Stewart-Treves Syndrome 

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: William D James, MD   more...
 
Updated: Apr 25, 2011
 

Background

Stewart-Treves syndrome is a rare, deadly cutaneous angiosarcoma that develops in long-standing chronic lymphedema.[1] (Schwartz, 1988). Most commonly, this tumor is a result of lymphedema induced by radical mastectomy to treat breast cancer. Unfortunately, although the breast cancer may be cured with such radical surgery, this second primary cancer may be responsible for the patient's worsening course. The term Stewart-Treves syndrome is broadly applied to an angiosarcoma that arises in a chronically lymphedematous region due to any cause, including congenital lymphedema and other causes of secondary lymphedema unassociated with mastectomy. As reported by Durr et al in 2004, this lymphangiosarcoma occurs as a rare complication.[2] Lymphangiosarcoma is a misnomer because this malignancy seems to arise from blood vessels instead of lymphatic vessels. A more appropriate name is hemangiosarcoma.

In 1906, Lowenstein first described angiosarcoma in a patient's arm that had been affected by severe posttraumatic lymphedema for 5 years.[3] In 1948, Stewart and Treves reported this rare secondary malignancy in 6 cases of angiosarcoma in postmastectomy lymphedema.[4] They recognized that an edematous arm after radical mastectomy for breast cancer may suggest recurrent breast cancer, but that long-standing chronic edema without recurrent cancer may occasionally produce "a heretofore unrecognized and unreported sequel ... long after the malignant breast neoplasm has apparently been arrested ... a new specific tumor." Stewart and Treves suggested that these angiosarcomas were probably not observed previously because they were mistaken for recurrent, inoperable, cutaneous manifestations of breast cancer.

Lymphangiosarcoma has been described in Milroy disease and in idiopathic, congenital, traumatic, or filarial lymphedema.[5, 6]

Next

Pathophysiology

The pathogenic mechanism by which lymphedema may induce angiosarcoma has been the subject of controversy. Stewart and Treves found a high incidence of third malignancies in patients with postmastectomy angiosarcoma. Thus, they speculated that a systemic carcinogenic factor was the main causative factor in the pathogenesis of lymphangiosarcomas.

In 1979, Schreiber and others postulated the concept of local immunodeficiency in the presence of lymphedema.[7] This theory is supported by experimental evidence. In 1960, Stark and associates demonstrated that homograft skin transplanted to lymphedematous arms survive much longer than those transplanted to healthy arms.[8] Therefore, lymphedema may cause some degree of local immunodeficiency and lead to oncogenesis.

The possibility that radiation therapy has an important role in the induction of lymphangiosarcoma is also postulated. Sternby et al reported that in their study, the patient with the shortest interval between radical mastectomy and the onset of the tumor (8 mo) received both preoperative radiation therapy of the breast and involved axillary lymph nodes followed by fractionated radiation.[9] Others suggest that irradiation is not an essential factor in the pathogenesis of this tumor. Finally, irradiation may be an indirect cause of lymphangiosarcomas because it may cause axillary node sclerosis and thereby accelerate and aggravate the edema.

Clinical data from Swedish women with previous breast cancer who developed angiosarcomas/lymphangiosarcomas on the thoracic wall/upper extremity between 1958 and 2008 showed 31 angiosarcomas developed at a median age of 71 years.[10] The 14 females treated for breast cancer with radical mastectomy and radiotherapy from 1949-1988 developed angiosarcomas in edematous arms after a median 11 years, whereas 17 females treated by segmental resection, antihormonal treatment, and radiotherapy from 1980-2005 developed angiosarcomas in the irradiated field on the thoracic wall after a median 7.3 years.

Previous
Next

Epidemiology

Frequency

International

Currently, approximately 400 cases of Stewart-Treves syndrome are reported in the world literature. In 1962, Schirger calculated that the incidence of this disease is 0.45% in patients who survive at least 5 years after radical mastectomy.[11] Another analysis calculated it as occurring in 0.03% of patients surviving 10 or more years after radical mastectomy.[12]

Mortality/Morbidity

Lymphangiosarcomas are extremely aggressive tumors with a high local recurrence rate and a tendency to metastasize early to many areas. Long-term survivors are the exceptions. Metastatic angiosarcoma to the lungs and chest wall are the most common cause of death in patients with Stewart-Treves syndrome. Metastases to the liver and bones can also occur. Lymphangiomas are associated with a high rate of local recurrence and metastasis, even after aggressive surgical treatment.

Race

No racial predominance exists for Stewart-Treves syndrome.

Sex

Most patients with Stewart-Treves syndrome are women with a history of breast cancer that has been treated with radical mastectomy, which causes chronic lymphedema.

Age

Stewart-Treves syndrome usually occurs in middle-aged or elderly women, a few years or many years after mastectomy.

In 1981, Sordillo and associates reported a peak incidence in persons aged 65-70 years.[13] In 1972, Woodward et al described a series of 23 patients in a review of 163 cases of Stewart-Treves syndrome from the literature.[14] They recorded an average patient age of 68.8 years at the onset of lymphangiosarcoma; the youngest patient was aged 44 years and the oldest, 84 years.

Previous
Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Coauthor(s)

Geover Fernandez, MD, FAAD  Staff Physician, Department of Dermatology, University of Medicine and Dentistry New Jersey, New Jersey Medical School

Geover Fernandez, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and American Society for MOHS Surgery

Disclosure: Nothing to disclose.

Specialty Editor Board

Abby S Van Voorhees, MD  Assistant Professor, Director of Psoriasis Services and Phototherapy Units, Department of Dermatology, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania

Abby S Van Voorhees, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, National Psoriasis Foundation, Phi Beta Kappa, Sigma Xi, and Women's Dermatologic Society

Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Merck Salary Management position; Abbott Honoraria Speaking and teaching; Amgen Honoraria Review panel membership; Centocor Honoraria Consulting; Leo Consulting; Merck None Other

Michael J Wells, MD  Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Christen M Mowad, MD  Associate Professor, Department of Dermatology, Geisinger Medical Center

Christen M Mowad, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Glen H Crawford, MD  Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital

Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD  Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System

William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology

Disclosure: Elsevier Royalty Other

References

  1. Gonne E, Collignon J, Kurth W, et al. [Angiosarcoma consecutive to chronic lymphoedema: a Stewart-Treves syndrome]. Rev Med Liege. Jul-Aug 2009;64(7-8):409-13. [Medline].

  2. Dürr HR, Pellengahr C, Nerlich A, Baur A, Maier M, Jansson V. Stewart-Treves syndrome as a rare complication of a hereditary lymphedema. Vasa. Feb 2004;33(1):42-5. [Medline].

  3. Lowenstein S. Der atiologische zusammenhang zwischen akutem ein-maligem trauma und sarkon. Beitr Z klin Clir. 1906;48:780.

  4. Stewart FW, Treves N. Lymphangiosarcoma in postmastectomy lymphedema: A report of six cases in elephantiasis chirurgica. Cancer. 1948;1:64-81.

  5. Hallel-Halevy D, Yerushalmi J, Grunwald MH, Avinoach I, Halevy S. Stewart-Treves syndrome in a patient with elephantiasis. J Am Acad Dermatol. Aug 1999;41(2 Pt 2):349-50. [Medline].

  6. Offori TW, Platt CC, Stephens M, Hopkinson GB. Angiosarcoma in congenital hereditary lymphoedema (Milroy's disease)--diagnostic beacons and a review of the literature. Clin Exp Dermatol. Mar 1993;18(2):174-7. [Medline].

  7. Schreiber H, Barry FM, Russell WC, Macon WL 4th, Ponsky JL, Pories WJ. Stewart-Treves syndrome. A lethal complication of postmastectomy lymphedema and regional immune deficiency. Arch Surg. Jan 1979;114(1):82-5. [Medline].

  8. Stark RB, Dwyer EM, De Forest M. Effect of surgical ablation of regional lymph nodes on survival of homografts. Ann NY Acad Sci. 1960;87:140-148.

  9. Sternby NH, Gynning I, Hogeman KE. Postmastectomy angiosarcoma. Acta Chir Scand. 1961;121:420-432.

  10. Styring E, Fernebro J, Jonsson PE, et al. Changing clinical presentation of angiosarcomas after breast cancer: from late tumors in edematous arms to earlier tumors on the thoracic wall. Breast Cancer Res Treat. Jan 20 2010;[Medline].

  11. Schirger A. Postoperative lymphedema: etiologic and diagnostic factors. Med Clin North Am. Jul 1962;46:1045-50. [Medline].

  12. Wierzbicka-Hainaut E, Guillet G. [Stewart-Treves syndrome (angiosarcoma on lyphoedema): A rare complication of lymphoedema]. Presse Med. Dec 2010;39(12):1305-8. [Medline].

  13. Sordillo PP, Chapman R, Hajdu SI, Magill GB, Golbey RB. Lymphangiosarcoma. Cancer. Oct 1 1981;48(7):1674-9. [Medline].

  14. Woodward AH, Ivins JC, Soule EH. Lymphangiosarcoma arising in chronic lymphedematous extremities. Cancer. Aug 1972;30(2):562-72. [Medline].

  15. Tomita K, Yokogawa A, Oda Y, Terahata S. Lymphangiosarcoma in postmastectomy lymphedema (Stewart-Treves syndrome): ultrastructural and immunohistologic characteristics. J Surg Oncol. Aug 1988;38(4):275-82. [Medline].

  16. Yap BS, Yap HY, McBride CM, Bodey GP. Chemotherapy for postmastectomy lymphangiosarcoma. Cancer. Mar 1 1981;47(5):853-6. [Medline].

  17. Styring E, Fernebro J, Jönsson PE, Ehinger A, Engellau J, Rissler P, et al. Changing clinical presentation of angiosarcomas after breast cancer: from late tumors in edematous arms to earlier tumors on the thoracic wall. Breast Cancer Res Treat. Aug 2010;122(3):883-7. [Medline].

  18. Bassotti A, Driban N, Huczak L, Zaccarria S. Angiosarcoma en linfedema cronico posmastectomia (Sindrome de Stewart-Treves). Med Rev. 2008;4:1-20.

  19. Schwartz RA, Kardashian JF, McNutt NS, Crain WR, Welch KL, Choy SH. Cutaneous angiosarcoma resembling anaplastic Kaposi's sarcoma in a homosexual man. Cancer. Feb 15 1983;51(4):721-6. [Medline].

  20. Salameire D, Templier I, Charles J, et al. An "anaplastic" Kaposi's sarcoma mimicking a Stewart-Treves syndrome. A case report and a review of literature. Am J Dermatopathol. Jun 2008;30(3):265-8. [Medline].

  21. Kunkel T, Mylonas I, Mayr D, Friese K, Sommer HL. Recurrence of secondary angiosarcoma in a patient with post-radiated breast for breast cancer. Arch Gynecol Obstet. Nov 2008;278(5):497-501. [Medline].

  22. Nakazono T, Kudo S, Matsuo Y, et al. Angiosarcoma associated with chronic lymphedema (Stewart-Treves syndrome) of the leg: MR imaging. Skeletal Radiol. Jul 2000;29(7):413-6. [Medline].

  23. Schindera ST, Streit M, Kaelin U, Stauffer E, Steinbach L, Anderson SE. Stewart-Treves syndrome: MR imaging of a postmastectomy upper-limb chronic lymphedema with angiosarcoma. Skeletal Radiol. Mar 2005;34(3):156-60. [Medline].

  24. McConnell AH, Haslam P. Angiosarcoma in post-mastectomy lymphedema: report of five cases and review of the literature. Br J Surg. 1959;46:322-32.

  25. Grobmyer SR, Daly JM, Glotzbach RE, Grobmyer AJ 3rd. Role of surgery in the management of postmastectomy extremity angiosarcoma (Stewart-Treves syndrome). J Surg Oncol. Mar 2000;73(3):182-8. [Medline].

  26. Breidenbach M, Rein D, Schmidt T, et al. Intra-arterial mitoxantrone and paclitaxel in a patient with Stewart-Treves syndrome: selection of chemotherapy by an ex vivo ATP-based chemosensitivity assay. Anticancer Drugs. Apr 2000;11(4):269-73. [Medline].

  27. Goetze S, Schmook T, Audring H, Ziegenbein C, Worm M, Schulze P. [Successful treatment of Stewart-Treves syndrome with liposomal doxorubicin]. J Dtsch Dermatol Ges. Jan 2004;2(1):49-52. [Medline].

  28. Paydas S, Yapar Z, Gonlusen G. Stewart-Treves syndrome: questionable response to weekly paclitaxel. Chemotherapy. 2010;56(1):66-8. [Medline].

  29. Fujisawa Y, Ito M, Mori K, Okada S, Nakamura Y, Kawachi Y, et al. Intra-arterial mitoxantrone/paclitaxel in angiosarcoma of the lower limb associated with chronic lymphedema (Stewart-Treves syndrome) in a patient with cervical cancer. Eur J Dermatol. Jan 14 2011;[Medline].

  30. Furue M, Yamada N, Takahashi T, et al. Immunotherapy for Stewart-Treves syndrome. Usefulness of intrapleural administration of tumor-infiltrating lymphocytes against massive pleural effusion caused by metastatic angiosarcoma. J Am Acad Dermatol. May 1994;30(5 Pt 2):899-903. [Medline].

  31. Roy P, Clark MA, Thomas JM. Stewart-Treves syndrome--treatment and outcome in six patients from a single centre. Eur J Surg Oncol. Nov 2004;30(9):982-6. [Medline].

  32. Hultberg BM. Angiosarcomas in chronically lymphedematous extremities. Two cases of Stewart-Treves syndrome. Am J Dermatopathol. Oct 1987;9(5):406-12. [Medline].

  33. Schwartz RA. Kaposi's sarcoma. In: Schwartz RA, ed. Skin Cancer: Recognition and Management. 1988:80-8.

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.