THE CLINICAL PHOTOS
What These Diseases Look Like
Peripheral blood smears, bone marrow biopsies, and histologic patterns. Tap any image for full view.
CML: peripheral smear
Burkitt: starry sky
APL: Auer rods
The Six Translocations
Each translocation creates a fusion gene or puts a normal gene under the wrong promoter. The result: a protein that is either permanently active or massively overproduced.
- t(9;22) BCR-ABL: constitutive tyrosine kinase (CML)
- t(14;18) BCL-2 overexpression: blocks apoptosis (follicular lymphoma)
- t(8;14) c-MYC overexpression: maximal cell cycle drive (Burkitt lymphoma)
- t(11;14) Cyclin D1 overexpression: G1/S checkpoint bypass (mantle cell lymphoma)
- t(15;17) PML-RARA fusion: blocks myeloid differentiation (APL)
- t(11;22) EWS-FLI1 fusion: aberrant transcription factor (Ewing sarcoma)
★
The pattern: "Philadelphia chromosome, translocation t(9;22). Approximately 95% of patients will have it." About 95% of CML patients carry this translocation. Imatinib, a tyrosine kinase inhibitor ending in "-tinib," targets BCR-ABL and turned CML from a fatal disease into a manageable chronic one.
01 · PATTERN LOCK
Translocation Match Game
Select a translocation on the left, then its disease on the right. Wrong pairs get full teaching.
Translocation
Disease
02 · CLINICAL DEDUCTION
Elimination Game
Four vignettes. Clues narrow the field one by one. Only one diagnosis survives.
A 7-year-old boy from Uganda presents with a rapidly enlarging mass on his right jaw over 3 weeks. The mass is firm and non-tender, approximately 6 cm. Labs show LDH 1,450 U/L. Biopsy obtained.
Follicular Lymphoma
Burkitt Lymphoma
Mantle Cell Lymphoma
Hodgkin Lymphoma
Clue 1: Biopsy shows a "starry sky" pattern with sheets of basophilic cells and scattered tangible-body macrophages. Follicular shows nodular follicles. Mantle cell shows monotonous small cells. Follicular and Mantle Cell eliminated.
Clue 2: African child with jaw mass. Endemic Burkitt is strongly EBV-associated. Hodgkin presents with painless cervical lymphadenopathy and Reed-Sternberg cells. Translocation: t(8;14), overexpressing c-MYC. Hodgkin eliminated.
Burkitt Lymphomat(8;14) · c-MYC · Starry sky · EBV endemic form · Jaw mass · Fastest-growing human tumor
A 52-year-old man with fatigue and early satiety. Spleen palpable 8 cm below costal margin. WBC 148,000/mcL, all stages of myeloid maturation, basophilia 6%, 2% blasts. LAP score low.
AML
CML
CLL
Leukemoid Reaction
Clue 1: All stages of myeloid maturation with only 2% blasts. AML shows >20% blasts with maturation arrest. CLL is lymphocytic. AML and CLL eliminated.
Clue 2: LAP score is low. Leukemoid reaction has HIGH LAP (healthy neutrophils). CML neutrophils are neoplastic with low alkaline phosphatase. Basophilia clinches CML. Translocation: t(9;22), Philadelphia chromosome, BCR-ABL. Treatment: imatinib. Leukemoid Reaction eliminated.
Chronic Myelogenous Leukemiat(9;22) · Philadelphia chromosome · BCR-ABL · Low LAP · Basophilia · Imatinib
A 28-year-old woman presents with gum bleeding, ecchymoses, and fatigue over 1 week. Labs: WBC 1,800, platelets 22,000, fibrinogen 78 (low), D-dimer elevated. Smear shows cells with heavy azurophilic granules and multiple Auer rods in bundles.
AML (M2)
APL (M3)
ALL
CML blast crisis
Clue 1: Multiple Auer rods in bundles (faggot cells) are pathognomonic for APL. Other AML subtypes may have single Auer rods. ALL has no Auer rods (lymphoblastic). AML (M2) and ALL eliminated.
Clue 2: DIC (low fibrinogen, high D-dimer, bleeding). Procoagulant granules from abnormal promyelocytes trigger the clotting cascade. CML blast crisis does not classically present with DIC and faggot cells. Translocation: t(15;17), PML-RARA. Treatment: ATRA. "A simple vitamin tablet saves lives." CML blast crisis eliminated.
Acute Promyelocytic Leukemia (APL)t(15;17) · PML-RARA · DIC · Auer rods · ATRA forces maturation · Most curable AML
A 14-year-old boy presents with left thigh pain worsening over 6 weeks, not responsive to NSAIDs. X-ray shows a lytic lesion in the diaphysis of the femur with a lamellated periosteal reaction. Biopsy shows sheets of small round blue cells. Immunostaining is CD99 positive.
Osteosarcoma
Ewing Sarcoma
Chondrosarcoma
Lymphoma of bone
Clue 1: Diaphysis location and "onion-skin" (lamellated) periosteal reaction. Osteosarcoma affects the metaphysis and shows a sunburst pattern. Chondrosarcoma is a tumor of older adults. Osteosarcoma and Chondrosarcoma eliminated.
Clue 2: Small round blue cells and CD99 positive are the histologic and immunophenotypic hallmarks of Ewing sarcoma. Primary bone lymphoma is CD99 negative. Translocation: t(11;22), EWS-FLI1. Peak ages 10 to 20. Lymphoma of bone eliminated.
Ewing Sarcomat(11;22) · EWS-FLI1 · Onion-skin periosteal reaction · Diaphysis · CD99+ · Small round blue cells
03 · BOARD-STYLE WALKTHROUGH
Clinical Vignettes
25 original board-style questions with post-answer clue highlights and tap-to-reveal teaching chains.
