WBR0430

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Will Gibson, Yazan Daaboul, M.D., and Alison Leibowitz [1])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathology
Sub Category	SubCategory::Hematology, SubCategory::Oncology
Prompt	[[Prompt::A 78-year-old man presents to the physician’s office with complaints of back pain and fatigue for the past few weeks. The patient explains that unlike his previous pains, his current back pain awakens him at night and is not relieved by medications. Evaluation reveals normochromic normocytic anemia, elevated concentration of serum calcium, and renal insufficiency. Peripheral smear of the patient’s blood demonstrates rouleaux formation. Which of the following markers is most frequently used for the staging of the patient's condition?]]
Answer A	AnswerA::BUN/creatinine ratio
Answer A Explanation	[[AnswerAExp::The BUN/creatinine ratio may distinguish between types of renal injury (pre-renal, instrinsic, or post-renal). Renal function, however, is associated with the prognosis of multiple myeloma.]]
Answer B	AnswerB::Serum β2 microglobulin and albumin concentrations
Answer B Explanation	AnswerBExp::Serum β2 microglobulin and albumin concentrations are used by the ISS for staging multiple myeloma.
Answer C	AnswerC::Serum CA-125 concentration
Answer C Explanation	AnswerCExp::Serum CA-125 concentration may be helpful in the diagnosis and follow-up of patients with ovarian cancer.
Answer D	AnswerD::Serum calcium concentration
Answer D Explanation	AnswerDExp::Multiple myeloma causes lytic lesions in the bone, which releases calcium stored in bone. However, serum calcium concentratiaon is not used for the staging of multiple myeloma.
Answer E	AnswerE::Spread to lymph nodes
Answer E Explanation	AnswerEExp::The majority of solid tumors are staged with the classical TNM staging system. However, multiple myeloma is not staged by the classical TNM staging system, and spread to lymph node is not useful in the staging of multiple myeloma.
Right Answer	RightAnswer::B
Explanation	[[Explanation::Multiple myeloma is a plasma cell proliferative disorder characterized by monoclonal gammopathy (elevated concentration of IgM and IgG). It frequently manifests with hypercalcemia, renal insufficiency, anemia (usually normocytic normochromic, but may be mildly macrocytic), and lytic bone lesions. Rouleaux formation on peripheral smear is also characteristic. The gold standard for the diagnosis of multiple myeloma is serum and urine protein electrophoresis to evaluate for paraprotein peaks in abnormal zones. Multiple myeloma is not usually staged using the TNM system. Instead, the International Staging System (ISS) for multiple myeloma depends on concentrations of serum β2 microglobulin and albumin. Stage I: Serum β2 microglobulin < 3.5 mg/L and serum albumin ≥ 3.5 g/dL Stage II: Between stage I and III Stage III: Serum β2 microglobulin ≥ 5.5 mg/L β2 microglobulin is an important structural component of the functional MHC class I complex and is expressed by all nucleated cells. β2 microglobulin is overexpressed by myeloma cells for reasons that are poorly understood. β2 microglobulin is also readily filtered by the glomerulus and therefore is a marker of renal function. The serum concentration of β2 microglobulin thus reflects a combined measure of the tumor burden and decline in renal function among patients with multiple myeloma. The association of declining albumin with myeloma prognosis is less clear. Educational Objective: Multiple myeloma is a plasma cell proliferative disorder characterized by monoclonal gammopathy (elevated concentration of IgM and IgG). It frequently manifests with hypercalcemia, renal insufficiency, anemia, and lytic bone lesions. Rouleaux formation on peripheral smear is also characteristic. Multiple myeloma is not usually staged using the TNM system. Instead, the International Staging System (ISS) for multiple myeloma depends on concentrations of serum β2 microglobulin and albumin. References: Mihou D, Katodritou E, Zervas K. Multiple myeloma staging based on the combination of beta-2-microglobulin and albumin: the role of albumin in the model. Hematology. 2007;12(6):527-31. Greipp PR, San miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23(15):3412-20. First Aid 2014 page 393]]
Approved	Approved::Yes
Keyword	WBRKeyword::β2 microglobulin, WBRKeyword::Albumin, WBRKeyword::Cancer, WBRKeyword::Plasma cell proliferative disorder, WBRKeyword::Multiple myeloma, WBRKeyword::Anemia, WBRKeyword::Hypercalcemia, WBRKeyword::Bone, WBRKeyword::Staging, WBRKeyword::ISS, WBRKeyword::Rouleaux formation, WBRKeyword::Rouleaux
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