Paget's disease is a dangerous pathology in which the restoration of bone tissue slows down, and an abnormal formation appears in its place. The disease can progress on any bones of the human skeleton and usually affects 3 or more bones. In the absence of timely diagnosis and prompt access to qualified medical help, treatment will be extremely difficult and will require a very long period of time.
Causes of the disease and risk factors
Paget cells, from which malignant tumors develop, are glandular cells derived from the epithelium of the milk ducts. The main theories of Paget's cancer development are epidermotropic and in situ transforming theories.
The epidermotropic theory, to which oncologists are more often inclined, is based on conclusions demonstrating that in the vast majority of cases Paget's disease occurs against the background of other forms of breast cancer (BC). According to this theory, cancer cells move along the milk ducts from the primary tumor to the nipple, where they attach and divide.
The transformative theory explains the development of Paget's cancer by spontaneous malignancy of epithelial cells of the nipple and areola. This is confirmed by the fact that in a certain percentage of patients with Paget's disease, no other breast tumors were found.
Risk factors:
- hereditary predisposition (often typical for cases of the disease in men);
- age over 60 years;
- excess weight;
- alcohol abuse;
- injuries and damage to the nipple;
- hormonal imbalances - early puberty, late menopause, infertility;
- concomitant diseases – scleroderma, cervical cancer;
- taking hormonal medications;
- contact with carcinogens (chemicals, radiation).
Causes of thrombosis in the superior vena cava system
– basically the same as other venous thromboses. It may also develop as a complication of venous catheterization (cubital, subclavian catheter), sometimes arising as a result of prolonged compression or uncomfortable position of the upper limb (for example, during sleep).
The most common is thrombosis of the axillary or subclavian vein (Paget-Schrötter syndrome). Within 24 hours, swelling of the entire upper limb occurs with cushion-like swelling of the hand. There may be slight bursting pain. The color of the limb is unchanged or slightly cyanotic.
Symptoms of the disease
In the first stages of Paget's cancer, symptoms appear that are similar to skin diseases and manifestations of allergies, to which patients often do not attach much importance. This:
- changes in pigmentation of the nipple and areola;
- slight roughening and/or flaking of the skin, itching;
- discomfort when touched, increased sensitivity, slight pain in the affected area.
Often patients use ointments or compresses to relieve symptoms and do not consult a doctor, thereby worsening the prognosis of the disease. It is very important when the first, even nonspecific signs appear, to visit a doctor and undergo the necessary examination to make a diagnosis. Early diagnosis gives a chance for successful treatment and absence of relapses.
As the disease progresses, the following symptoms appear:
- swelling, increase in the size and shape of the nipples;
- increased pain, inflammation;
- discharge from the nipples is purulent, possibly containing blood;
- the formation of ulcers, erosions, crusts, when removed, a weeping surface is exposed;
- enlarged axillary lymph nodes;
- feeling unwell, weakness, fever.
In the later stages, retraction of the nipple is noted, but most often it flattens (the result of the growth of the underlying tumor) Source: Pogodina E.M. Paget's breast cancer / E.M. Pogodina [and others] // 2006. - No. 1. - pp. 65-70..
Deep vein thrombosis
– a more severe illness, usually requiring the patient to stay in a hospital.
There are deep vein thrombosis of the leg, popliteal vein, femoral vein, iliofemoral (ileofemoral) thrombosis. Often there is damage to thrombosis of several sections (for example, the popliteal and femoral veins, deep veins of the leg and popliteal vein, etc.).
Deep vein thrombosis manifests itself primarily as swelling and moderate pain. Moreover, the higher the level of thrombosis, the more pronounced the edema. Thus, with thrombosis of the deep veins of the leg, there may be moderate swelling of the leg, sometimes the swelling is so insignificant that it is detected only when measuring the circumference of the leg (compared to the healthy leg). With thrombosis of the femoral or iliac (continuation of the femoral) veins, the entire leg, up to the groin, and in severe cases, the lower part of the abdominal wall swells.
In the photo - the left lower limb is cyanotic, thickened to the groin - deep vein thrombosis at the level of the iliofemoral segment (ileofemoral thrombosis).
Thrombosis, as a rule, is unilateral, so only one leg swells. Bilateral edema is observed with thrombosis of the inferior vena cava, deep vein thrombosis in both legs (which is quite rare).
Another symptom of thrombosis is pain. It is usually moderately expressed, pulling, sometimes bursting, is relatively constant in nature, and can intensify in a standing position. In case of deep vein thrombosis of the leg, the Homans, Lowenberg, Luvellubri, Meyer, Payra symptoms are positive.
With deep vein thrombosis, there may also be a slight increase in temperature, increased venous pattern, etc.
Paget's classification of cancer
The disease is classified according to its forms, stages, location, and occurrence simultaneously with other types of breast cancer.
Forms of the disease:
- psoriatic – there are small pink papules covered with dry whitish scales;
- ulcerative - the presence of ulcerations in the form of a crater;
- tumor – the neoplasm is located in the thickness of the mammary gland;
- acute eczematoid - characterized by a weeping, fine-grained rash, ulcerations on the nipple;
- chronic eczematoid - crusts form, when they are separated, a weeping area is exposed;
- Paget's pigmented carcinoma.
Sometimes Paget's disease develops extramammary - outside the mammary gland, in areas of the body that have apocrine sweat glands (perineum and vulva in women, scrotum and penis in men).
Stages of the disease according to TNM classification:
| 0 | the tumor is localized within the tissue from which it originated and does not grow into adjacent tissues |
| I | tumor size up to 2 cm, no metastases to nearby lymph nodes and distant organs |
| II | tumor from 2 to 5 cm, metastases are possible in the lymph nodes on the affected side, which are not fused to each other and the underlying tissues |
| IIIA | tumor more than 5 cm, metastases in lymph nodes fused to each other and to the underlying tissues |
| IIIB | the primary tumor invades surrounding tissue |
| IV | there are distant metastases, the primary tumor can be of any size |
In half of the cases, Paget's cancer is located within the nipple and areola. In 40% of patients, to the manifestations in this area is added a tumor palpated in the parapapillary zone. In 10%, the disease is detected by cytological analysis of a smear of discharge from the mammary gland before the appearance of visual symptoms.
Clinical recommendations of the Ministry of Health of the Russian Federation contain the following Paget classification of cancer:
- isolated;
- in combination with intraductal breast cancer;
- in combination with infiltrating ductal carcinoma.
In the majority (67-100%) of cases of breast cancer, the nipple is combined with intraductal carcinoma of the mammary gland. Isolated nipple damage is less common (7-8%) Source: Nikitina E.A. Paget's cancer of the breast (literature review) / E.A. Nikitina [et al.] // Tumors of the female reproductive system. - 2021. - No. 4. - pp. 37-46..
Diagnosis of Paget's cancer
The first signs of the disease are a reason to visit a mammologist or oncologist. The doctor will conduct a thorough collection of the patient’s life and illness history, a general examination, palpation of the breast, and prescribe the necessary studies. To make a diagnosis of Paget's disease, the following are prescribed:
- mammography;
- breast ultrasound;
- CT scan;
- tumor biopsy followed by cytological analysis of the contents;
- cytological examination of a smear.
To detect metastases in the lymph nodes and distant metastases, ultrasound of the lymph nodes, biopsy of sentinel lymph nodes, radiography, computed tomography of bones and various organs, and scintigraphy are performed.
Since Paget's disease has similar symptoms to other diseases, a careful differential diagnosis is necessary. Oncopathology should be differentiated from the following conditions:
- dermatitis and eczema of the nipples;
- psoriasis;
- herpes;
- breast tuberculosis;
- syphilis;
- mycosis fungoides;
- melanoma;
- superficial basalioma.
Treatment of Paget's cancer
The main method of treatment is removal of the mammary gland followed by remote gammatherapy, chemotherapy or hormone therapy. Sometimes radiation is given before surgery to reduce the size of the tumor and reduce the area of intervention.
In the early stages, removal of the nipple-areola complex and the neoplasm with part of the affected gland is indicated. For non-invasive cancer at later stages, a simple mastectomy is performed - removal of the mammary gland with a section of the pectoralis minor muscle. Invasive Paget's cancer is an indication for extended mastectomy: removal of the breast with muscles, subcutaneous fat and lymph nodes.
Subsequently, reconstructive mammoplasty is recommended for patients.
Disease prognosis and prevention
The prognosis of Paget's cancer depends on timely diagnosis and treatment. The success of therapy is influenced by the stage at which the tumor is detected, the presence of affected lymph nodes and their number, morphological signs of the tumor, its aggressiveness, and the patient’s age. Often the disease is detected in late stages due to the nonspecificity of symptoms, and this type of cancer is quite aggressive, so there is a risk of relapses.
The average life expectancy for Paget's disease is three years; in the presence of metastases and an infiltrative component, it decreases to 1 year.
There is no specific prevention of the disease. To detect cancer early, you should periodically perform breast self-examination and consult a doctor if even minor symptoms appear.
Sources:
- Vavilov A.M. Clinical and morphological diagnosis of Paget’s disease / A.M. Vavilov, O.R. Katunina // Almanac of Clinical Medicine. — 2006.
- Kolobukhov A.E. Paget's cancer of the breast: treatment results / A.E. Kolobukhov [et al.] // International reviews: clinical practice and health. — 2021. — No. 2. — P. 42-47.
- Nikitina E.A. Paget's cancer of the breast (literature review) / E.A. Nikitina [et al.] // Tumors of the female reproductive system. - 2016. - No. 4. — P. 37-46.
- Pogodina E.M. Paget's breast cancer / E.M. Pogodina [and others] // 2006. - No. 1. — P. 65-70.
- Pogodina E.M. Paget's cancer of the breast: clinical picture, diagnosis, treatment / E.M. Pogodin // Bulletin of the Russian Cancer Research Center named after. N.N. Blokhin RAMS. — 1995.
- Fetisova E.Yu. Surgical approaches to the treatment of patients with Paget's cancer / Fetisova E.Yu. [and others] // Tumors of the female reproductive system. - 2015. - No. 2. — P. 35-39.
The information in this article is provided for reference purposes and does not replace advice from a qualified professional. Don't self-medicate! At the first signs of illness, you should consult a doctor.
Superficial vein thrombosis
ATTENTION! Deep vein thrombosis is dangerous due to the detachment of a blood clot and its migration into the pulmonary artery (pulmonary embolism), which most often leads to serious consequences or instant death!
Superficial veins are affected by thrombosis most often with varicose veins. Blockage of the vessel is accompanied by inflammation of the surrounding tissues. That is why the terms “thrombophlebitis” (phlebitis - inflammation of a vein), “varicothrombophlebitis” (inflammation of varicose veins) are used for this type of thrombosis.
Usually, in the area of varicose veins on the lower leg, pain and redness appear along the vein; in the area of redness, the vein itself is palpated as a dense, painful “cord”. There may be a slight increase in body temperature. In general, thrombophlebitis of the superficial veins is not dangerous; there is no detachment of a blood clot with pulmonary embolism (with the exception of inflammation of the great saphenous vein on the thigh and the small saphenous vein in the popliteal region, this will be discussed below). With adequate treatment, the inflammatory phenomena subside, and the patency of the veins is partially or completely restored over time.
The great saphenous vein (GSV) runs under the skin from the ankle joint along the inner surface of the leg to the groin fold. In the groin it flows into the deep femoral vein. That is why thrombophlebitis of the GSV is dangerous due to the transition of thrombosis from the superficial (GSV) to the deep (femoral) vein - ascending thrombophlebitis of the GSV. But thrombosis of the femoral vein is dangerous due to the detachment of a blood clot and pulmonary embolism. Therefore, if there are signs of GSV thrombosis (redness, pain along the inner surface of the thigh), you should urgently consult a surgeon or call an ambulance. Such patients are hospitalized and, if there is a threat of thrombosis spreading to the femoral vein, the GSV is ligated closer to the groin - this is a simple operation under local anesthesia.
A similar situation, but much less frequently, occurs with thrombophlebitis of the small saphenous vein (SSV). It runs along the back of the leg and drains into the popliteal (deep) vein in the popliteal fossa.
