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Sample QuestionsFree hematology and oncology board review sample questions

11 board-style questions with answers and explanations, one for each major blueprint area.
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Written and reviewed by Veli Bakalov, MD, hematologist and medical oncologist

11 board-style questions across the ABIM Medical Oncology and Hematology blueprints, one per major area, each with the answer, explanation and references. They come from the free HemeOncBuddy Qbank, which has 2,182 more with tutor, test and timed modes.

Question 1 · Solid Tumors · Breast

A 42-year-old otherwise healthy woman has recently been diagnosed with a clinical pT2N0, estrogen receptor-positive, progesterone receptor-positive, and HER2-negative breast cancer. She is adopted and does not know her family history. You recommend she undergo genetic testing given her young age at diagnosis and her unknown family history.

Which of the following gene mutations is also associated with an increased risk of ovarian cancer?

  1. Li-Fraumeni syndrome (TP53)
  2. Cowden syndrome (PTEN)
  3. Hereditary diffuse gastric cancer syndrome (CDH1)
  4. Lynch syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM)
Show answer and explanation

Answer: D. Lynch syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM)

Of the listed genetic mutations associated with breast cancer, only the Lynch syndrome genes (MLH1, MSH2, MSH6, PMS2, EPCAM) have been associated with an increased risk of ovarian and endometrial cancer.

References: Daly MB, Pilarski R, Yurgelun MB, et al. NCCN guidelines insights: genetic/familial high-risk assessment: breast, ovarian, and pancreatic, Version 1.2020. J Natl Compr Canc Netw. 2020;18(4):380-391. doi:10.6004/jnccn.2020.0017; NCCN Genetic/Familial High-Risk Assessment; Lynch syndrome

Study it: board review note.

Question 2 · Solid Tumors · Gastrointestinal

A 70-year-old woman with a history of stage IIIA ascending colon cancer is evaluated at your clinic. Immunohistochemistry reveals a loss of MLH1 and PMS2 expression in tumor cells, but expression within normal limits in adjacent normal colon tissue. She received adjuvant chemotherapy with capecitabine and oxaliplatin. Three months after completing adjuvant chemotherapy, her carcinoembryonic antigen (CEA) level has increased and restaging scans reveal metastatic disease.

Which of the following genetic alterations would you expect to find in this patient?

  1. KRAS G12D mutation
  2. APC inactivating mutation
  3. HER2 amplification
  4. BRAF V600E mutation
Show answer and explanation

Answer: D. BRAF V600E mutation

In this patient with a right-sided colon tumor, loss of MLH1 and PMS2 only in the tumor tissue, normal MLH1 and PMS2 expression in adjacent colon cells, and advanced age, findings point to a sporadic mismatch repair (MMR)-deficient case, unrelated to Lynch syndrome. This happens as a result of hypermethylation of MLH1 promoter sequence and phenotypically behaves like MMR-deficient or high microsatellite instable (MSI-high) tumors. Tumor Comprehensive Genetic Assessment (TCGA) data reveals that BRAF V600E mutations are frequent in MSI tumors (about 47% of cases). Genes that are frequently altered in microsatellite stable colorectal cancers are APC, RAS, TP53, and PI3KCA. HER2 amplifications constitute a minority of colorectal cancer cases (3%-6%).

References: Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012;487(7407):330-337. Published 2012 Jul 18. doi:10.1038/nature11252; Inamura K. Colorectal cancers: an update on their molecular pathology. Cancers (Basel). 2018;10(1):26. Published 2018 Jan 20. doi:10.3390/cancers10010026

Study it: board review note.

Question 3 · Solid Tumors · Thoracic

A 58-year-old lifelong nonsmoker presents with cough and is found to have a 4 cm right lower lobe mass with bilateral lung nodules and a malignant pleural effusion. Core biopsy shows adenocarcinoma. Next-generation sequencing reveals an EGFR exon 19 deletion, and PD-L1 tumor proportion score is 60%. She has an ECOG performance status of 0 and no symptomatic central nervous system disease.

Which first-line systemic therapy is most appropriate?

  1. Pembrolizumab monotherapy
  2. Osimertinib
  3. Carboplatin, pemetrexed, and pembrolizumab
  4. Carboplatin and paclitaxel
Show answer and explanation

Answer: B. Osimertinib

For metastatic EGFR exon 19 deletion or L858R NSCLC, the third-generation EGFR tyrosine kinase inhibitor osimertinib is the preferred first-line option, with the FLAURA trial demonstrating superior progression-free and overall survival versus first-generation EGFR inhibitors. A high PD-L1 score does not change this; immune checkpoint inhibitors are notably less effective in EGFR-mutant disease and carry added toxicity risk when combined or sequenced with TKIs.

References: FLAURA trial (osimertinib first-line EGFR-mutant NSCLC), NEJM 2018

Study it: board review note.

Question 4 · Solid Tumors · Genitourinary

A 67-year-old man presents with bone pain and is found to have a PSA of 240 ng/mL with multiple osteoblastic metastases on bone scan involving the spine, pelvis, ribs, and femurs (high-volume disease). Biopsy confirms Grade Group 5 adenocarcinoma. He has an ECOG performance status of 1 and good organ function.

In addition to androgen deprivation therapy, which of the following is the most appropriate initial systemic treatment?

  1. Addition of an androgen receptor pathway inhibitor (e.g., abiraterone or an ARPI), with or without docetaxel
  2. ADT alone
  3. Sipuleucel-T
  4. Radium-223
Show answer and explanation

Answer: A. Addition of an androgen receptor pathway inhibitor (e.g., abiraterone or an ARPI), with or without docetaxel

In metastatic castration-sensitive prostate cancer, ADT alone is no longer adequate. Trials such as LATITUDE/STAMPEDE (abiraterone), TITAN (apalutamide), ARCHES/ENZAMET (enzalutamide), and CHAARTED/STAMPEDE (docetaxel) established that adding an ARPI (with intensification to a triplet of ADT + ARPI + docetaxel in fit patients with high-volume disease per PEACE-1/ARASENS) improves overall survival. Sipuleucel-T and radium-223 are reserved for the castration-resistant setting.

References: LATITUDE; ARASENS; PEACE-1

Study it: board review note.

Question 5 · Malignant Heme · Leukemia

A 70-year-old man is found on routine labs to have a lymphocyte count of 22,000/microL. Flow cytometry of peripheral blood shows a clonal B-cell population that is CD5 positive, CD23 positive, CD19 positive, with dim surface immunoglobulin and dim CD20.

Which diagnosis does this immunophenotype most strongly support?

  1. Burkitt lymphoma
  2. Chronic lymphocytic leukemia
  3. Follicular lymphoma
  4. Hairy cell leukemia
Show answer and explanation

Answer: B. Chronic lymphocytic leukemia

The classic CLL immunophenotype is a CD5-positive, CD23-positive, CD19-positive clonal B-cell population with dim surface immunoglobulin and dim CD20. This combination, with an absolute clonal B-lymphocytosis of at least 5,000/microL, defines CLL. Follicular lymphoma is CD10-positive/CD5-negative, and hairy cell leukemia expresses CD11c, CD25, CD103, and CD123.

References: iwCLL criteria; iwCLL 2018 diagnostic criteria (Hallek et al, Blood 2018)

Study it: board review note.

Question 6 · Malignant Heme · Lymphoma

A 45-year-old woman with advanced classic Hodgkin lymphoma has a history of bleomycin-related pulmonary toxicity from a prior unrelated exposure, raising concern about BV-AVD-associated peripheral neuropathy as well. Her oncologist discusses a checkpoint-inhibitor-based frontline approach studied in a recent randomized trial.

Which agent, combined with AVD, improved progression-free survival versus BV-AVD in frontline advanced-stage Hodgkin lymphoma?

  1. Rituximab
  2. Blinatumomab
  3. Nivolumab
  4. Bevacizumab
Show answer and explanation

Answer: C. Nivolumab

The SWOG S1826 trial randomized advanced-stage Hodgkin lymphoma patients to nivolumab-AVD versus BV-AVD and showed improved progression-free survival with the PD-1 inhibitor nivolumab. Reed-Sternberg cells frequently have 9p24.1 alterations amplifying PD-L1/PD-L2, providing the biologic rationale. Rituximab targets CD20 (not on classic RS cells), and blinatumomab and bevacizumab have no established role here.

References: SWOG S1826 (Herrera NEJM 2024); Herrera AF et al. Nivolumab+AVD in Advanced-Stage Classic Hodgkin's Lymphoma (SWOG S1826). NEJM 2024

Study it: board review note.

Question 7 · Malignant Heme · Multiple Myeloma

A 58-year-old woman with newly diagnosed multiple myeloma has good performance status and adequate organ function, making her a candidate for high-dose therapy with autologous stem cell transplant. Her oncologist plans an anti-CD38-based induction quadruplet supported by recent randomized data.

Which induction regimen reflects this approach (as studied in the PERSEUS trial)?

  1. Melphalan and prednisone alone
  2. R-CHOP
  3. Single-agent dexamethasone
  4. Daratumumab plus bortezomib, lenalidomide, and dexamethasone (D-VRd)
Show answer and explanation

Answer: D. Daratumumab plus bortezomib, lenalidomide, and dexamethasone (D-VRd)

For transplant-eligible newly diagnosed myeloma, daratumumab (anti-CD38) added to bortezomib, lenalidomide, and dexamethasone (D-VRd) improved progression-free survival and deepened responses, as shown in PERSEUS (and GRIFFIN). Melphalan-prednisone and single-agent dexamethasone are outdated as primary induction, and R-CHOP is a lymphoma regimen.

References: PERSEUS (Sonneveld NEJM 2024); GRIFFIN; PERSEUS: D-VRd vs VRd, transplant-eligible NDMM (Sonneveld P, NEJM 2024)

Study it: board review note.

Question 8 · Malignant Heme · MDS/MPN

A 68-year-old woman with anemia is diagnosed with MDS. Her bone marrow shows more than 15% ring sideroblasts on iron staining, and NGS identifies an SF3B1 mutation. She is transfusion-dependent but has lower-risk disease. Erythropoiesis-stimulating agents have failed.

Which agent is indicated to reduce transfusion burden in this lower-risk, ring-sideroblast-positive MDS?

  1. Decitabine
  2. Lenalidomide
  3. Luspatercept
  4. Ruxolitinib
Show answer and explanation

Answer: C. Luspatercept

Luspatercept is an erythroid maturation agent that traps TGF-beta superfamily ligands and improves late-stage erythropoiesis. The MEDALIST trial showed it reduced transfusion dependence in lower-risk MDS with ring sideroblasts who were refractory to or ineligible for ESAs. The SF3B1 mutation is tightly associated with the ring sideroblast phenotype and a relatively favorable prognosis.

References: MEDALIST; Fenaux et al., MEDALIST trial (luspatercept in RS+ lower-risk MDS), NEJM 2020

Study it: board review note.

Question 9 · Benign Heme · Hemostasis & thrombosis

A 44-year-old woman presents with confusion, fever, and bruising. Labs show hemoglobin 8 g/dL, platelets 15,000/microL, elevated LDH, low haptoglobin, and numerous schistocytes on the peripheral smear. Renal function is only mildly impaired, and coagulation studies (PT/PTT) are normal. ADAMTS13 activity is severely reduced.

What is the most appropriate immediate treatment?

  1. Platelet transfusion
  2. Broad-spectrum antibiotics alone
  3. Heparin infusion
  4. Urgent plasma exchange (with corticosteroids), with consideration of caplacizumab
Show answer and explanation

Answer: D. Urgent plasma exchange (with corticosteroids), with consideration of caplacizumab

This is thrombotic thrombocytopenic purpura: microangiopathic hemolytic anemia, thrombocytopenia, and neurologic changes with severely deficient ADAMTS13 activity (autoantibody-mediated). The cornerstone of therapy is urgent plasma exchange, which removes the inhibitor and replaces ADAMTS13, combined with corticosteroids. Caplacizumab (anti-von Willebrand factor) accelerates platelet recovery. Platelet transfusion is generally avoided unless life-threatening hemorrhage occurs, as it may worsen microthrombi.

References: ADAMTS13; plasma exchange; HERCULES (caplacizumab); HERCULES trial, caplacizumab in acquired TTP (Scully, NEJM 2019)

Study it: board review note.

Question 10 · Benign Heme · Anemias

A 70-year-old woman with rheumatoid arthritis on chronic therapy has a normocytic anemia with hemoglobin 10.4 g/dL. Ferritin is 280 ng/mL, transferrin saturation is 14%, total iron-binding capacity is low-normal, and C-reactive protein is elevated.

What is the central mediator responsible for the iron-restricted state in this condition?

  1. Erythropoietin deficiency
  2. Intravascular hemolysis
  3. Hepcidin excess
  4. Vitamin B12 deficiency
Show answer and explanation

Answer: C. Hepcidin excess

In anemia of inflammation, inflammatory cytokines (notably IL-6) drive hepatic hepcidin production, which degrades ferroportin and traps iron in macrophages and enterocytes, producing a low transferrin saturation with normal-to-high ferritin. This functional iron restriction limits erythropoiesis. The key principle is that hepcidin excess is the unifying mechanism of anemia of chronic disease.

References: Weiss G, Goodnough LT. Anemia of Chronic Disease. N Engl J Med. 2005;352(10):1011-1023.

Study it: board review note.

Question 11 · Cross-cutting · Transplant & immunotherapy

A 70-year-old woman on pembrolizumab for non-small cell lung cancer develops progressive dyspnea and a dry cough over two weeks. Chest CT shows new bilateral ground-glass opacities, and an infectious workup including respiratory cultures is negative.

Which is the most appropriate treatment for this likely immune-related toxicity?

  1. Continue immunotherapy unchanged and provide supplemental oxygen only
  2. Hold the checkpoint inhibitor and start corticosteroids for immune-related pneumonitis
  3. Initiate antifibrotic therapy (pirfenidone) as first-line treatment
  4. Begin diuresis for presumed heart failure
Show answer and explanation

Answer: B. Hold the checkpoint inhibitor and start corticosteroids for immune-related pneumonitis

New bilateral ground-glass opacities with dyspnea and a negative infectious workup in a patient on a PD-1 inhibitor are characteristic of immune-related pneumonitis, a potentially fatal toxicity. Management is to hold the checkpoint inhibitor and start systemic corticosteroids; steroid-refractory cases may require additional immunosuppression such as infliximab or mycophenolate. Prompt recognition is essential because pneumonitis can progress rapidly.

References: Checkpoint inhibitor pneumonitis; irAE guidelines; ASCO irAE Management Guideline Update, JCO 2021

Study it: board review note.

Frequently asked questions

Where can I find free hematology oncology board review questions?

These 11 questions come from the free HemeOncBuddy Qbank, which has 2,182 heme/onc board review questions with explanations, references, and tutor, test and timed modes. No login is needed.

Are these real ABIM questions?

No. They are original board-style questions written for HemeOncBuddy. They follow the ABIM blueprint areas but are not taken from any ABIM, ASCO or ASH exam.

Do these questions help with the LKA and the in-training exam?

Yes. The LKA, the ITE and the certification exams test the same blueprint areas. See the LKA and in-training exam guides for how to practice for each format.

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