Papillary thyroid cancer pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]
Overview
On gross pathology, a painless enlarging mass is a characteristic finding of papillary thyroid cancer. On microscopic histopathological analysis, Orphan Annie eye nuclear inclusions and psammoma bodies are characteristic findings of papillary thyroid cancer.
Pathogenesis
- Lymphatic spread is more common than hematogenous spread
- Multifocality is common
- The so-called Lateral Aberrant Thyroid is actually a lymph node metastasis from papillary thyroid carcinoma.[1]
- Papillary microcarcinoma is a subset of papillary thyroid cancer defined as measuring less than or equal to 1 cm.[2] The highest incidence of papillary thyroid microcarcinoma in an autopsy series was reported by Harach et al. in 1985, who found 36 of 101 consecutive autopsies to have an incidental microcarcinoma.[3] Michael Pakdaman et al. report the highest incidence in a retrospective surgical series at 49.9 percent of 860 cases.[4] Management strategies for incidental papillary microcarcinoma on ultrasound (and confirmed on FNAB) range from total thyroidectomy with radioactive iodine ablation to observation alone. Harach et al. suggest using the term "occult papillary tumor" to avoid giving patients distress over having cancer. It was Woolner et al. who first arbitrarily coined the term "occult papillary carcinoma" in 1960, to describe papillary carcinomas ≤ 1.5 cm in diameter.[5]
Although papillary carcinoma has a propensity to invade lymphatics, it is less likely to invade blood vessels.[6] These kinds of tumors are most commonly unencapsulated, and they have a high tendency to metastasize locally to lymph nodes, which may produce cystic structures near the thyroid that are difficult to diagnose because of the paucity of malignant tissue.[7][8] Furthermore, papillary tumors may metastasize to the lungs and produce a few nodules or the lung fields may exhibit a snowflake appearance throughout.
Other characteristics of the papillary carcinoma is that E.M. shows increased mitochondria, increased RER, as well as increased apical microvilli. Moreover, papillary carcinomas have an indolent growth, and 40 percent of cases spread out of the capsule.[9]
Genetics
Mutations associated with papillary thyroid cancer are mainly two forms of chromosomal translocation and one form of point mutation. These alterations lead to activation of a common carcinogenic pathway—the MAPK/ERK pathway.
Chromosomal translocations involving the RET proto-oncogene (encoding a tyrosine kinase receptor that plays essential roles in the development of neuroendocrine cells) located on chromosome 10q11 occur in approximately a fifth of papillary thyroid cancers. The fusion oncoproteins generated are termed RET/PTC proteins (ret/papillary thyroid carcinoma), and constitutively activate RET and the downstream MAPK/ERK pathway. The frequency of ret/PTC translocations is significantly higher in papillary cancers arising in children and after radiation exposure. The gene NTRK1 (encoding the TrkA receptor), located on chromosome 1q, is similarly translocated in approximately 5 percent to 10 percent of papillary thyroid cancers.
Approximately a third to a half of papillary thyroid carcinomas harbor point mutations in the BRAF oncogene, also activating the MAPK/ERK pathway. In those cases the BRAF mutations found were V600E mutation. After performing a multivariate analysis, it was found that the absence of tumor capsule was the only parameter associated (P=0.0005) with BRAF V600E mutation. According to recent studies, papillary cancers carrying the common V600E mutation tend to have a more aggressive long term course. BRAF mutations are frequent in papillary carcinoma and in undifferentiated cancers that have developed from papillary tumors.
Papillary thyroid cancer can also be caused by a mutation in the BRAF gene.
Associated Conditions
- Gardner syndrome[10]
- Cowden syndrome
Gross Pathology
- Solitary nodule which can extend into trachea and vocal cords
Microscopic Pathology
- Characteristic Orphan Annie eye nuclear inclusions (nuclei with uniform staining, which appear empty)[11] and psammoma bodies on light microscopy. The former is useful in identifying the follicular variant of papillary thyroid carcinomas.[12]
- Histologically papillary carcinoma demonstrates 'delicate stalks of epithelial cells' which account for its name.
References
- ↑ Escofet X, Khan AZ, Mazarani W, Woods WG (2007). "Lessons to be learned: a case study approach. Lateral aberrant thyroid tissue: is it always malignant?". J R Soc Health. 127 (1): 45–6. doi:10.1177/1466424007073207. PMID 17319317.
- ↑ Shaha AR (2007). "TNM classification of thyroid carcinoma". World J Surg. 31 (5): 879–87. doi:10.1007/s00268-006-0864-0. PMID 17308849.
- ↑ Harach HR, Franssila KO, Wasenius VM (1985). "Occult papillary carcinoma of the thyroid. A "normal" finding in Finland. A systematic autopsy study". Cancer. 56 (3): 531–8. doi:10.1002/1097-0142(19850801)56:3<531::AID-CNCR2820560321>3.0.CO;2-3. PMID 2408737.
- ↑ Pakdaman MN, Rochon L, Gologan O, Tamilia M, Garfield N, Hier MP, Black MJ, Payne RJ (2008). "Incidence and histopathological behavior of papillary microcarcinomas: Study of 429 cases". Otolaryngol Head Neck Surg. 139 (5): 718–22. doi:10.1016/j.otohns.2008.08.014. PMID 18984270.
- ↑ Woolner LB, Lemmon ML, Beahrs OH, Black BM, Keating FR (January 1960). "Occult papillary carcinoma of the thyroid gland: a study of 140 cases observed in a 30-year period". J. Clin. Endocrinol. Metab. 20: 89–105. doi:10.1210/jcem-20-1-89. PMID 13845950.
- ↑ "Thyroid, Papillary Carcinoma". Retrieved 2010-07-15.
- ↑ Grani, G; Fumarola, A (Jun 2014). "Thyroglobulin in Lymph Node Fine-Needle Aspiration Washout: A Systematic Review and Meta-analysis of Diagnostic Accuracy". The Journal of Clinical Endocrinology and Metabolism. 99 (6): 1970–82. doi:10.1210/jc.2014-1098. PMID 24617715.
- ↑ "The Thyroid and its Diseases". Retrieved 2010-07-15.
- ↑ "Papillary Carcinomas". Retrieved 2010-07-15. [dead link]
- ↑ Accessed on October, 29 2015 "Papillary thyroid cancer [Dr Yuranga Weerakkody and Dr Frank Gaillard et al.].Radiopedia 2015" Check
|url=value (help). - ↑ "Papillary Carcinoma of Thyroid (Hi Pow)". University of Connecticut Health Center. Retrieved 2008-09-14.
- ↑ Yang GC, Liebeskind D, Messina AV (2001). "Ultrasound-guided fine-needle aspiration of the thyroid assessed by Ultrafast Papanicolaou stain: data from 1135 biopsies with a two- to six-year follow-up". Thyroid. 11 (6): 581–89. doi:10.1089/105072501750302895. PMID 11442006.
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