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==Natural History, Complications and Prognosis==
==Natural History, Complications and Prognosis==
A number of organ systems are commonly involved, the most common symptoms being [[bone pain]] usually involving the [[spine]] and the [[ribs]]. These frequently lead to pathological fractures and resultant [[hypercalcemia]]. Also common are infections such as [[pneumonia|pneumonias]] and [[pyelonephritis]]. [[Renal failure]] from [[hypercalcemia]] and [[Bence Jones protein]] filtration, [[anemia]] from suppressed bone marrow production and neurological symptoms from brain [[metastasis]] are also prominent.
If left untreated, most of patients with multiple myeloma may progress to develop [[fatigue]], [[bone pain]], and [[pallor]].<ref>Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Prognosis</ref> Complications that can develop as a result of multiple myeloma are [[anemia]], [[renal failure]], skeletal complications, and neurological complications.<ref>Multiple myeloma. National Cancer Institute(2015) www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq#link/_40_toc Accessed on September, 20th 2015</ref>
 
The prognosis of multiple myeloma is good with treatment, while without treatment, multiple myeloma will result in death with a median survival of 7 months.<ref>Multiple myeloma. National Cancer Institute(2015) www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq#link/_40_toc Accessed on September, 20th 2015</ref><ref>Multiple myeloma. Librepathology (2015)http://www.wikidoc.org/index.php?title=Multiple_myeloma_pathophysiology&action=edit&section Accessed on September, 20th 2015=1</ref> Multiple myeloma is associated with a 10 year survival of 3%. The presence of [[plasma cell leukemia]] or soft tissue plasmacytomas is associated with a particularly poor prognosis among patients with multiple myeloma.<ref>Plasma cell neoplasm. Cancer.gov (2015)http://www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq#link/_40_toc Accessed on September, 20th 2015</ref> According to a report published by National Cancer Institute there is a 43.25% chance of 5 year survival.<ref>Multiple myeloma. National Cancer Institute(2015) www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq#link/_40_toc Accessed on September, 20th 2015</ref>
According to a report published by National Cancer Institute there is a 43.25 chance of 5 year survival.<ref>{{Cite web  | last =  | first =  | title = Myeloma - SEER Stat Fact Sheets | url = http://seer.cancer.gov/statfacts/html/mulmy.html | publisher =  | date =  | accessdate = 17 February 2014 }}</ref>
 
Complications associated with [[multiple myeloma]] include renal failure, hematologic complications, infections, bony and neurological complications.


==Diagnosis==
==Diagnosis==

Revision as of 14:00, 22 September 2015

Multiple myeloma Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Multiple myeloma is a type of cancer of plasma cells which are immune system cells in bone marrow that produce antibodies. Its prognosis, despite therapy, is generally poor, and treatment may involve chemotherapy and stem cell transplant. It is part of the broad group of diseases called hematological malignancies.

Pathophysiology

Multiple myeloma arises from post-germinal center B lymphocytes, that are normally involved in production of human immunoglobulins.[1][2][3][4][5] Development of multiple myeloma is the result of multiple genetic translocation between the immunoglobulin heavy chain gene and oncogenes which leads to dysregulated multiplication of plasma cells.[6][7] On microscopic histopathological analysis, abundant eosinophilic cytoplasm, eccentrically placed nucleus, and russell bodies bodies are characteristic findings of multiple myeloma.[8]

Causes

There are no established causes for multiple myeloma.

Differentiating Multiple Myeloma from other Diseases

Multiple myeloma must be differentiated from monoclonal gammopathy of undetermined significance(MGUS), isolated plasmacytoma of the bone, and extramedullary plasmacytoma.[9]

Epidemiology and Demographics

In 2012, the incidence of multiple myeloma was approximately 6.3 per 100,000 cases with a mortality rate of 3.3 per 100,000 cases in the United States.[10] The prevalence of multiple myeloma was estimated to be 89,658 cases in 2012 in the United States.[11][12] Multiple myeloma is the second most common blood cancer after non-Hodgkin's lymphoma & 14th most common cancer overall in United States.[13][14][15] Male are more commonly affected with multiple myeloma than female. The male to female ratio is approximately 2 to 1.[16][17] Multiple myeloma usually affects individuals of the African American and Native Pacific Islanders race. Asian individuals are less likely to develop multiple myeloma.[18] The incidence of multiple myeloma increases with age; the median age at diagnosis is between 65 to 70 years years.[19]

Risk Factors

The most potent risk factor in the development of multiple myeloma is old age. Other risk factors include positive family history, positive history of monoclonal gammopathy of undetermined significance (MGUS), and occupational exposure to radiation and toxic chemicals.[20][21][22]

Screening

There is insufficient evidence to recommend routine screening for multiple myeloma.[23][24]

Natural History, Complications and Prognosis

If left untreated, most of patients with multiple myeloma may progress to develop fatigue, bone pain, and pallor.[25] Complications that can develop as a result of multiple myeloma are anemia, renal failure, skeletal complications, and neurological complications.[26] The prognosis of multiple myeloma is good with treatment, while without treatment, multiple myeloma will result in death with a median survival of 7 months.[27][28] Multiple myeloma is associated with a 10 year survival of 3%. The presence of plasma cell leukemia or soft tissue plasmacytomas is associated with a particularly poor prognosis among patients with multiple myeloma.[29] According to a report published by National Cancer Institute there is a 43.25% chance of 5 year survival.[30]

Diagnosis

Staging

International Staging System for multiple myeloma, based on β2-microglobulin (β2M) levels and serum albumin levels, was published by International myeloma working group in 2003 and is the most widely used staging system. It is used for both guiding treatment as well as predicting prognosis.[31]

Laboratory Findings

The most frequently advised tests are complete blood count (CBC), erythrocyte sedimentation rate (ESR), Basic metabolic panel, electrophoresis, immunohistochemistry and imaging procedures like X ray, CT scans and MRI's.

History and Symptoms

The sign and symptomatology associated with multiple myeloma is most commonly associated with following 4 systems: Calcium (elevated), kidneys (renal failure), blood (anemias) and cells and bones (fractures and pains).

Some of the most common symptoms include weakness, bone pains, back pain, numbness and paresthesia, bleeding and recurrent infections.

Most common signs include pallor, pain without tenderness, altered sensations on neurological examination etc.

Physical Examination

Multiple myeloma affects not only the bone marrow, but also spreads to other organ systems. This therefore, requires a detailed assessment of various organ systems. A number of times, any of these physical findings may warrant a further evaluation, and thus leads to an incidental diagnosis of multiple myeloma. Pallor, purpura, signs of cord compression, hepatosplenomegaly, bony pain without tenderness and carpal tunnel syndrome are some of the most common physical findings, in a patient presenting with multiple myeloma.

X Ray

Simple radiography is the current gold standard for the initial diagnosis and evaluation of relapses of multiple myeloma. Well defined punched out bony lesions and hair on end appearance are two characteristic findings. The long bones and the spine must always be evaluated. The evaluation of other bones merit consideration based on the symptoms of the patient.

CT

Computed Tomography scan is not the best modality for the diagnosis of multiple myeloma. Contrast CT scans lead to renal failure in multiple myeloma more frequently than otherwise. Hence, other modalities are preferred over CT scan. However, occasionally a CT scan is performed to measure the size of soft tissue plasmacytomas among patients with multiple myeloma.

MRI

The workup of suspected multiple myeloma includes a skeletal survey.Magnetic resonance imaging (MRI) is more sensitive than simple X-ray in the detection of lytic lesions, and may supersede skeletal survey, especially when vertebral disease is suspected.

Other Imaging Findings

Positron emitted tomography (PET) scan has been shown to be highly sensitive and specific, when combined with MRI it can achieve 100% diagnostic efficacy. The use of PET scan has led to earlier diagnosis of multiple myeloma, more accurate therapy assessment, and better prediction of patient outcome. However, these have not been employed as a standard of care by the International Myeloma Working Group.

Treatment

Medical Therapy

The treatment of multiple myeloma is based on differentiating suitability for transplantation or not. Those who are candidates for transplantation are treated with a combination of dexamethasone and one of the following lenalidomide/bortezomib. Alkylating agents are usually avoided in such candidates. Several other agents are also used these include thalidomide, prednisone, melphalan etc.

Surgery

Surgery is not a main treatment for multiple myeloma. Emergency surgery may be needed to help support weight-bearing bones in the spine or legs to prevent bones from breaking.

References

  1. Multiple myeloma. Radiopaedia (2015)http://radiopaedia.org/articles/multiple-myeloma-1 Accessed on September, 20th 2015
  2. Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology
  3. Multiple myeloma. Medlineplus (2015)https://www.nlm.nih.gov/medlineplus/multiplemyeloma.html
  4. Multiple myeloma. National cancer institute (2015) Accessed on September, 20th 2015
  5. Multiple myeloma. MedlinePlus (2015) https://www.nlm.nih.gov/medlineplus/multiplemyeloma.html#cat5 Accessed on September, 20th 2015
  6. Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology
  7. Multiple myeloma. Medlineplus (2015)https://www.nlm.nih.gov/medlineplus/multiplemyeloma.html
  8. Multiple myeloma. Librepathology (2015)http://www.wikidoc.org/index.php?title=Multiple_myeloma_pathophysiology&action=edit&section=1
  9. "Myeloma - SEER Stat Fact Sheets". Retrieved 17 February 2014.
  10. Plasma cell neoplasm.National cancer institute (2015)http://www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq#cit/section_1.1
  11. Seer stat fact sheet. National cancer institute (2015)http://seer.cancer.gov/statfacts/html/mulmy.html Accessed on September, 20th 2015
  12. Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology
  13. Collins, CD. (2005). "Problems monitoring response in multiple myeloma". Cancer Imaging. 5 Spec No A: S119–26. doi:10.1102/1470-7330.2005.0033. PMID 16361127.
  14. Seer stat fact sheet. National cancer institute (2015)http://seer.cancer.gov/statfacts/html/mulmy.html Accessed on September, 20th 2015
  15. Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September, 20th 2015
  16. Multiplemyeloma.Wikipedia(2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September, 20th 2015
  17. Multiple myeloma. Radiopaedia (2015)http://radiopaedia.org/articles/multiple-myeloma-1 Accessed on September, 20th 2015
  18. Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September, 20th 2015
  19. Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September, 20th 2015
  20. Press Releases. Compugen (2015)http://www.cgen.com/media-center/press-releases/-314 Accessed on September, 20th 2015
  21. Multiple myeloma. Radiopaedia (2015)http://radiopaedia.org/articles/multiple-myeloma-1 Accessed on September, 20th 2015
  22. Multiple myeloma. The American Cancer Society (2015) http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-risk-factors Accessed on September, 20 2015
  23. Multiple Myeloma Prevention and Screening.(2015)http://www.mdanderson.org/patient-and-cancer-information/cancer-information/cancer-types/multiple-myeloma/prevention/index.html
  24. Can multiple myeloma be prevented?(2015)http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-prevention
  25. Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Prognosis
  26. Multiple myeloma. National Cancer Institute(2015) www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq#link/_40_toc Accessed on September, 20th 2015
  27. Multiple myeloma. National Cancer Institute(2015) www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq#link/_40_toc Accessed on September, 20th 2015
  28. Multiple myeloma. Librepathology (2015)http://www.wikidoc.org/index.php?title=Multiple_myeloma_pathophysiology&action=edit&section Accessed on September, 20th 2015=1
  29. Plasma cell neoplasm. Cancer.gov (2015)http://www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq#link/_40_toc Accessed on September, 20th 2015
  30. Multiple myeloma. National Cancer Institute(2015) www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq#link/_40_toc Accessed on September, 20th 2015
  31. Greipp PR, San Miguel J, Fonseca R, Avet-Loiseau H, Jacobson JL, Rasmussen E, Crowley J, Durie BMG. Development of an international prognostic index (IPI) for myeloma: report of the international myeloma working group. Hematology Journal 2003;4:S42. NLM ID 100965523.


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