title: Intratumoural lymph vessel density is related to presence of lymph node metastases and separates encapsulated from infiltrative papillary thyroid carcinoma.
abstract: Papillary thyroid carcinoma (PTC) gives frequently rise to nodal metastases via lymphatic vessels while follicular thyroid carcinoma (FTC) metastasises mainly via blood vessels to lung and bones. The follicular variant of PTC (FVPTC) encompasses the infiltrative subtype (I-FVPTC), which shares most of the features of classic PTC (CPTC), and the encapsulated subtype (E-FVPTC), which appears to be related to minimally invasive FTC. In an attempt to contribute to the understanding of the aforementioned differences, we evaluated intratumoural and peritumoural lymph vessels density (LVD), using the immunomarker D2-40 in a series of E-FVPTC, I-FVPTC, and CPTC with known BRAF and RAS status. None of the E-FVPTC cases presented extra-thyroid extension, lymph vessel invasion or nodal metastases, at variance with I-FVPTC and CPTC cases. The BRAF V600E mutation was detected in 8.3% of E-FVPTC, 25.0% of I-FVPTC and in 40.7% of CPTC, while N-RAS Q61R mutation was detected only in 10.3% of FVPTC cases. Only one case of E-FVPTC (8.3%) had intratumoural D2-40-stained vessels in contrast to their presence in 76.5% of the cases of I-FVPTC. Intratumoural LVD determined by D2-40 expression correlated with the occurrence of extra-thyroid extension, lymph vessel invasion and lymph node metastases in PTC cases. At variance with intratumoural LVD, peritumoural LVD was not associated with any clinic-pathological or molecular feature, being similar in E-FVPTC, I-FVPTC and CPTC. Our study highlights the role of intratumoural lymph vessels in PTC nodal metastisation and reinforces the importance of distinguishing E-FVPTC from I-FVPTC regarding invasiveness, metastatic pattern and molecular profile.
authors.affiliation: Pathology Department, Hospital de São João, Porto, Portugal. catarinaeloy@hotmail.com
authors.forename: C
authors.initials: C
authors.lastname: Eloy
authors.forename: J
authors.initials: J
authors.lastname: Santos
authors.forename: P
authors.initials: P
authors.lastname: Soares
authors.forename: M
authors.initials: M
authors.lastname: Sobrinho-Simões
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma; D002291:Carcinoma, Papillary; D018265:Carcinoma, Papillary, Follicular / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D002648:Child; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000175:diagnosis / Q000473:pathology*; D042601:Lymphatic Vessels / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000175:diagnosis / Q000473:pathology*; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism; D012189:Retrospective Studies; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D015689:Oncogene Protein p21(ras)
references.citation: Am J Pathol. 2002 Sep;161(3):947-56
references.pmid: 12213723
references.citation: Hum Pathol. 2000 Apr;31(4):439-42
references.pmid: 10821490
references.citation: Yonsei Med J. 2004 Oct 31;45(5):818-21
references.pmid: 15515191
references.citation: Surgery. 1992 Dec;112(6):1130-6; discussion 1136-8
references.pmid: 1455315
references.citation: Am J Surg. 1998 Nov;176(5):442-7
references.pmid: 9874430
references.citation: J Surg Oncol. 1996 Oct;63(2):95-8
references.pmid: 8888801
references.citation: J Clin Oncol. 2009 Jun 20;27(18):2977-82
references.pmid: 19414674
references.citation: Mod Pathol. 2005 Nov;18(11):1424-31
references.pmid: 15920537
references.citation: Am J Pathol. 1999 Dec;155(6):1967-76
references.pmid: 10595926
references.citation: Cancer Res. 2000 Aug 15;60(16):4324-7
references.pmid: 10969769
references.citation: Endocr Relat Cancer. 2006 Sep;13(3):931-44
references.pmid: 16954441
references.citation: Mod Pathol. 2000 Aug;13(8):861-5
references.pmid: 10955452
references.citation: Virchows Arch. 2002 Apr;440(4):418-24
references.pmid: 11956824
references.citation: J Biomech Eng. 2002 Apr;124(2):237-43
references.pmid: 12002134
references.citation: Head Neck. 1998 Mar;20(2):152-8
references.pmid: 9484947
references.citation: J Int Med Res. 2008 Jul-Aug;36(4):699-703
references.pmid: 18652765
references.citation: Virchows Arch. 2005 Nov;447(5):787-93
references.pmid: 16189702
references.citation: Clin Cancer Res. 2002 May;8(5):1125-31
references.pmid: 12006528
references.citation: Diagn Pathol. 2010 Jan 22;5:8
references.pmid: 20205756
references.citation: Arch Otolaryngol Head Neck Surg. 2003 Jul;129(7):716-9
references.pmid: 12874070
references.citation: Carcinogenesis. 2006 Sep;27(9):1729-38
references.pmid: 16597644
references.citation: Virchows Arch. 2011 Sep;459(3):265-76
references.pmid: 21796448
references.citation: Oncol Rep. 1998 Nov-Dec;5(6):1343-8
references.pmid: 9769366
references.citation: Cancer. 2006 Sep 15;107(6):1255-64
references.pmid: 16900519
references.citation: J Clin Endocrinol Metab. 2006 Jan;91(1):213-20
references.pmid: 16219715
references.citation: Mod Pathol. 2005 Aug;18(8):1127-33
references.pmid: 15803188
references.citation: Clin Cancer Res. 2005 Nov 15;11(22):8063-9
references.pmid: 16299237
references.citation: Gynecol Oncol. 2007 Oct;107(1):45-51
references.pmid: 17604828
references.citation: Surgery. 2001 May;129(5):552-8
references.pmid: 11331447
references.citation: Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2006 Jun;31(3):414-6, 419
references.pmid: 16859137
references.citation: Am J Clin Pathol. 2003 Jul;120(1):71-7
references.pmid: 12866375
references.citation: Surgery. 1999 Dec;126(6):1056-61; discussion 1061-2
references.pmid: 10598188
references.citation: J Natl Cancer Inst. 2002 Mar 20;94(6):417-21
references.pmid: 11904313
references.citation: Mod Pathol. 2011 Apr;24 Suppl 2:S10-8
references.pmid: 21455197
references.citation: Endocr Pathol. 2010 Jun;21(2):101-7
references.pmid: 20336393
references.citation: Int J Surg Pathol. 2010 Jun;18(3 Suppl):209S-212S
references.pmid: 20484293
references.citation: Endocr Pathol. 2002 Winter;13(4):313-20
references.pmid: 12665649
references.citation: J Clin Endocrinol Metab. 2008 Oct;93(10):3943-9
references.pmid: 18682506
references.citation: Am J Surg Pathol. 2010 Jun;34(6):868-72
references.pmid: 20463572
references.citation: Mod Pathol. 2010 Sep;23(9):1191-200
references.pmid: 20526288