What is Paget’s disease

Pagets disease of the breast is named after the 19th century British doctor Sir James Paget, who, in 1874, noted a relationship between changes in the nipple and breast cancer. Several other diseases are named after Sir James Paget, including Paget’s disease of bone and extramammary Paget’s disease, which includes Paget’s disease of the vulva and Paget’s disease of the penis. These other diseases are not related to Paget’s disease of the breast.

Paget’s disease of the breast

Paget disease of the breast also known as Paget disease of the nipple and mammary Paget disease, is a rare type of cancer involving the skin of the nipple and usually, the darker circle of skin around it, which is called the areola. Most people with Paget disease of the breast also have one or more tumors inside the same breast. These breast tumors are either ductal carcinoma in situ or invasive breast cancer ¹.

Paget disease of the breast is named after the 19th century British doctor Sir James Paget, who, in 1874, noted a relationship between changes in the nipple and breast cancer. Several other diseases are named after Sir James Paget, including Paget disease of bone and extramammary Paget disease, which includes Paget disease of the vulva and Paget disease of the penis. These other diseases are not related to Paget disease of the breast.

Malignant cells known as Paget cells are a telltale sign of Paget disease of the breast. These cells are found in the epidermis (surface layer) of the skin of the nipple and the areola. Paget cells often have a large, round appearance under a microscope; they may be found as single cells or as small groups of cells within the epidermis.

Figure 1. Paget’s disease of the breast

Footnote: (a and b) Paget’s disease of the nipple. The clinical appearance is usually a thickened, eczematoid crusted lesion with irregular borders. (c) Scaly, erythematous, crusty pigmentation and thickened plaques on the nipple, spreading to the surrounding areolar areas. (d) Advanced lesions show skin thickening, redness, erythema, erosion of the nipple and scaling around the nipple-areola.

[Source ²]

Who gets Paget’s disease of the breast?

Paget’s disease of the breast occurs in both women and men, but most cases occur in women. Approximately 1 to 4 percent of all cases of breast cancer also involve Paget’s disease of the breast. The average age at diagnosis is 57 years, but the disease has been found in adolescents and in people in their late 80s ³.

Paget’s disease of the breast symptoms

The symptoms of Paget’s disease of the breast are often mistaken for those of some benign skin conditions, such as dermatitis or eczema ⁴. These symptoms may include the following:

• Itching, tingling, or redness in the nipple and/or areola
• Flaking, crusty, or thickened skin on or around the nipple
• A flattened nipple
• Discharge from the nipple that may be yellowish or bloody

Because the early symptoms of Paget’s disease of the breast may suggest a benign skin condition, and because the disease is rare, it may be misdiagnosed at first. People with Paget’s disease of the breast have often had symptoms for several months before being correctly diagnosed.

Paget’s disease of the breast causes

Doctors do not fully understand what causes Paget’s disease of the breast. The most widely accepted theory is that cancer cells from a tumor inside the breast travel through the milk ducts to the nipple and areola. This would explain why Paget’s disease of the breast and tumors inside the same breast are almost always found together ⁴.

A second theory is that cells in the nipple or areola become cancerous on their own ⁴. This would explain why a few people develop Paget’s disease of the breast without having a tumor inside the same breast. Moreover, it may be possible for Paget’s disease of the breast and tumors inside the same breast to develop independently ⁴.

Paget’s disease of the breast diagnosis

A nipple biopsy allows doctors to correctly diagnose Paget’s disease of the breast. There are several types of nipple biopsy, including the procedures described below.

• Surface biopsy: A glass slide or other tool is used to gently scrape cells from the surface of the skin.
• Shave biopsy: A razor-like tool is used to remove the top layer of skin.
• Punch biopsy: A circular cutting tool, called a punch, is used to remove a disk-shaped piece of tissue.
• Wedge biopsy: A scalpel is used to remove a small wedge of tissue.

In some cases, doctors may remove the entire nipple ⁴. A pathologist then examines the cells or tissue under a microscope to look for Paget cells.

Most people who have Paget’s disease of the breast also have one or more tumors inside the same breast. In addition to ordering a nipple biopsy, the doctor should perform a clinical breast exam to check for lumps or other breast changes. As many as 50 percent of people who have Paget’s disease of the breast have a breast lump that can be felt in a clinical breast exam. The doctor may order additional diagnostic tests, such as a diagnostic mammogram, an ultrasound exam, or a magnetic resonance imaging scan to look for possible tumors ⁴.

Paget’s disease of the breast treatment

For many years, mastectomy, with or without the removal of lymph nodes under the arm on the same side of chest (known as axillary lymph node dissection), was regarded as the standard surgery for Paget’s disease of the breast ⁵. This type of surgery was done because patients with Paget’s disease of the breast were almost always found to have one or more tumors inside the same breast. Even if only one tumor was present, that tumor could be located several centimeters away from the nipple and areola and would not be removed by surgery on the nipple and areola alone ⁴.

Studies have shown, however, that breast-conserving surgery that includes removal of the nipple and areola, followed by whole-breast radiation therapy, is a safe option for people with Paget’s disease of the breast who do not have a palpable lump in their breast and whose mammograms do not reveal a tumor ⁵.

People with Paget’s disease of the breast who have a breast tumor and are having a mastectomy should be offered sentinel lymph node biopsy to see whether the cancer has spread to the axillary lymph nodes. If cancer cells are found in the sentinel lymph node(s), more extensive axillary lymph node surgery may be needed ⁶. Depending on the stage and other features of the underlying breast tumor (for example, the presence or absence of lymph node involvement, estrogen and progesterone receptors in the tumor cells, and HER2 protein overexpression in the tumor cells), adjuvant therapy, consisting of chemotherapy and/or hormonal therapy, may also be recommended.

Paget’s disease of the breast prognosis

The prognosis, or outlook, for people with Paget’s disease of the breast depends on a variety of factors, including the following:

• Whether or not a tumor is present in the affected breast
• If one or more tumors are present in the affected breast, whether those tumors are ductal carcinoma in situ or invasive breast cancer
• If invasive breast cancer is present in the affected breast, the stage of that cancer

The presence of invasive cancer in the affected breast and the spread of cancer to nearby lymph nodes are associated with reduced survival.

According to National Cancer Institute’s Surveillance, Epidemiology, and End Results program, the 5-year relative survival for all women in the United States who were diagnosed with Paget disease of the breast between 1988 and 2001 was 82.6 percent. This compares with a 5-year relative survival of 87.1 percent for women diagnosed with any type of breast cancer. For women with both Paget’s disease of the breast and invasive cancer in the same breast, the 5-year relative survival declined with increasing stage of the cancer (stage I, 95.8 percent; stage II, 77.7 percent; stage III, 46.3 percent; stage IV, 14.3 percent) ⁷, ⁸.

Paget’s disease of bone

Paget’s disease of bone causes your bones to grow too large and weak. They also might break easily. Paget’s disease of bone is a chronic disorder that can result in enlarged and misshapen bones. Paget’s disease of bone can lead to other health problems, too, such as arthritis and hearing loss. You can have Paget’s disease in any bone, but it is most common in the spine, pelvis, skull, and legs. Paget’s disease of bone might affect one or several bones, but not your entire skeleton. More men than women have Paget’s disease of bone. Paget’s disease of bone is most common in older people.

The excessive breakdown and formation of bone tissue causes affected bone to weaken—resulting in bone pain, misshapen bones, fractures, and arthritis in the joints near the affected bones. Paget’s disease of bone typically is localized, affecting just one or a few bones, as opposed to osteoporosis, for example, which affects all the bones in the body.

Scientists do not know for sure what causes Paget’s disease of bone. In some cases, a virus might be responsible. In most cases, however, scientists suspect that environmental factors play a role. For example, scientists are studying the possibility that a slow-acting virus may cause Paget’s disease. In some cases, Paget’s disease of bone tends to run in families and so far two genes have been identified that predispose affected people to develop Paget’s disease.

Paget’s disease of bone is more common in older people and those of northern European heritage. Research suggests that a close relative of someone with Paget’s disease is seven times more likely to develop the disease than someone without an affected relative.

Many people do not know they have Paget’s disease of bone because they have no symptoms or their symptoms are mild. Sometimes the symptoms may be confused with those of arthritis or other disorders. In other cases, the diagnosis is made only after the patient has developed complications. For others, symptoms can include:

• Persistent bone or joint pain
• Enlarged bones – deformities in any of your bones
• Broken bones
• Damaged cartilage in joints
• Symptoms of a nerve problem, such as numbness, tingling or loss of movement

Paget’s disease of bone can sometimes lead to further, potentially serious problems.

These include:

• Broken bones (fractures). Fragile bones that break more easily than normal
  
• Arthritis. Long bones in the leg may bow, distorting alignment and increasing pressure on nearby joints. In addition, pagetic bone may enlarge, causing joint surfaces to undergo excessive wear and tear. In these cases, pain may be caused by a combination of Paget’s disease of bone and osteoarthritis.
• Hearing loss. Loss of hearing in one or both ears may occur when Paget’s disease of bone affects the skull and the bone that surrounds the inner ear. Treating Paget’s disease of bone may slow or stop hearing loss. Hearing aids also may help.
• Heart problems. In severe Paget’s disease of bone, the heart works harder to pump blood to affected bones. This usually does not result in heart failure except in some people who also have hardening of the arteries.
• Kidney stones. Kidney stones are more common in patients with Paget’s disease of bone due to too much calcium in the blood.
• Nervous system problems. Pagetic bone can cause pressure on the brain, spinal cord, or nerves and reduced blood flow to the brain and spinal cord.
• Osteogenic sarcoma. Rarely, Paget’s disease of bone is associated with the development of a malignant tumor of the bone. When there is a sudden onset or worsening of pain, sarcoma should be considered.
• Loose teeth. When Paget’s disease of bone affects the facial bones, the teeth may loosen. This may make chewing more difficult.
• Vision loss. Rarely, when the skull is involved, the nerves to the eye may be affected, causing some loss of vision.

Paget’s disease of bone is not associated with osteoporosis. Although Paget’s disease of bone and osteoporosis can occur in the same patient, they are completely different disorders. Despite their marked differences, several medications for Paget’s disease of bone also are used to treat osteoporosis.

Doctors use blood tests and imaging tests to diagnose Paget’s disease of bone. Early diagnosis and treatment can prevent some symptoms from getting worse. There’s currently no cure for Paget’s disease of bone, but treatment can help relieve the symptoms. Treatments include medicines and sometimes surgery. A good diet and exercise might also help.

If you don’t have any symptoms, your doctor may suggest keeping an eye on your condition and delaying treatment until any problems occur.

The main treatments for Paget’s disease of bone are:

• Bisphosphonate medication – medicines that help control bone regeneration
• Painkillers – usually over-the-counter painkillers such as paracetamol and ibuprofen
• Supportive therapies – including physiotherapy, occupational therapy and devices such as walking sticks or shoe inserts
• Surgery – this may be needed if further problems develop, such as fractures, deformities or severe joint damage

Ensuring you get enough calcium and vitamin D can also help. Some people may need to take supplements.

Figure 2. Paget’s disease of bone

Footnote: Left. Sclerotic expansile scapula. Midlle skull. Diffuse sclerotic fluffy lesions like cotton wool. Right. Diaphyseal lucent lesion like a blade of grass.

[Source ⁹]

Will my children get Paget’s disease of bone too?

Paget’s disease of bone does not always run in families; however, research suggests that a close relative of someone with Paget’s disease of bone is seven times more likely to develop the disease than someone without an affected relative. Finding and treating Paget’s disease of bone early is important, so some doctors recommend that children and siblings of a person with Paget’s disease be tested for the disease every 2 to 3 years after the age of 40.

To screen for Paget’s disease of bone, a doctor uses the serum alkaline phosphatase (ALP) test. If the serum alkaline phosphatase (ALP) level is high, suggesting that there might be Paget’s disease of bone, the doctor can perform a test called a bone scan to learn which bones may be affected. The doctor will typically order an x ray of the affected bones to make sure the diagnosis of Paget’s disease of bone is correct.

Is there a special diet I should follow for Paget’s disease of bone?

There is no special diet to prevent or help treat for Paget’s disease of bone. For overall bone health, you should eat a balanced diet rich in calcium and vitamin D. The Institute of Medicine of the National Academy of Sciences recommends 1,000 mg (milligrams) of calcium daily for adults age 19 to 50. Women over age 50 and men over age 70 should increase their intake to 1,200 mg daily. To help your body use the calcium, the Institute of Medicine of the National Academy of Sciences recommends 600 International Units (IU) of vitamin D up to age 70 and 800 IU after 70.

What about exercise? Can I still be active?

Exercise is important for people with for Paget’s disease of bone. Being active can help you maintain healthy bones, control your weight, and keep your joints moving. But, you should talk with your doctor before starting an exercise program to make sure what you plan to do is safe and will not put too much stress on the bones that are affected by for Paget’s disease of bone. For example, your doctor might advise you to try walking instead of jogging if you have for Paget’s disease of bone in your legs.

Paget’s disease of bone symptoms

Many patients do not know they have Paget’s disease of bone because they have no symptoms. Sometimes the symptoms may be confused with those of arthritis or other disorders. In other cases, the diagnosis is made only after the patient has developed complications.

Paget’s disease of bone symptoms can include:

• Pain, which can occur in any bone affected by the disease or result from arthritis, a complication that develops in some patients
• Headaches and hearing loss, which may occur when Paget’s disease affects the skull
• Pressure on nerves, which may occur when Paget’s disease affects the skull or spine
• Increased head size, bowing of a limb, or curvature of the spine, which may occur in advanced cases
• Hip pain, which may occur when Paget’s disease affects the pelvis or thighbone.
• Damage to cartilage of joints, which may lead to arthritis.

Any bone or bones can be affected, but Paget’s disease of bone occurs most frequently in the spine, pelvis, legs, or skull. Generally, symptoms progress slowly, and the disease does not spread to normal bones.

Paget’s disease of bone complications

Paget’s disease of bone can sometimes lead to further problems.

The main complications are outlined below.

Broken bones

Bones affected by Paget’s disease of bone tend to be more fragile than normal bone and are more likely to break (fracture) – even after a relatively minor injury.

Signs of a fracture include:

• sudden, severe pain
• swelling or tenderness around the injured area
• bleeding, if the bone has damaged the tissue and skin

It’s not clear whether bisphosphonate medication helps prevent or treat fractures. If you break a bone, you may need surgery to align the broken bones so that they heal correctly.

Bone deformities

It’s common for Paget’s disease of bone to affect the appearance of affected bones.

For example, the condition can cause:

• enlarged or misshapen bones
• the legs to curve outwards (bow legs)
• the spine to curve to the sides (scoliosis)
• the upper back to become very hunched over (kyphosis)

As with fractures, it’s not clear whether bisphosphonates can help prevent deformities. If they do occur, surgery may be carried out to correct them.

Hearing loss

If Paget’s disease of bone affects the skull, there’s a significant risk that it could lead to permanent hearing loss and possibly total deafness.

This can occur as a result of damage to the bones or nerves that connect the ears to the brain.

It’s not known whether treating Paget’s disease of bone helps reduce the risk of losing your hearing, but treatment is usually recommended if the condition is affecting your skull.

Too much calcium in the blood

In rare cases, the increased cycle of bone renewal in Paget’s disease of bone can result in calcium building up in the blood. This is known as hypercalcemia.

It usually only occurs in people who have been confined to bed after an operation or a fracture.

Symptoms of hypercalcaemia can include:

• extreme tiredness
• depression
• drowsiness
• constipation
• new or worsening bone pain

Hypercalcaemia can be treated using medicines to lower blood calcium levels and slow down bone regeneration.

Heart failure

The new bone that forms in people with Paget’s disease of bone often contains more blood vessels than normal bone, which can mean the heart has to work harder to pump blood around the body.

Very occasionally, the heart may not be able to pump enough blood around the body. This is known as heart failure.

Symptoms of heart failure can include:

• shortness of breath
• extreme tiredness and weakness
• swelling in the legs, ankles and feet (oedema)

Heart failure can be treated with medication and in some cases heart surgery.

Bone cancer

Bone cancer is a rare complication of Paget’s disease of bone. It’s estimated to affect between 1 in 100 and 1 in 1,000 people with the condition.

Symptoms of bone cancer are similar to those of Paget’s disease of bone. They can include:

• bone pain
• swelling around the affected bone
• a lump in the affected bone

Osteosarcoma is a very serious type of cancer that can spread to other parts of the body quickly. But if it’s caught early enough, it may be possible to cure it by removing the affected bone.

Paget’s disease of bone causes

Bone cells regenerate in a similar way to skin – old bone is removed and replaced by new bone. This is known as bone remodeling.

Two cells are responsible for this:

• osteoclasts – cells that absorb old bone
• osteoblasts – cells that make new bone

In Paget’s disease of bone, something goes wrong with the osteoclast cells and they start to absorb bone at a much faster rate than usual.

The osteoblasts then try to produce new bone more quickly, but the new bone is larger and weaker than normal.

It’s not clear what triggers this, but you’re at a higher risk if you have a family history of Paget’s disease of bone. You may inherit a genetic fault that means you’re much more likely to develop the condition.

Paget’s disease of bone diagnosis

Paget’s disease of bone is almost always diagnosed using x rays but may be discovered initially by either of the following tests:

• Alkaline phosphatase (ALP) blood test. An elevated level of alkaline phosphatase in the blood can be suggestive of Paget’s disease of bone.
• An X-ray can show whether your bones have become enlarged as a result of Paget’s disease of bone.
• Bone scans. Bone scans are useful in determining the extent and activity of the condition. For this scan, a small amount of a radioactive substance is injected into your blood. This collects in areas where there’s a lot of bone renewal taking place. For this scan, a small amount of a radioactive substance is injected into your blood. This collects in areas where there’s a lot of bone renewal taking place.

If a blood test or bone scan suggests Paget’s disease of bone, the affected bone(s) should be x rayed to confirm the diagnosis.

Early diagnosis and treatment are important to minimize complications. Siblings and children of people with Paget’s disease of bone may wish to have an alkaline phosphatase (ALP) blood test every 2 or 3 years starting around the age of 40. If the alkaline phosphatase level is higher than normal, a bone scan may be used to identify which bone or bones are affected and an x ray of these bones is used to verify the diagnosis of Paget’s disease of bone.

Further tests

Further tests are usually only needed if you have signs of more severe Paget’s disease of bone or your doctor thinks there’s a chance you could have bone cancer (although this is very rare).

In these cases, you may be advised to have a:

• bone biopsy – a sample of bone is removed under anaesthetic so it can be looked at in detail
• computerized tomography (CT) scan – a series of X-rays of the affected bone are taken to create a detailed three-dimensional image
• magnetic resonance imaging (MRI) scan – a type of scan where a strong magnetic field and radio waves are used to create an image of the affected bone

Paget’s disease of bone treatment

Drug therapy

The Food and Drug Administration (FDA) has approved several medications to treat Paget’s disease of bone. The medications work by controlling the excessive breakdown and formation of bone that occurs in the disease. The goal of treatment is to relieve bone pain and prevent progression of the disease. People with Paget’s disease of bone should talk to their doctors about which medication is right for them. It is also important to get adequate calcium and vitamin D through diet and supplements as prescribed by your doctor, except for patients who have had kidney stones.

Bisphosphonates are a class of drugs used to treat a variety of bone diseases. Several bisphosphonates are currently available to treat Paget’s disease of bone. Calcitonin is a naturally occurring hormone made by the thyroid gland. The medication may be appropriate for some patients.

Bisphosphonates

Bisphosphonates are medicines that help regulate bone growth. They work by affecting the cells that absorb old bone (osteoclasts).

There are several bisphosphonates available, including:

• risedronate – a tablet taken once a day for two months
• zoledronate – a one-off injection
• pamidronate – six weekly injections or three fortnightly injections

These can help regulate bone growth and reduce pain for several years at a time. Treatment can be repeated when the effect starts to wear off.

The most common side effect of risedronate is an upset stomach. The main side effects of zoledronate and pamidronate are flu-like symptoms that last a day or two.

If you’re unable to have bisphosphonates, you may need daily injections of another medicine that prevents bone loss called calcitonin.

Painkillers

Over-the-counter painkillers such as paracetamol and ibuprofen can help relieve pain caused by Paget’s disease of bone.

Make sure you read the packet or leaflet before taking painkillers, to check whether they’re suitable for you and to find out how much to take.

If these don’t help reduce your pain, your doctor can prescribe more powerful painkillers.

Supportive therapies

Some people with Paget’s disease of bone benefit from supportive therapies such as physiotherapy or occupational therapy.

These therapies involve exercises and techniques that can help reduce pain, improve movement and make everyday tasks easier.

Devices that reduce the weight placed on the affected bones may also help, such as:

• a walking stick or frame
• orthotics – insoles made of plastic that fit inside your shoe to help support your feet
• braces that support the spine in the correct position

Some therapists also use treatments such as transcutaneous electrical nerve stimulation (TENS) – a method of pain relief involving the use of a mild electrical current. The scientific evidence for TENS isn’t strong, but some people find it helpful.

Surgery

Medical therapy before surgery helps decrease bleeding and other complications. Patients who are having surgery should discuss pretreatment with their doctor. Surgery may be advised for three major complications of Paget’s disease of bone:

• Fractures. Surgery may allow fractures to heal in better position.
• Severe degenerative arthritis (osteoarthritis). Hip or knee replacement may be considered if disability is severe and medication and physical therapy are no longer helpful.
• Bone deformity. Cutting and realigning pagetic bone (a procedure called an osteotomy) may reduce the pain in weight-bearing joints, especially the knees.

Surgery that may be done include procedures to:

• realign the bones after a fracture so that they heal correctly
• remove and replace a damaged joint with an artificial one, such as a hip replacement or knee replacement
• cut and straighten deformed bones
• move bone away from a squashed (compressed) nerve

These operations are usually done under general anaesthetic, so you’ll be asleep and won’t experience any pain while they’re carried out.

Complications resulting from enlargement of the skull or spine may injure the nervous system. However, most neurological symptoms, even those that are moderately severe, can be treated with medication and do not require neurosurgery.

Diet and exercise

There is no special diet to prevent or help treat Paget’s disease of bone. Calcium and vitamin D help keep your bones healthy. If you have Paget’s disease of bone, it’s important to ensure you get enough of these.

You get calcium from your diet. It’s found in foods such as:

• dairy foods – such as milk and cheese
• green leafy vegetables – such as broccoli and cabbage
• soya beans, soya drinks with added calcium and tofu

You get most of your vitamin D from sunlight, although it’s also found in some foods such as oily fish.

According to the Institute of Medicine of the National Academy of Sciences, women age 50 and older and men age 70 and older should get 1,200 mg of calcium and at least 600 IU (International Units) of vitamin D every day to maintain a healthy skeleton. People age 70 and older need to increase their vitamin D intake to 800 IU. People with a history of kidney stones should discuss calcium and vitamin D intake with their doctor.

Exercise is important because it helps preserve skeletal health, prevent weight gain, and maintain joint mobility. Patients should discuss any new exercise program with their doctor before beginning, to avoid any undue stress on affected bones.

Paget’s disease of bone prognosis

The outlook for people diagnosed with Paget’s disease of bone is generally good, particularly if treatment is given before major changes have occurred in the affected bones. Treatment can reduce symptoms but is not a cure. Osteogenic sarcoma, a form of bone cancer, is an extremely rare complication that occurs in less than 1 percent of all patients with Paget’s disease of bone.

Extramammary Paget’s disease

Extramammary Paget’s disease is an uncommon cancer characterized by a chronic eczema-like rash of the skin around the anogenital regions of males and females. Under the microscope extramammary Paget’s disease looks very similar to the more common type of mammary Paget’s disease that occurs on the breast.

In women extramammary Paget’s disease the most common area involved is the vulva. First symptoms are usually itching and burning of of one or more persistent plaques. These may spread to the labia, mons pubis, vagina and thighs. Perianal lesions may extend up into the anal canal.

The location of extramammary Paget disease is useful in predicting the risk of associated cancer. For example, 25-35% of extramammary Paget disease arising near the anus is associated with an underlying colorectal cancer.

Figure 3. Extramammary Paget’s disease

Paget’s disease of the vulva

Paget’s disease of the vulva is a condition in which adenocarcinoma cells (cancer cells) are found in the top layer of the vulvar skin. Up to 25% of patients with vulvar Paget’s disease also have an invasive vulvar adenocarcinoma (in a Bartholin gland or sweat gland). In the remaining patients, the cancer cells are found only in the skin’s top layer and have not grown into the tissues below ¹⁰.

Figure 4. Paget’s disease of vulva

Footnote: Clinical appearance and histological findings of the biopsy specimen. Eczematoid nodules on the vulva was observed (A). Typical full thickness atypia (B), cellular atypia combined with basal Paget cells (C), and pagetoid distribution of Paget cells were observed (D) (H&E: ×100 and ×400).

[Source ¹¹]

How is extramammary Paget’s disease classified?

Extramammary Paget’s disease has been classified into several subtypes:

• Type 1a Primary cutaneous extramammary Paget’s disease arises from apocrine glands within the epidermis (in situ) or underlying skin appendages
• Type 1b Primary cutaneous extramammary Paget’s disease (15-25%) is associated with invasive Paget’s disease or adenocarcinoma in situ.
• Type 2 Extramammary Paget’s disease originates from underlying anal or rectal adenocarcinoma
• Type 3 Extramammary Paget’s disease originates from bladder adenocarcinoma

Sometimes the extramammary Paget’s disease has been present for 10–15 years before evidence of cancer or metastases appear.

Who gets extramammary Paget’s disease?

Extramammary Paget’s disease most commonly occurs in the vulva of women aged between 50–60 years. Extramammary Paget’s disease can also affect males of similar age.

Extramammary Paget’s disease signs and symptoms

The most common symptom of extramammary Paget’s disease is mild to intense itching of a lesion found around the groin, genitalia, perineum or perianal area. Pain and bleeding may occur from scratching lesions that have been around for a long time. Thickened plaques may form that can become red, scaly and crusty. Although they may appear similar to eczema, they fail to clear up with topical steroid creams.

Extramammary Paget’s disease causes

Skin biopsy of the lesion is performed to get an accurate diagnosis of extramammary Paget’s disease as there are several other genital skin diseases that may appear similar. Under microscopy, the presence of Paget cells along with other histological findings confirms diagnosis. Special stains may be necessary to distinguish Paget’s disease from early melanoma (melanoma in situ). See extramammary Paget’s disease pathology.

Further tests may include:

• Evaluation of lymph nodes by ultrasound scan or fine needle aspirate
• Search for other malignancies including PAP smear (cervical smear), pelvic imaging to look for underlying cancer, colonoscopy, mammography.

Extramammary Paget’s disease treatment

Wide local excision, vulvectomy, or if available, margin-controlled surgical excision (Mohs micrographic surgery) is the standard treatment for extramammary Paget’s disease . Paraffin sections are preferred over frozen sections. The margin is sometimes difficult to define particularly when lesions are spread sporadically throughout the anogenital region. Reconstruction may require skin grafting or flap repair.

Recurrence is common (30-50%), so patients should be re-examined every 3 months after surgery for the next 2 years, after which annual follow-ups are recommended. Recurrence generally leads to further surgery.

Non-surgical treatments for recurrent disease may include:

• Radiotherapy
• Laser ablation
• Photodynamic therapy
• 5-fluorouracil cream
• Imiquimod cream

Extramammary Paget’s disease prognosis

Extramammary Paget’s disease has a low mortality. Prognosis depends on underlying cancer, if present.

1. Caliskan M, Gatti G, Sosnovskikh I, et al. Paget’s disease of the breast: the experience of the European Institute of Oncology and review of the literature. Breast Cancer Research and Treatment 2008;112(3):513–521.[↩]
2. Karakas C. Paget’s disease of the breast. J Carcinog [serial online] 2011 [cited 2018 Sep 28];10:31. Available from: http://www.carcinogenesis.com/text.asp?2011/10/1/31/90676[↩]
3. Kanitakis J. Mammary and extramammary Paget’s disease. Journal of the European Academy of Dermatology and Venereology 2007;21(5):581–590.[↩]
4. Harris JR, Lippman ME, Morrow M, Osborne CK, editors. Diseases of the Breast. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2009.[↩][↩][↩][↩][↩][↩][↩]
5. Kawase K, Dimaio DJ, Tucker SL, et al. Paget’s disease of the breast: there is a role for breast-conserving therapy. Annals of Surgical Oncology 2005;12(5):391–397.[↩][↩]
6. Sukumvanich P, Bentrem DJ, Cody HS, et al. The role of sentinel lymph node biopsy in Paget’s disease of the breast. Annals of Surgical Oncology 2007;14(3):1020–1023.[↩]
7. Ries LAG, Eisner MP. Cancer of the Female Breast. In: Ries LAG, Young JL, Keel GE, et al., editors. SEER Survival Monograph: Cancer Survival Among Adults: U.S. SEER Program, 1988–2001, Patient and Tumor Characteristics. Bethesda, MD: National Cancer Institute, SEER Program, 2011. https://seer.cancer.gov/archive/publications/survival/[↩]
8. Chen CY, Sun LM, Anderson BO. Paget disease of the breast: changing patterns of incidence, clinical presentation, and treatment in the U.S. Cancer 2006;107(7):1448–1458.[↩]
9. Paget disease of the bone: a triad of forms. https://radiopaedia.org/cases/paget-disease-of-the-bone-a-triad-of-forms[↩]
10. What Is Vulvar Cancer? https://www.cancer.org/cancer/vulvar-cancer/about/what-is-vulvar-cancer.html[↩]
11. Kim, Sung-Ae et al. “Primary Extramammary Paget’s Disease Combined with Bowen’s Disease in Vulva.” Annals of dermatology (2011).[↩]