Cystic & Smoking-Related Lung Diseases and Organizing Pneumonia

Reading a cystic lung CT

What counts as a cyst. A lung cyst is a round air space with a thin (usually <2 mm) but perceptible wall. Centrilobular emphysema has no wall and often contains a central dot, the centrilobular artery; honeycombing is stacked subpleural cysts within fibrotic lung. Other mimics include Pneumocystis pneumatoceles, bronchiectasis and amyloid or light-chain deposition.

Pattern plus patient. Where the cysts sit, and who the patient is (a young smoker, a woman of reproductive age, someone with tuberous sclerosis, facial papules or Sjögren syndrome), usually names the disease.

Pulmonary Langerhans cell histiocytosis

Who and why. More than 90% of patients are current smokers, usually aged 20–40. Clonal Langerhans cells (CD1a+, S100+, langerin/CD207+, often carrying BRAF V600E, with tennis-racket Birbeck granules on electron microscopy) gather with eosinophils around small airways as stellate peribronchiolar nodules.

Findings. HRCT shows upper- and mid-zone centrilobular nodules, some cavitating, that evolve into bizarre bilobed or cloverleaf cysts while the costophrenic angles are spared. Patients have cough, dyspnea or a spontaneous pneumothorax; DLCO is the most reduced PFT value. Extrapulmonary disease includes central diabetes insipidus from pituitary stalk infiltration and lytic skull or bone lesions. A typical CT in a smoker often suffices; BAL with >5% CD1a+ cells supports the diagnosis, and biopsy settles doubtful cases.

Treatment. Smoking cessation comes first and often stabilizes or regresses disease. Steroids are unproven; cladribine is reserved for progressive or multisystem disease, and transplant for end-stage lung disease or severe pulmonary hypertension.

Lymphangioleiomyomatosis

Mechanism. LAM affects almost exclusively women, sporadically in the reproductive years or with tuberous sclerosis complex. Loss of TSC1 or TSC2 unleashes mTOR, and estrogen-responsive, smooth-muscle-like LAM cells (HMB-45+) spread along airways, vessels and lymphatics.

Findings. HRCT shows diffuse, uniform, round thin-walled cysts from apex to base with normal lung between them. Progressive dyspnea with obstruction and a low DLCO, recurrent spontaneous pneumothorax, chylous pleural effusion or ascites, and renal angiomyolipomas (fat-containing tumors that can bleed) are the hallmarks; pregnancy can worsen the disease.

Diagnosis and treatment. Typical cysts plus tuberous sclerosis, an angiomyolipoma, a chylous effusion or an elevated VEGF-D establish LAM without lung biopsy. Sirolimus, an mTOR inhibitor, stabilizes FEV1 and shrinks chylous collections and angiomyolipomas; it is started for impaired or declining lung function. Estrogen-containing contraceptives and hormone therapy are stopped, pregnancy risk is discussed, pleurodesis is offered after the first pneumothorax because recurrence is so common, and transplant is considered for advanced disease.

Do not confuse LAM with autoimmune alveolar proteinosis, which shows crazy-paving ground glass without cysts, carries anti-GM-CSF antibodies and is treated with whole-lung lavage.

Other cystic and smoking-related diseases

Birt-Hogg-Dubé syndrome. An autosomal dominant FLCN (folliculin) mutation causes basal subpleural and paramediastinal cysts with recurrent pneumothorax but usually preserved lung function, small whitish fibrofolliculomas on the face and neck, and multiple bilateral renal tumors (chromophobe and oncocytic types) that call for lifelong periodic renal MRI.

Lymphocytic interstitial pneumonia. A polyclonal lymphocytic infiltrate widens the alveolar septa in Sjögren syndrome, HIV (an AIDS-defining illness in children) and other autoimmune or hypergammaglobulinemic states. HRCT shows ground glass, centrilobular nodules and thin-walled perivascular cysts. Treatment targets the underlying disease, such as antiretroviral therapy in HIV, with or without steroids; LIP can evolve into MALT lymphoma.

Smoking also drives combined pulmonary fibrosis and emphysema (upper-lobe emphysema with basal fibrosis, near-normal spirometry, a very low DLCO and frequent pulmonary hypertension). By contrast, hypersensitivity pneumonitis and sarcoidosis are less common in smokers.

Cryptogenic organizing pneumonia

Presentation. A subacute flu-like illness (cough, dyspnea, fever, malaise and weight loss over weeks) persists through one or more antibiotic courses. CT shows bilateral patchy peripheral or peribronchovascular consolidations that migrate between scans, often with a reversed halo (atoll) sign of central ground glass ringed by consolidation. PFTs show restriction with a low DLCO.

In an immunocompromised host, a reversed halo sign should raise concern for invasive mold infection, especially mucormycosis.

Diagnosis. Biopsy shows plugs of loose granulation tissue (Masson bodies) filling alveolar ducts and alveoli with preserved lung architecture. "Cryptogenic" applies only after secondary causes are excluded: infection, drugs such as amiodarone and methotrexate, connective tissue disease, radiation and aspiration.