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What Is It? One of the three main types of blood cell cancer- leukemia, lymphoma, and myeloma that in combination account for 10% of all cancers diagnosed in the US. Myeloma is a cancer of the plasma cells (produce antibodies) in the bone marrow that are a part of the immune system.  Myeloma is frequently called multiple myeloma since it affects several different antibody producing cell lines.  It produces disease by crowding out other cells and precursors to cells in the bone marrow. In multiple myeloma, the massively produced antibodies spill out into the systemic blood circulation and cause organ damage. The early symptoms are bone pain (severe) over the chest and especially low back, and less commonly the upper and lower extremities, bone fractures, weakness and numbness in the extremities due to radicular pain from the bone fractures, weakness and fatigue (due to anemia), weight loss (due to nausea/vomiting/loss of appetite from elevated calcium levels.  Frequent urination, increase in thirst, and constipation occur due to elevated calcium levels.  These high levels may cause confusion or even coma. Kidney failure occurs due to elevated proteins from the immunoglobulin hyperproduction and the blood becomes excessively thick (hyperviscosity) producing blurring of the vision, bleeding from the nose, and heart failure. There may be purple lumps under the skin called extramedullar plasmacytomas.  There are frequent infections.

Incidence: 30,300 new cases in the US were diagnosed in 2015 (approximately 10 per hundred thousand population).  The prevalence is 103,463 patients living with the disease (active or in remission) in the US at any one time.

Location: Pain may be global in the bones, but most frequently starts in the low back and chest wall

Anatomy: The replacement of bone marrow by plasma cells causes anemia and fractures due to development of holes in the bone. 

Onset: Gradual

Character: Constant aching bone pain

Intensity: Severe in the back

Worsens: with fractures, when standing

Relieved by: -

Causes: Unknown- cancer of the plasma cells is the mechanism

Diagnosis: Elevated blood calcium, anemia (too few red blood cells), kidney dysfunction, high protein levels in the blood.  Weight loss is due to high calcium levels that produce nausea, vomiting, and loss of appetitie. Electrophoresis is a blood test that measures the antibodies.  Blood uric acid may be elevated if there is a high cell turnover rate. Total protein, albumin, and globulin levels are obtained.  A skeletal survey via xray or CT scan.  Bone scans miss many of the lesions therefore are not indicated. Kidney function will also be tested since this is a frequent organ that will demonstrate dysfunction. Usually a bone marrow biopsy will be required to make the diagnosis.  C-reactive protein and beta-2 microglobulin are both used for determining the prognosis. X-rays typically show punched out round lesions in the skull, spine, ribs, and pelvis.   

Outcome: Myeloma has a 49% 5 year survival rate and 12,650 will die from myeloma in 2016.

Associated with: Age over 65, African American race, having a family member with this, MGUS (monoclonal gammopathy of undetermined significance), other plasmacytoma.

Treatment: Stem cell transplantation is the most effective way to treat this type of cancer.  Chemotherapy is a second line therapy for those that cannot withstand the potential complications from the stem cell transplant. Bisphophonates (e.g. Fosamax, Boniva, etc. ) are used to slow the bone destruction. 

Differential Diagnosis: Leukemia, sarcoma, other carcinoma, other generalized pain, metastatic disease, waldenstrom macroglobulinemia

Complications: Bone fractures, coma, weight loss, death

Malignant Bone Tumors


What is it?    One of several types of cancer affecting the bone, either primary or metastatic.  These can cause pain in the bone, especially constant pain that seems to worsen at night.


-Multiple Myeloma (MM)- the most common primary bone cancer affecting 6 per 100,000 each year or about 30,000 people in the US newly diagnosed each year or 96,000 total living with the disease each year.  MM affects primarily the spine, pelvis, and ribs, although it may affect any bone including the calvarium (skull) and may cause pain by fracturing bones or pressure development inside the bones due to an excess productions of plasma cells. It affects patients primarily age 50 to 70 but can be outside this bracket.  MM is formed by malignant plasma cells (these are B lymphocytes that have transformed into plasma cells- part of the immune system).  Multiple plasma cell tumor types is called MM.  In MM there are low blood counts due to plasma cells crowding out normal cells from the bone marrow, and low platelet counts leading to bruising and bleeding and infections.  MM sends a signal to the osteoclasts (a type of bone cell) to break down more bone, but doesn't send a corresponding signal to osteoblasts to make more bone, therefore the bone develops a "moth eaten look" or like a shotgun blast.  Therefore with weakened bones, there is an increased risk of fractures.  The antibodies made by the plasma cells in MM damage the kidneys through the production of amyloid- a combination of light chains of proteins produced by the plasma cells, and ultimately deposited in several organs making them dysfunctional.  Only late does kidney damage show up in amyloidosis, sometimes only after the kidneys have failed.  About 15,000 people a year in the US die from MM each year.  Treatments are radiation and chemo.  The 5 year survival is about 50%.

-Osteosarcoma (OS).  This is the second most common bone cancer affecting up to to 5 per million population (1/10 that of MM) with 400 new diagnoses each year. , primarily teenagers and children.  It is the most common primary bone cancer of children and teenagers. It is extremely rare before the age of 5.  Blacks have a higher risk of developing this disease than whites. About 4% carry a gene to transmit this mutation and it may be associated with retinoblastoma (an eye tumor), multiple cancers, strong family history, after radiation treatment for other cancers.  These malignant tumors primarily affect the femur, tibia, humerus, pelvis, and skull.  It has metastasized 20% of the time when first diagnosed.  Pain, swelling, decreased joint motion are common with fracture less commonly seen.  Chemotherapy and surgery are the primary treatments. The 5 year survival is 76% for those younger than 15 and 66% for those older than 15.

-Ewing's sarcoma.  This malignant bone tumor occurs after age 5 and before age 20 in most, involves the femur, tibia, pelvis, humerus, and ribs.  The lower extremity is involved 41% of the time, the pelvis 26%, chest wall 16%, upper extremity 9%, spine 6%, and hand/foot 3%.  However, Ewing's may develop primary tumors outside of the bone including in the trunk (32%), extremities (26%), head and neck (18%), retroperitoneum (16%).  25% of Ewing's patients have metastatic disease at the time of diagnosis.  Typically it is treated with chemotherapy and surgery, or radiation.  It is seen in one out of a million or about 225 children and teenagers in the US.   Ewing's is 9 times greater in whites than in blacks.  The disease may be localized, metastatic, or recurrent.  It arises from a mesenchymal stem cell.  The 5 year survival rate is 78% for those younger than 15 and 60% for those age 15-19.

-Chondrosarcoma.  This malignancy of the cartilage is seen primarily in the hip, femur, pelvis, or shoulder, or the wide portion of the long bones.  It occurs primarily in men between 60 and 80 years old and has an incidence of 5 per million- the same as osteosarcoma, but occurs in much older patients.  It is the second most common primary malignancy of the bone, and there are several types of chondrosarcomas, depending on their origin, presentation, location within the bone, and the histological grade of the lesion.  The pain is constant, not relieved by rest and interferes with sleep.  There may be hip or knee pain as the first symptoms if it is located in the femur.  Upper and lower extremity lesions als can cause weakness and disability in addition to pain.  Surgery is the primary method of treatment since chemo and radiation have very little effect on some of the tumors.  The 5 year survival rates depend on the histological grade:  Grade 1: 90%, Grade 2: 81%,  Grade 3: 29% ,  Undifferentiated 0%- the 1 year survival rate is < 10%. 


Metastatic means the tumors arise from a distant source and invade the bone and bone marrow.  The incidence of metastatic (secondary) bone cancer is much higher than primary bone cancer.  The breast, prostate, lung, and kidney as primary sources of cancer are responsible for 75% of all cases of metastatic bone cancer.  70% of people with advanced prostate carcinoma or breast carcinoma have bone metastasis. Overall, 1.2 million cases of cancer are diagnosed each year in the US, and half of these tumors can spread to the bone.  There is about four times the incidence of metastatic bone cancer compared to primary bone cancer.  Metastatic bone disease is detected on MRI, PET scans, Bone scans, and CT scans.

Symptoms of Bone Metastasis

  1. Bone pain may be the first symptom that cancer has spread to the bone, although there are many other common causes of bone pain that have nothing to do with cancer.  The bone pain is intermittent at first, worse at night, and may improvement with movement.  Later it becomes constant. It is sometimes a dull ache, sometimes like a bruise, sometimes sharp and intermittent depending on the person.
  2. Bone fractures may occur due to weakened bone that is infiltrated with cancer.  The most common fractures are in the humerus (arm), femur (thigh), tibia (leg), and thoracic/lumbar spine.  Infiltration of the vertebral bodies with metastatic tumors especially in the thoracic spine, lumbar spine, and sacrum may cause compression fractures.
  3. Spinal cord compression may cause loss of bowel or bladder control, pain in the back or neck, numbness or weakness below the level of the tumor.   The tumor may infiltrate the spinal canal or may cause fractures of the vertebral bodies with subsequent compression of the spinal canal.  The compression may occur suddenly and is a medical emergency.
  4. Elevated blood levels of calcium.  When metastatic tumors infiltrate the spine, then the calcium in the bone is released causing elevated blood calcium that may cause serious illnesses including constipation, loss of appetite, extreme thirst, dehydration, muscle spasms, agitation, passing large amounts of urine, sleepiness, tiredness, weakness, irregular heartbeat, confusion, seizures, incoordination.
  5. Anemia and fatigue


-Breast Cancer-  12% of women in the US will develop invasive breast cancer at some time during their lifetime.  In 2016, there will be nearly 250,000 new cases of invasive breast cancer diagnosed and there will be 40,000 deaths from breast cancer.  Of these initially diagnosed breast cancer, 10% will be Stage IV metastatic and 20-30% of recurrent breast cancer will be metastatic.  Most of these are with bone metastasis (70%).   There are approximately 155,000 women living with metastatic breast cancer in the US.  The incidence is higher in blacks and the death rate is higher in blacks.  Breast cancer is the number one cause of cancer deaths in women under age 50.   Of all the breast cancers diagnosed, 1% are in men. 

70% of breast cancer deaths are due to bone metastasis while 10% are due to brain metastasis.  The most common sites for breast cancer bony metastasis are the spine, ribs, skull, pelvis, humerus, or femur.

The median survival rate from metastatic breast cancer is 36 months and the five year survival rate with metastatic breast cancer is 22%.

-Lung Cancer-  Lung cancer is the leading cause of cancer death in the US with 46 deaths per 100,000.  There are 224,000 new cases of lung cancer each year and 158,000 deaths from lung cancer.  About 25% of all cancer deaths are due to lung cancer, and the number dying of lung cancer exceed the combined totals of colon, breast, and prostate cancer.  Bone metastasis affect 30-40% of those with advanced lung cancer.  The most common bones lung cancer spreads to are the spine (thoracic and lower abdomen), the pelvis, humerus and femur, and somewhat uniquely to the hands and feet (most cancers do not spread to the hands and feet).  The pain is often worse at night especially when resting in bed.  Compression fractures of the spine may occur and invasion of the spinal canal may result in spinal stenosis with weakness or tingling in the lower extremities when walking.   The 5 year survival rate for early lung cancer before metastasis is 52% while metastatic lung cancer has a 5 year survival rate of 4%.


-Thyroid Cancer- Thyroid cancer metastasizes most commonly to the lung and to a lesser degree to the bone. There are 62,000 cases of thyroid cancer in the US each year with about 80% in women.  There are 2,000 deaths each year from thyroid cancer.  There are several types of thyroid cancers.  On diagnosis of thyroid carcinoma, 5% will have bone metastasis.  Papillary thyroid cancer is 70% of all thyroid cancers but only 1-7% develop bone metastasis.   Follicular thyroid cancer has a much higher bone metastasis rate compared to other types of thyroid cancer.  The 5 year survival rate for papillary or follicular metastatic thyroid cancer is 50%, for medullary metastatic thyroid cancer is 28%, and for anaplastic thyroid cancer is 7%. 


-Kidney Cancer-  There are 63,000 people in the US developing renal cell cancer each year and 14,000 die of the disease each year.  Nearly 1/3 of patients with renal cell carcinoma will have bony metastasis on diagnosis and 40% of those with surgical resection of the primary tumor will have a relapse with bony metastasis.  Following the lung, the bone in renal cell cancer is the second most common location of metastasis.  The most common sites for metastasis are the pelvis and ribs (48%) followed by the spine (42%), then the long bones and skull. The overall 5 year survival rate for those with all stages of kidney cancer is 74% but for those with distant metastasis, the 5 year survival drops to 12%.


-Prostate Cancer- There are 181,000 new cases of prostate cancer each year and 26,000 deaths.  80% of the time the bony metastasis are to the hips, spine, and pelvis.  There are over 2.8 million men living with prostate cancer in the US each year.   The overall 5 year survival rate is 99%, however if there are distant metastasis, the 5 year survival rate drops to 29%.

Ref.  seer.cancer.gov


Hypercalcemia Bone Pain


What Is It? Hypercalcemia is an increase in the blood levels of calcium due to excess calcium being leeched from the bones, causing bone pain.  Hypercalcemia is not a disease, but is a laboratory finding that has many causes including hyperactivity of the parathyroid gland (hyperparathyroidism), cancer (especially lung and breast or metastatic), tuberculosis, sarcoidosis, immobility due to disease or condition, medications such as lithium, and hereditary factors (rare).  Other causes of hypercalcemia (but rarely cause bone pain) include excessive calcium dietary intake, excessive vitamin D supplements, and dehydration.  Of all these causes, more than 90% are due to primary hyperparathyroidism and malignancy. Hypercalcemia may be transient (19%) or sustained (81%).  Approximately 3 times as many cases are due to malignancy compared to primary hyperparathyroidism.

Incidence: 0.6% of the population overall

Location: Long bones, global bone pain

Anatomy: -Malignancy causes hypercalcemia usually through metastatic disease (tumors growing in the bone far removed from the primary cancer source).  The metastatic disease causes a dysruption in the normal turnover process of the bone being made and remodeled.  This causes lytic (punched out appearance on x-ray) lesions, sclerotic appearance (hardening of the bone), and progressive growthleading to microfractures, and stretching of the periosteum causing pain in the bones.

-Primary hyperparathyroidism refers to an overactivity of the parathyroid glands (usually 4-6) lying in the neck, adjacent to the thyroid gland.  The parathyroid glands function is to monitor and adjust calcium levels in the blood within a narrow range.  They do this by varying the amount of parathyroid hormone they produce.  A low calcium level causes an increase in parathyroid hormone (a small protein) production that causes bones to release their calcium into the bloodstream to provide a constant level of calcium for the brain, nervous system, and muscles to work properly.  The parathyroids also stimulate the gut to absorb more calcium in cases where blood calcium levels are low.  Primary hyperparathyroidism is a disconnect in this feedback mechanism between the calcium levels in the blood and the parathyroid hormone output- ie. the parathyroid glands continue to make more parathyroid hormone in spite of the calcium levels being too high. Virtually 100% of the time, this is due to a tumor (usually not malignant) of the parathyroid glands.  Bone pain may result from too much calcium being removed from the bones causing osteopenia, osteoporosis, and fractures.  

-Sarcoidosis may have bone pain that occurs due to cystic lesions, punched out lesions, osteolysis, or defects in the cortex with granulomas in the medullary cavity (center of the long bones) in severe cases of sarcoidosis.  These lesions are seen mainly in the bones of the hands and feet but may be also found in the skull, nasal bones, and vertebrae.  Most of these lesions do not cause pain, but uncommonly sarcoidosis will manifest as bone pain.

-Tuberculosis of the bones may lead to bone pain, especially in the spine (Pott's Disease) and in the joints when TB invades these structures. TB can cause joint pain also or may cause osteomyelitis, a painful infection of the bone.

Onset: Gradual in most

Character: Severe aching deep in the bones

Intensity: Severe

Worsens: Nighttime (malignancy)

Relieved by: NSAIDS, treatment of the cause

Causes: see above

Diagnosis: Serum calcium levels above 10.2 are abnormal and deserve investigation; x-rays and history are important

Outcome: Depends on the cause

Associated with: Kidney stones (too much calcium in the blood can cause kidney stones), kidney failure (severe hypercalcemia can damage the kidneys), confusion, coma, heart arrhythmias, osteoporosis

Treatment: For primary hyperparathyroidism, surgical excision of the parathyroid glands is necessary.  For metastatic disease, NSAIDs and possible radiation treatment or cryo/radiofrequency may be useful.  

Differential Diagnosis: Excess oral calcium or vitamin D (these usually do not cause bone pain)

Complications: Bone fractures, other symptoms of hypercalcemia (excessive thirst, frequent urination, GI upset and nausea, vomiting and constipation, bone pain, confusion, lethargy, fatigue, kidney stones, kidney failure, gastric ulcer, arrhythmias)





What Is It? A type of malignant cancer of the white blood cells leading to excessive sweating especially at night, fatigue and weakness that do not resolve upon resting, bone pain and tenderness all over the body, fever or chills, lymphadenopathy (swollen non tender lymph nodes, especially in the neck and under the arms), weight loss, spleen and liver enlargement, petechiae (red rash), easy bruising, numerous infections

Incidence: The prevalence (number living with leukemia) in the US is 334,000 (one out of every thousand people).  The incidence is 60,000 new cases per year in the US. The overall incidence is about 15 out of 100,000 people each year in the US. Depends on the type: Acute Myelogenous Leukemia (AML) affects the granulocytes- ie. eosinophils and neutrophil types of white blood cells.  21,000 new cases are seen each year in both adults and children.

Acute Lymphocytic Leukemia (ALL) only occurs in children and affects the lymphocytes that are produced bone marrow.  Approximately 6,000 new cases are diagnosed each year. 

Chronic Myelogenous Leukemia (CML) is a slower onset disease affecting the neutrophil and eosinophil white cells , mainly in adults, with 7,000 new cases annually diagnosed.

Chronic Lymphocytic Leukemia (CLL) is a slower onset disease affecting people over 55, with 15,000 new cases seen each year.

Location:  Originates in leucocytes  (white blood cells).  The difference between leukemia and lymphoma is that in leukemia the cancer is primarily confined to the bone marrow whereas in lymphoma, the cancer is in the lymph nodes and other tissues (that may also include the bone marrow)

Anatomy: The lymphocytes are a type of white blood cell arising from the liver and spleen whereas the granulocytes are composed of the neutrophils and eosinophils made in the bone marrow.

Onset: Weeks to months

Character: Deep aching bone pain

Intensity: Moderate

Worsens: Night time

Relieved by: -

Causes: All are genetic mutations induced or "switched on" by environmental factors or endogenously mutated.  The mechanisms of how all the genetic mutations occur is unknown.  There are associations with other conditions as listed below

Diagnosis: CBC and liver function tests, lymph node biopsy, bone scan, flow cytometry, and biopsy of tissues for staging.

Outcome: Survival from leukemia depends on the stage of the leukemia, type of leukemia, age of the patient, and specific treatment protocol employed. These are constantly changing protocols.  Childhood 5 year survival rates overall: ALL 85%, AML 70%, CML 80%.  Adult plus children combined 5 year survival rates overall: ALL 70.1% overall, AML 26% overall, CML 62%, CLL 85%.  

Associated with: Family history of leukemia, smoking (AML), Down's syndrome, preleukemia (myelodysplastic disorders), benzene exposure, high radiation exposure, prior treatment of cancer with ionizing radiation or chemotherapy

Treatment: Chemotherapy, radiation, bone marrow transplantation, stem cells all depending on the staging of the leukemia

Differential Diagnosis: Lymphoma, other types of leukemia

Complications: Metastasize (spread) to the lungs, kidneys, heart, gastrointestinal tract, and testes.