Paraneoplastic Syndrome

The first report of Paraneoplastic syndrome is attributed to a French physician, M Auche, who described the involvement in a peripheral nervous system in cancer patients in 1890. This syndrome is a group of signs and symptoms caused by a substance that is produced by a tumor, or in reaction to a tumor. Paraneoplastic syndrome is defined as a rare disorder triggered by a response to neoplasm of an immune system that is altered. These are clinical syndromes produced by tumor although they occur remotely from the tumor itself.

The symptoms may be of any nature – endocrine, neuromuscular or musculoskeletal, cardiovascular, cutaneous, hematologic, gastrointestinal, renal or miscellaneous. Fever is the most common sign. Other clinical symptoms may be benign but syndromes could be varied; from a malignant carcinoid syndrome to Cushing syndrome. In cancer patients, the central nervous system involvement can be detected and it is a prominent manifestation of cancer.

Because of their protean manifestations, Paraneoplastic syndromes are managed by a medical team of physicians, including medical oncologists, surgeons, radiation oncologists, endocrinologists, hematologists, neurologists and dermatologists.

Causes

This syndrome can be due to a number of causes, including hormones or biologically active products, made by tumor, which blocks normal hormone, autoimmunity, immune-complex production and immune suppression. But, this is not caused by the primary tumor itself, or by its metastases, or by compression, infection, nutritional deficiency, or treatment of tumor.

Patients with family history of malignancies are at an increased risk and should be screened for cancer. Paraneoplastic syndromes occur typically among middle-aged to older patients. They are mostly diagnosed with cancers of the lung, breast, ovaries, or lymphatic system or lymphoma.

These symptoms sometimes appear before the diagnosis of a malignancy. When the tumor breaks immune tolerance and begins to attack the normal tissue expressing that protein, this syndrome become prominent.

Types of Paraneoplastic Syndrome

Due to the complexity of this syndrome, its clinical presentations may vary greatly. Hence, Paraneoplastic syndromes is divided into four main categories - endocrine, neurological, mucocutaneous, and hematological syndromes as well as a host of others including rheumatologic, renal, gastrointestinal, Cutaneous and miscellaneous.

Fever, dysgeusia, anorexia, and cachexia are included under miscellaneous category. Fever is associated with lymphomas, acute leukemias, sarcoma and carcinomas.

Rheumatologic syndrome includes polyarthritis, particularly in patients with myelomas, lymphomas, acute leukemia, malignant tumors of the colon, pancreas, prostrate. Scleroderma may precede the evidence of tumor. Widespread form of malignancies of breast, uterus and lung can be observed.

Renal syndrome is characterized by hypokalemic nephropathy, and it occurs in 50% of individuals with ACTH secreting tumors of the lung. Nephrotic syndrome is observed in patients with Hodgkin lymphoma, non Hodgkin lymphoma, malignancies of lung, thyroid, colon, breast, ovary and pancreatic head.

Watery diarrhea and electrolyte imbalance, leads to asthenia, confusion and exhaustion, all characteristic of gastrointestinal syndromes. Severe prostaglandins lead to malabsorption and unavailability of nutrients.

Hematologic syndromes are related to anemia, thrombocytosis, disseminated intravascular coagulation, and leukemoid reactions from several types of cancers. Leukemoid reactions due to immature white blood cells in the blood stream are accompanied by hypereosinophilia and itching.

Cutaneous syndromes are manifested by itching and flushes, alopecia, or hypertrichosis. Blackish pigmentation of the skin usually occurs in patients with metastatic melanomas or pancreatic tumors.

Endocrine syndromes resemble common endocrine disorders. Increased serum and urine cortisol concentrations are common examples of this malignancy.

Neurologic or neuromuscular syndromes relate to cancers and such disorders affect 6% of all patients with cancer. Neuromuscular symptoms mimic common neurological conditions. Myasthenia gravis is a common Paraneoplastic syndrome in patients with thymoma, a malignancy arising from epithelial cells of the thymus.

Paraneoplastic limbic encephalitis is characterized by depression, seizures, irritability and short term memory loss and neurologic symptoms rapidly resemble dementia.

Paraneoplastic cerebellar degeneration causes gait difficulties, dizziness, nausea and diplopia. Sensory neuropathy affects lower and upper extremities and there is progressive memory loss, either symmetric or asymmetric.

Diagnosis

As Paraneoplastic syndromes may evolve over weeks to months, they usually stabilize regardless whether the patient's underlying condition improves or worsens. Since this is the first manifestation of cancer, patients should undergo investigation for cancer. Other diagnoses are membrane disease, dementia, encephalopathy, encephalitis, myelitis, anemia, bone marrow failure, chronic fatigue syndrome, mixed connective tissue disease, polycythemia vera and polymyalgia rheumatica among others.

Complete laboratory tests in blood, urine, cerebrospinal fluid, protein electrophoresis, assays for auto antibodies, Endoscopy and imaging studies including whole body scans and FDG-PET scans are prescribed to detect extremely small tumors especially useful for patients with neurologic diseases.

Treatment of Paraneoplastic Syndrome

Treatment for this syndrome varies depending upon the type and location of tumors. The first option of treatment of the underlying tumor is by therapeutic protocols, a combination of surgery, radiation, chemotherapy. Second therapeutic option is for patients with clearly identifiable antibodies by intravenous immunoglobulins, steroids, or plasma exchange.

Surgical treatment is typically directed toward the underlying neoplasm although some Paraneoplastic disorders may resolve rapidly without surgery on the primary tumor.

Bone Marrow Aspiration

Bone marrow refers to the spongy tissue that is found inside the larger bones such as spine, breast bone, hips, ribs, legs and skull. Marrow has two parts – both solid and liquid. If the solid portion of the bone is sampled, it is called biopsy. Aspiration procedure is used to collect the liquid part of the marrow.

Both the procedures show whether the bone marrow is healthy and making normal amounts of blood cells. This procedure is normally used by doctors to diagnose and monitor blood and marrow diseases, including cancer. In bone marrow aspiration, the doctor uses a needle to draw a sample of the fluid portion. For a biopsy, a larger needle is used to take the sample of the solid part.

Most often bone marrow aspiration and bone biopsy is done at once. Together, they make the bone marrow examination. Although they are different procedures, they offer complementary information about bone marrow cells.

Why is it done?

Bone marrow aspiration and biopsy offer detailed information about the condition of the bone marrow and blood cells. In case the blood tests indicate that cell counts are abnormal, and information is not sufficient about a suspected problem, this is done. The doctor may perform bone marrow exam to diagnose a disease condition involving the bone marrow or blood cells:

• To determine a disease progression
  
• To check the iron levels and metabolism and
  
• To monitor treatment of a disease.

Pre bone marrow aspiration procedure

It is imperative to inform the doctor about any medications and supplements the patient is consuming. This can increase the risk of bleeding after a bone marrow aspiration. In case of anxiety or worry, better talk to the health care provider so that a sedative medication could be given before the aspiration in addition to a numbing agent through local anesthesia at the site where the needle is inserted.

Bone marrow aspiration is done in a hospital, a clinic or in a doctor's room. A specialist in blood disorders – a hematologist – or an oncologist, who is a specialist in cancer does the procedure with a nurse and a trained technologist. It usually takes about half an hour for the exam and if any intravenous sedation is given, extra time is taken for pre and post procedure care.

The patient's blood pressure and heart rate are checked. Some form of anesthesia is administered before the bone marrow aspiration as it can be painful. For many, local anesthesia is sufficient. You will be fully awake during the aspiration, but the site is numbed to reduce pain. If you are quite anxious, intravenous IV sedation is given before the marrow procedure.

Bone marrow aspiration procedure

The area for inserting the biopsy needle is marked and cleaned. The bone marrow fluid (aspirate) is usually collected from the top ridge of the back of the hipbone, and if it is done from the breast bone or the front of the hip near the groin. In young children and kids, the sample is taken from the lower leg bone, just below the knee. The patient will be made to lie down on the abdomen or side.

The bone marrow aspiration is usually done before the biopsy. A small incision is made to insert the needle easier. A hollow needle is inserted through the bone and into the bone marrow. Several samples are taken and aspiration takes only a few minutes. While the health care team ensures that sufficient quantity of sample is drawn, sometimes a 'dry tap' may occur, that is fluid cannot be withdrawn. The needle is moved for another attempt.

Post aspiration procedure

After the bone marrow exam, pressure is applied to the where the needle was inserted to stop the bleeding. A smaller bandage is placed on the site. If local anesthesia had been administered the patient is asked to lie back for 10-15 minutes and apply pressure on the biopsy site. In case, IV sedation had been given, you are taken into a recovery area as sedatives may cause impaired judgment, memory lapses or slowed response.

Tenderness may be felt for a week or more after the bone marrow exam, and the doctor administers pain reliever. You need to keep the bandage dry for 24 hours and not shower or bathe, or swim or use the hot tub. It is okay to get the aspiration site wet after 24 hours. In case bleeding soaks through the bandage, or does not stop even with direct pressure, consult the doctor. The doctor also needs to be contacted if there is persistent fever, worsening pain, swelling at the procedure site and increasing redness or drainage at the procedure site. Also it is advised to avoid rigorous activity for a couple of days to minimize bleeding and discomfort.

Results from bone marrow aspiration

The sample is sent to a laboratory for analysis. The results are available in a few days. The pathologist or hematologist evaluates the samples to check the health of the marrow and if it has enough healthy blood cells and also for abnormal cells. The doctor confirms or rules out a diagnosis and how advanced the disease is or if the treatment is working. Sometimes, follow-up tests are done.

Risks of bone marrow examination

This is a safe procedure and complications are rare. But some complications include:

Excessive bleeding which can happen in people with low platelet count.
Infection in those with weakened immune systems.
Discomfort that could be long lasting in the biopsy site.
Heart and lung problems can be caused due to penetration of the breastbone.
Sedation can cause allergic reaction, nausea and irregular heartbeats in some.

Uses of bone marrow exams

These are used for many conditions including:

• Anemia
  
• Bone marrow disorders which include myelodysplastic syndrome and myelofibrosis.
  
• Blood cell conditions such as Leukopenia, leukocytosis, thrombocytopenia, thrombocytosis, pancytopenia and polycythemia – which produce too few or too many of certain types of blood.
  
• Cancers of the bone marrow or of blood including leukemia, lymphomas and multiple myeloma.
  
• Cancers that have spread to other areas including breast.
  
• Hemochromatosis and
  
• Infections.

While problems with bone marrow can create lasting and serious health problems, bone marrow exams, such as aspiration and biopsy are important to help determine the status and extent of problems in the cells to evaluate and determine further treatment and management.

Hodgkin's Disease

Hodgkin's Disease refers to a condition that was first described by British physician Thomas Hodgkin. Hodgkin's disease or Hodgkin's lymphoma is a malignant growth of lymph cells. This uncommon form of cancer of the lymph system is characterized by abnormal growth of cells in the lymph system thereby spreading beyond it. It progressively compromises the body's immune system. While Hodgkin's disease can occur to a person at any time of his life, it is noticed in early adulthood or late adulthood. Usually, Hodgkin's disease begins in the lymph nodes and may spread to other parts of the body. The difference between Hodgkin's disease and non-Hodgkin's lymphoma is that tumors in Hodgkin's syndrome contain large cells called Reed-Sternberg cells.

Patients suffering from Hodgkin's disease notice painless swelling in the lymph nodes of the neck, armpit or groin. There may be fever and fatigue. The patient loses weight and feels drained of energy. Unexplained itching and lower back pain may also be noticed.

Most often diagnosis of Hodgkin's lymphomas is made during physical check-ups. A biopsy is done to test for the presence of Reed-Sternberg cells that are characteristic to Hodgkin's lymphomas. Blood test will reveal abnormal blood cell count and ESR. Bone marrow aspiration is done to aid diagnosis and treatment. Cellular activity can be traced with Positron Emission Tomography (PET) scan. Treatment for Hodgkin's disease depends on the stage that the disease is in. This determines the extent and region of lymph nodes that have been affected.

Radiation therapy is resorted to when a limited area is affected by Hodgkin's disease. Here high-energy rays are used to kill cancer cells and stop their proliferation. Often it is used in combination with chemotherapy. Chemotherapy may involve a combination of drugs that work together.