Lymphangiosarcoma is a rare malignant neoplasm of endothelial origin that develops against the background of pronounced, long–existing lymphedema of the limb. The most studied and frequently occurring type of lymphangiosarcoma is Stewart-Treves syndrome. Its early signs are purple spots on the skin, dense subcutaneous nodules and the formation of ulcers, late – visceral metastases. This disease is diagnosed by biopsy with further histological examination of the material and instrumental methods – CT, MRI and PET. Treatment includes early surgery, radiation and chemotherapy.
ICD 10
D18.1 C49.1
General information
Lymphangiosarcoma (post-mastectomy lymphangioendothelioma, Stewart-Treves syndrome) is a highly malignant tumor that develops against the background of long–term chronic lymphostatic edema of the limb. Most patients with this disease have a history of radical mastectomy for breast cancer. For the first time , lymphangioendothelioma was described in detail in 1948 by pathologist F. Stewart and surgeon N. Treves (USA). The tumor belongs to the category of rare, develops in 0.07-0.45% of operated women with lymphedema. As a result of improving the methods of conservative and surgical treatment of breast cancer, the prevalence of Stewart-Treves syndrome is progressively decreasing. Most often, lymphangiosarcoma affects middle-aged and elderly women.
Causes
The exact cause of lymphangioendothelioma is unclear. Under the influence of certain triggers, malignant transformation of vascular endothelial cells occurs, which acquire the ability to divide uncontrollably with the possibility of early metastasis. The factors underlying the formation of this tumor may be:
- Prolonged lymphedema. Lymph stagnation in the vessels of the extremities most often occurs after a radical mastectomy for breast cancer, especially if the operation was accompanied by a regional lymphadenectomy. Cases of the development of lymphangiosarcoma after injuries, operations on the pelvic organs, filariasis, diseases of the veins of the lower extremities are described.
- Radiation therapy. According to the observations available in clinical oncology, lymphangiosarcoma occurs 10 times more often in patients who have undergone combined breast cancer treatment (mastectomy + radiation therapy). As a result of X-ray therapy, inflammation of the lymphatic vessels (lymphangitis) occurs, their patency is impaired, lymph retention occurs. In addition, exposure increases the risk of DNA mutations, which can trigger the process of carcinogenesis.
- Hereditary predisposition. There are isolated reports of the development of neoplasms against the background of hereditary forms of primary lymphedema with an autosomal recessive nature of inheritance. This indicates that genetic defects can also be etiological factors. Lymphangiosarcoma never develops with edema of the extremities of renal or cardiac origin.
Pathogenesis
Edema after mastectomy occurs on the side of the operation as a result of severe anatomical and functional disorders in the lymphatic outflow and circulation system – lymphostasis, scarring of the wound, interstitial fibrosis. The pathogenetic mechanism by which lymphostasis can initiate tumor development is still the subject of controversy and discussion. Oncologists note more frequent detection of other malignant neoplasms in patients with lymphangiosarcoma, which serves as a reason to consider the impact of carcinogens as a determining factor in the pathogenesis of the development of this tumor.
There is no single point of view regarding the histogenesis of the tumor. Some experts tend to believe that lymphangiosarcoma develops from lymphatic vessels and is not associated with breast cancer, others believe that it arises from carcinoma cells. Microscopically, atypical endothelial cells with brightly colored nuclei, a large number of anastomosing blood vessels, pronounced hyalinosis of perivascular spaces, infiltration of tumor stroma by lymphocytes are visualized. The lymphatic vessels along the edge of the drug are lined with unchanged endothelium and filled with lymph, which is associated with prolonged lymphostasis and is not typical for other vascular tumors.
Symptoms
Signs of lymphangioendothelioma occur on average 5-10 years after mastectomy. In most cases, there is a unilateral lesion of the upper limb on the side of the previous operation. The first symptoms ‒ these are purple, purple or cyanotic spots that quickly turn into nodules, less than a centimeter in diameter, rising above the surface of the skin. Soon, satellites (pinkish formations), hemorrhages and “vascular asterisks” appear around the nodules.
In the future, the elements merge, forming massive nodes of bluish-black color with a diameter of up to 5-10 centimeters and towering over the skin by 2-3 centimeters. As a result of a violation of the trophic tissues, ulceration of the skin over the tumor appears and its decay. The ulcer gradually increases in size, has an uneven shape, and is covered with a grayish fibrin coating. There is often a release of serous-hemorrhagic fluid from an ulcerative defect.
Complications
Lymphangiosarcoma quickly sprouts the chest wall, often metastasizes to visceral organs (pleura, lungs, ovaries, liver) with the development of characteristic symptoms (pleurisy, ascites). Due to the occurrence of necrotic changes in tissues, toxic decomposition products spread throughout the body, causing cancer intoxication. With the defeat and destruction of blood vessels, bleeding can develop, which prevents the healing of the ulcerative defect, and also leads to anemia. In some cases, a wound infection occurs in the area of the ulcer, which threatens to progress up to gangrene of the limb, sepsis and multiple organ failure.
Diagnostics
Oncologists, lymphologists, and dermatologists participate in the diagnosis of lymphangiosarcoma. Clarification of anamnestic data gives an idea of a mastectomy or radiation therapy for a tumor lesion of the mammary glands or another cause of lymphedema. Physical examination makes it possible to identify a tumor in the early stages before the development of necrotic defects and metastasis to other organs. Of the clarifying methods for the diagnosis of this disease are used:
- Biopsy and histological examination. Morphological verification is the main method of confirming the diagnosis. The histological picture characteristic of lymphangiosarcoma makes it possible to differentiate it with Kaposi’s sarcoma, melanoma, angioendothelioma, cutaneous metastases of visceral cancer.
- Instrumental methods. An MRI of the soft tissues of the limb helps to visualize the depth of the tumor germination. In order to determine the presence of metastases in distant organs, abdominal ultrasound, pelvis and retroperitoneal space, chest CT , PET-CT are used. To detect bone metastases, scintigraphy is indicated.
- Clinical tests. Changes in peripheral blood are nonspecific (leukocytosis, anemia, increased markers of systemic inflammation – ESR, CRP, fibrinogen), so they are not decisive in making a diagnosis, but they allow you to assess the patient’s condition before prescribing treatment. There are no specific cancer markers for the detection of lymphangiosarcoma.
Treatment
The choice of therapeutic tactics depends on the age of the patient, the causes of tumor formation, its local prevalence and the presence of distant metastases. The treatment regimen for lymphangiosarcoma is developed collectively by specialists-oncologists, chemotherapists, radiologists. The combination of a surgical approach with conservative antitumor therapy is considered the most effective. The main stages include:
- Removal of the affected limb. With lymphangiosarcoma, early wide excision of all pathologically altered tissues is indicated. The operation of choice is amputation or exarticulation of the limb. Despite the crippling nature, such surgical interventions contribute to an increase in the life expectancy of such patients.
- Radiation therapy. It can be performed both at the preoperative stage to reduce the prevalence of the tumor, and after surgery to destroy the remaining malignant cells. In order to prevent the lymphogenic spread of metastases, irradiation of regional lymph nodes is indicated.
- Drug therapy. It is usually prescribed in the presence of distant metastases. Doxorubicin, paclitaxel, and ifosfamide have proven antitumor activity against neoplasms. At the moment, a number of studies are being conducted to evaluate the effectiveness of immunotherapy with monoclonal antibodies acting on PD1 and CTLA4 receptors. This method of treatment is aimed at activating and strengthening its own immune response against tumor cells.
Prognosis and prevention
The prognosis for lymphangiosarcoma is unfavorable. This tumor is highly malignant and rapidly metastasizes. Deaths are most often caused by damage to the lungs, liver and other organs. The five-year survival rate with timely diagnosis and the full scope of treatment varies between 15-20%. The average life expectancy from the moment of diagnosis is 6-9 months. Prevention is divided into primary and secondary. Primary includes the diagnosis of neoplasms at an early stage and timely comprehensive treatment. Secondary is indicated in the presence of chronic edema of the limb and consists in conducting physical therapy and light massage to stimulate lymph outflow.