Sage Journals: Discover world-class research

Abstract

Vascular transformation of lymph node sinuses (VTSs) is defined as phenotypic transformation of the lymph node sinusoidal lining from lymphatic to vascular endothelium. The pathogenesis of VTS remains unclear. Thus far, VTS has not been characterized at the molecular level. Herein, we shed some light on VTS pathogenesis while providing a detailed description of its clinical, histopathologic, immunophenotypic, and molecular features. Our specimens involved 2 women and 3 men, aged 36 to 66 years (mean 49 years old). The lymph nodes were in the right inguinal (n = 2), left axillary (n = 1), right renal perihilar (n = 1), and left external iliac (n = 1) regions. The lesions ranged from 0.5 cm to 1.5 cm (mean 0.9 cm). All 5 specimens showed no recurrences on follow-up. Three specimens exhibited a spindle cell subtype, 1 specimen showed a mixed subtype, and another specimen displayed solid subtype. Immunohistochemically, VTS demonstrated variable staining for CD31, CD34, ERG, D2-40, and SMA. Next-generation sequencing revealed mutations in ataxia-telangiectasia mutated (Tier I/II) and NBN (variants of uncertain significance [VUSs]) genes in 1 specimen, while mutations in POLE (VUS), FANCI (VUS), ARID1A (VUS), ERBB4 (VUS), and MSH6 (VUS) genes were seen in 3 other specimens. The VUS genomic alterations were regarded as germline mutations given their variant allele frequency approaching 50%. In conclusion, most genomic alterations in VTS are germline VUS with rare pathogenic Tier I/II mutation detected in 1 specimen. Based on our case series, it is appropriate to consider VTS as a nonneoplastic process until more data exist.

Keywords

VTS vascular transformation of lymph node sinuses vascular neoplasm molecular analysis VUS variant of unknown significance

Get full access to this article

View all access options for this article.

References

Haferkamp

Rosenau

Lennert

. Vascular transformation of lymph node sinuses due to venous obstruction. Arch Pathol. 1971;92(2):81–83.

Michal

Koza

. Vascular transformation of lymph node sinuses-a diagnostic pitfall: histopathologic and immunohistochemical study. Pathol Res Pract. 1989;185(4):441–444.

Moonim

Al-Riyami

Tungekar

. Nodular spindle cell vascular transformation in a retroperitoneal lymph node: morphological approach and differential diagnosis. Histopathology 2008; 53(4):476–479.

Samet

Gilbey

Talmon

, et al. Vascular transformation of lymph node sinuses. J Laryngol Otol. 2001;115(9):760–762.

Steinmann

Földi

, et al. Morphologic findings in lymph nodes after occlusion of their efferent lymphatic vessels and veins. Lab Invest. 1982;47(1):43–50.

Cook

Czerniak

Chan

, et al. Nodular spindle-cell vascular transformation of lymph nodes. A benign process occurring predominantly in retroperitoneal lymph nodes draining carcinomas that can simulate Kaposi’s sarcoma or metastatic tumor. Am J Surg Pathol. 1995;19(9):1010–1020.

Fukunaga

. Expression of D2-40 in lymphatic endothelium of normal tissues and in vascular tumours. Histopathology. 2005;46(4):396–402.

Basha

Hsi

. Immunohistochemical analysis of endothelial cells in vascular transformation of lymph node sinuses: vascular or lymphatic differentiation? Appl Immunohistochem Mol Morphol. 2019;27(6):482–489.

Chai

Hamilton

Han-Lee

Feng

. Nodular spindle cell vascular transformation in pelvic lymph nodes with discovered on GIST1 (DOG1) positivity mimicking metastatic gastrointestinal stromal tumor. Cureus. 2020;12(8):e9632.

10.

Mignano

Russell

. Nodular vascular transformation of the lymph node sinuses mimicking sarcomatoid change in renal cell carcinoma: a potential diagnostic pitfall. Int J Surg Pathol. 2020;28(6):637–642.

11.

Truong

Hong

Chen

. Novel characterization and live imaging of Schlemm's canal expressing prox-1. PLoS One. 2014;9(5):e98245.

12.

Thomson

Gil

Ramirez

, et al. Ascending vasa recta are angiopoietin/Tie2-dependent lymphatic-like vessels. J Am Soc Nephrol. 2018;29(4):1097–1107.

13.

Pawlak

Bálint

Lim

, et al. Lymphatic mimicry in maternal endothelial cells promotes placental spiral artery remodeling. J Clin Invest. 2019;129(11):4912–4921.

14.

Hong

Harvey

Noh

, et al. Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate. Dev Dyn. 2002;225(3):351–357.

15.

Ide

Shimoyama

Horie

. Vascular transformation of sinuses in bilateral cervical lymph nodes. Head Neck. 1999;21(4):366–369.

16.

Chan

Warnke

Dorfman

. Vascular transformation of sinuses in lymph nodes. A study of its morphological spectrum and distinction from Kaposi's sarcoma. Am J Surg Pathol. 1991;15(8):732–743.

17.

Haematolymphoid tumours. Lyon (France): International Agency for Research on Cancer; Forthcoming 2024. (WHO classification of tumours series, 5th ed.; vol. 11).

18.

Richards

Aziz

Bale

, et al. ACMG laboratory quality assurance committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–424.

19.

Banin

Moyal

Shieh

S-Y

, et al. Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science.1998; 281(5383):1674–1677.

20.

Canman

Lim

D-S

Cimprich

, et al. Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science.1998;281(5383):1677–1679.

21.

Broeks

Urbanus

Floore

, et al. ATM-heterozygous germline mutations contribute to breast cancer-susceptibility. Am J Hum Genet. 2000;66(2):494–500.

22.

Schaffner

Idle

Stilgenbauer

, et al. Mantle cell lymphoma is characterized by inactivation of the ATM gene. Proc Nat Acad Sci 2000; 97:2773–2778.

23.

Datto

Duncavage

, et al. Standards and guidelines for the interpretation and reporting of sequence variants in cancer: a joint consensus recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn. 2017;19(1):4–23.

24.

Varon

Vissinga

Platzer

, et al. Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell. 1998;93(3):467–476.

25.

Wiegand

Shah

Al-Agh

, et al. ARID1A mutations in endometriosis-associated ovarian carcinomas. New Eng J Med. 2010;363(16):1532–1543.

26.

Prickett

Agrawal

Wei

, et al. NISC comparative sequencing program, Rosenberg, S. A., samuels, Y. Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4. Nature Genet. 2009;41(10):1127–1132.

27.

Palles

Cazier

J-B

Howarth

, et al. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nature Genet2013. 45(2):136–144. Note: Erratum: Nature Genet. 45: 713 only, 2013.

28.

Miyaki

Konishi

Tanaka

, et al. Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer. (Letter) Nature Genet. 1997;17(3):271–272.

29.

National Center for Biotechnology Information. ClinVar. (2019); https://www.ncbi.nlm.nih.gov/clinvar .

30.

Mersch

Brown

Pirzadeh-Miller

, et al. Prevalence of variant reclassification following hereditary cancer genetic testing. JAMA. 2018;320(12):1266–1274.

Molecular Characterization of Vascular Transformation of Lymph Node Sinuses via Oncomine Comprehensive Assay

Abstract

Keywords

Get full access to this article

References