Are You Confident of the Diagnosis?
Characteristic findings on physical examination
Mondor’s disease is characterized by a sudden onset of an asymptomatic subcutaneous cord-like induration on the thoracoabdominal wall (Figure 1). The overlying skin does not have inflammatory signs and it is freely mobile. Usually it is asymptomatic, although pain may be present, specially on palpation, and with twisting or stretching movements. It is usually localized on the anterolateral thoracoabdominal wall, affecting the superior epigastric venous system or the lateral thoracic vein. It may also present in the groin or penis, due to the involvement of the lower part of the thoracoepigastric venous system. There are reports of Mondor’s disease in the antecubital fossa, the posterior cervical region, the mammary area, and axilla.
Expected results of diagnostic studies
The diagnosis is usually clinical. Ultrasonography: usually reveals a distended flowless vein longer than a mammary duct, with a beaded appearance. Sometimes it is able to visualize a thrombus. It is useful to rule out the presence of a tumour that might compress the veins. Coagulation tests can reveal levels of protein C and S, antithrombin III, anticardiolipin antibodies, factor V Leiden (activated protein C resistance). Serologic tests can exclude sexually transmitted diseases, in the case of penile Mondor’s disease.
Histopathology is useful in rare locations or ulcerated lesions. It presents as prominent vessels with plump endothelial cells, an inflammatory infiltrate, and connective tissue proliferation in the vessel wall (Figure 2). Necrosis, ulceration. and thrombus can be found. Inmunohistochemical staining can distinguish between blood and lymphatic vessels. Blood vessels are positive for CD31 and CD34 monoclonal antibodies and for von Willebrand factor, and negative for LYVE1 and D240.
The differential diagnosis includes:
Subacute angiitis, such as cutaneous polyarteritis nodosa and angiitis due to drugs. Clinically they present with skin inflammation and pain, and usually with ulceration. Angiitis usually affects arteries, not veins.
Inflammatory breast cancer. Mondor’s disease has a characteristic clinical picture of a sudden appearance of a linear cord with progressive improvement that is not usual in breast cancer.
Spigelian hernia. There are reports of Mondor’s disease mimicking a strangulated Spigelian hernia. Surgical exploration might be necessary to make the diagnosis.
With respect to the penis, the differential can include:
Syphilis. This could present as a cord-like induration in the penis.
Sclerosing lymphangitis of the penis. Ultrasonography should be performed and a biopsy may be necessary to distinguish between veins and lymphatics.
Peyronie’s disease. There is a fibrotic plaque on the penis that causes penile deformity, including penile curvature, hinging, narrowing, shortening and painful erections.
Who is at Risk for Developing this Disease?
The incidence is unknown but is probably higher than reported due to its self-limited condition. There are only about 400 reports in the literature. Following breast cancer surgery and aesthetic mammoplasties, the incidence has been estimated at 1%.
Mondor’s disease usually affects middle-aged women (three times more frequently than men), and in the case of penile Mondor’s disease, it is sexually active men who are at risk.
What is the Cause of the Disease?
The precise etiology is unknown. Predisposing factors are related to vessel-wall damage, stasis, and a hypercoagulable state (Virchow’s triad) and include:
-trauma: surgery, excision of axillary nodes, electrocution, muscular strain, sexual relations (when it occurs in the penis)
-venous compression: tight clothes, large breasts, tumours.
-infections: secondary syphilis, herpes zoster, tuberculosis and enterovirus
– vasoconstrictor drugs
-anatomical variation in the venous arcade-mammary carcinoma (unproven)
Mondor’s disease is considered a form of superficial thrombophlebitis. Initially an inflammatory cell infiltrate proliferates in the vein, and a thrombus occludes the lumen. Secondarily, a hard cord results as a consequence of the connective tissue proliferation. Lastly, the vein is recanalized.
Systemic Implications and Complications
It is imperative to rule out breast cancer when the disease presents as a thoracic lesion. Some authors consider Mondor’s disease as a synchronous cancer marker.
It is also important to rule out hypercoagulabitlity conditions that could lead to isolated phlebitis, or even present as a part of a generalized superficial thrombophlebitis. Sometimes it presents associated to deep vein thrombosis, or other thrombotic events such as pulmonary embolism, coronary syndromes or stroke. In such a case, consider treatment with anticoagulant or antiaggregant therapies.
Rest and reassurance
-Anticoagulant ointments:like heparin ointments. Although topical heparin products are not available in the United States, in other countries they are used for the treatment of thrombophlebitis. The active ingredient in topical heparin is Heparinoid, a mixture of sulphated glycosaminglycoruans derived from hog mucosa. Compared to heparin (average molecular weight of 12,000 to 15,000 daltons), heparinoid has a lower molecular weight (average 5,000 to 6,000). The efficacy is unproven, because of lack of well-designed studies.
-Anaesthetic infiltrations around the lesion with lidocaine.
Nonsteroidal antiinflammatory drugs
Indomethasin is a potent inhibitor of cyclo-oxygenase.
–Dosage: 50mg daily in adults and in children 14 years and older. Taper as symptoms resolve.
-Interactions: Coadministration with other NSAIDs increases the risk of renal insufficiency and gastrointestinal bleeding. Probenecid may increase concentrations and possibly, toxicity of NSAIDs. It may decrease effect of hydralazine, captopril, and beta-blockers. It may decrease diuretic effects of furosemide and thiazides. It may increase protrombin time when taking anticoagulants, also it may increase risk of metotrexate toxicity and levels of phenytoin.
-Contraindications: Documented hypersensitivity, gastrointestinal bleeding, renal insufficiency…
-Precautions: Category B in pregnancy and category D in third trimester of pregnancy. It may mask signs of infection, cause fluid retention, peripheral edema, and deterioration of circulatory hemodynamics. It can inhibit platelet aggregation and prolong bleeding time, liver and kidney damage may occur (rare)
Aspirin inhibits prostaglandin synthesis
-Dosage: In adults, 325-650mg each 4-6 hours, not to exceed 4 g daily. Pediatric: dose 10-15 g/kg/dose every 4-6 hours, not to exceed 60-80mg/kg/day.
-Interactions: Effects may decrease with antiacids and urinary alkalinizers, corticosteroids decrease salicylate serum levels, additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants, may antagonize uricosuric effects of probenecid, and increase the toxictiy of phenytoin and valproic acid, doses more than 2g/day may potentiate the glucose-lowering effect of sulfonylurea drugs.
-Contraindications: Documented hypersensitivity, liver damage, hypoprothrombinemia, vitamin K deficiency, bleeding disorders, asthma. Do not use in children (<16years) with flue because of the risk of Reye syndr
-Precautions: Category C in pregnancy, category D in third trimestrer. It may cause transient decrease of the renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, in those with a history of blood coagulation defects, or in those taking anticoagulants.
Surgical Treatment (only in persistent disease or recurrences)
-Superficial vein resection
Optimal Therapeutic Approach for this Disease
After ruling out associated systemic disorders (with a hypercouagable workup and age appropriate cancer screening), conservative therapy is recommended, as Mondor’s disease is a self-limited condition. Avoid overaggresive treatment, to prevent physical and emotional trauma. In most cases, a proper explanation, strong reassurance, and temporary rest (or sexual abstinence in the case of penile Mondor’s disease) is enough. Antiinflammatory drugs combined with anticoagulant ointments (heparin oinments) might decrease the time to resolution. (which varies between 4-8 weeks) (heparin oinments are available outside USA only)
In cases with pain, usually symptomatic treatment with antiinflammatory drugs is enough. If that is inadequate for controlling the pain , anaesthetic infiltrations with lidocaine around the lesion would be valuable. In recurrent or persistent disease, a thrombectomy or superficial vein resection may be warranted. Patients found to have a hypercouaguable state should be referred to a hematologist; alternatively, patients may be referred to a hematologist to perform the hypercoauguable work-up.
In almost every case, the disease heals without treatment in appoximately 4-8 weeks. Reassurance during follow-up outpatient visits is beneficial. It is essential for the clinician to recognize and differentiate the condition from a carcinoma. As in other forms of migratory thrombophlebitis, Mondor’s disease may be a marker of an undiagnosed carcinoma; therefore, continuous reassessments are encouraged.
Unusual Clinical Scenarios to Consider in Patient Management
In recurrent or persistent disease, it may be necessary to perform a thrombectomy or superficial vein resection to avoid new episodes or achieve long-term pain control. When associated with deep vein thrombosis or other thrombotics events, antiaggregant or anticoagulant therapy should be considered.
Migratory thrombophelibitis is seen as a paraneoplastic syndrome. It is felt to be secondary to a malignancy induced hypercouagable state. This finding has been termed the Trousseau sign. Most frequently caused by pancreatic or lung cancer.
What is the Evidence?
Álvarez-Garrido, H, Garrido-Ríos, AA, Sanz-Muñoz, C. “Mondor’s disease”. Clin Exp Dermatol. vol. 34. 2009. pp. 753-6. (Brief review of Mondor’s disease. It explains the clinical features, pathogenesis, and main approach to this disease.)
Ichinose, A, Fukunaga, A, Terashi, H. “Objective recognition of vascular lesions in Mondor’s disease by immunohistochemistry”. J Eur Acad Dermatol Venereol. vol. 22. 2008. pp. 168-73. (The article focuses on the differential diagnosis between veins and lymphatics. To clearly identify the cell types they perform inmunohistochemical analyses with two markers. LYVE 1, which is specifically expressed in endothelial cells of lymphatic vessels, and with von Willebrand factor, which is used for identifying the endothelial cells of blood vessels, however, it can also be positive for endothelial cells of lymphatic vessels.)
Shousha, S, Chun, J. “Ulcerated Mondor´s disease of the breast”. Histopathology. vol. 52. 2008. pp. 395-6. (It reports a case of Mondor’s disease affecting the breast presented like a painful and ulcerated nodule. The histological study showed a totally occluded blood vessel, consistent with superficial thrombophlebitis with associated necrosis, inflammation, vascular proliferation and ulceration.)
Thatipelli, M, Hand, D, Irwin, W. “A variant of Mondor’s disease”. Vasc Med. vol. 12. 2007. pp. 135-6. (It shows the ultrasound picture of Mondor’s disease involving the superficial epigastric vein and the complete resolution of the thrombus on follow-up ultrasound.)
Kumar, B, Narang, T, Radotra, B. “Mondor’s disease of the penis: a forgotten disease”. Sex Transm Infect. vol. 81. 2005. pp. 480-2. (This is a study of 18 patients with penile Mondor’s disease. Biopsy for histopathological examination and inmunohistochemical analyses with CD31 and CD34 was done in 11 patients. Lymphatics were not involved in any of them. In their opinion, Mondor’s disease is a better term for description of the condition than nonvenereal sclerosing lymphangitis.)
Pappo, I, Wasserman, I, Sthal-Kent, V. “Mondor’s disease of the axilla: a rare complication of sentinel node biopsy”. Breast J. vol. 10. 2004. pp. 253-5. (This is a good review of the etiology of Mondor’s disease describing three patients with breast cancer who developed axillary Mondor’s disease folowing a sentinel node biopsy.)
Yanik, B, Conkbayir, I, Öner, Ö. “Imaging findings in Mondor’s disease”. J Clin Ultrasound. vol. 31. 2003. pp. 103-7. (In Mondor’s disease, gray-scale sonography shows hypoechoic or anechoic noncompressible tubular structures that represent the thrombosed vein in the subcutaneous fat. These structures are usually longer and located more superficially than those seen in the case of a dilated mammary duct. In addition, unlike a dilated lactiferous duct, a thrombosed vein in the periareolar region does not terminate in the retroareolar region. Thus, these differing characteristics can help distinguish between a thrombosed vein and a dilated duct. On color doppler imaging, no flow signal is detected within the hypoechoic tubular structure.)
Dirschka, T, Winter, K, Bierhoff, E. “Mondor’s disease: a rare cause of anterior chest pain”. J Am Acad Dermatol. vol. 49. 2003. pp. 905-6. (A good review of Mondor’s disease and the histopathological findings. The authors found a thickened vessel wall as a result of the proliferation of fibroblasts and smooth muscle cells, with few lymphocytes and histiocytes scattered in the vessel wall and the perivascular soft tissue. The lumen of the vein was almost obliterated by fibrous tissue as a result of an organized thrombus.)
Shetty, MK, Waton, AB. “Mondor´s disease of the breast:sonographic and mammographic findings”. Am J Roentgenol. vol. 177. 2001. pp. 893-6. (A wide review of the sonographic and mammographic findings in Mondor’s disease. The combination of a sonographic finding of a superficial vessel [with or without a intraluminal thrombus and without flow on Doppler imaging] and a mammographic finding of a tubular density is the typical sign of Mondor’s disease of the breast.)
Mayor, M, Burón, I, Calvo-Mora, J. “Mondor’s disease”. Int J Dermatol. vol. 39. 2000. pp. 922-5. (It reports four cases of Mondor’s disease affecting the anterolateral thoraco-abdominal wall, describing the clinical signs and possible etiopathogenic features. No cases were related to a hypercoagulability state or malignant disease. The outcome was favorable in all patients with conservative treatment.)
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