.

        -  All participants will have intact parathyroid hormone (PTH), calcium and electrolytes
           checked preoperatively, in the morning after surgery, 2 weeks, and 6 months
           postoperatively.

        -  Postoperative flexible laryngoscopy will be performed on postoperative day 1 (or
           postoperative day 2, if it cannot be performed on the first postoperative day) and 6
           months postoperatively if vocal cord abnormality is found on postoperative day 1

        -  Postoperative assessment of QOL will be done on day 1, 2 weeks, 3 months and 6 months,
           1, 5 and 10 years postoperatively.

        -  Participants with postoperative hypoparathyroidism (low PTH and hypocalcemia) will be
           treated with calcium replacement with or without vitamin D analogue. Serum PTH and
           electrolytes will be monitored until resolved.

        -  Stim-Tg will be checked at 3 months postoperatively (prior to RAI scan/ablation, if
           indicated) and at 1 year postoperatively or 1 year post-remnant ablation. 1 year stim-Tg
           evaluation will be performed in patients enrolled at the NIH but is optional in patients
           enrolled at non-NIH site(s) Unstimulated Tg, thyroid function tests, and
           anti-thyroglobulin antibodies will be checked annually for 10 years.

        -  Soft tissue neck ultrasonography will be performed in all patients preoperatively and
           every year postoperatively for the first 10 years.

        -  If biochemical evidence of tumor recurrence occurs, patients will undergo appropriate
           radiographic studies and/or nuclear scintigraphy. Tissue biopsy of suspicious lesion(s)
           will be performed if clinically indicated.