Understanding the Lymph System
I thought it would be helpful for readers to understand the lymph system, the anatomy, what it does, and how it helps with immunity.
Listed below are information pages that should be quite helpful and each page has many additional links for more a more in depth study.
Pathology of the Lymph Nodes and Lymphoma
With the advent of better and more effective cancer treatments, the survival rate for all cancers has risen dramatically. With this progress, a new and often misunderstood and misdiagnosed complication has arisen.
Many cancer survivors , having overcome cancer, find themselves with sudden and often unexplained swelling, usually of the arms or of the legs.
This swelling occurs because of one of several factors.
First, the swelling begins after lymph nodes have been removed for cancer biopsies.
Second, the swelling may start as a result of radiation damage to either the lymph nodes and/or the lymph system.
Due to either the removal of lymph nodes or damage to the lymph system, your body is no longer able to rid itself of excess fluids. The fluids collect in the limbs effected and swelling begins.
This swelling is called lymphedema and it can effect either your leg or your arm. The swelling that occurs is permanent, and while it is not curable it is treatable.
Hopefully, in the future with radiological scans becoming more sensitive and with increased use of such techniques such as the small needle biopsy, we can put an end to this epidemic of secondary lymphedema from cancer biopsy.
In the situation of any permanent leg swelling whether the cause is known or unknown, the diagnoses of lymphedema must be considered
There are several groups of people who experience leg or arm swelling from known causes, but it doesn't go away or unknown causes where the swelling can actually get worse as time goes by.
Group One
This group includes those who have had the injuries, infections, insect bites, trauma to the leg, surgeries or reaction to a medication. When this swelling does not go away, and becomes permanent it is called secondary lymphedema.
Group Two
Another extremely large group that experiences permanent leg or arm swelling are cancer patients, people who are morbidly obese, or those with the condition called lepedema. What causes the swelling to remain permanent is that the lymph system has been so damaged that it can no longer operate normally in removing the body's waste fluid.
In cancer patients this is the result of either removal of the lymph nodes for cancer biopsy, radiation damage to the lymph system, or damage from tumor/cancer surgeries.
This is also referred to as secondary lymphedema.
Group Three
Group three consists of people who have leg or arm swelling from seemingly unknown reasons. There may be no injury, no cancer, no trauma, but for some reason the leg simply is swollen all the time.
The swelling may start at birth, it may begin at puberty, or may begin in the 3rd, 4th or even 5th decade of life or sometimes later.
This type of leg or arm swelling is called primary lymphedema. It can be caused by a genetic defect, malformation or damage to the lymph system while in the womb or at birth or be part of another birth condition that also effects the lymph system.
This is an extremely serious medical condition that must be diagnosed early, and treated quickly so as to avoid painful, debilitating and even life threatening complications. Treatment should NOT include the use of diuretics.
Lymphedema is defined simply as an accumulation of excessive protein rich fluid in the tissues of the leg. The accumulation of fluid causes the permanent swelling caused by a defective lymph system.
A conservative estimate is that there may be 1-2 million people in the United States with some form of primary lymphedema and two to three million with secondary lymphedema.
If you are an at risk person for arm lymphedema there are early warning signs you should be aware of. If you experience any or several of these symptoms, you should immediately make your physician aware of them.
1.) Unexplained aching, hurting or pain in the arm or leg
2.) Experiencing “fleeting lymphedema.” This is where the limb may swell, even slightly, then return to normal. This may be a precursor to full blown arm lymphedema or leg lymphedema.
3.) Localized swelling of any area. Sometimes lymphedema may start as swelling in one area, for example the hand, or between the elbow and hand. This is an indication of early lymphatic malfunction.
4.) Any arm inflammation, redness or infection.
5.) You may experience a feeling of tightness, heaviness or weakness of the arm.
The symptoms for leg lymphedema are very similar to ones for the arm.
The preferred treatment today is decongestive therapy. The forms of therapy are complete decongestive therapy (CDT) or manual decongestive therapy (MLD), there are variances, but most involve these two type of treatment.
It is a form of massage therapy where the leg is very gently massaged to actually move the fluid out of the leg and into an area where the lymph system still functions normally.
With these massage treatments, swelling is reduced and then the patient is fitted with a pre-measured custom pressure garment to keep the swelling down and/or is taught to use compression wraps to maintain the leg size.
1. Infections such as cellulitis, lymphangitis, erysipelas. This is due not only to the large accumulation of fluid, but it is well documented that lymphodemous limbs are localized immunocompromised.
2. Draining wounds that leak lymphorrhea which is very caustic to surrounding skin tissue and acts as a port of entry for infections.
3. Increased pain as a result of the compression of nerves usually caused by the development of fibrosis and increased build up of fluids.
4. Loss of Function due to the swelling and limb changes.
5. Depression - Psychological coping as a result of the disfigurement and debilitating effect of lymphedema.
6. Deep venous thrombosis again as a result of the pressure of the swelling and fibrosis against the vascular system. Also, can happen as a result of cellulitis, lymphangitis and infections.
7. Sepsis, Gangrene are possibilities as a result of the infections.
8. Possible amputation of the limb.
9. Pleural effusions may result if the lymphatics in the abdomen or chest are to overwhelmed to clear the lung cavity of fluids.
10. Skin complications such as splitting, plaques, susceptibility to fungus and bacterial infections.
11. Chronic localized inflammations.
No, at the present time there is no cure for lymphedema. But it can be treated and managed and most of the complications can be avoided. Life with lymphedema can still be active and full, with proper treatment, patient education, and patient life style adaptation.
For extensive information on lymphedema, please visit our home page:
Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan.
email: Harutaka Katano (katano@nih.go.jp)
Merkel cell carcinoma is a rare malignancy that sometimes occurs in the skin of elderly people. Recently, a new human polyomavirus, Merkel cell polyomavirus (MCPyV) was identified in Merkel cell carcinoma. In the present study, MCPyV-DNA was detected in 6 of 11 (55%) cases of Merkel cell carcinoma by nested PCR and real-time PCR. Histologically, MCPyV-positive cases showed round and vesicular nuclei with a fine granular chromatin and small nucleoli, whereas MCPyV-negative cases showed polygonal nuclei with diffusely distributed chromatin. Real-time PCR analysis to detect the MCPyV gene revealed that viral copy numbers ranged 0.04-0.43 per cell in cases of Merkel cell carcinoma. MCPyV was also detected in 3 of 49 (6.1%) cases of Kaposi's sarcoma (KS), but not in 192 DNA samples of other diseases including 142 autopsy samples from 20 immunodeficient patients. The MCPyV copy number in KS was lower than that in Merkel cell carcinoma. PCR successfully amplified a full-length MCPyV genome from a case of KS. Sequence analysis revealed that the MCPyV isolated from KS had 98% homology to the previously reported MCPyV genomes. These data suggest that the prevalence of MCPyV is low in Japan, and is at least partly associated with the pathogenesis of Merkel cell carcinoma.
The study, "Mammalian Merkel Cells are Descended from the Epidermal Lineage", was recently published in the online version of Developmental Biology and is slated its future print edition.
"Merkel cells," discovered by Friedrich Sigmund Merkel in 1875, are found in multiple regions of the skin and make contact with specialized never fibers, participating in the perception of touch.
"A real mystery surrounding Merkel cells was their developmental site of origin. Conflicting evidence suggested that these cells arose from either the skin or neural crest lineages, but there was no definitive proof of either origin," said lead author, Dr. Maricich.
Using genetically engineered mouse lines, the researchers were able to delete Atoh1, a gene essential to the formation of Merkel cells, from different areas of developing embryos. This "conditional deletion" of Atoh1 in the neural crest did not affect the Merkel cell population, however using this same technique in the skin lineage resulted in the loss of all Merkel cells.
"Knocking out Atoh1 in the neural crest line caused other problems for developing embryos, but Merkel cells were completely unaffected. However, loss of Atoh1 expression in the skin deleted all the Merkel cells," said Dr. Maricich. "This showed us that we had specifically targeted the Merkel cells and that Atoh1 expression by skin cells is necessary to their development."
The researchers also fate mapped the cells, a technique used to trace developmental fates of embryonic tissues. This analysis further supported their conditional knockout findings.
"The techniques used in this study will help neuroscientists to further explore the function of Merkel cells, including the behavioral consequences when only Merkel cells have been deleted," said Ellen Lumpkin, Ph.D., a study co-author and assistant professor of neuroscience, molecular physiology and biophysics and molecular and human genetics at the Baylor College of Medicine.
"It is thought that Merkel cells give rise to Merkel cell carcinoma, a rare but aggressive form of skin cancer that responds poorly to current treatments," said Dr. Maricich. "In addition to solving a 130 year-old mystery, our data may be relevant to the understanding of Merkel cell carcinoma, and may provide important clues in the search for novel therapeutic targets."
Funding for this study came from the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Both are of the National Institutes of Health.
Departments of *Pathology and Immunology daggerMolecular Microbiology, Division of Anatomic and Molecular Pathology, Washington University School of Medicine, St Louis, MO.
The recently described Merkel cell polyomavirus (MCPyV) is reportedly present in 50% to 80% of Merkel cell carcinomas (MCC). Although the virus has been shown to be absent from other cutaneous neoplasms, its association with malignancies that are histologically similar to MCC, specifically small cell carcinoma of the lung and other high-grade neuroendocrine tumors, has yet to be thoroughly investigated. To address this issue, we identified a set of 74 cases of visceral high-grade neuroendocrine tumors from a variety of anatomic sites, including 32 cases from the lung, 16 cases from the gastrointestinal tract, 20 cases from the female reproductive system, 3 cases from soft tissue, 2 cases from the head and neck region, and 1 case from the bladder. Using a set of primers optimized to detect MCPyV in formalin-fixed tissue, polymerase chain reaction (PCR)-based testing showed evidence of MCPyV DNA in only 1 of the 74 tumors; however, clinicopathologic review of the positive case (a neuroendocrine tumor of the small intestine) disclosed that the patient had a history of primary MCC of the buttock. PCR-based testing also showed no evidence of the related WU and KI polyomaviruses in the set of 74 cases. We conclude that, when evaluated by PCR-based testing, MCPyV is a specific marker for MCC that can be helpful in distinguishing cases of metastatic MCC from other high-grade neuroendocrine tumors. Our results also suggest that MCPyV does not have a role in the oncogenesis of visceral high-grade neuroendocrine tumors.
Lippincott, Williams & Wilkins
