Egan, A.

Abstract Introduction: Erdheim-Chester disease (ECD) is an exceptionally rare non-Langerhans cell histiocytic malignant disorder but presents a unique diagnostic challenge due to its diverse clinical manifestations from mild symptoms to severe, life-threatening multiorgan disease. Here, we report a case of ECD that presented with pleuro-pulmonary and vascular involvement rather than skeletal lesions. Case description: A 75-year-old man with a history of systemic lupus erythematosus, rheumatoid arthritis, and chronic obstructive pulmonary disease presented with syncope, anorexia, fatigue, and weight loss. He was noted to be in atrial fibrillation. Subsequent imaging studies, including. The CTA of chest and PET-CT scans showed hyperdense wall thickening in multiple arteries and veins, including the pulmonary arteries and veins, aortic arch, thoracic and abdominal aorta, and iliac arteries as well as pulmonary nodules suggestive of a large vessel vasculitis associated with systemic inflammation. The patient underwent a pleural biopsy which only demonstrated nonspecific inflammation. He subsequently underwent surgical wedge biopsy of a superior right lower lobe and multiple pleural biopsies showed atypical histiocytic infiltrate suspicious for a histoplasmic neoplasm with the atypical histiocytes characterized by plump to spindled nuclei with focal emperipolesis. Atypical histiocytes were positive for CD163, factor 13a, cyclin D1 suggestive of ECD. As further testing demonstrated a negative BRAFV600E mutation, the patient was initiated on cobimetinib 40 mg daily. He responded to therapy with subjective and objective improvement. There has been no radiographic evidence of recurrence. Discussion: The diagnosis of ECD relies on clinical presentation, imaging studies, and distinctive pathological findings. Overall, the prognosis depends on the degree of histiocytic damage before initiation of treatment; degree of inflammation; age; digestive tract involvement. A biopsy revealing non-Langerhans cell histiocytosis, supported by immunohistochemistry exams, is essential for confirming the diagnosis. Diagnosing ECD is challenging due to its rarity and multisystem involvement necessitating a multidisciplinary approach. Pulmonary involvement, seen in 43% of cases, often presents with features of interstitial lung disease but does not significantly impact overall prognosis. Recent evidence implicates the BRAFV600E mutation in ECD pathogenesis, suggesting new therapeutic possibilities.

Abstract Introduction: Lung cancer is the most frequently diagnosed cancer and leading cause of cancer death worldwide. While adenocarcinoma is the most common subtype of lung cancer, invasive mucinous adenocarcinoma (IMA) only represents an estimated 2-5% of lung adenocarcinomas. IMA has an incidence of just 0.2% among primary lung cancer patients. This rare form of lung cancer provides a significant diagnostic challenge due to its varied clinical and radiological manifestations, often exhibiting features overlapping with pneumonia. We present a case of IMA with radiographic findings of numerous cavitary nodules, an uncommon morphology reported in 3.5% of cases of IMA, originally thought to represent atypical multifocal pneumonia. Description of Case: A 76-year-old man with a history of coronary artery disease status post percutaneous coronary intervention on dual antiplatelet therapy; hypertension; chronic kidney disease; and 40 pack-year smoking history presented to primary care with 6 weeks of worsening cough productive of clear sputum and shortness of breath. He denied a history of fevers, night sweats, unintentional weight loss, recent travel, or sick contacts. A chest x-ray revealed extensive nodular parenchymal opacities in the lower lobes bilaterally concerning for multifocal pneumonia. Subsequent CT chest showed numerous bilateral, poorly-defined nodules with irregular margins and cavitary lesions. He was admitted for acute hypoxic respiratory failure in the setting of presumed atypical multifocal pneumonia. He completed a course of vancomycin and piperacillin/tazobactam. Notably, bronchoscopy with bronchoalveolar lavage and cytology were negative for infection and malignancy, respectively. Additional noninvasive infectious and inflammatory workup was negative and he was ultimately discharged. He was then readmitted to the ICU for respiratory failure where he eventually underwent transbronchial biopsy. Tissue biopsy revealed moderately-differentiated adenocarcinoma with mucinous features. PD-L1 staining was 0%. Genetic testing revealed two separate TP53 mutations, a KRAS G12D mutation, and SMAD4 alteration. Chemotherapy with carboplatin and pemetrexed was initiated inpatient. He had objective and subjective improvement and was ultimately discharged to continue treatment in the outpatient setting. Discussion: This case represents an uncommon presentation of an already rare form of lung cancer underscoring the diagnostic difficulty in the setting of overlapping clinical and radiological manifestations. Clinicians must consider malignancy when a patient with presumed pneumonia is not improving despite antibiotics. Bronchoscopy with both BAL and transbronchial biopsy is often required to make the diagnosis and exclude other etiologies. Early consideration of alternative diagnoses can improve patient outcomes and help avoid progressive respiratory failure.