Trousseau's syndrome in the head and neck

Medical Intelligence Am J Otalaryngol 6:405-408, 1985

Trousseau's Syndrome in the Head and Neck PHILIP G. LIU, M.D., JOSEPH B. JACOBS,M.D., AND DEBORAHREEDE,M.D. Thromboses in Trousseau's syndrome are typically confined to the vascu{ar system of the extremities and viscera. The authors report a case of sequential bilateral internal and external jugular-vein thromboses secondary to this paraneoplastic hypercoagulable state. The etiologies of commonly encountered head and neck venous thromboses are infection, trauma, and obstruction. This article purports that head and neck venous thromboses without a proximal inflammatory or mechanical cause may be the initial manifestation of an occult malignancy, Upon establishing the presence of a hypercoagulable state, further evaluation may lead to the early diagnosis of such an occult malignancy.

More than a century ago, Armand Trousseau first described a syndrome of migratory thrombophlebitis associated with gastric carcinoma. 1 Since then, clinical, post-mortem, and hematologic studies have confirmed and expanded the definition of Trousseau's syndrome to encompass a broa.d spectrum of coagulation disorders associated with a wide variety of malignant tumors. 2'a The typical anatomic presentation of Trousseau's syndrome is in the vascular system of the extremities 2,4,5 and occasionally the viscera. 2 Vascular thrombosis secondary to this syndrome presenting in the head and neck has been reported rarely and is known to occur only intracranially. 6 We have been unable to find a report of Trousseau's syndrome occurring extracranially in the head and neck. This article describes a case of sequential bilateral external and internal jugular-vein thromboses, which were the initial m a n i f e s t a t i o n of an occult malignancy. REPORT OF A CASE

A 77-year-old woman had a tender right supraclavicular mass of 24 hours' duration. Five months prior to this episode, she was treated for left external jugular thrombosis. Head, neck, and Received March 4, 1985, fi'om the Departments of Otolaryngology [Drs. Lie and Jacobs~ and Radiology(Dr. Reede), New York UniversityMedical Center, New York. Accepted for publicationApril 15, 1985. Address correspondence and reprint requests to Dr. Noel L. Cohen: Department of Otolaryngology,New YorkUniversity Medical Center, 550 First Ave., New York, NY 10016.

lung contrast-enhanced computerized tomegraphic [CT) scans performed at that time showed left external and internal jugular-vein thromboses and a fibrotic right apical lung lesion (Fig. 1). Her previous chest x-ray films revealed a similar apical pattern. Because the patient was a heavy cigarette smoker with severe chronic obstructive pulmonary disease (COPD), more invasive evaluation of this lesion was deferred. She was treated successfully with a 10-day course of intravenous heparin and antibiotics. There was no evidence of concomitant local inflammation, distal vascular obstruction, systemic infection, or estrogen use. She had undergone a left carotid-artery endarterectomy eight years previously. On physical examination, the patient appeared frail but sprightly and was mildly short of breath. Her temperature was 38.4~ and respirations were 28 per minute. Head and neck examination revealed a tender, slightly erythematous mass, measuring approximately I x 3 cm in the rfght supraclavicular triangle and extending superolaterally from the upper border of the mid-clavicle. There was some prominence of the superficial neck veins, but no evidence of facial or orbitoretinal edema. The remainder of the otolaryngologic examination showed no evidence of tumor or infection. The lungs produced bilateral wheezes and an increased anteroposterior diameter of the chest. On cardiac auscultation, a grade 2/6 systolic murmur was heard. The abdomen, extremities, and vascular systems were normal. Routine laboratory results were remarkable for a decreased partial thromboplastin time and throm-

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slowly to treatment during which time she was thought to have axillary adenopathy on the left side. A lymph node biopsy specimen showed metastatic mucus-producing adenocarcinoma. She refused further diagnostic studies and died two months after admission. DISCUSSION

Figure 1. Contrast CT scan showing left external jugular thrombosis {tom prior admission (white arrow).

bocytosis. A chest roentgenogram showed right apical pleural thickening. Clinical Course

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The patient began a course of intravenous heparin and cefazolin. Contrast-enhanced CT scans from the base of skull to the thoracic outlet showed bilateral internal jugular-vein thrombosis and right external jugular-vein thrombosis with slight perivascular inflammation (Fig. 2). There was extensive venous collateralization, and the subclavian and innominate veins were patent. A periapical (fibrotic) lesion in the right lung apex was seen. A repeat CT scan of the chest demonstrated no change in the apical pattern. Because of the recurrent nature of the thrombosis and the absence of proximal mechanical or inflammatory etiology to explain the bilateral thrombosis, these clinical findings were believed to represent a hypercoagulable state, possibly secondary to underlying malignancy. A coagulation profile showed normal levels of coagulation factors but moderate thrombocytosis and hyperfibrinogenemia. The activated partial thromboplastin time was prolonged and fibrin split products were negative, retrospectively thought to be so because of the heparin effect. Bronchoscopy with washings and biopsies disclosed no tumor. The gastrointestinal tract showed no evidence of malignancy on conventional contrast studies or CT scan with visualization of the pancreas. Mammograms and bone scans were noncontributory. A bone-marrow specimen showed only reactive cells. The patient's thrombophlebitis responded

Unlike the venous system of the extremities and viscera, the veins in the head and neck, even in the presence of localized disease, appear to be less susceptible to thrombosis. The structure and location of head and neck veins makes them less predisposed to stasis since they are mostly valveless. They have a distensible wall, allowing constant collapse and expansion by the action of respiration and the pump effect of the heart, and gravity aids in central emptying in the upright position. Our review of the literature regarding Trousseau's syndrome in the head and neck revealed only 18 cases reported to date. These all consisted of cerebral sinus and venous thromboses attributable to this paraneoplastic state, and in two of these cases, thrombosis was the initial sign of malignancy. At the time of writing, there has been no report of Trousseau's syndrome occurring extracranially in the head and neck. Etiology of Venous Thrombosis in the Head and Neck

Tc place Trousseau's syndrome with head and neck manifestations into proper perspective, the etiology of head and neck venous thrombosis is

Figure 2, Contrast CT showing r~ght external and internal jugular thromboses on present admission, White arrow indicates right external jugular vein; black arrow indicates right internal jugular vein,

LIU ET AL. outlined in Table 1. The etiology of head and neck venous thrombosis can be broadly categorized into local versus systemic pathologic activation of coagulation and resultant thrombosis.

Localized Factors Otolaryngologists are well aware of localized disease of the head and neck that triggers coagulation and thrombosis of adjacent vessles, including local inflammatory and infectious disease causing thrombophlebitis. Infections of paranasal sinus and otologic, facial, orodental, and neck spaces may cause contiguous thrombophlebitis. 7-~a In t h e antibiotic era, reports of these v e n o u s t h r o m b o s e s have become infrequent. Recently, however, reports of venous thrombosis in the extracraniat region of the head and neck appear to be increasing. This may be because of the greater awareness of this entity in the medical community, an increasing rate of trauma to these veins, and more frequent diagnosis b e c a u s e of w i d e s p r e a d use of contrast CT. 7-13 Indeed, the more recently reported venous thromboses in this region have had mechanical causes, such as central venous catheterization, pacemaker wiring, and neck-vein injection (as seen with drug abuse, chemotherapy, or trauma). ~4'~s In these situations, vascular-wall damage acts as a localized nidus of thrombus formation. Other mechanical etiologies are vascular stasis and obstructive states, such as jugular foramen syndrome and thoracic outlet syndromes w h e r e i n resistance to central venous emptying is increased. *a Systemic Factors (The

Hypercoagulable State) Once local factors as explanations of a head and neck thrombosis have been ruled out, a thorough evaluation for a hypercoagulable state is indicated. The "hypercoagulable state" can be defined as any intrinsic hematologic aberration predisposing to thrombus formation. 17 Estrogen use, 14 pregnancy, the postpartum state, myelo-

TABLE 1. Etiology of Head and Neck Venous Thrombosis Localized factors Infectious and inflammatory diseases Trauma Obstruction Systemic factors (hypercoagulablestate) Estrogen use Pregnancy and postpartum period Myeloproliferative disorders Thrombohemorrhagic states* Malignancy * Includes acute DIC and its various causes.

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Figure 3. Coagulationprofile of DIC.

proliferative disorders, thrombohemorrhagic states, and solid and hematologic malignancy 2''~ are causes of the hypercoagulable storey Some evidence attributes the hypercoagulable state in Trousseau's syndrome to an overcompensated chronic disseminated intravascular coagulation (DIC)3,18,19 The abnormal activation of coagulation may be caused by the interaction of the tumor, procoagulant, T-cells, and monocytes that triggers the extrinsic coagulation system, a This clotting factor utilization may exist in a chronic, low-grade, subclinical state until compensatory synthesis of fibrinogen, clotting factors, and platelets build up to thrombogenic levels, ultimately resulting in clinical thrombosis. In chronic DIC, a clinical spectrum exists that ranges from undercompensation with a bleeding tendency, rather than thrombosis (usually in acute DIC), to overcompensation with a predisposition to thrombosis, rather than hemorrhage. In Trousseau's syndrome, the former situation is quite rare, usually occurring with hematologic malignancy, and the latter is much more frequent, occurring usually with solid tumors, 2 particularly adenocarcinomas. Although no tests are specific for the hypercoagulable state, the coagulation profile diagnostic of DIC is well known (Fig. 3). 58 When conversion of fibrinogen to fibrin is accelerated with consequent increased fibrinolysis, decreased clotting factors and increased levels of fibrin split products (FSP) may be seen. Conversion of fibrinogen to fibrin is accompanied by the release of fibrinopeptide A (FPA). 19 This moiety has a 4.5-minute half-life and is a sensitive marker of ongoing intravascular coagulation. 3 With overcompensated DIG, thrombocytosis, shortened partial thromboplastin time (PTT), prothrombin time [PT), and increased fibrinogon may be found. 2~ Aside from fibrin degradation Volume 6 products and fibrinopeptide A, the other coagNumber 5 ulation measurements are nonspecific and may September 1985 occur in many acute phase reactions. Clinical 407 correlation is necessary when the more specific laboratory markers of DIC are not present.

TROUSSEAU'S SYNDROME

Neoplastic Evaluation

References

In patients with primary head and neck thromboses and coagulation profiles indicative of an underlyirlg DIC without obvious cause, a search for malignancy in consultation with a hematologist-oncologist should be initiated. The relative i n c i d e n c e of neoplasms associated with this thromhotic phenomena may aid in the systematic search for an occult malignancy. In a review of 541 cases of Trousseau's syndrome, the frequency of associated tumor types in decreasing order was as follows: lung (25.6 per cent), pancreas (17.4 per cent), stomach (16.8 per cent), colon [15.2 per cent), prostate (6.5 per cent), and miscellaneous tumors (18.5 per cent), with head and neck carcinoma constituting less than 1 per cent}

1. Troussaau A: Phlegmasia Alba Dolens: Cliniqua Medicole de l ' H o t e l - - D i e u de Paris. London, New Sydenham Sectary 3:94, 1865 2. Sack G H Jr, Levitt ~, Belt W: Trousseau's syndrome and other manifestations of clinical disseminated coagulopathy in patient~ with neoplasm: clinical, pathologic and therapeutic features. Medicine 56:1-37, 1977 3, RicHes FR, Edwards RL: Activation of blood coagulation in cancer: Troasseau's syndrome revisited. Blood 62:14-28, 1982 4. Hoerr SO, Harper JR: On peripheral thrombophlebitis-its occurrence as a presenting symptom of malignant disease of pancreas, biliary tract or duodenum, lAMA 164:2033-2044, 1981 5. LiebermanJS, Barrero J, Urdanetta E, et ah Thrombophlebitis and cancer. JAMA177:542-545, 1961 6, Hickey WF, Garnick MB, Henderson IC, et ah Primary cerebral venous thrombosis in patients with cancer: a rarely diagnosed paraneoplastic syndrome, Am J Med 73:740-750, 1982 7. Wing V, Seheible W: Sonography of jugular vein thrombosis. Am J Radiol 140:333-336, 1983 8. Bradway W, Biondi RJ, Kaufman JL, et ah Internal jugular thrombosis and pulmonary emboli (letter). Chest 89:335-336, 1981 9. Merhar GL, Colby DP, Clark RA, et ah Computed tomographic demonstration of cervical abscess and jugular vein thrombosis: a complication of intravenous drug abuse in the neck. Arch Otolaryngoi 107:313315, 1981 10. Pat~l S, Brennan ]: Diagnosis of internal jugular vein thrombosis by computed tomegraphy, j Comput Assist Tomog 5:197-200, 1981 l t . McNetll R: fntemal jugular vein thrombosis. Head Neck Surg 3:247-250, 1981 12, Yau PC, Norante [D: Thrombophlebitis of the internal jugular vein secondary to pharyngitis. Arch Otolaryngol 106:507-508, 1980 13. Claus H: Ueber I00 Falle Septico-Pyamie Neck Angina. Med Klin 27:1269-1271, 1931 14, Southwick HW: Neck mass caused by thrmnbus iu the external jugular vein, Am J Surg 131:382-385, 1976 15. de Bruigh WP, Stadt HH: Bilateral thrombosis of internal jugular veins after multiple percutaneous cannulation. Anesth Analg 60:408-409, 1981 16, Graus F, Slatkin NE: Papilledema in the metastatic jugular foramen syndrome. Arch Neurol 40:816-818, 1983 17. Williams WJ, Beutler Z, Eislev A], et ah Hematology, ed 3. New York, McGraw-Hill Book Co, 1983, p 14741490 18. Owen CA Jr, Browie EJW: Chronic intravascular coagulation synd~-omes, a summary. Mayo Clin Proc 49:673-679, 1974 19. Yoda Y, Abe T: Fibrinopeptide A (FPA) level and fibrinogen k~netics in patients with malignant disease. Thromb Haemost 46:706-709, 1981 20. Mil]Br SP, Sanchez-Ava]os ], Stefanek T, et ah Coagulation disorders in cancer: I. Clinical and laboratory studies. Cancp:r 20:1452-3465, 1967 21. Weick ]K: Intravascular coagulation in cancer. Detain Oncal 5:203~211, 1978

Clinical Presentation The intracranial manifestations of Trousseau's syndrome vary according to the site of thrombosis. The 18 cases of documented cerebral sinus and venous thrombosis secondary to this syndrome had primarily neurologic focal signs and symptoms. The superior sagittal and lateral sinuses were the most frequent sit~s of involvement. 6 Clinical manifestations frequently encountered were headaches, seizures, focal paresthesias, motor deficits, and depressed mental status. In our case, aside from an absence of proximal causes, the clinical manifestations were not notably different from jugular thrombosis from other causes. Mild perivascular inflammation with pain, a tender cord-like mass, and lowgrade fever were the salient clinical features. The coagulation profile of our patient was not specific, partly because it was done after therapeutic heparin administration. Furthermore, the more specific marker for intravascular coagulation, fibrinopeptide A, was not assayed. Nevertheless, the coagulation profile of increased fibrinogen, shortened PT/PTT, and thrombocytosis in the absence of a proximal etiology for the thrombosis, combined with the discovery of a metastatic adenocarcinoma established the diagnosis of Trousseau's syndrome.

Acknowledgment. The authors thank Dr. Henriette Lackner of the Department of Hematology at NYU Medical Center for reviewing the manuscript. American Journal of Otolaryngology 408