Papillary thyroid carcinoma

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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, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)
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

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

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)[19]
  • CD10 - Highlights the morules [20]
  • 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 [21]
    • 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:[22]

  • Papillae - usu. prominent.
  • Squamous morules - key features.[23]
  • 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:[24]

  • Abundant oncocytic tumour cells with apical nuclei.
  • Classic features of PTC:
    • Grooves and and abundant pseudoinclusions.[25]
  • >70% papillary architecture.[25]
  • +/-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. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ 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.
  22. ↑ 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.
  23. ↑ 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.
  24. ↑ 24.0 24.1 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.
  25. ↑ 25.0 25.1 Thompson, Lester D. R. (2006). Endocrine Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 86. ISBN 978-0443066856.
  26. ↑ Sathiyamoorthy, S.; Maleki, Z. (Jan 2014). "Cytomorphologic overlap of differentiated thyroid carcinoma and lung adenocarcinoma and diagnostic value of TTF-1 and TGB on cytologic material.". Diagn Cytopathol 42 (1): 5-10. doi:10.1002/dc.22997. PMID 23637102.
  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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