Trousseau sign of malignancy

The Trousseau sign of malignancy or Trousseau's Syndrome is a medical sign involving episodes of vessel inflammation due to blood clot (thrombophlebitis) which are recurrent or appearing in different locations over time (thrombophlebitis migrans or migratory thrombophlebitis). The location of the clot is tender and the clot can be felt as a nodule under the skin.^[1] Trousseau's syndrome is a rare variant of venous thromboembolism (VTE) that is characterized by recurrent, migratory thrombosis in superficial veins and in uncommon sites, such as the chest wall and arms. This syndrome is particularly associated with pancreatic and lung cancer. ^[2] Trousseau's Syndrome can be an early sign of gastric or pancreatic cancer,^[3] typically appearing months to years before the tumor would be otherwise detected.^[4] Heparin therapy is recommended to prevent future clots.^[5] The Trousseau sign of malignancy should not be confused with the Trousseau sign of latent tetany caused by hypocalcemia.

History

Armand Trousseau first described this finding in the 1860s; he later found the same sign in himself, was subsequently diagnosed with pancreatic cancer and died soon thereafter.^[6] Dr. Trousseau presciently attributed thromboembolism in malignancy to changes in blood composition rather than local inflammatory or mechanical forces. By correlating clinical observation with surgical and autopsy findings, Dr. Trousseau recognized that a localized cancer could induce a generalized hypercoagulable state in which thrombosis could occur elsewhere in the body, such as in extremities with visceral malignancy. Dr. Trousseau described several cases in which recurrent thrombosis was the presenting feature of visceral cancer, and his confidence in the utility of this connection led him to say, "So great, in my opinion, is the semiotic value of phlegmasia in the cancerous cachexia, that I regard this phlegmasia as a sign of the cancerous diathesis as certain as sanguinolent effusion into the serous cavities."

Pathophysiology

Some malignancies, especially gliomas (25%), as well as adenocarcinomas of the pancreas and lung, are associated with hypercoagulability (the tendency to form blood clots) for reasons that are incompletely understood, but may be related to factors secreted by the tumors, in particular a circulating pool of cell-derived tissue factor-containing microvesicles.^[7] Some adenocarcinomas secrete mucin that can interact with selectin found on platelets, thereby causing small clots to form ^[8][9]

In patients with malignancy-associated hypercoagulable states, the blood may spontaneously form clots in the portal vessels, the deep veins of the extremities (such as the leg), or the superficial veins anywhere on the body. These clots present as visibly swollen blood vessels (vasculitis), especially the veins, or as intermittent pain in the affected areas.

References

1. Trousseau's sign of visceral malignancy in GPnotebook, retrieved November 2012
2. Caine, Graham (Nov 2002). "The Hypercoagulable State of Malignancy: Pathogenesis and Current Debate". Neoplasia 4: 465–473. doi:10.1038/sj.neo.7900263. PMC 1550339. PMID 12407439. Retrieved 24 April 2015.
3. Callander, N; S I Rapaport (1993). "Trousseau's syndrome.". Western Journal of Medicine 158 (4): 364–371. ISSN 0093-0415. PMC 1022062. PMID 8317122.
4. "Trousseau sign" at Dorland's Medical Dictionary
5. Callander, N; S I Rapaport (1993). "Trousseau's syndrome.". Western Journal of Medicine 158 (4): 364–371. ISSN 0093-0415. PMC 1022062. PMID 8317122.
6. Samuels MA, King ME, Balis U (2002). "Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 31-2002. A 61-year-old man with headache and multiple infarcts". N. Engl. J. Med. 347 (15): 1187–94. doi:10.1056/NEJMcpc020117. PMID 12374880.
7. Del Conde I, Bharwani LD, Dietzen DJ, Pendurthi U, Thiagarajan P, López JA.(2007) Microvesicle-associated tissue factor and Trousseau's syndrome. J Thromb Haemost 5:70-4
8. Wahrenbrock M, Borsig L, Le D, Varki N, Varki A (2003). "Selectin-mucin interactions as a probable molecular explanation for the association of Trousseau syndrome with mucinous adenocarcinomas". J Clin Invest 112: 853–862. doi:10.1172/jci200318882.
9. Varki, Ajit (2007). "Trousseau's syndrome: multiple definitions and multiple mechanisms". Blood 110 (6): 1723–1729. doi:10.1182/blood-2006-10-053736. ISSN 0006-4971. PMC 1976377. PMID 17496204.