Differential Diagnosis for Thyroid Nodules

The patient presents with two thyroid nodules, one of which has been extensively characterized with imaging, cytology, and molecular testing. Based on the provided information, the differential diagnosis can be categorized as follows:

• Single Most Likely Diagnosis

  • NIFTP (Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features): 40% likelihood. The presence of an NRAS mutation, atypia of undetermined significance with Hurthle cells on cytology, and the nodule's characteristics on ultrasound (isoechoic, smooth margins, peripheral vascularity) along with the absence of high-risk genetic markers, make NIFTP a highly plausible diagnosis. The ThyroSeq report's indication of an intermediate-to-high probability of cancer or NIFTP further supports this likelihood.

• Other Likely Diagnoses

  • Minimally Invasive Follicular Carcinoma: 25% likelihood. The combination of cytological findings, molecular results, and ultrasound characteristics could also suggest a minimally invasive follicular carcinoma, especially given the presence of an NRAS mutation which is more commonly associated with follicular-patterned neoplasms.
  • Minimally Invasive Hurthle-Cell Carcinoma: 20% likelihood. The presence of Hurthle cells in the cytology and the NRAS mutation could also point towards a Hurthle-cell carcinoma, although the distinction between benign and malignant Hurthle-cell neoplasms can be challenging without histological examination.
  • Benign Adenoma: 10% likelihood. Despite the atypia of undetermined significance, a significant portion of such lesions can still be benign, especially in the context of autoimmune thyroiditis which can cause cellular atypia.

• Do Not Miss Diagnoses

  • Classic Papillary Thyroid Carcinoma: <5% likelihood. Although the molecular testing did not detect a BRAF mutation (common in papillary thyroid carcinoma), and the ultrasound features are not highly suggestive of this diagnosis, papillary carcinoma can sometimes present with atypical features. Missing this diagnosis could have significant implications for treatment and prognosis.
  • Medullary Thyroid Carcinoma: <1% likelihood. The calcitonin level is less than 1 pg/mL, which effectively rules out medullary thyroid carcinoma. However, this diagnosis is included in the "do not miss" category due to its potential for aggressive behavior and the importance of early detection for familial cases.

• Rare Diagnoses

  • Other Rare Thyroid Neoplasms (e.g., Hyalinizing Trabecular Tumor, Thyroid Lymphoma): <1% likelihood. These diagnoses are rare and not directly suggested by the provided information but could be considered in the differential diagnosis of thyroid nodules with atypical features.
  • Metastatic Disease to the Thyroid: <1% likelihood. Although extremely rare, metastases to the thyroid gland from other primary cancers could present as nodules. The clinical context and additional imaging would be crucial in suspecting such a diagnosis.