eMedicine Specialties > Dermatology > Malignant Neoplasms

Stewart-Treves Syndrome: Differential Diagnoses & Workup

Author: Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Coauthor(s): Geover Fernandez, MD, FAAD, Staff Physician, Department of Dermatology, University of Medicine and Dentistry New Jersey, New Jersey Medical School
Contributor Information and Disclosures

Updated: Nov 13, 2009

Differential Diagnoses

Angioedema, Acquired
Lymphangioma
Angioedema, Hereditary
Lymphocytoma Cutis
Angioendotheliomatosis
Malignant Melanoma
Angiolymphoid Hyperplasia with Eosinophilia
Metastatic Carcinoma of the Skin
Kaposi Sarcoma
Lymphangiectasia

Other Problems to Be Considered

Telangiectatic metastatic breast disease to the skin
Hemangioendotheliomas
Hemangiopericytomas

Anaplastic Kaposi sarcoma can mimic Stewart-Treves syndrome.15,16

Some authors have suggested a distinction between Stewart-Treves syndrome and cutaneous postradiation angiosarcoma.17

Workup

Laboratory Studies

  • Although Stewart-Treves syndrome is also known as lymphangiosarcoma, ultrastructural and immunohistologic studies show that this malignancy arises from blood vessels rather than lymphatic vessels.
  • The following immunohistologic and ultrastructural findings can be used to confirm that the tumor originates from blood vessels.
    • Antibodies against factor VIII–related antigen are markers for endothelial cells. Although malignant endothelial cells may not always show positive staining with this marker, a more sensitive endothelial marker, lectin Ulex europaeus-I, is more likely to react with hemangiosarcoma tumor cells. However, the specificity of this marker is reduced in people with blood group O because normal epithelial cells and carcinomas also bind this lectin in these individuals.
    • CD34 antigen is a marker of vascular endothelial cells and does not react with the lymphatic endothelium.
    • Antikeratin antibodies show no evidence of keratin in this malignancy; this finding confirms that the tumor cells are nonepithelial in origin.
    • Positive staining for laminin, CD31, collagen IV, and vimentin can aid in diagnosing the tumors as angiosarcomas.

Imaging Studies

  • MRI is recommended to evaluate the local extent of angiosarcomas. However, its true value is in question because of poor results in delineating the margin of the tumor. It may be low in signal intensity on T2-weighting and short-tau inversion recovery (STIR) imaging, reflecting the densely cellular, fibrous stroma and sparsely vascularized tumor histology.18,19 Additional administration of intravenous contrast medium may reveal significant enhancement of the tumorous lesions.
  • Chest CT scanning should be performed to rule out metastatic disease to the lungs before the patient undergoes extensive surgery.
  • Chest radiography can help in identifying pulmonary metastases and pleural effusion.

Procedures

  • Analysis of a biopsy specimen is essential to the diagnosis of lymphangiosarcoma.
  • Fine-needle aspiration is inadequate for diagnosis of Stewart-Treves syndrome.

Histologic Findings

Histologically, angiosarcomas in Stewart-Treves syndrome are indistinguishable from angiosarcomas in nonlymphedematous sites. Postlymphedema angiosarcomas are characterized by proliferating vascular channels, which dissect the dermal collagen and, often, the obliterate appendages. Tumor endothelial cells lining these channels show marked hyperchromatism and pleomorphism. Mitoses are commonly seen in these tumor cells. The vascular endothelial cells appear round or oval, and they are protuberant and often project into the lumen. Erythrocytes can be seen inside these vascular channels. The overlying epidermis may be hyperkeratotic and acanthotic, or it may be atrophic. Prominent proliferation of reticular fibers can be seen in association with this malignancy.

At electron microscopic examination, lymphangiosarcoma cells are surrounded by a complete basal lamina. In some tumor cells, pinocytosis, intercellular junctions, and cytoplasmic intermediate filaments are observed. In addition, Weibel-Palade bodies and erythrophagocytosis are often present. These ultrastructural findings suggest a vascular endothelial origin rather than a lymphatic endothelial origin.

Staging

In 1959, McConnell and Haslam divided the course of development of lymphangiosarcoma into 3 stages.20 This staging system lacks universal application.

  • Stage 1 - Prolonged lymphedema
    • This stage is characterized by extensive edema that causes the degeneration of fat and collagen mainly in the deep part of the dermis.
    • Edema separates the collagen bands, creating a misperception of an increased amount of fibrous tissue in the area.
  • Stage 2 - Premalignant angiomatosis
    • This stage involves multiple foci of small, proliferating channels in the dermis and subdermis. These vessels are lined by hyperplastic endothelial cells, as well as normal, flattened cells.
    • The areas of angiomatosis vary in size, ranging from 100 µm to a couple of centimeters in diameter.
    • Superficial areas can be seen as bruises or vesicles, whereas deeper areas are seen as areas of induration and hemorrhage.
    • Early lesions show little evidence of malignancy, but more advanced lesions reveal early malignant transformation with an increased number of mitotic figures and pleomorphic cells.
  • Stage 3 - Frankly malignant angiosarcoma
    • These aggressive tumors develop from areas of premalignant angiomatosis.
    • The histologic features of this malignancy are described above in stage 2.

More on Stewart-Treves Syndrome

Overview: Stewart-Treves Syndrome
Differential Diagnoses & Workup: Stewart-Treves Syndrome
Treatment & Medication: Stewart-Treves Syndrome
Follow-up: Stewart-Treves Syndrome
References
[ CLOSE WINDOW ]

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

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

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

  13. 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].

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

  15. 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].

  16. 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].

  17. 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].

  18. 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].

  19. 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].

  20. 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.

  21. 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].

  22. 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].

  23. 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].

  24. 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].

  25. 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].

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

  27. Caldwell JB, Ryan MT, Benson PM, James WD. Cutaneous angiosarcoma arising in the radiation site of a congenital hemangioma. J Am Acad Dermatol. Nov 1995;33(5 Pt 2):865-70. [Medline].

  28. Cozen W, Bernstein L, Wang F, Press MF, Mack TM. The risk of angiosarcoma following primary breast cancer. Br J Cancer. Oct 1999;81(3):532-6. [Medline].

  29. Heitmann C, Ingianni G. Stewart-Treves syndrome: lymphangiosarcoma following mastectomy. Ann Plast Surg. Jan 2000;44(1):72-5. [Medline].

  30. Krause KI, Hebert AA, Sanchez RL, Solomon AR Jr. Anterior abdominal wall angiosarcoma in a morbidly obese woman. J Am Acad Dermatol. Aug 1986;15(2 Pt 2):327-30. [Medline].

  31. Laguerre B, Lefeuvre C, Kerbrat P, Hassel M. [Stewart-Treves syndrome arising in post-traumatic lymphedema]. Bull Cancer. Mar 1999;86(3):279-82. [Medline].

  32. Muller R, Hajdu SI, Brennan MF. Lymphangiosarcoma associated with chronic filarial lymphedema. Cancer. Jan 1 1987;59(1):179-83. [Medline].

  33. Ruocco V, Schwartz RA, Ruocco E. Lymphedema: an immunologically vulnerable site for development of neoplasms. J Am Acad Dermatol. Jul 2002;47(1):124-7. [Medline].

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

  35. Sinclair SA, Sviland L, Natarajan S. Angiosarcoma arising in a chronically lymphoedematous leg. Br J Dermatol. Apr 1998;138(4):692-4. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

Stewart-Treves syndrome, cutaneous angiosarcoma, postmastectomy angiosarcoma, lymphangiosarcoma in postmastectomy lymphedema, postlymphedema angiosarcoma, hemangiosarcoma in chronic lymphedema, hemangiosarcoma in postmastectomy lymphedema, postmastectomy lymphedema, lymphangiosarcoma, Milroy disease, Milroy's disease, idiopathic lymphedema, congenital lymphedema, traumatic lymphedema, filarial lymphedema

[ CLOSE WINDOW ]

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, UMDNJ-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.

Medical Editor

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; Genentech Honoraria Consulting; Incyte Grant/research funds Other; Warner Chilcott Honoraria Consulting; Merck Salary Management position; Abbott  Speaking and teaching

Pharmacy Editor

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.

Managing Editor

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.

CME Editor

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

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
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.