thyroid papillary carcinoma

Digital cases

Classic type

 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).

Follicular variant

 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.

Diffuse sclerosing

 JRC:2675 : Papillary carcinoma, diffuse sclerosing variant in a 30 y/o female.
 JRC:15046 : Papillary carcinoma, diffuse sclerosing.

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

 JRC:18925 : Multifocal thyroid papillary carcinoma (thyroid sclerosing occult carcinoma).
 JRC:19200 : Multifocal thyroid 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.

Pediatric TPC

 90% of childhood thyroid malignancies are papillary thyroid carcinoma.

Clinical synopsis

 thyroid nodule / thyroid mass / thyroid lesion
 women of reproductive age (70%)
 6% occult tumorsat autopsy (1 to 10 mm)
 46% multicentric
 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)

Morphological synopsis

 Macroscopy

• solid, white, firm
• often multifocal (20%)
• encapsulated (10%) or infiltrative;
• variable cysts
• fibrosis
• calcification
• Usually solid
• Unencapsulated so may appear multifocal

 Follicular architecture
 characteristic nuclei

• enlarged, oval
• optically clear or ground glass
• overlapping
• 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)
 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

Cytology

 Cellular aspirate with little colloid
 Papillary fronds and sheets of cells
 Dense blue-grey cytoplasm with well-defined cell boundaries
 Intranuclear inclusions
 Nuclear grooves
 Psammoma bodies
 Multinucleate histiocytes particularly where there is cystic degeneration
 ‘Chewing-gum’ colloid.

Immunohistochemistry

 cytokeratin+
 thyroglobulin+
 TTF1+
 CK19+ (KRT19)
 chromogranin−

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

 macrofollicular TPC

• large follicles
• multinodular goitre-like on low power

 follicular TPC

• mainly follicular architecture with no papillary areas
• classical papillary carcinoma nuclear features

 oncocytic TPC

• 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

 columnar TPC

• pseudostratified cells with hyperchromatic nuclei

 solid TPC

• relatively more common in children
• sheets of cells with classical nuclear features
• local invasion

 microcarcinoma TPC

• <1cm
• often incidental finding in adults
• in children may metastasize

 cribriform-morular TPC
 diffuse sclerosing TPC
 follicular TPC
 encapsulated TPC
 encapsulated follicular TPC
 Hashimoto thyroiditis TPC
 nodular fasciitis like stroma TPC
 tall cell TPC
 Warthin-like TPC
 well differentiated TPC

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#)

Prognosis

 5-20% have local recurrences
 14% with nodal metastases
 10-15% distant metastases (lung, bones, CNS)
 Lymphatic spread
 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.

 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

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%): BRAF-associated thyroid papillary carcinoma (#17199440#)
 KRAS mutations (10%)
 RET mutations (5% to 30%)

 BRAF

• 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.

See also

 ovarian papillary thyroid carcinoma (malignant struma ovarii)
 thyroid carcinomas

• thyroid follicular carcinoma

References

 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#