thyroid papillary carcinoma
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Clinical synops
5-20% have local recurrences
10-15% distant metastases (lung, bones, CNS)is
women of reproductive age (70%)
90% of childhood thyroid malignancies are papillary
6% Occult tumorsat autopsy (1 to 10 mm)
46% multicentric
14% with nodal metastases
Occult tumors in up to 24% with other thyroid disease, surprisingly with male predominance
painless nodule
mass in neck or cervical node
- 67% in thyroid only, 13% in thyroid and cervical nodes, 20% in nodes only
Risk factors
ionizing radiation before age 20 (for acne, tonsillitis, tinea capitis)
post-Chernobyl or nuclear explosions at Marshall Islands
Hashimoto thyroiditis
Gardner syndrome with germline APC mutations
multiple hamartomas syndrome (Cowden syndrome)
Prognosis
10 year survival:
- 98%, similar to general population
- 100% if under age 20, even with nodal metastases
Cervical node involvement does not affect the prognosis.
Poorer prognosis:
- age 40+ or elderly
- male
- local invasion
- distant metastases (bone worse than lung)
- large tumor size
- tall cell/columnar variant
- diffuse sclerosing variant
- exposure to radiation
- lymphatic invasion
Synopsis
Gross: solid, white, firm, often multifocal (20%), encapsulated (10%) or infiltrative; variable cysts, fibrosis, calcification
complex, branching papillae with fibrovascular cores associated with follicles
nuclei are overlapping with finely dispersed optically clear chromatin (also called ground-glass, Orphan-Annie nuclei, not seen in cytology or frozen section material)
micronucleoli
eosinophilic intranuclear inclusions (cytoplasmic invaginations)
nuclear longitudinal grooves (folding of redundant nuclear membrane)
psammoma bodies
- present in 50% in papillary stalk in fibrous stroma between tumor cells;
- +/- specific for papillary carcinoma
+/- vascular invasion (5%)
+/- dense fibrosis
+/- squamous metaplasia
+/- solid areas
+/- inflammatory cells: lymphocytes, histiocytes, histiocytic multinucleate giant cells, Langerhans cells
+/- spindle cell metaplasia
+/- mitotic figures
+/- mucinous metaplasia
Differential diagnosis
lymphocytic thyroiditis with reactive nuclear changes
- nuclei are still round, no inclusions
- background of lymphocytes and plasma cells without fibrosis
hyperplastic ultimobranchial body rests / solid cell nests
- in lateral lobes
- round to oval structures
- +/- chromatin clearing or grooves
- central cysts
- mucin
- squamous metaplasia
- cytokeratin strongly positive, thyroglobulin negative
papillary foci of Graves’disease
- strong p27 staining vs. weak in papillary carcinoma
tumoral metastases
Variants
columnar TPC
cribriform-morular TPC
diffuse sclerosing TPC
follicular TPC
encapsulated TPC
encapsulated follicular TPC
Hashimoto thyroiditis TPC
macrofollicular TPC
microcarcinoma TPC
nodular fasciitis like stroma TPC
oncocytic TPC
solid TPC
tall cell TPC
Warthin-like TPC
well differentiated TPC
Predisposition
familial papillary thyroid carcinoma (FPTC)
familial adenomatous polyposis (FAP) (16400511, 15256777, 7698732)
Chromosomal comparative genomic hybridization (CGH)
low prevalence of aberrations
majority of tumors showing no evidence of chromosomal instability
gains: chromosomes 1, 5, 7, 11, 15, 17, and 22
losses: chromosomes 4, 18, and 19
Regional amplification
TP73 (1p36 amplification)
SNRPN (15q12 amplification)
PDGFB (22q13 amplification)
Gene mutations
Oncogenic activation of BRAF (35% to 69%), RAS (10%), or RET (5% to 30%) is common in PTC, and the mutations correlate with tumor subtype, patient age, and clinical behavior.
BRAF mutations (35% to 69%) (17199440)
RAS mutations (10%)
RET mutations (5% to 30%)
See also
ovarian papillary thyroid carcinoma (malignant struma ovarii).
References
Finn S, Smyth P, O’Regan E, Cahill S, Toner M, Timon C, Flavin R, O’Leary J, Sheils O. Low-level genomic instability is a feature of papillary thyroid carcinoma: an array comparative genomic hybridization study of laser capture microdissected papillary thyroid carcinoma tumors and clonal cell lines. Arch Pathol Lab Med. 2007 Jan;131(1):65-73. PMID: 17227125
McCarthy RP, Wang M, Jones TD, Strate RW, Cheng L. Molecular evidence for the same clonal origin of multifocal papillary thyroid carcinomas. Clin Cancer Res. 2006 Apr 15;12(8):2414-8. PMID: 16638846