WBR0430

Author	[[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Will Gibson and Alison Liebowitz)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathology
Sub Category	SubCategory::Hematology, SubCategory::Oncology
Prompt	[[Prompt::A 78-year-old male presents to the physician’s office with complaints of back pain, which is not relieved by medications, and fatigue of several weeks duration. Evaluation reveals anemia, elevated levels of serum calcium, and renal insufficiency. A peripheral smear of the patient’s blood shows characteristic “rouleaux formation”, characteristic of multiple myeloma. Which of the following markers is most frequently used for the staging of multiple myeloma?]]
Answer A	AnswerA::BUN/Creatinine ratio
Answer A Explanation	[[AnswerAExp::The BUN/Creatinine ratio aids in distinguishing between types of renal injury (pre-renal, instrinsic, or post-renal). It is not useful for staging multiple myeloma.]]
Answer B	AnswerB::β2 microglobulin and albumin levels
Answer B Explanation	AnswerBExp::Serum β2 microglobulin and albumin levels are used by the ISS for staging multiple myeloma.
Answer C	AnswerC::CA-125 level
Answer C Explanation	AnswerCExp::CA-125 levels are frequently checked in the follow-up of patients with ovarian cancer, but should not be used for diagnostic purposes.
Answer D	AnswerD::Serum calcium
Answer D Explanation	AnswerDExp::Multiple myeloma causes lytic lesions in the bone, thereby releasing stored calcium. However, serum calcium is not a prognostic marker for multiple myeloma patients.
Answer E	AnswerE::Spread to lymph nodes
Answer E Explanation	[[AnswerEExp::Most solid tumors utilize the TNM staging system in which the following three stages exist. Stage 1: Tumor is confined to the primary site. Stage 2: The tumor has spread to the lymph nodes. Stage 3: The tumor has distant metastases. In contrast, the International Staging System is used for multiple myeloma. Lymph node involvement is not one of the criteria in this framework.]]
Right Answer	RightAnswer::B
Explanation	[[Explanation::Multiple myeloma, a common hematologic cancer characterized by monoclonal gammopathy, frequently manifests with hypercalcemia, renal insufficiency, anemia, and lytic bone lesions (mnemonic: CRAB – Calcium, Renal, Anemia, Bone). Rouleaux formation on peripheral smear is also characteristic of multiple myeloma. Multiple myeloma staging does not utilize the TNM system. Instead, the International Staging System (ISS) for multiple myeloma depends on levels 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 Recall that 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 unknown reasons. β2 microglobulin is also readily filtered by the glomerulus and therefore reflects renal function. The serum concentration of β2 microglobulin thus reflects a combined measure of the tumor burden and decline in renal function in myeloma patients. It is the single greatest independent predictor of prognosis. The association of declining albumin with myeloma prognosis is less clear. Nevertheless, the International Staging System ultimately uses both β2 microglobulin and albumin to determine stage. Educational Objective: Multiple myeloma staging does not utilize the TNM system. Instead, the International Staging System (ISS) for multiple myeloma is dependent on levels 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.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Beta-2-microglobulin, WBRKeyword::Albumin, WBRKeyword::Multiple myeloma, WBRKeyword::Anemia, WBRKeyword::Hypercalcemia, WBRKeyword::Bone, WBRKeyword::Renal, WBRKeyword::Staging, WBRKeyword::ISS, WBRKeyword::Rouleaux formation, WBRKeyword::Rouleaux
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