A 35-year-old man presents with a mass on the central part of his neck. He reports it has been growing steadily for the past 2 weeks, and he has also been experiencing fatigue and recurrent fevers. No significant past medical history. The patient denies any smoking history, or alcohol or recreational drug use. He denies any recent travel in the previous 6 months. On physical examination, there are multiple enlarged submandibular and cervical lymph nodes that are firm, mobile, and non-tender. A biopsy of one of the lymph nodes is performed and shows predominantly lymphocytes and histiocytes present in a pattern ‘resembling popcorn’. A flow cytometry analysis demonstrates cells that are CD19 and CD20 positive and CD15 and CD30 negative. Which of the following is the most likely diagnosis in this patient?

Nodular lymphocyte-predominant Hodgkin lymphoma

Nodular sclerosis classical Hodgkin lymphoma

Lymphocyte depleted Hodgkin lymphoma

Mixed cellularity classical Hodgkin lymphoma

Lymphocyte rich classical Hodgkin lymphoma

A 52-year-old postmenopausal woman seeks evaluation at a medical clinic with complaints of back pain and increased fatigue for 6 months. For the past week, the back pain has radiated to her legs and is stabbing in nature (7/10 in intensity). There are no associated paresthesias. She unintentionally lost 4.5 kg (10.0 lb) in the past 6 months. There is no history of trauma to the back. The past medical history is insignificant and she does not take any medications. The physical examination is normal. The laboratory results are as follows: Hemoglobin 10 g/dL Hematocrit 30% Mean corpuscular volume 80 fL Serum creatinine 1.5 mg/dL Serum total protein 9 g/dL Serum albumin 4.2 g/dL Serum calcium 11.2 mg/dL A peripheral blood smear shows normocytic normochromic cells. An X-ray reveals multiple osteolytic lesions in the vertebrae and long bones. Serum protein electrophoresis shows a monoclonal spike. A bone marrow biopsy shows increased plasma cells making up greater than 50% of the total cell population. Which of the following is the most likely diagnosis in this patient?

Monoclonal gammopathy of unknown significance

A 7-year-old boy presents to his primary care physician for a general checkup. The patient has been feeling poorly for the past several weeks and has been losing weight. He states that he often feels weak and too tired to play with his friends. He is no longer interested in many recreational activities he used to be interested in. The patient's parents state that a few of their child's friends have been sick lately. His temperature is 102°F (38.9°C), blood pressure is 77/48 mmHg, pulse is 110/min, respirations are 24/min, and oxygen saturation is 98% on room air. On exam, you note a fatigued appearing child who has lost 10 pounds since his last appointment. Left upper quadrant tenderness and a mass is noted on abdominal exam. Which of the following best describes the most likely diagnosis?

Smudge cells on peripheral smear

Infection sensitive to oseltamivir

Parental mistreatment of the child

A 31-year-old female undergoing treatment for leukemia is found to have a frontal lobe abscess accompanied by paranasal swelling. She additionally complains of headache, facial pain, and nasal discharge. Biopsy of the infected tissue would most likely reveal which of the following?

Spherules containing endospores

Budding yeast with a narrow base

A 24-year-old woman complains of intermittent fever and joint pain. She says that these symptoms have been present for the past month. Before that, she had no signs or symptoms and was completely healthy. She has also lost her appetite and some weight. A complete blood count (CBC) showed severe pancytopenia. What is the next best step in evaluating this patient?

Repeated CBCs for several weeks and reassess

Hematologic malignancies overview for USMLE Step 2 CK: High-Yield Internal Medicine Lessons

Heme Malignancies - Blood Cancer Basics

Core Defect: Uncontrolled proliferation of hematopoietic cells, leading to bone marrow failure & organ infiltration.
Key Symptoms: Often nonspecific. Anemia (fatigue), neutropenia (infections), thrombocytopenia (bleeding). Constitutional "B" symptoms: fever, drenching night sweats, unintentional weight loss >10%.
Diagnosis: Starts with CBC & peripheral smear; confirmed with bone marrow biopsy & aspirate.

⭐ Auer rods-pathognomonic, eosinophilic needle-like inclusions in the cytoplasm-are virtually diagnostic for Acute Myeloid Leukemia (AML).

Leukemias - Proliferation Gone Wild

Uncontrolled proliferation of hematopoietic stem cells, leading to bone marrow failure.
Acute Leukemias: Rapid onset, >20% blasts in marrow. Presents with pancytopenia (fatigue, infections, bleeding).
Chronic Leukemias: Insidious onset, well-differentiated (mature) cells. Often asymptomatic, found on routine CBC.

Myeloid (AML/CML): Involves precursors of granulocytes, monocytes, RBCs, or platelets.
Lymphoid (ALL/CLL): Involves B or T lymphocytes.

⭐ ALL is the most common childhood malignancy. In adults, AML and CLL are most common.

Hematopoietic Stem Cell Differentiation: Myeloid & Lymphoid

Lymphomas - Lymph Node Nightmares

Hodgkin Lymphoma (HL):
- Characterized by Reed-Sternberg (RS) cells (CD15+, CD30+).
- Contiguous, predictable spread; localized, single group of nodes.
- Better prognosis than NHL.
- 📌 Mnemonic for B-symptoms: Fat Weeping Nun (Fever, Weight loss, Night sweats).
Non-Hodgkin Lymphoma (NHL):
- Diverse group of B-cell & T-cell malignancies.
- Non-contiguous, widespread spread; multiple peripheral nodes.
- Associated with immunosuppression (HIV, autoimmune disease).

Reed-Sternberg Cells: Owl Eye Appearance

⭐ B symptoms (unexplained fever >38°C, drenching night sweats, weight loss >10% in 6 months) are common in HL and indicate a worse prognosis.

Plasma Cell Neoplasms - Myeloma Madness

Multiple Myeloma (MM): Malignant plasma cell clone producing monoclonal immunoglobulin (M-protein), leading to end-organ damage.
📌 CRAB Criteria: Calcium (>11.5 mg/dL), Renal insufficiency (Cr >2), Anemia (Hgb <10), Bone lytic lesions.
Key Labs: M-spike on protein electrophoresis (IgG > IgA), Bence-Jones proteinuria.

Multiple Myeloma: Skull X-ray and CT with lytic lesions

⭐ Rouleaux formation (RBCs stacked like coins) is caused by ↑ serum paraproteins that decrease RBC surface charge.

Leukemias arise in the bone marrow; lymphomas originate in lymphoid tissue.

Acute leukemias feature >20% blasts and rapid onset; chronic leukemias show mature cells and an insidious course.

Hodgkin lymphoma is defined by Reed-Sternberg cells and spreads contiguously; Non-Hodgkin lymphomas are diverse and spread non-contiguously.

Multiple myeloma is a plasma cell cancer causing CRAB symptoms (hyperCalcemia, Renal failure, Anemia, Bone lesions).

Key translocations: CML has t(9;22) Philadelphia chromosome; APL has t(15;17).

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