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papillary thyroid carcinoma

Monday 15 March 2004

TPC; PTC; thyroid papillary carcinoma

Types

- classic PTC / classic papillary thyroid carcinoma
- FV-PTC / follicular variant of papillary thyroid carcinoma

  • IFV-PTC / infiltrative FV-PTC
  • EFV-PTV / encapsulated FV-PTC
    • IEFV-PTC / invasive encapsulated FV-PTC
    • NIEFV-PTC / non-invasive encapsulated FV-PTC

Images

- typical papillary thyroid carcinoma

- FNA of papillary thyroid carcinoma

- Thyroid papillary carcinoma with oncocytic features

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−
- CD56-

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

Classically characterized by its papillary appearance, papillary thyroid carcinoma is the most common malignant neoplasm of the thyroid.

Several variants of papillary carcinoma have been described considering:
- size (microcarcinoma);
- nature of the tumor boundaries (encapsulated);
- architecture (follicular, macrofollicular, cribriform-morular, solid, micropapillary);
- cellular characteristics (tall cell, columnar, oncocytic, clear cell, hobnail);
- additional tumor components (papillary carcinoma with focal insular component, papillary carcinoma with spindle and giant cell carcinoma, papillary carcinoma with squamous cell carcinoma, papillary carcinoma with mucoepidermoid carcinoma);
- stromal features (papillary carcinoma with fasciitis like stroma);
- or a combination of the abovementioned characteristics (diffuse sclerosing, Warthin-like).

- macrofollicular TPC

  • large follicles
  • multinodular goitre-like on low power

- follicular TPC

- oncocytic TPC

- 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
- multifocal thyroid papillary carcinoma

Molecular biology

Mutations in include BRAF V600E (most common in tall cell variant), RET-PTC (more common in children and after radiation), NTRK1 fusions, and RAS mutations.

APC mutations, as found in FAP (familial adenomatous polyposis), are found in the cribriform morular variant.

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
  • exposure to radiation
  • male
  • local invasion
  • lymphatic invasion
  • distant metastases (bone worse than lung)
  • large tumor size
  • tumor subtypes
    • 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.
    • tall cell/columnar variant
    • PTC with a prominent hobnail pattern is a moderately differentiated PTC variant with aggressive clinical behavior and significant mortality. (19956062)
    • diffuse sclerosing variant

Predisposition

- familial papillary thyroid carcinoma (FPTC)
- familial adenomatous polyposis (FAP) (16400511, 15256777, 7698732)

Genetics

See HP:20195

See also

- ovarian papillary thyroid carcinoma (malignant struma ovarii)
- thyroid carcinomas

  • thyroid follicular 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.

Open references

- Variants of Papillary Thyroid Carcinoma: Multiple Faces of a Familiar Tumor.
Sak SD. Turk Patoloji Derg. 2015;31 Suppl 1:34-47. doi : 10.5146/tjpath.2015.01313 PMID: 26177316 (Free)

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

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