Certainly many carcinomas (epithelial derived tumors) spread at least in part through the lymphatic system since lymph node metastases exist, and also are part of clinical prognostication. That in itself does not rule out direct dissemination to the blood. Is there any data on the relative contribution of lymphatic spread and direct blood spread?
Since lymph node (local) metastases have prognostic value one would expect them to be part of the mechanism of disease, i.e. there would be a mechanistic progression from lymph node metastases to diatant metastases. Is this born out by clinical observation? Can it, and has it, be mimicked in animal models?
dear Christer, the one route of dissemination does not preclude the other and vice versa. Cancer cells have been identified in the blood of patients with practically all types of carcinomas (Clin Cancer Res. 2004 Oct 15; 10(20):6897-904.). Additionally, circulating tumor cells have been identified as an independent prognostic factor associated with detrimental prognosis eg in the setting of breast cancer (NCI J Natl Cancer Inst (2014) 106 (5)). on the other hand, lymphatic infiltration is a well established negative prognostic factor, associated with increased chances for metastatic relapse. these combined indicate, that both routes of metastatic dissemination operate not competing, but rather complementing each other as facilitators of metastatic relapse. hope that this helps.
Here is a usefull book about this field : http://link.springer.com/book/10.1007/978-90-481-2247-9
I can offer you the pdf , contact me : [email protected]
Dear Christer,currently metastazing as a process may be explainad by means of two different theories - Ewing's hemodinamic and Paedget's 'seed and soil'. Some tumors actually tend to have 'pramry arrest' rather in lymphatic than in blood capillaries. ...But not everything is so simple here...)))
Melanoma can metastasize to distant organs without prior clinically apparent regional lymph node metastases. Resection of clinically occult or clinically apparent regional lymph node metastases, prophylactic, or therapeutic, has not been shown to prevent distal dissemination. This raises the probability that the metastatic process is a multi-focal process rather than via lymphatic or haematogenous dissemination and lends support to the viral aetiology hypothesis of melanoma and other neoplasms. Distant metastases have been observed as long as twenty years after regional lymph node metastases in melanoma. See also Blake Cady letter NEJM February 13, 2014
Article Final trial report of sentinel-node biopsy versus nodal obse...
dear Christer, the one route of dissemination does not preclude the other and vice versa. Cancer cells have been identified in the blood of patients with practically all types of carcinomas (Clin Cancer Res. 2004 Oct 15; 10(20):6897-904.). Additionally, circulating tumor cells have been identified as an independent prognostic factor associated with detrimental prognosis eg in the setting of breast cancer (NCI J Natl Cancer Inst (2014) 106 (5)). on the other hand, lymphatic infiltration is a well established negative prognostic factor, associated with increased chances for metastatic relapse. these combined indicate, that both routes of metastatic dissemination operate not competing, but rather complementing each other as facilitators of metastatic relapse. hope that this helps.
The paper by Shenov and colleagues merits consideration for this discussion.
Am J Surg Pathol. 1987 Feb;11(2):140-6. Malignant melanoma primary in lymph node. The case of the missing link. Shenoy BV, Fort L 3rd, Benjamin SP.
Circulating cancer cells in the blood are not necessarily the seeds of the next metastasis. They may be innocent and impotent bystanders, terminal phenotypes of the neoplastic process, marching to their death. Their prognostic value, if it exists, (Alao J.P. et al Melanoma Research 1999, 9, 395-399) maybe a reflection of the activity of the focus from which they emanate, not necessarily their vigour to establish new foci in distant organs. They can of course be the carriers of the “iogenic” factor (virus?) that established the neoplasm in the first instance.
Interestingly, the opposite question has been asked in ovarian cancer where the tumors are presumed to metastasize by direct extension from the ovary/fallopian tube into the peritoneal cavity. Evidence for hematogenous spread was recently provided through an animal model:
http://www.ncbi.nlm.nih.gov/pubmed/25026212
You are right in your question.
One has to remember that lymphatics and blood circulation are anatomically connected. Therefore the lymph node metastasis are also sources of hematogenous metastasis, like primary cancer site.
I would like to point to a recent review from a former colleague of mine:
Article The lymph node pre-metastatic niche
- Badges
- Science topic
- Similar topics
- Medicine
- Oncology
- Cancer Research
- Cancer Biology