Stewart–Treves syndrome is a

lymphangiosarcoma Lymphangiosarcoma is a rare cancer which occurs in long-standing cases of primary or secondary lymphedema (swelling due to lymphatic system obstruction). It involves either the upper or lower lymphedematous extremities but is most common in upper ...

, a rare disorder marked by the presence of an

angiosarcoma Angiosarcoma is a rare and aggressive cancer that starts in the endothelial cells that line the walls of blood vessels or lymphatic vessels. Since they are made from Endothelium, vascular lining, they can appear anywhere and at any age, but older ...

(a malignant tumor of blood or lymph vessels) in a person with chronic (long-term)

lymphedema Lymphedema, also known as lymphoedema and lymphatic edema, is a condition of localized edema, swelling caused by a compromised lymphatic system. The lymphatic system functions as a critical portion of the body's immune system and returns inters ...

. Although it most commonly refers to

malignancies Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not ...

associated with chronic lymphedema resulting from

mastectomy Mastectomy is the medical term for the surgical removal of one or both breasts, partially or completely. A mastectomy is usually carried out to treat breast cancer. In some cases, women believed to be at high risk of breast cancer choose to have ...

and/or

radiotherapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle ...

for

breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

, it may also describe

s that result from congenital and other causes of chronic secondary

Lymphangiosarcoma Lymphangiosarcoma is a rare cancer which occurs in long-standing cases of primary or secondary lymphedema (swelling due to lymphatic system obstruction). It involves either the upper or lower lymphedematous extremities but is most common in upper ...

arising from cancer-related

has become much less common with better surgical techniques,

radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...

, and conservative treatment. The prognosis, even with wide surgical excision and subsequent radiotherapy, is poor.

Signs and Symptoms

usually occurs many years following a

, usually between 5 and 15 years. Cutaneous angiosarcoma can begin as a "spreading bruise" or a raised purple-red

papule A papule is a small, well-defined bump in the skin lesion, skin. It may have a rounded, pointed or flat top, and may have a umbilication, dip. It can appear with a Peduncle (anatomy), stalk, be thread-like or look warty. It can be soft or firm a ...

before progressing to tissue infiltration,

edema Edema (American English), also spelled oedema (British English), and also known as fluid retention, swelling, dropsy and hydropsy, is the build-up of fluid in the body's tissue (biology), tissue. Most commonly, the legs or arms are affected. S ...

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

fungation,

ulceration An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected Organ (biology), organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caus ...

, and even

hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, ...

as tumor size increases. The second most frequent location is in a lymphedematous upper extremity secondary to

radical mastectomy Radical mastectomy is a surgical procedure that treats breast cancer by removing the breast and its underlying chest muscle (including pectoralis major and pectoralis minor), and lymph nodes of the axilla (armpit). Breast cancer is the most commo ...

. This is known as the "Stewart Treves tumor".

Lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by injury or diseases. The term ''Lesion'' is derived from the Latin meaning "injury". Lesions may occur in both plants and animals. Types There is no de ...

s range in size from 3 to 6 cm on average, although untreated

s can grow to 20 cm or more. Severe persistent

of an upper extremity is common in Stewart-Treves syndrome patients and is often the first sign. In patients who underwent a

initially appears on the arm of the side operated on. The

edematous Edema (American English), also spelled oedema (British English), and also known as fluid retention, swelling, dropsy and hydropsy, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may inclu ...

area spreads from the arm to the forearm and the dorsal side of the hand and fingers. Pain is initially absent, though skin distention may cause local discomfort. Recurrent

erysipelas Erysipelas () is a relatively common bacterial infection of the superficial layer of the skin ( upper dermis), extending to the superficial lymphatic vessels within the skin, characterized by a raised, well-defined, tender, bright- red rash, ...

may occur in sites with long-standing chronic

. Stewart-Treves syndrome

lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by injury or diseases. The term ''Lesion'' is derived from the Latin meaning "injury". Lesions may occur in both plants and animals. Types There is no de ...

s often present as several reddish blue

macules A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this sys ...

nodules Nodule may refer to: *Nodule (geology), a small rock or mineral cluster *Manganese nodule, a metallic concretion found on the seafloor *Nodule (medicine), a small aggregation of cells *Root nodule Root nodules are found on the roots of plants, p ...

that may develop polypoid. Small satellite areas can form around these areas and become confluent, producing a growing

. A

bullous A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this sys ...

component is occasionally visible. As the

grows and spreads, the overlying atrophic

epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and Subcutaneous tissue, hypodermis. The epidermal layer provides a barrier to infection from environmental pathogens and regulates the ...

may

ulcerate Ulcerate is a New Zealand-based extreme metal band formed by guitarist Michael Hoggard and drummer Jamie Saint Merat in 2000. The band have released seven studio albums to date. The band have been featured in numerous articles as one of New Ze ...

, resulting in repeated episodes of

bleeding Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethr ...

and

infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

. Advanced cutaneous tumors may exhibit

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who i ...

Cause

Angiosarcoma Angiosarcoma is a rare and aggressive cancer that starts in the endothelial cells that line the walls of blood vessels or lymphatic vessels. Since they are made from Endothelium, vascular lining, they can appear anywhere and at any age, but older ...

is found to occur in 0.07% to 0.45% of people who survive at least 5 years after a

. Although the majority of Stewart-Treves syndrome-related

s are caused by post-mastectomy

development has been linked to persistent

of any origin. The precise mechanism underlying persistent

and

remains unknown. Stewart and Treves proposed that a systemic

carcinogen A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruse ...

ic component was to blame for this process. It has also been proposed that lymphedematous areas undergo

neoplastic A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

change with the establishment of

collateral circulation Collateral circulation is the alternate Circulatory system, circulation around a blocked blood vessel, artery or vein via another path, such as nearby minor vessels. It may occur via preexisting vascular redundancy (analogous to redundancy (engi ...

. Other hypotheses include a

malignant transformation Malignant transformation is the process by which cells acquire the properties of cancer. This may occur as a primary process in normal tissue, or secondarily as ''malignant degeneration'' of a previously existing benign tumor. Causes There are ...

caused by lymphatic drainage blockage and decreased

antigen presentation Antigen presentation is a vital immune process that is essential for T cell immune response triggering. Because T cells recognize only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen fragment can ...

, resulting in

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

evading immune monitoring at an "

immunologically privileged site Certain sites of the mammalian body have immune privilege (no immune response), meaning they are able to tolerate the introduction of antigens without eliciting an inflammatory immune response. Tissue grafts are normally recognised as foreign ant ...

." Although this syndrome was first described in patients following a

, it can also occur in the context of

congenital A birth defect is an abnormal condition that is present at childbirth, birth, regardless of its cause. Birth defects may result in disability, disabilities that may be physical disability, physical, intellectual disability, intellectual, or dev ...

hereditary Heredity, also called inheritance or biological inheritance, is the passing on of traits from parents to their offspring; either through asexual reproduction or sexual reproduction, the offspring cells or organisms acquire the genetic inform ...

lymphatic Lymph () is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues to be recirculated. At the origi ...

malformations such as

Turner syndrome Turner syndrome (TS), commonly known as 45,X, or 45,X0,Also written as 45,XO. is a chromosomal disorder in which cells of females have only one X chromosome instead of two, or are partially missing an X chromosome (sex chromosome monosomy) lea ...

Noonan syndrome Noonan syndrome (NS) is a genetic disorder that may present with mildly unusual facial features, short height, congenital heart disease, bleeding problems, and skeletal malformations. Facial features include widely spaced eyes, light-colored ...

, Milroy disease, lymphedema praecox, and lymphedema tarda. Chronic

s, chronic

venous stasis Venous stasis, or venostasis, is a condition of slow blood flow in the veins, usually of the legs. Presentation Complications Potential complications of venous stasis are: * Venous ulcers * Blood clot formation in veins (venous thrombosis), tha ...

morbid obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

malignant Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malig ...

obstruction, and

surgical procedures Many surgical procedure names can be broken into parts to indicate the meaning. For example, in gastrectomy, "ectomy" is a suffix meaning the removal of a part of the body. "Gastro-" means stomach. Thus, ''gastrectomy'' refers to the surgical rem ...

that disrupt

flow.

Diagnosis

Despite the fact that Stewart-Treves syndrome is also known as

, ultrastructural and immunohistologic investigations demonstrate that this cancer is caused by blood

arteries An artery () is a blood vessel in humans and most other animals that takes oxygenated blood away from the heart in the systemic circulation to one or more parts of the body. Exceptions that carry deoxygenated blood are the pulmonary arteries in ...

rather than

lymphatic vessel The lymphatic vessels (or lymph vessels or lymphatics) are thin-walled vessels (tubes), structured like blood vessels, that carry lymph. As part of the lymphatic system, lymph vessels are complementary to the cardiovascular system. Lymph vessel ...

s. The immunohistologic and ultrastructural results listed below can be utilized to confirm that the tumor is derived from blood vessels: *

Antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...

against

factor VIII Coagulation factor VIII (Factor VIII, FVIII, also known as anti-hemophilic factor (AHF)) is an essential blood clotting protein. In humans, it is encoded by ''F8'' gene. Defects in this gene result in hemophilia A, an X-linked bleeding disorder ...

-related antigen are

endothelial cell The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and th ...

markers. *

CD34 antigen CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species. CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first descr ...

is a vascular

marker that does not react with

endothelial cells The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the res ...

. * Antikeratin antibodies reveal no evidence of

keratin Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. It is the key structural material making up Scale (anatomy), scales, hair, Nail (anatomy), nails, feathers, horn (anatomy), horns, claws, Hoof, hoove ...

in this

, confirming that the

tumor cells A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

are not

epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

in origin. * Positive staining for

laminin Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major constituents of the basement membrane, namely the basal lamina (the protein network foundation for most cells and organs). Laminins are vital to bi ...

CD31 Platelet endothelial cell adhesion molecule (PECAM-1) also known as cluster of differentiation 31 (CD31) is a protein that in humans is encoded by the ''PECAM1'' gene found on chromosome 17, chromosome17q23.3. PECAM-1 plays a key role in removi ...

collagen IV Collagen IV (ColIV or Col4) is a type of collagen found primarily in the basal lamina. The collagen IV C4 domain at the C-terminus is not removed in post-translational processing, and the fibers link head-to-head, rather than in parallel. Also, ...

, and

vimentin Vimentin is a structural protein that in humans is encoded by the ''VIM'' gene. Its name comes from the Latin ''vimentum'' which refers to an array of flexible rods. Vimentin is a Intermediate filament#Type III, type III intermediate filamen ...

can help identify

Magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...

is recommended to assess the local extent of

s. In patients with chronic

identified by

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...

within the

should be assessed for Stewart-Treves syndrome. In patients with chronic

fluorodeoxyglucose []Fluorodeoxyglucose (International Nonproprietary Name, INN), or fluorodeoxyglucose F 18 (United States Adopted Name, USAN and United States Pharmacopeia, USP), also commonly called fluorodeoxyglucose and abbreviated []FDG, 2-[]FDG o ...

(FDG) CT scan, PET/CT scanning may show tumor spread, including Metastasis, metastases, and detect probable

change.

Treatment

The treatment of choice is a large resection or

amputation Amputation is the removal of a Limb (anatomy), limb or other body part by Physical trauma, trauma, medical illness, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as cancer, malign ...

of the affected limb.

Radiation therapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a therapy, treatment using ionizing radiation, generally provided as part of treatment of cancer, cancer therapy to either kill or control the growth of malignancy, malignant cell (biology), ...

can precede or follow surgical treatment.

Tumors A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

that have advanced locally or have

metastasized Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

can be treated with mono or polychemotherapy, systemically or locally. However,

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

and

have not been shown to improve survivorship significantly. In cases of upper limbs, forequarter amputation (disarticulation of upperlimb along with

clavicle The clavicle, collarbone, or keybone is a slender, S-shaped long bone approximately long that serves as a strut between the scapula, shoulder blade and the sternum (breastbone). There are two clavicles, one on each side of the body. The clavic ...

and

scapula The scapula (: scapulae or scapulas), also known as the shoulder blade, is the bone that connects the humerus (upper arm bone) with the clavicle (collar bone). Like their connected bones, the scapulae are paired, with each scapula on either side ...

) is preferred.

Prognosis

Early detection is key. Prognosis is generally poor, and the 5 year survival rate of patients with

is less than 5%.

Incidence

In the 1960s, the incidence five years after a

varied from 0.07% to 0.45%. Today, it occurs in 0.03% of patients surviving 10 or more years after radical

History

Stewart-Treves syndrome was first documented in 1948, when Drs. Fred Stewart and

Norman Treves Norman or Normans may refer to: Ethnic and cultural identity * The Normans, a people partly descended from Norse Vikings who settled in the territory of Normandy in France in the 9th and 10th centuries ** People or things connected with the Norma ...

reported a case series detailing six patients with

who had chronic

following a

References

External links

{{DEFAULTSORT:Stewart-Treves syndrome Breast cancer Vascular diseases Vascular-related cutaneous conditions Syndromes affecting the breast