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Straight from the Progress Note question bank, each with a cited explanation. No account needed.
A 38-year-old man with HIV (CD4 count 90 cells/microliter) presents with violaceous plaques on the skin and hard palate. Biopsy is shown below; cells stain positive for a latent viral nuclear antigen by immunohistochemistry. Which statement about its pathogenesis is correct?
Answer: A. Kaposi sarcoma requires latent HHV-8 (KSHV) infection of spindle cells; the latency-associated nuclear antigen (LANA) is expressed in nearly all lesions and promotes cell survival and proliferation in part by disrupting the p53 and Rb tumor suppressor pathways, contributing to the neoplastic phenotype. Option B incorrectly attributes transformation directly to HIV rather than to HHV-8 infection, which is the necessary oncogenic driver; HIV instead contributes indirectly through immunosuppression and cytokine effects. Option C incorrectly labels LANA as a lytic-cycle marker, when it specifically marks latent infection. Option D contradicts the well-established viral-driven neoplastic nature of the lesion. Option E is incorrect because HHV-8 seroprevalence substantially exceeds the incidence of clinically apparent Kaposi sarcoma, indicating that host immunosuppression is an important additional contributing factor.
Source: Cesarman, E., et al. (2019). Kaposi sarcoma. Nature Reviews Disease Primers, 5(1).
A 6-year-old boy with a history of dactylitis presents with acute severe abdominal pain, pallor, and a rapidly enlarging spleen; hemoglobin has dropped from a baseline of 8 g/dL to 4 g/dL. A peripheral blood smear image is shown below. Which of the following conditions most directly triggers erythrocyte sickling in this patient's disease, based on the underlying molecular mechanism?
Answer: A. In sickle cell disease, deoxygenation of hemoglobin S exposes a hydrophobic valine residue substituted for glutamic acid at position 6 of the beta-globin chain, promoting polymerization of hemoglobin tetramers into rigid fibers that distort the erythrocyte into its characteristic sickle shape. Repeated sickling and unsickling damage the red cell membrane, shortening erythrocyte lifespan and predisposing to vaso-occlusion and, in young children, acute splenic sequestration crisis as seen in this patient. Heinz body formation reflects oxidative hemoglobin denaturation characteristic of G6PD deficiency, not HbS polymerization, and reduced spectrin content describes the membrane defect of hereditary spherocytosis rather than sickle cell disease.
Source: Kato, G. J., et al. (2018). Sickle cell disease. Nature Reviews Disease Primers, 4, 18010.
A patient presents with ptosis and diplopia that worsens throughout the day. Edrophonium administration transiently improves symptoms. Which underlying mechanism is most likely?
Answer: D. Myasthenia gravis is caused by IgG antibodies against postsynaptic acetylcholine receptors at the neuromuscular junction. This leads to fatigable muscle weakness that improves with acetylcholinesterase inhibitors like edrophonium. Presynaptic calcium channel antibodies are seen in Lambert-Eaton syndrome. Dopamine depletion is associated with Parkinson disease. Demyelination and upper motor neuron loss describe other neurologic disorders.
Source: Gilhus, et al. (2019). Myasthenia gravis. Nature Reviews Disease Primers.
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