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Episode 128
DIP Episode 128 - USMLE Step 2CK Rapid Review Series 9 (IM) and a small update on the newer Step 2CK Questions
MixedMedium4 - HighHas Q&A
Step 2Step 3COMLEXMedicineUSMLEStep 2Step 3COMLEX
Topic
Multiple Myeloma; Acute Leukemias (ALL, CLL, AML); Systemic Vasculitis (GPA vs MPA); Scleroderma; Cardiac Murmur Workup.
Key Takeaway
The USMLE Step 2CK emphasizes pattern recognition and differential diagnosis across multiple systems, requiring students to synthesize findings from hematology, rheumatology, and cardiology rather than simply recalling isolated facts.
Runtime: 44 min
Published: 2019-07-28
Completed audio: Yes
Completed notes: Yes
Anki made: No
Section: RAPID REVIEW SERIES
Episode Notes
Source / episode info
- Episode: 128
- Published: 2019-07-28
- Source: Episode page
One-liner
This episode reviews high-yield patterns in hematologic malignancies (Myeloma, Leukemia), systemic vasculitis (GPA/MPA), connective tissue diseases (Scleroderma), and cardiac physical exam findings, emphasizing differential diagnosis over rote memorization.
High-yield summary
- Multiple Myeloma: Classic triad includes hypercalcemia, renal insufficiency, anemia, and bone pain due to osteoclast activation; lytic lesions are common. The mnemonic for associated cancers causing lytic lesions is L-T-R (Lung, Thyroid, Renal) + Multiple Myeloma.
- Acute Leukemias: Remember the age extremes: ALL in childhood/young adults; CLL in elderly patients. Smudge cells are pathognomonic for CLL.
- CML Management: CML is associated with the Philadelphia chromosome ({t}(9;22)) and BCR-ABL fusion protein, treated with a tyrosine kinase inhibitor (TKI) like Imatinib.
- Vasculitis Differentiation: Granulomatosis with Polyangiitis (GPA) is strongly associated with c-ANCA positive findings. Microscopic Polyangiitis (MPA) and other ANCA vasculitides are typically p-ANCA positive.
- Scleroderma Diagnosis: The limited form is characterized by the CREST criteria (Calcinosis, Raynaud's phenomenon, esophageal dysmotility, Sclerodactyly, Telangiectasia). Anti-centromere antibodies are associated with the limited form.
- Cardiac Murmur Workup: Any systolic murmur 2/6 or any murmur needs workup (Echo), unless it is a very faint systolic ejection murmur (1/6).
Learning objectives
- Differentiate between various acute and chronic leukemias based on age of onset, peripheral smear findings, and immunophenotype.
- Apply the mnemonic L-T-R to identify potential sources of lytic bone lesions in multiple myeloma.
- Distinguish between primary systemic vasculitides (e.g., GPA vs MPA) using specific ANCA antibodies and clinical presentations.
- Recognize the key features and associated antibodies for limited versus diffuse cutaneous systemic sclerosis.
- Interpret physical exam findings, particularly cardiac murmurs, to determine the necessity of advanced imaging (Echo).
Board exam buzzwords
| Condition | Key Finding | Association | Board Exam Tip |
| Multiple Myeloma | Lytic bone lesions; Hypercalcemia | Osteoclast activation; Plasma cell proliferation | Remember the mnemonic: Lung, Thryoid, Renal + MM. |
| Chronic Lymphocytic Leukemia (CLL) | Smudge cells on peripheral smear | Age-related accumulation of mature B-cells | CLL is an "old person's disease." |
| Granulomatosis with Polyangiitis (GPA) | c-ANCA positive; Sinusitis, Hemoptysis | Type III hypersensitivity reaction | GPA classically involves the upper airways. |
| Limited Systemic Sclerosis | CREST criteria; Anti-centromere antibodies | Calcinosis, Raynaud's, esophageal dysmotility, Sclerodactyly, Telangiectasia | The anti-Scl-70 antibody is associated with the diffuse form. |
Rapid review table
| Topic | Key Point | Context | Exam Relevance |
| Multiple Myeloma | Plasma cell infiltration of bone marrow; Lytic lesions | Hypercalcemia, renal failure, anemia (CRAB criteria) | Must differentiate from other causes of lytic bone disease. |
| CML | {t}(9;22) translocation; BCR-ABL fusion protein | Chronic myeloproliferative disorder; progressive phase | Treatment is a TKI (Imatinib). |
| GPA vs MPA | GPA = c-ANCA positive; MPA/other = p-ANCA positive | Systemic vasculitis presenting with glomerulonephritis and airway disease. | Knowing the specific ANCA type helps narrow the diagnosis significantly. |
| Scleroderma Crisis | Vasospastic episodes (Raynaud's); Scleroderma Renal Crisis (SRC) | Anti-centromere/Anti-Scl-70 antibodies; Fibroblast dysregulation | Avoid vasodilators and Triptans during crises due to risk of vasospasm. |
Board-speak -> diagnosis
| Board-speak / Vignette phrase | Diagnosis / Concept | Why it fits |
| Elderly patient with pancytopenia, dry tap on bone marrow aspiration, and history of myeloproliferative disorder. | Primary Myelofibrosis (PMF) or Aplastic Anemia | Dry tap suggests fibrosis/replacement; PMF is a key differential for this triad. |
| Young child presenting with fever, weight loss, and positive T-cell immunophenotyping on flow cytometry. | Acute Lymphoblastic Leukemia (ALL) | ALL is the most common childhood leukemia, often associated with Down syndrome. |
| Middle-aged man with elevated WBC count, smudge cells on smear, and recurrent infections. | Chronic Lymphocytic Leukemia (CLL) | CLL is characterized by mature B-cell accumulation, typically seen in older adults, and smudge cells are classic findings. |
| Patient presenting with hemoptysis, sinusitis, and glomerulonephritis; c-ANCA positive. | Granulomatosis with Polyangiitis (GPA) | GPA classically presents with upper airway/sinus involvement and is associated with c-ANCA antibodies. |
| 35-year-old female with Raynaud's phenomenon, esophageal dysmotility, and anti-centromere antibodies. | Limited Systemic Sclerosis (CREST Syndrome) | The constellation of symptoms and specific antibody profile define the limited cutaneous form. |
| Patient presenting with a systolic murmur 2/6 at the apex during an annual physical exam. | Mitral Stenosis workup required | Any significant or concerning murmur requires further investigation, typically starting with TTE (Transthoracic Echocardiogram). |
Differential diagnosis / distinguishing features
Dry Tap on Bone Marrow Aspiration
| Key Features | Distinguishing Findings | Next Step |
| Primary Myelofibrosis (PMF) | Pancytopenia, dry tap; Often associated with a myeloproliferative disorder. | Rule out other causes of marrow failure/fibrosis. |
| Aplastic Anemia | Pancytopenia, dry tap; Bone marrow hypocellularity. | Determine underlying cause (e.g., nutritional deficiency). |
| Osteosclerosis/Infection | Localized bone pathology or infection. | Perform appropriate imaging and cultures. |
Cardiac Murmur Workup
| Key Features | Distinguishing Findings | Next Step |
| Systolic murmur 2/6 (or any murmur) | Suggests structural heart disease; Mitral Stenosis often presents with a diastolic rumble and opening snap. | Transthoracic Echocardiogram (TTE) is mandatory. |
| Faint systolic ejection murmur (1/6) | Usually benign; Low suspicion of significant valvular pathology. | Reassurance, but always consider the patient's risk factors. |
Management pearls
- For suspected Multiple Myeloma, perform SPEP and UPEP to look for a monoclonal spike (M-spike). A bone marrow biopsy showing >10\% plasma cells is required for diagnosis.
- In CML, the \text{t}(9;22) translocation leads to BCR-ABL protein, which must be inhibited by TK Is like Imatinib.
- When managing scleroderma renal crisis (SRC), Angiotensin II Receptor Blockers (AR Bs) or Endothelin Inhibitors are preferred agents over vasodilators due to the risk of inducing further vasospasm.
- If a patient has an asthma history, avoid adenosine analogs (e.g., Regadenoson) and nonselective beta-blockers during cardiac stress testing due to risks of bronchoconstriction/bronchospasm.
Don't miss
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Lytic Bone Lesions: The mnemonic L-T-R (Lung, Thyroid, Renal) is crucial for remembering common sources of lytic bone lesions besides Multiple Myeloma.
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CLL Presentation: CLL is typically an insidious disease presenting in the elderly with recurrent infections and lymphocytosis; it is not a rapidly progressive illness like ALL.
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ANCA Vasculitis Specificity: Always correlate clinical presentation (e.g., upper airway involvement) with the specific ANCA antibody type (c-ANCA -> GPA).
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Cardiac Murmur Threshold: The threshold for mandatory echo workup is generally a murmur of 2/6 or greater, regardless of whether it is systolic or diastolic.
Integration & clinical reasoning
OMM / COMLEX integration
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For COMLEX: know these viscerosomatics / Chapman points, but don't let OMM distract from emergent diagnosis and management.
- Hematology -> Nephrology: Multiple Myeloma causes kidney failure via light chain deposition (cast nephropathy).
- Rheumatology -> Pulmonology/Nephrology: Systemic Sclerosis can cause pulmonary hypertension and renal crisis (SRC).
- Immunology -> Airway/Kidney: ANCA vasculitides target small vessels, causing glomerulonephritis (nephritic syndrome) and often affecting the sinuses/airways.
Concept connections / cross-references
- For detailed review on connective tissue disorders and their specific antibodies: [Link to Scleroderma Episode]
- For comprehensive coverage of hematologic malignancies and bone marrow pathology: [Link to Hematology Episode]
- For general principles of vasculitis classification and management: [Link to Vasculitis Episode]
High-yield association table
| Condition | Association | Mechanism | Clinical Significance |
| Multiple Myeloma | Lytic Bone Lesions | Osteoclast activation by plasma cells; Plasma cell infiltration. | Leads to CRAB criteria (Hypercalcemia, Renal failure, Anemia, Bone pain). |
| CML | Philadelphia Chromosome ({t}(9;22)) | BCR-ABL fusion protein creates a constitutively active tyrosine kinase. | Requires specific TKI therapy (Imatinib); prognosis improves dramatically with treatment. |
| GPA | c-ANCA positive | Autoantibodies targeting cytoplasmic components of neutrophils/granulocytes. | Strong association with upper airway involvement and necrotizing vasculitis. |
| Scleroderma | Anti-centromere antibodies | Associated with the limited cutaneous form (CREST). | Indicates a specific subset of systemic sclerosis requiring targeted management. |
Key terms glossary
| Term | Definition | Context | Example |
| Smudge Cells | Fragile, discoid lymphocytes seen on peripheral smear. | Chronic Lymphocytic Leukemia (CLL) | Pathognomonic finding for CLL; due to cell fragility during blood collection. |
| c-ANCA | Cytoplasmic anti-neutrophil cytoplasmic antibody. | Granulomatosis with Polyangiitis (GPA) | Highly specific marker for GPA, suggesting upper airway involvement. |
| CREST Syndrome | A limited form of systemic sclerosis defined by five criteria. | Connective Tissue Disease | Calcinosis, Raynaud's, esophageal dysmotility, Sclerodactyly, Telangiectasia. |
| BCR-ABL Fusion Protein | Abnormal protein formed by the {t}(9;22) translocation. | Chronic Myeloid Leukemia (CML) | The molecular target for tyrosine kinase inhibitors like Imatinib. |
Study optimization
| Topic | Study Approach | Priority | Resources |
| Hematologic Malignancies | Use algorithms: Age extremes, smear findings, and specific translocations/antibodies. | High | Review flowcharts comparing ALL vs CLL vs AML; memorize the L-T-R mnemonic. |
| Systemic Vasculitis | Focus on ANCA specificity (c-ANCA -> GPA) and clinical presentation (airway involvement). | Medium-High | Create a comparison table of vasculitides, linking symptoms to antibodies. |
| Cardiac Murmur Workup | Apply physical exam rules: Use the murmur grade/type to determine if an Echo is needed; know stress test contraindications. | High | Practice interpreting murmurs and correlating them with underlying pathology (e.g., opening snap -> MS). |
Question pattern recognition
- The "Best Answer" Trap: In multiple choice questions, do not choose the answer that seems most obvious (e.g., just because there is bone pain, assume osteoporosis); instead, select the diagnosis that best explains all given lab and clinical findings (e.g., Multiple Myeloma).
- The "Age Extreme" Pattern: When diagnosing leukemia, always consider age: young -> ALL; old -> CLL.
- The "Specific Antibody/Organ System" Link: High-yield questions link specific antibodies to specific organ systems or diseases (e.g., Anti-centromere -> CREST).
Test yourself
Common mistakes to avoid
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Misinterpreting Bone Pain: Assuming that any palpable step-off or bone pain in an elderly patient automatically means osteoporosis; a thorough workup for Multiple Myeloma is required first.
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Confusing ANCA Markers: Mistaking which specific antibody (c-ANCA vs p-ANCA) correlates with which vasculitis (GPA vs MPA). Always link the clinical presentation (e.g., upper airway involvement -> GPA/c-ANCA).
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Ignoring Age Extremes in Leukemia: Failing to consider that CLL is an "old person's disease" and ALL is a pediatric malignancy, even if the patient presents atypically.
Common traps
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The "Most Obvious Answer" Trap (MM): The question may highlight a palpable step-off or bone pain, leading the student to choose osteoporosis/fracture workup (DEXA scan). However, the combination of hypercalcemia, renal failure, and lytic lesions points overwhelmingly to Multiple Myeloma.
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The "Single Symptom" Trap (Vasculitis): A patient may only present with glomerulonephritis. The student must use the full clinical picture (e.g., sinusitis/hemoptysis) combined with serology (c-ANCA) to pinpoint GPA, rather than just treating the kidney failure.
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The "Drug Choice" Trap (Scleroderma): When managing a vasospastic crisis, choosing a drug that causes or worsens vasoconstriction (like Triptans) is incorrect; the goal is to avoid agents that trigger spasm.