Regional lymph nodes and hematogenous metastasis of cancer

Abstract

Aim. Morphological study of the microvasculature of regional lymph nodes in relation to the cancer of the lymph nodes as possible additional or alternative metastasis pathways.

Methods. The lymph nodes of 150 cancer patients (1263 nodes in total), regional to cancer of various localization, were studied. Histological sections staining with hematoxylin and eosin by Van-Gieson’s method, pyronine by Brachet’s method, toluidine blue and picro-Mallory were prepared. An immunohistochemical study was performed using monoclonal antibodies to pan-cytokeratins, CD31, type IV collagen, CD3, CD20, and CD68. The area of metastases to the lymph nodes was determined by using a morphometric grid and used to identify the four study groups. In addition, the immunomorphological reactions of the lymph nodes were taken into account in each group.

Results. It was identified that the microvasculature of the lymph nodes can be involved in the metastatic process along with the lymphatic pathways. At the same time, there is a decrease in vascular wall function and violation of the rheological properties of blood, accompanied by the deposition of intra- and extravascular fibrin. Hematogenous metastasis is largely influenced by the state of lymph node sinuses, in which blood is found, and in some observations — by the expression of CD31 (a marker of blood endothelium). Hematogenous dissemination of cancer often begins after the appearance of lymph node metastases. The greater the anatomical extent of lymph node metastases, the more often tumor cells are present in the blood vessels. In addition, an isolated lesion of the microvasculature with the presence of tumor cells in the extranodal vessels without metastases in the lymph node itself was revealed. It was observed that the invasion of tumor cells into the microvasculature depended on the immunomorphological reactions of the lymph nodes.

Conclusion. The microvasculature of regional lymph nodes can be both an additional and an alternative lymphogenous metastasis pathway of cancer; at the same time, vascular invasion is accompanied by microcirculation disorders and depends on the volume of metastases and the immunomorphological reactions of the lymph nodes.

Keywords

cancer / regional lymph nodes / hematogenous metastasis / morphological examination

References

[1] Kim H.J., Choi G.S. Clinical implications of lymph node metastasis in colorectal cancer: Current status and future perspectives. Ann. Coloproctol. 2019; 35 (3): 109–117. DOI: 10.3393/ac.2019.06.122019.

[2] Bazha­nov A.B., Tsyplakov D.E. State of regional lymph nodes and prognosis in stomach cancer. Kazan Medical Journal. 2017; 98 (3): 328–333. (In Russ.) DOI: 10.17750/KMJ2017-328.

[3] Бажанов А.Б., Цыплаков Д.Э. Состояние регионарных лимфатических узлов и прогноз при раке желудка. Казанский мед. ж. 2017; 98 (3): 328–333. DOI: 10.17750/KMJ2017-328.

[4] Carr I. Lymphatic metastasis. Cancer Metastasis Rev. 1983; 2 (3): 307–317. DOI: 10.1007/BF00048483.

[5] Basha B.M., Hsi E.D. 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. DOI: 10.1097/PAI.0000000000000661.

[6] Tsyplakov D.E. Changes in the microvasculature of regional lymph nodes in the process of cancer metastasis. Kazan Medical Journal. 1987; (1): 29–31. (In Russ.)

[7] Цыплаков Д.Э. Изменения микроциркуляторного русла регионарных лимфатических узлов в процессе метастазирования рака. Казанский мед. ж. 1987; (1): 29–31.

[8] Sarkisov D.S., Pe­rov Yu.L. Mikroskopicheskaya tekhnika. (Microscopic technique.) M.: Meditsina. 1996; 544 р. (In Russ.)

[9] Саркисов Д.С., Перов Ю.Л. Микроскопическая техника. М.: Медицина. 1996; 544 с.

[10] Zerbino D.D., Lukase­vich L.L. Method for determining the “age” of fibrin in the syndrome of disseminated intravascular blood coagulation. Arkhiv patologii. 1984; (8): 72–75. (In Russ.)

[11] Зербино Д.Д., Лукасевич Л.Л. Методика для определения «возраста» фибрина при синдроме диссеминированного внутрисосудистого свёртывания крови. Архив патол. 1984; (8): 72–75.

[12] Petrov S.V., Raykhlin N.T. Rukovodstvo po immunogistokhimicheskoy diagnostike opukholey cheloveka. (Guidelines for the immunohistochemical diagnosis of human tumors.) Kazan: DESIGNstudio “RED”. 2012; 624 р. (In Russ.)

[13] Петров С.В., Райхлин Н.Т. Руководство по иммуногистохимической диагностике опухолей человека. Казань: DESIGNstudio «RED». 2012; 624 с.

[14] Stefa­nov S.B. Morphometric grid of random step as a means of accelerated measurement of morphogenetic elements. Tsitologiya. 1974; (6): 785–787. (In Russ.)

[15] Стефанов С.Б. Морфометрическая сетка случайного шага как средство ускоренного измерения элементов морфогенеза. Цитология. 1974; (6): 785–787.

[16] Tsyplakov D.E., Ziganshina L.E. The role of microcirculatory factors in cancer metastasis. Voprosy onkologii. 1988; (8): 932–936. (In Russ.)

[17] Цыплаков Д.Э., Зиганшина Л.Е. Роль микроциркуляторных факторов в метастазировании рака. Вопр. онкол. 1988; (8): 932–936.

[18] Tsyplakov D.E., Petrov S.V. Effect of the microvasculature on the cellular immune response in the lymph nodes regional to the cancer (immunohistochemical and ultrastructural study). Gematologiâ i transfuziologiâ. 1995; (6): 3–7. (In Russ.)

[19] Цыплаков Д.Э., Петров С.В. Влияние кровеносного микроциркуляторного русла на клеточный иммунный ответ в лимфатических узлах, регионарных к раковой опухоли (иммуногистохимическое и ультраструктурное исследование). Гематол. и трансфузиол. 1995; (6): 3–7.

[20] Yin T., Ji X.L., Shen M.S. Relationship between lymph node sinuses with blood and lymphatic metastasis of gastric cancer. World J. Gastroenterol. 2003; 9 (1): 40–43. DOI: 10.3748/wjg.v9.i1.40.

[21] Coste A., Karagiannis G.S., Wang Y., Xue E.A., Lin Y., Skobe M., Jones J.G., Oktay M.H., Condeelis J.S., Entenberg D. Hematogenous dissemination of breast cancer cells from lymph nodes is mediated by tumor microenvironment of metastasis doorways. Front. Oncol. 2020; 10: 571100. DOI: 10.3389/fonc.2020.571100.

[22] Pereira E.R., Kedrin D., Seano G., Gautier O., Meijer E., Jones D., Chin S.M., Kitahara S., Bouta E.M., Chang J., Beech E., Jeong H.S., Carroll M.C., Taghian A.G., Padera T.P. Lymph node metastases can invade local blood vessels, exit the node, and colonize distant organs in mice. Science. 2018; 359 (6382): 1403–1407. DOI: 10.1126/science.aal3622.

[23] Okur O., Sagiroglu J., Kir G., Bulut N., Alimoglu O. Diagnostic accuracy of sentinel lymph node biopsy in determining the axillary lymph node metastasis. J. Can. Res. Ther. 2020; 16 (6): 1265–1268. DOI: 10.4103/jcrt.JCRT_1122_19.

[24] Kodama T., Mori S., Nose M. Tumor cell invasion from the marginal sinus into extranodal veins during early-stage lymph node metastasis can be a starting point for hematogenous metastasis. J. Cancer Metastasis Treat. 2018; 4: 56. DOI: 10.20517/2394-4722.2018.61.

[25] Tsyplakov D.E., Bazha­nov A.B. Morphometric and immunohistochemical study of regional lymph nodes in gastric cancer. Kazan Medical Journal. 2015; 96 (6): 971–978. (In Russ.) DOI: 10.17750/KMJ2015-971.

[26] Цыплаков Д.Э., Бажанов А.Б. Морфометрическое и иммуногистохимическое исследование регионарных лимфатических узлов при раке желудка. ­Казанский мед. ж. 2015; 96 (6): 971–978. DOI: 10.17750/KMJ2015-971.

RIGHTS & PERMISSIONS

Eco-Vector