Correct!
5. All of the above
Choices 1,2,3 and 4 are correct, and therefore choice 5 is the best answer. The thoracic CT shows “cystic lung disease”- numerous thin-walled cysts relatively randomly distributed throughout the lung parenchyma. A careful analysis of the skin in this setting can be useful to assess for the presence of skin lesions- hamartomas of the hair follicles known as fibrofolliculomas- that may suggest the diagnosis of Birt-Hogg-Dubé syndrome. Similarly, a detailed family history and possibly a genetic analysis would be very useful as many patients with Birt-Hogg-Dubé syndrome and lymphangioleiomyomatosis have relatives with the disorders, as both conditions are associated with an autosomal dominant pattern of inheritance. The folliculin gene within chromosome band 17p111 is mutated in many patients with Birt-Hogg-Dubé syndrome, and therefore genetic testing can be of benefit for establishing this diagnosis. Patients with lymphangioleiomyomatosis frequently have mutations in the tuberous sclerosis genes TSC1 and TSC 2, whose protein products are hamartin and tuberin, respectively, and therefore genetic analysis is of benefit for establishing the diagnosis of lymphangioleiomyomatosis as well. Analysis of any prior imaging studies of the abdomen would be of benefit as patients with Birt-Hogg-Dubé syndrome frequently have hereditary renal tumors, such as chromophobe renal cell carcinomas and hybrid oncocytomas. Similarly, patients with lymphangioleiomyomatosis may have renal angiomyolipomas. Therefore, detection of solid renal lesions on abdominal imaging studies in patients with cystic lung disease specifically raises the possibility of either Birt-Hogg-Dubé syndrome or lymphangioleiomyomatosis. Finally, an “autoimmune panel”, including assessment of measures of systemic inflammation, such as C-reactive protein and the erythrocyte sedimentation rate, as well as various autoantibodies, such as SS-A, SS-B, anti-neutrophil cytoplasmic (ANCA), myeloperoxidase, complement titers, antinuclear antibody, anti-double –stranded DNA, and serine proteinase 3, would be useful to assess for autoimmune disorders that could be associated with lymphocytic interstitial pneumonia, which could potentially cause the cystic lesions in this patient).
Further clinical course. The patient underwent lip / minor salivary gland biopsy, which showed lymphocytic sialadenitis. Her erythrocyte sedimentation rate, C-reactive protein, PR-3 autoantibody and antinuclear antibody levels were all elevated. A polyclonal gammopathy was also noted. Flexible fiberoptic bronchoscopy showed no specific abnormalities (only non-specific chronic inflammation).
Which of the following would provide the highest likelihood of establishing a diagnosis for this patient? (Click on the correct answer to proceed to the next panel)