The most likely diagnosis is lymphangitic carcinomatosis. Pulmonary metastases most commonly present as multiple, peripheral, or subpleural pulmonary nodules but can also present as solitary pulmonary nodules or lymphangitic spread. Lymphangitic spread of tumor is most commonly associated with adenocarcinoma (lung, breast, and gastrointestinal tract), melanoma, lymphoma, and leukemia; it should be considered if an interstitial abnormality is identified on CT in a patient with one of these malignancies, and is best defined with high-resolution CT if suspected. This patient presents with likely metastatic breast cancer to the mediastinal and hilar lymph nodes with new interstitial changes on chest CT, which raises concern for lymphangitic spread.

Atypical pneumonia can present with interstitial changes. However, this patient has no symptoms to suggest an infection, did not improve with appropriate antibiotic therapy, has had symptoms for 1 month, and has unexplained mediastinal and hilar lymphadenopathy.

Bronchiolitis obliterans organizing pneumonia may be associated with solid-organ malignancies. However, the most common radiographic presentation shows areas of lung consolidation.

The usual CT scan findings associated with idiopathic pulmonary fibrosis are bilateral peripheral and lower lobe–predominant interstitial thickening with honeycombing. Clubbing is present in approximately half of patients. It is not associated with mediastinal and hilar lymphadenopathy.

Patients with radiation pneumonitis present with cough and/or dyspnea approximately 6 weeks after the exposure. CT imaging typically shows hazy opacities with ground-glass attenuation. Affected areas are most commonly found in the field of radiation but can occasionally occur outside the field. The abnormalities in classic radiation pneumonitis typically resolve within 6 months but can progress to a well-demarcated area of fibrosis with volume loss and bronchiectasis. Radiation fibrosis is not consistent with this patient's time course or imaging findings.