A 46-year-old, previously healthy man develops sudden-onset, sharp, left-sided flank pain radiating to the groin. CT scan of the abdomen reveals a left ureteral calculus, which he passes spontaneously in the urine. Other, incidental findings include a left lower lobe lung nodule and foci of calcifications in the spleen. Chest imaging shows several small calcified nodules in both lungs and a calcified mediastinal lymph node. The patient has had no pulmonary symptoms and is a lifelong nonsmoker. He is a farmer who lives in Ohio and has not traveled recently. Physical examination shows no abnormalities. Tuberculosis skin test shows a

Question

A 46-year-old, previously healthy man develops sudden-onset, sharp, left-sided flank pain radiating to the groin.  CT scan of the abdomen reveals a left ureteral calculus, which he passes spontaneously in the urine.  Other, incidental findings include a left lower lobe lung nodule and foci of calcifications in the spleen.  Chest imaging shows several small calcified nodules in both lungs and a calcified mediastinal lymph node.  The patient has had no pulmonary symptoms and is a lifelong nonsmoker.  He is a farmer who lives in Ohio and has not traveled recently.  Physical examination shows no abnormalities.  Tuberculosis skin test shows a <5 mm induration at 48 hours.  Repeat chest imaging 3 months later reveals no changes.  Which of the following is the most likely cause of the observed findings in this patient?

Quizplus · Accepted Answer

This patient has calcified lung, mediastinal, and splenic lesions that are stable over time and asymptomatic, raising suspicion for a contained granulomatous infection. The most likely cause is the dimorphic fungus Histoplasma capsulatum, which exists as a mold in the soil of the Ohio and Mississippi River Valleys. This pathogen is inhaled into the lungs, converts to yeast form, and is phagocytosed by alveolar macrophages. Macrophages cannot initially eliminate the organism due to microbial virulence factors that prevent phagolysosome formation and acidification. Therefore, H capsulatum is able to replicate within the macrophage and spread through the draining lymphatic system and (often) into the reticuloendothelial system (eg, spleen, liver). After about 2 weeks, patients with intact immunity develop a cell-mediated immune response that contains the infection within granulomas. Over time, the granulomas fibrose and calcify and can be visualized on radiographic imaging at the initial sites of infection (eg, lungs, hilar and mediastinal lymph nodes, spleen). In healthy patients, most infections with H capsulatum are asymptomatic and are therefore often discovered incidentally. (Choice B) Metastatic cancer often causes multiple lung lesions. However, these lesions generally enlarge in size over time and calcification is rare. (Choice C) Miliary tuberculosis is marked by multiple pulmonary lesions and clinical illness (eg, fever, night sweats); calcified lesions would be atypical. Although primary tuberculosis is often associated with a calcified lung and an ipsilateral hilar lymph node lesion (Ranke complex), tuberculosis is unlikely in this case given the patient's negative tuberculin skin test. (Choice D) Parathyroid adenoma is a benign tumor that does not spread to the lungs. It is often associated with hypercalcemia. (Choice E) Silica inhalation can cause innumerable, small, rounded opacities in the upper lobes of the lungs that may fibrose over time, resulting in pulmonary disease. Silica exposure is primarily occupational (eg, miners, sandblasters). Educational objective: Histoplasma capsulatum replicates within macrophages and often spreads from the lungs through the pulmonary lymphatics to the reticuloendothelial system (eg, spleen, liver). Most healthy individuals quickly contain the infection within granulomas and do not become ill; a minority develop self-limited pneumonia. Over time, the granulomas at the initial sites of infection calcify and may be seen incidentally on radiographic imaging. __________ References: The calcified lung nodule: what does it mean? (http://www.ncbi.nlm.nih.gov/pubmed/20582171)

A 46-Year-Old, Previously Healthy Man Develops Sudden-Onset, Sharp, Left-Sided Flank