Table 1.
Main Clinical Characteristics of PDTC Compared to DTC and ATC
| DTC | PDTCa | ATC | |
|---|---|---|---|
| Origin | (i) Follicular thyroid cells (de novo) or (ii) follicular thyroid adenoma progression (follicular thyroid carcinoma) | (i) Follicular thyroid cells (de novo) or (ii) DTC progression | (i) Follicular thyroid cells (de novo) or (ii) DTC/PDTC progression |
| Prevalence | 90% of thyroid cancers (17) | 2–15% of thyroid cancers (1) | 2% of thyroid cancers (17) |
| Diagnostic criteria | Cytology and/or architecture | Turin: cytology, architecture, and proliferative grading (9); MSKCC: proliferative grading (8) | Cytology and/or architecture |
| Clinicopathologic characteristics | Median age 51 years (33), female-to-male ratio 3:1 (33) | Median age 59 years (32), female-to-male ratio 1.6:1 (32) | Median age 58–76 years (23), female-to-male ratio 1.8:1 (23) |
| 21% of patients present with extrathyroidal extension (18) | 69% of patients present with extrathyroidal extension (32) | >90% of patients present with locoregional invasion (24,28) | |
| 40–75% of patients develop metastases in neck lymph nodes (37) | 50–85% of patients develop metastases in neck lymph nodes (1,36) | 20–50% of patients present with distant metastases (24,28) | |
| 10–33% of patients develop distant metastases (38) | |||
| 85% of patients develop distant metastases (36) | |||
| Predictors of poor survival on multivariate analysis | Age (≥55 years) (21) male sex, tumor size, multicentricity, histologic grade and type, extrathyroidal extension, distant metastasis at presentation, and completeness of resection (19) | Age (>45 years) (7), T4a pathological stage (32), extrathyroidal extension (8,39), mitosis and necrosis (7), distant metastasis at presentation (32) | Age (>70 years) (30,31), acute symptoms (31), leukocytosis (31), T4b stage (31), tumor size >5 cm (31), distant metastasis at presentation (27,31), radiation dose <60 Gy (30); survival significantly improved if: age <60 years (27), tm confined to thyroid (27), combined surgery with EBRT (27), radical surgery versus palliative resection (29) |
| Management | Surgery (lobectomy or total thyroidectomy and central or lateral neck dissection if clinically or radiologically suspicious lymph nodes). Adjuvant RAI and thyrotropin suppression therapy. Adjuvant EBRT and systemic therapy for aggressive RAI-refractory DTC. Standardized guidelines for management of DTC involve the risk of death, risk of recurrence, and response to therapy stratification (20). | Surgeryb (total thyroidectomy and central or lateral neck dissection if clinically or radiologically suspicious lymph nodes). Adjuvant treatment benefits inconclusive. Standardized guidelines for management of PDTC are lacking. | Surgery (extended total thyroidectomy and central and lateral neck dissection) and/or radiochemotherapy. Standardized guidelines for management of ATC (25). |
| Outcomes | 10-year disease-specific survival >90% (18). Cause of disease-specific deaths: continuous trend away from local recurrence toward distant disease (22). | Intermediate prognosis between DTC and ATC (Level IV evidence) (1). Five-year overall survival 62–85% (7,32). Five-year disease-specific survival 66% (32,45). Distant disease represents the major cause of death (32). | Median survival five months, median one-year survival 20% (23). Uncontrollable locoregional disease with invasion of vital structures in the neck represents the major cause of death (29). |
| Most common molecular drivers mutations (predominant histological type) | BRAF (classical or tall-cell PTC) (51), RAS (follicular histotypes) (17), RTK fusions (PTC) (53), PAX8/PPARγ fusion (follicular histotypes) (53) | BRAF, RAS, TERT promoter (46) | BRAF, RAS, TERT promoter, TP53, PI3K/AKT, SWI/SNF, HMTs (46,52), CDKN2A (52) |
b
Initial surgery with clearance of all gross disease important for satisfactory locoregional control in PDTC.
PDTC, poorly differentiated thyroid carcinoma; DTC, differentiated thyroid carcinoma; ATC, anaplastic thyroid carcinoma; RAI, radioactive iodine; EBRT, external beam radiation therapy; PTC, papillary thyroid carcinoma; SWI/SNF, switch/sucrose non-fermentable; HMT, histone methyltransferases.