Thyroid Papillary Microtumor: Validation of the (Updated) Porto Proposal Assessing Sex Hormone Receptor Expression and Mutational BRAF Gene Status

Am J Surg Pathol. 2020 Sep;44(9):1161-1172. doi: 10.1097/PAS.0000000000001522.

Abstract

Given the high incidence and excellent prognosis of many papillary thyroid microcarcinomas, the Porto proposal uses the designation papillary microtumor (PMT) for papillary microcarcinomas (PMCs) without risk factors to minimize overtreatment and patients' stress. To validate Porto proposal criteria, we examined a series of 190 PMC series, also studying sex hormone receptors and BRAF mutation. Our updated Porto proposal (uPp) reclassifies as PMT incidental PMCs found at thyroidectomy lacking the following criteria: (a) detected under the age of 19 years; (b) with multiple tumors measuring >1 cm adding up all diameters; and (c) with aggressive morphologic features (extrathyroidal extension, angioinvasion, tall, and/or hobnail cells). PMCs not fulfilling uPp criteria were considered "true" PMCs. A total of 102 PMCs were subclassified as PMT, 88 as PMC, with no age or sex differences between subgroups. Total thyroidectomy and iodine-131 therapy were significantly more common in PMC. After a median follow-up of 9.6 years, lymph node metastases, distant metastases, and mortality were only found in the PMC subgroup. No subgroup differences were found in calcifications or desmoplasia. Expression of estrogen receptor-α and estrogen receptor-β, progesterone receptor, and androgen receptor was higher in PMC than in nontumorous thyroid tissue. BRAF mutations were detected in 44.7% of PMC, with no differences between subgroups. In surgical specimens, the uPp is a safe pathology tool to identify those PMC with extremely low malignant potential. This terminology could reduce psychological stress associated with cancer diagnosis, avoid overtreatment, and be incorporated into daily pathologic practice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Papillary / chemistry*
  • Carcinoma, Papillary / genetics*
  • Carcinoma, Papillary / pathology
  • Carcinoma, Papillary / therapy
  • DNA Mutational Analysis
  • Estrogen Receptor alpha / analysis
  • Estrogen Receptor beta / analysis
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mutation*
  • Predictive Value of Tests
  • Proto-Oncogene Proteins B-raf / genetics*
  • Radiotherapy, Adjuvant
  • Receptors, Androgen / analysis
  • Receptors, Progesterone / analysis
  • Receptors, Steroid / analysis*
  • Reproducibility of Results
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Sex Factors
  • Thyroid Neoplasms / chemistry*
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / therapy
  • Thyroidectomy
  • Treatment Outcome
  • Young Adult

Substances

  • AR protein, human
  • Biomarkers, Tumor
  • ESR1 protein, human
  • ESR2 protein, human
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Receptors, Androgen
  • Receptors, Progesterone
  • Receptors, Steroid
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf

Supplementary concepts

  • Papillary Thyroid Microcarcinoma