ADOPTING ORPHAN DISEASES RARE INTERSTITIAL LUNG DISEASES

adoptingorphandiseaseskapak

DIFFERENTIAL DIAGNOSIS INRARE INTERSTITIAL LUNG DISEASES THROUGH RADIOLOGICAL HINTS

Furkan Ufuk

The University of Chicago Medicine, Department of Radiology, Chicago, IL, USA

Ufuk F. Differential Diagnosis in Rare Interstitial Lung Diseases through Radiological Hints. In: Altinisik G, McCormack FX, editors. Adopting Orphan Diseases: Rare Interstitial Lung Diseases. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.9-24.

ABSTRACT

Thin-slice computed tomography (CT) has become the cornerstone for diagnosing in interstitial lung diseases (ILDs), allowing radiologists to triage patients by pattern, distribution, and ancillary systemic clues long before histology is available. Thin-section volumetric acquisitions <1.25 mm recommended by the Society of Thoracic Radiology and recent Fleischner updates maximise conspicuity of subtle cysts, nodules, and septal thickening while standardising terminology across centres. Among cystic disorders, pulmonary Langerhans-cell histiocytosis typically shows upperand mid-zone centrilobular nodules that cavitate into irregular cysts with relative costophrenic sparing, strongly associated with cigarette smoking; lymphangioleiomyomatosis demonstrates innumerable uniformly thin-walled cysts scattered throughout enlarged lungs that often spare pericostophrenic angles and may coexist with chylous effusion or renal angiomyolipoma; and Birt-Hogg-Dubé syndrome produces fewer, variably shaped lentiform cysts clustered in basal-medial regions, frequently heralded by spontaneous pneumothorax. The “crazy-paving” pattern is a mosaic of ground-glass opacities (GGOs) with superimposed interand intralobular septal thickening remains the signature of pulmonary alveolar proteinosis (PAP), although it is recognised as a non-specific pattern shared with infection and acute lung injury. Smooth septal thickening with background GGOs in a child or young adult, particularly when accompanied by hepatosplenomegaly, should raise concern for Niemann-Pick disease type B or other lysosomal storage disorders. Diffuse hyperdense calcific micronodules generating the “black pleura sign” and “sandstorm appearance” are virtually diagnostic of pulmonary alveolar microlithiasis (PAM). Integrating these imaging signatures with clinical context accelerates multidisciplinary consensus, reduces unnecessary biopsies, and positions radiology at the forefront of precision therapeutics for these uncommon but morbid entities.

Keywords: Interstitial lung disease; Computed tomography; Langerhans-cell histiocytosis; Lymphangioleiomyomatosis; Birt-Hogg-Dubé syndrome; Cystic lung disease

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