Papillary thyroid cancer pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2] Ammu Susheela, M.D. [3]

Overview

The exact pathogenesis of papillary thyroid cancer is not fully understood. Papillary thyroid cancer has been associated with somatic rearrangement of RET protooncogene. On gross pathology, an ill-defined tumor, irregular borders, and firm consistency are characteristic findings of papillary thyroid cancer. There is no unique consensus on the definition of histological subtypes of papillary thyroid cancer.

Physiology



 
 
 
 
 
 
Growth factor binds to Receptor tyrosine kinase (RET, NTRK1)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
GDP substitution by GTP
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RAS activation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BRAF activation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MEK ativation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ERK activation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
cell differentiation
 
 
cell proliferation
 
 
cell survival
 
The above algorithm is adopted from Endocrine patology book[2]

Pathogenesis

Genetics

Associated Conditions

Gross Pathology

Papillary thyroid cancer gross pathology[8]
  • On gross pathology, an ill-defined tumor, irregular borders, and firm consistency are characteristic findings of papillary thyroid cancer.[2]
  • Calcification may also be present.
  • Other less common features include:

Microscopic Pathology

  • Papillary thyroid carcinoma has numerous histological subtypes. Each subtype has some specific characteristics.[2][6][9]
  • There is no unique consensus on the definition of each subtype, so different pathologists may not agree with these definitions.
  • Cytologic features of papillary thyroid cancer are diagnostic for this tumor. These features include:
    • Enlarged, irregular, oval shape nuclei that are overlapped because of the nuclear enlargement
    • Nuclear clearing
    • Ground glass appearance with prominent nuclear grooves
    • Pink cytoplasmic invaginations
Papillary thyroid cancer subtype Features on Histopathological Microscopic Analysis
Follicular
Conventional
Tall cell
Columnar cell
  • Pseudostratified cells
  • Overlapping enlarged nuclei
Oncocytic
Solid
Diffuse sclerosing
Papillary thyroid carcinoma with prominent hobnail features
Clear cell
Cribriform-Morular
Macrofollicular
  • Composed of macrofollicles
  • Cytological features of papillary thyroid cancer
Papillary thyroid cancer Image
  • Micrograph of papillary thyroid carcinoma, tall cell variant - high magnification
  • "Tall cells": the largest dimension is 3x the smaller dimension
  • Abundant eosinophilic cytoplasm
  • Lack of pseudostratification is a significant differentiator from columnar cell variant of papillary thyroid carcinoma
H&E stain. Contributed in wikimedia.commons
  • Micrograph showing oncocytic variant of papillary thyroid carcinoma
  • Large cells with abundant eosinophilic cytoplasm
H&E stain, Contributed in wikimedia.commons
  • Micrograph showing cribriform-Morular variant of papillary thyroid carcinoma
  • Cribriform pattern with solid and spindle cell areas
  • Squamous morules
H&E stain, Contributed in wikimedia.commons
  • Micrograph (high power view) showing nuclear changes in papillary thyroid carcinoma (PTC), which include:
    • Groove formation
    • Optical clearing
    • Eosinophilic inclusions and overlapping of nuclei
H&E stain. Contributed in wikimedia.commons
  • Micrograph (high power view) of PTC demonstrating nuclear clearing and overlapping nuclei
H&E stain. Contributed in wikimedia.commons
  • Micrograph of papillary thyroid carcinoma demonstrating prominent papillae with fibrovascular cores
H&E stain. Contributed in wikimedia.commons
H&E stain. Contributed in wikimedia.commons
H&E stain. Contributed in wikimedia.commons

Immunohistochemistry

Histopathological Video

Video

References

  1. Adeniran AJ, Zhu Z, Gandhi M, Steward DL, Fidler JP, Giordano TJ, Biddinger PW, Nikiforov YE (February 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.
  2. 2.0 2.1 2.2 2.3 Lloyd, Ricardo V. (2010). doi:10.1007/978-1-4419-1069-1. Missing or empty |title= (help)
  3. Nikiforov YE (2002). "RET/PTC rearrangement in thyroid tumors". Endocr. Pathol. 13 (1): 3–16. PMID 12114746.
  4. Tallini G, Asa SL (November 2001). "RET oncogene activation in papillary thyroid carcinoma". Adv Anat Pathol. 8 (6): 345–54. PMID 11707626.
  5. Nikiforov YE, Koshoffer A, Nikiforova M, Stringer J, Fagin JA (November 1999). "Chromosomal breakpoint positions suggest a direct role for radiation in inducing illegitimate recombination between the ELE1 and RET genes in radiation-induced thyroid carcinomas". Oncogene. 18 (46): 6330–4. doi:10.1038/sj.onc.1203019. PMID 10597232.
  6. 6.0 6.1 6.2 Lloyd, Ricardo V.; Buehler, Darya; Khanafshar, Elham (2011). "Papillary Thyroid Carcinoma Variants". Head and Neck Pathology. 5 (1): 51–56. doi:10.1007/s12105-010-0236-9. ISSN 1936-055X.
  7. Hall, Joseph E.; Abdollahian, Davood J.; Sinard, Robert J.; Eisele, David W. (2013). "Thyroid disease associated with cowden syndrome: A meta-analysis". Head & Neck. 35 (8): 1189–1194. doi:10.1002/hed.22971. ISSN 1043-3074.
  8. Image courtesy of Dr David Cuete. Radiopaedia (original file ‘’here’’.Creative Commons BY-SA-NC
  9. Kunjumon, DeepaThomas; Upadhyaya, Krishnaraj (2014). "Histopathological features of Papillary Thyroid Carcinoma with special emphasis on the significance of nuclear features in their diagnosis". Archives of Medicine and Health Sciences. 2 (1): 16. doi:10.4103/2321-4848.133786. ISSN 2321-4848.

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