Papillary thyroid carcinoma

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Papillary thyroid carcinoma, abbreviated PTC, is the most common thyroid gland malignancy. It usually has an indolent course.

Papillary thyroid carcinoma
Diagnosis in short

Papillary thyroid carcinoma. H&E stain.
LM nuclear changes: nuclear membrane irregularities (e.g. raisinoid shape), +/-nuclear grooves, +/-nuclear pseudoinclusions, +/-nuclear clearing, nuclear enlargement (usu. mild), nucleoli; architectural changes: overlap of nuclei, papillae (not required), +/-psammoma bodies
Subtypes tall cell variant, columnar cell variant, follicular variant, cribriform-morular variant, diffuse sclerosing variant, Warthin-like variant, solid variant, oncocytic variant, others
LM DDx lymphocytic thyroiditis (Graves disease, Hashimoto thyroiditis), solid cell nest of thyroid, follicular thyroid carcinoma, follicular thyroid adenoma, adenomatoid nodule
IHC HBME-1 +ve, CK19 +ve, Galectin-3 +ve, thyroglobulin +ve, TTF-1 +ve
Staging thyroid cancer staging
Site thyroid gland
Syndromes familial adenomatous polyposis (cribriform-morular variant)
Signs thyroid mass
Prevalence very common
Prognosis usu. good
Clin. DDx other thyroid gland tumours

General

Medical school memory device P's:

  • Palpable lymph nodes.
  • Popular - most common malignant neoplasm of the thyroid.
  • Prognosis is good.
  • Pre-Tx iodine scan.
  • Post-Sx iodine scan.
  • Psammoma bodies.

Notes:

  • PTC is associated with radiation exposure.[1]
  • Papillary thyroid microcarcinoma is defined as a tumour with a maximal dimension of 1.0 cm or less.[2]

Prognosis

Prognosis can be predicted by MAICS score. It which includes:[3]

  • Metastases.
  • Age.
  • Invasion of surround tissues.
  • Completeness of excision.
  • Size of tumour.

Microscopic

Features:

  • Nuclear changes - key feature.
    1. "Shrivelled nuclei"/"raisin" like nuclei, nuclei with a wavy ("textured", convoluted) nuclear membrane -- usu. easy to find.
    2. Nuclear pseudoinclusions -- usu. harder to find; have high specificity (nuclear pseudoinclusions appear as a result of the very convoluted nuclear membrane wrapping around parts of the cytoplasm; true nuclear inclusions in contrast are seen only in viral infections).
    3. Nuclear grooves, seen as a result of the highly "textured" nuclear membrane.
    4. Nuclear clearing (only on permanent section) - also known as "Orphan Annie eyes".
  • Overlap of nuclei - "cells do not respect each other's borders" (easy to see at key feature at low power).
  • Classically has papillae (nipple-like shape); papilla (definition): epithelium on fibrovascular core.
    • Absence of papillae does not exclude diagnosis.
  • Psammoma bodies.
    • Circular, acellular, eosinophilic whorled bodies.
    • Not necessary to make diagnosis - but very specific in the context of a specimen labeled "thyroid".
    • Arise from infarction & calcification of papilla tips.[4]

Notes:

  • Psammoma bodies are awesome if you see 'em, i.e. useful for arriving at the diagnosis.
    • If there are no papillae structures -- you're unlikely to see psammoma bodies.
  • At low power look for cellular areas/loss of follicles.
  • Nuclear clearing seen in:
    • Hashimoto's and papillary thyroid carcinoma.[5]
    • May be an artifact of fixation/processing.
  • Nuclear overlapping is easy to see at lower power-- should be the tip-off to look at high power for nuclear features.
  • Nuclear inclusions are quite rare and not required to make the diagnosis -- but a very convincing feature if seen.
  • Papillae may be seen in Graves disease.
  • Thyroid tissue lateral to the jugular vein (often referred to as lateral aberrant thyroid tissue) is generally considered metastatic thyroid carcinoma (papillary thyroid carcinoma) even if it looks benign.[6]
    • This dictum is disputed.[7]
    • The level VI and VII lymph nodes are medial to the jugular.

DDx:

Subtypes of papillary thyroid carcinoma

There are many.

Poor prognosis variants:

Papillary thyroid carcinoma tall cell variant

General
  • ~10% of PTC.[11]
  • Often large > 6 cm.
Microscopic

Features:[12]

  • 50% of cells with height 2x the width.[13]
    • There is some disagreement on these criteria;[13] Raphael believes the height ought to be ~3x width, for 50% of the cells.[14]
  • Eosinophilic cytoplasm.
  • Well-defined cell borders.
  • Nucleus stratified; basal location, i.e. closer to the basement membrane.

Negative:

  • Nuclei not pseudostratified, if pseudostratified consider columnar cell variant.

Images:

  • PTC tall cell variant - intermed. mag. (WC)

  • PTC tall cell variant - high mag. (WC)

Papillary thyroid carcinoma columnar cell variant

General

Epidemiology:

  • Poor prognosis.
  • Very rare.
Microscopic

Features:[15]

  • Elongated nuclei (similar to colorectal adenocarcinoma) - key feature.
  • +/-Pseudostratification of the nuclei (like in colorectal adenocarcinoma), differentiates from tall cell variant.
  • Nuclear stratification - key feature.
  • "Minimal" papillary features.
  • "Tall cells".
  • Clear-eosinophilic cytoplasm.
  • Mitoses common.

Image: Columnar variant PTC (wiley.com).

Papillary thyroid carcinoma follicular variant

General
Microscopic

Features:[17]

  • Small tightly packed follicles - key feature.
  • Hypereosinophilic colloid.
  • Nuclear features of PTC.
  • +/-Fibrous capsule (common).

DDx:

Images:

Papillary thyroid carcinoma cribriform-morular variant

General
Microscopic

Features:

  • Circumscribed or even encapsulated neoplasm.
  • Morules - interspersed balls of squamoid cells
    • No keritinization or intercellular bridges.
    • Homogenous, lightly eosinophilic glassy nuclei (biotin accumulation).
  • Follicles
    • Cribriform, papillary, trabecular and solid patterns.
    • Columnar or cuboidal cells.
    • Little colloid
    • Papillary carcinoma nuclear features.

  • Thyroid - Papillary Carcinoma Cribriform Morular Variant - Medium power (SKB)

  • Thyroid - Papillary Carcinoma Cribriform Morular Variant - High power (SKB)

  • Thyroid - Papillary Carcinoma Cribriform Morular Variant - high power]]

  • Thyroid - Papillary Carcinoma Cribriform Morular Variant - High power (SKB)

  • Thyroid - Papillary Carcinoma Cribriform Morular Variant - CDX2 (SKB)

  • Thyroid - Papillary Carcinoma Cribriform Morular Variant - p16 (SKB)

  • Thyroid - Papillary Carcinoma Cribriform Morular Variant - ER (SKB)

  • Thyroid - Papillary Carcinoma Cribriform Morular Variant - beta catenin (SKB)


DDX:

  • Papillary thyroid carcinoma
  • Papillary thyroid carcinoma, tall cell variant
IHC
  • CDX2 - Highlights the morules (CDX2 is positive in the biotin rich nuclei associated with morule formation in a variety of situations)[20]
  • CD10 - Highlights the morules [21]
  • Beta-catenin - nuclear and cytoplasmic - all tumour cells.
  • Estrogen receptor - positive
  • TTF-1 - positive
Molecular
  • Up-regulating disturbances in the Wnt signaling pathway promote formation of morules with optically clear biotin rich nuclei [22]
    • Mutation of the beta-catenin gene
    • Mutation in APC
  • Examples
      • Well-differentiated fetal adenocarcinoma
      • Papillary thyroid carcinoma, cribriform morular variant (mutation in APC in familial variants)
      • Pancreatoblastoma

Papillary thyroid carcinoma diffuse sclerosing variant

General
  • Usually young adults, children.
Microscopic

Features:[23]

  • Papillae - usu. prominent.
  • Squamous morules - key features.[24]
  • Lymphocytes - abundant.
  • Fibrosis.

DDx:

  • Lymphocytic thyroiditis (esp. Hashimoto's thyroiditis).

Papillary thyroid carcinoma Warthin-like variant

Microscopic

Features:[15]

  • Eosinophilic cytoplasm.
  • Lymphocytic thyroiditis.
  • Papillae.

Papillary thyroid carcinoma solid variant

Features:[9]

  • Some studies suggest this has a poor prognosis.
  • More common in children.
  • Associated with Chernobyl nuclear accident.
Microscopic

Features:

  • Solid sheets >50% of tumour mass.[9]

Papillary thyroid carcinoma oncocytic variant

Features:

Microscopic

Features:[25]

  • Abundant oncocytic tumour cells with apical nuclei.
  • Classic features of PTC:
    • Grooves and and abundant pseudoinclusions.[26]
  • >70% papillary architecture.[26]
  • +/-Degenerative changes.

Note:

  • CK19 +ve -- though not specific or sensitive.

  • PTC oncocytic - low mag. (WC)

  • PTC oncocytic - intermed mag. (WC)

  • PTC oncocytic - high mag. (WC)

  • PTC oncocytic - very high mag. (WC)

IHC

Thyroid versus something else:

PTC versus benign:[27]

  • HBME-1 +ve (strong, diffuse).
  • CK19 +ve (strong, diffuse).
  • Galectin-3 +ve (strong, diffuse).

Molecular

  • Currently not widely used in a diagnostic context.

Tabular summary

Molecular changes in papillary thyroid carcinoma as per Adeniran et al:[28]

Molecular change Frequency Histology Notes
BRAF point mutations ~ 40% tall cell variant poorer prognosis, older individuals
RET/PTC rearrangments ~ 20% papillary architecture, psammoma bodies younger individuals
RAS point mutations ~ 15% exclusively follicular variant -

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HEMITHYROID, RIGHT, COMPLETION OF TOTAL THYROIDECTOMY:
- PAPILLARY THYROID CARCINOMA, FOLLICULAR VARIANT.
-- TUMOUR SIZE: 4 MM (MAXIMAL).
-- ARCHITECTURE: FOLLICULAR.
-- CYTOMORPHOLOGY: CLASSICAL.
-- HISTOLOGIC GRADE: G1 (WELL DIFFERENTIATED).
-- NO TUMOUR CAPSULE IDENTIFIED.
-- NEGATIVE FOR LYMPHOVASCULAR INVASION.
-- NEGATIVE FOR PERINEURAL INVASION.
-- NEGATIVE FOR EXTRATHYROIDAL EXTENSION.
-- SURGICAL MARGINS NEGATIVE FOR MALIGNANCY.

Note:

  • If it is a completion thyroidectomy and the staging changes one should do a full synoptic report.

Microcarcinoma

A. LEFT HEMITHYROID, THYROIDECTOMY COMPLETION:
- PAPILLARY THYROID MICROCARCINOMA.
-- MARGINS NEGATIVE FOR MALIGNANCY.
-- TUMOUR SIZE ~ 1 MILLIMETRE.
-- NEGATIVE FOR LYMPHOVASCULAR INVASION.
-- NEGATIVE FOR PERINEURAL INVASION.
- PALPATION THYROIDITIS, FOCAL.
- NODULAR HYPERPLASIA.

B. LYMPH NODES, LEVEL 6 AND 7, LYMPH NODE DISSECTION:
- TWO LYMPH NODES, NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 2 ).

THYROID GLAND, TOTAL THYROIDECTOMY:
- INCIDENTAL PAPILLARY THYROID MICROCARCINOMA.
-- MARGINS NEGATIVE FOR MALIGNANCY.
-- TUMOUR SIZE ~ 1 MILLIMETRE.
-- NEGATIVE FOR LYMPHOVASCULAR INVASION.
-- NEGATIVE FOR PERINEURAL INVASION.
- NODULAR HYPERPLASIA.
- ONE PARATHYROID GLAND.

Lymph node dissection

A. NECK, RIGHT LEVEL 2 AND 3, LYMPH NODE DISSECTION:
- ONE LYMPH NODE POSITIVE FOR PAPILLARY THYROID CARCINOMA ( 1 POSITIVE / 4 ).

B. NECK, RIGHT LEVEL 4, LYMPH NODE DISSECTION:
- TWO LYMPH NODES, NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 2 ).

C. NECK, RIGHT LEVEL 6 AND 7, LYMPH NODE DISSECTION:
- ONE LYMPH NODE POSITIVE FOR PAPILLARY THYROID CARCINOMA ( 1 POSITIVE / 3 ).

Micro

The sections show lymph nodes with tumour that has a papillary architecture. The tumour cell nuclei are enlarged and overlap. They also have nuclear grooves, nucleoli and abundant pseudoinclusions. The chromatin of the tumour cells has a powdery appearance.

See also

References

  1. ↑ Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Oberman, Harold A; Reuter, Victor E (2004). Sternberg's Diagnostic Surgical Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 564. ISBN 978-0781740517.
  2. ↑ Sethom, A.; Riahi, I.; Riahi, K.; Akkari, K.; Benzarti, S.; Miled, I.; Chebbi, MK. (Jan 2011). "[Management of thyroid microcarcinoma. Report of 13 cases].". Tunis Med 89 (1): 23-5. PMID 21267823.
  3. ↑ Hay, ID.; Thompson, GB.; Grant, CS.; Bergstralh, EJ.; Dvorak, CE.; Gorman, CA.; Maurer, MS.; McIver, B. et al. (Aug 2002). "Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940-1999): temporal trends in initial therapy and long-term outcome in 2444 consecutively treated patients.". World J Surg 26 (8): 879-85. doi:10.1007/s00268-002-6612-1. PMID 12016468.
  4. ↑ Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Oberman, Harold A; Reuter, Victor E (2004). Sternberg's Diagnostic Surgical Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 565. ISBN 978-0781740517.
  5. ↑ Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Oberman, Harold A; Reuter, Victor E (2004). Sternberg's Diagnostic Surgical Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 566. ISBN 978-0781740517.
  6. ↑ JOHNSON, RW.; SAHA, NC. (Jun 1962). "The so-called lateral aberrant thyroid.". Br Med J 1 (5293): 1668-9. PMC 1958877. PMID 14452106. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1958877/.
  7. ↑ Escofet, X.; Khan, AZ.; Mazarani, W.; Woods, WG. (Jan 2007). "Lessons to be learned: a case study approach. Lateral aberrant thyroid tissue: is it always malignant?". J R Soc Promot Health 127 (1): 45-6. PMID 17319317.
  8. ↑ Baloch, ZW.; LiVolsi, VA. (Jun 2006). "Cytologic and architectural mimics of papillary thyroid carcinoma. Diagnostic challenges in fine-needle aspiration and surgical pathology specimens.". Am J Clin Pathol 125 Suppl: S135-44. PMID 16830963.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 Gonzalez-Gonzalez, R.; Bologna-Molina, R.; Carreon-Burciaga, RG.; Gómezpalacio-Gastelum, M.; Molina-Frechero, N.; Salazar-Rodríguez, S. (2011). "Papillary thyroid carcinoma: differential diagnosis and prognostic values of its different variants: review of the literature.". ISRN Oncol 2011: 915925. doi:10.5402/2011/915925. PMC 3302055. PMID 22432054. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302055/.
  10. ↑ URL: http://emedicine.medscape.com/article/849000-overview#a0104. Accessed on: 1 May 2012.
  11. ↑ Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Reuter, Victor E; Stoler, Mark H (2009). Sternberg's Diagnostic Surgical Pathology (5th ed.). Lippincott Williams & Wilkins. pp. 505. ISBN 978-0781779425.
  12. ↑ Urano M, Kiriyama Y, Takakuwa Y, Kuroda M (April 2009). "Tall cell variant of papillary thyroid carcinoma: Its characteristic features demonstrated by fine-needle aspiration cytology and immunohistochemical study". Diagn. Cytopathol.. doi:10.1002/dc.21086. PMID 19373912.
  13. ↑ 13.0 13.1 Ghossein R, Livolsi VA (November 2008). "Papillary thyroid carcinoma tall cell variant". Thyroid 18 (11): 1179–81. doi:10.1089/thy.2008.0164. PMID 18925842.
  14. ↑ S. Raphael. 17 January 2011.
  15. ↑ 15.0 15.1 Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Reuter, Victor E; Stoler, Mark H (2009). Sternberg's Diagnostic Surgical Pathology (5th ed.). Lippincott Williams & Wilkins. pp. 506. ISBN 978-0781779425.
  16. ↑ Daniels, GH.. "What if many follicular variant papillary thyroid carcinomas are not malignant? A review of follicular variant papillary thyroid carcinoma and a proposal for a new classification.". Endocr Pract 17 (5): 768-87. doi:10.4158/EP10407.RA. PMID 21940284.
  17. ↑ Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 88. ISBN 978-0443066856.
  18. ↑ URL: http://www.thyroidcancercanada.org/types-of-thyroid-cancer.php?lang=en. Accessed on: 9 January 2013.
  19. ↑ Groen EJ, Roos A, Muntinghe FL, et al. (September 2008). "Extra-intestinal manifestations of familial adenomatous polyposis". Ann. Surg. Oncol. 15 (9): 2439–50. doi:10.1245/s10434-008-9981-3. PMC 2518080. PMID 18612695. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518080/?tool=pubmed.
  20. ↑ Wani, Y.; Notohara, K.; Nakatani, Y.; Matsuzaki, A. (Oct 2009). "Aberrant nuclear Cdx2 expression in morule-forming tumours in different organs, accompanied by cytoplasmic reactivity.". Histopathology 55 (4): 465-8. doi:10.1111/j.1365-2559.2009.03382.x. PMID 19817898.
  21. ↑ Cameselle-Teijeiro, J.; Alberte-Lista, L.; Chiarelli, S.; Buriticá, C.; Gonçalves, L.; González-Cámpora, R.; Nogales, FF. (Feb 2008). "CD10 is a characteristic marker of tumours forming morules with biotin-rich, optically clear nuclei that occur in different organs.". Histopathology 52 (3): 389-92. doi:10.1111/j.1365-2559.2007.02911.x. PMID 18081818.
  22. ↑ Gamachi, A.; Kashima, K.; Daa, T.; Nakatani, Y.; Tsujimoto, M.; Yokoyama, S. (Nov 2003). "Aberrant intranuclear localization of biotin, biotin-binding enzymes, and beta-catenin in pregnancy-related endometrium and morule-associated neoplastic lesions.". Mod Pathol 16 (11): 1124-31. doi:10.1097/01.MP.0000092953.20717.48. PMID 14614052.
  23. ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1122. ISBN 978-1416031215.
  24. ↑ Hirokawa, M.; Kuma, S.; Miyauchi, A.; Qian, ZR.; Nakasono, M.; Sano, T.; Kakudo, K.. "Morules in cribriform-morular variant of papillary thyroid carcinoma: Immunohistochemical characteristics and distinction from squamous metaplasia.". APMIS 112 (4-5): 275-82. doi:10.1111/j.1600-0463.2004.apm11204-0508.x. PMID 15233643.
  25. ↑ 25.0 25.1 Berho, M.; Suster, S. (Jan 1997). "The oncocytic variant of papillary carcinoma of the thyroid: a clinicopathologic study of 15 cases.". Hum Pathol 28 (1): 47-53. PMID 9013831.
  26. ↑ 26.0 26.1 Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 86. ISBN 978-0443066856.
  27. ↑ Mataraci, EA.; Ozgüven, BY.; Kabukçuoglu, F. (Mar 2012). "Expression of cytokeratin 19, HBME-1 and galectin-3 in neoplastic and nonneoplastic thyroid lesions.". Pol J Pathol 63 (1): 58-64. PMID 22535608.
  28. ↑ Adeniran, AJ.; Zhu, Z.; Gandhi, M.; Steward, DL.; Fidler, JP.; Giordano, TJ.; Biddinger, PW.; Nikiforov, YE. (Feb 2006). "Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas.". Am J Surg Pathol 30 (2): 216-22. PMID 16434896.
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