thyroid papillary carcinoma
Monday 15 March 2004
JRC:324 : Papillary carcinoma of the thyroid (typical, classic type).
JRC:2534 : Papillary carcinoma of the thyroid.
JRC:2661 : Papillary carcinoma of the thyroid in a 26 y/o female.
JRC:13269 : Post-radiation papillary carcinoma of the thyroid.
JRC:14619 : Papillary carcinoma of the thyroid.
JRC:14914 : Papillary carcinoma of the thyroid (typical, classic type).
JRC:18130 : Papillary carcinoma of the thyroid (diffuse, infiltrating; F, 18y/o).
JRC:18294 : Papillary carcinoma of the thyroid (classic type).
JRC:18913 : Papillary carcinoma of the thyroid (classic type).
JRC:2666 : Papillary carcinoma, encapsulated follicular variant in a 36 y/o male.
Tall cell variant
JRC:482 : Papillary carcinoma of the thyroid, tall cell variant.
JRC:14915 : Papillary carcinoma of the thyroid, tall cell variant, predominantly follicular.
JRC:15032 : Papillary carcinoma of the thyroid, tall cell variant, predominantly follicular.
Transformation to anaplastic carcinoma
JRC:18759 : Thyroid papillary carcinoma with transformation to anaplastic carcinoma.
Psammomatous thyroid papillary carcinoma
JRC:18764 : Psammomatous thyroid papillary carcinoma.
Thyroid Warthin-like papillary carcinoma
JRC:14938 : Warthin-like thyroid papillary carcinoma.
Multifocal papillary carcinoma
Thyroid papillary carcinoma with oncocytic features
- Thyroid papillary carcinoma with oncocytic features on Flickr by ddkri
Definition: Papillary thyroid carcinomas (PTC) are the most common thyroid tumors that usually have a good prognosis. Recurrence, metastases, and cancer death may occur in a few patients and are more commonly associated with more aggressive tumors, such as tall cell, columnar cell, or diffuse sclerosing variants of the PTC.
PTC with a prominent hobnail pattern is a moderately differentiated PTC variant with aggressive clinical behavior and significant mortality.
90% of childhood thyroid malignancies are papillary thyroid carcinoma.
thyroid nodule / thyroid mass / thyroid lesion
women of reproductive age (70%)
6% occult tumorsat autopsy (1 to 10 mm)
Occult tumors in up to 24% with other thyroid disease, surprisingly with male predominance
mass in neck or cervical node
- 67% in thyroid only, 13% in thyroid and cervical nodes, 20% in nodes only
ionizing radiation before age 20 (for acne, tonsillitis, tinea capitis)
post-Chernobyl or nuclear explosions at Marshall Islands
Gardner syndrome with germline APC mutations
multiple hamartomas syndrome (Cowden syndrome)
- solid, white, firm
- often multifocal (20%)
- encapsulated (10%) or infiltrative;
- variable cysts
- Usually solid
- Unencapsulated so may appear multifocal
- enlarged, oval
- optically clear or ground glass
- nuclear grooves
Variable areas of papillary architecture
- central stromal core
- same nuclear features of covering epithelium
Psammoma body formation
- concentric lamination, calcified
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)
eosinophilic intranuclear inclusions (cytoplasmic invaginations)
nuclear longitudinal grooves (folding of redundant nuclear membrane)
- 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
Cellular aspirate with little colloid
Papillary fronds and sheets of cells
Dense blue-grey cytoplasm with well-defined cell boundaries
Multinucleate histiocytes particularly where there is cystic degeneration
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
- squamous metaplasia
- cytokeratin strongly positive, thyroglobulin negative
papillary foci of Graves’disease
- strong p27 staining vs. weak in papillary carcinoma
- large follicles
- multinodular goitre-like on low power
- mainly follicular architecture with no papillary areas
- classical papillary carcinoma nuclear features
- prominent areas of oncocytic cells but similar nuclear features
clear cell TPC
- prominent clear cells areas but similar nuclear features
diffuse sclerosing TPC
- relatively more common in children
- diffuse thyroidal involvement
- stromal fibrosis
- lung metastases in 25%
-tall cell TPC
-* cells at least 3 times taller than width
- pseudostratified cells with hyperchromatic nuclei
- relatively more common in children
- sheets of cells with classical nuclear features
- local invasion
- often incidental finding in adults
- in children may metastasize
diffuse sclerosing TPC
encapsulated follicular TPC
Hashimoto thyroiditis TPC
nodular fasciitis like stroma TPC
tall cell TPC
well differentiated TPC
multifocal thyroid papillary carcinoma
Recurrence, metastases, and cancer death are more commonly associated with more aggressive tumors, such as tall cell, columnar cell, or diffuse sclerosing variants of the PTC.
PTC with a prominent hobnail pattern is a moderately differentiated PTC variant with aggressive clinical behavior and significant mortality. (#19956062#)
5-20% have local recurrences
14% with nodal metastases
10-15% distant metastases (lung, bones, CNS)
Rare metastasis outside LN
usually lung in diffuse sclerosing variant
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.
- age 40+ or elderly
- local invasion
- distant metastases (bone worse than lung)
- large tumor size
- tall cell/columnar variant
- diffuse sclerosing variant
- exposure to radiation
- lymphatic invasion
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
TP73 (1p36 amplification)
SNRPN (15q12 amplification)
PDGFB (22q13 amplification)
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%): BRAF-associated thyroid papillary carcinoma (#17199440#)
KRAS mutations (10%)
RET mutations (5% to 30%)
- Up to 60% of thyroid papillary carcinomas have mutations in the BRAF gene. However, follicular variant of papillary carcinoma has a much lower frequency of mutation.
- Papillary carcinomas of the thyroid with papillary growth and areas of follicular growth have a high frequency of BRAF mutations (BRAF-V600E).
- The BRAF mutational profile is identical in the follicular areas and in the conventional papillary growth areas.
ovarian papillary thyroid carcinoma (malignant struma ovarii)
- thyroid follicular carcinoma
Rapid Multiplex Real-time PCR by Molecular Beacons for Different BRAF Allele Detection in Papillary Thyroid Carcinoma. Orru G, Coghe F, Faa G, Pillai S, Manieli C, Montaldo C, Pilia F, Pichiri G, Piras V, Coni P. Diagn Mol Pathol. 2010 Mar;19(1):1-8. PMID: #20186005#
Papillary Thyroid Carcinoma With Prominent Hobnail Features: A New Aggressive Variant of Moderately Differentiated Papillary Carcinoma. A Clinicopathologic, Immunohistochemical, and Molecular Study of eight Cases. Asioli S, Erickson LA, Sebo TJ, Zhang J, Jin L, Thompson GB, Lloyd RV. Am J Surg Pathol. 2009 Dec 2. PMID: #19956062#
BRAF Mutational Analysis in Papillary Carcinomas With Mixed Follicular and Papillary Growth Patterns. Jakubowski M, Hunt JL. Am J Surg Pathol. 2009 Sep 4. PMID: #19738460#
Pyrosequencing analysis for detection of a BRAFV600E mutation in an FNAB specimen of thyroid nodules. Kim SK, Kim DL, Han HS, Kim WS, Kim SJ, Moon WJ, Oh SY, Hwang TS. Diagn Mol Pathol. 2008 Jun;17(2):118-25. PMID: #18382358#
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#