A unique case of diffuse alveolar-septal pulmonary amyloidosis

Introduction: AL amyloidosis is characterized by the deposition of light chain immunoglobulins & is the most common subtype characterized by systemic involvement. We report a rare case of systemic AL amyloidosis with diffuse alveolar septal involvement. Case Report: A 72-year-old female with systemic amyloidosis,10 pack-year smoking history presented with a 3-month history of productive cough and worsening dyspnea. Her physical examination was unremarkable. Chest x-ray revealed bilateral increased interstitial marking with right lower lobe calcified granuloma. Echocardiogram was notable for mildly reduce ejection fraction, diffuse LV hypokinesis, and left ventricular diastolic dysfunction. Right heart catheterization confirmed cardiac AL amyloidosis. CT chest revealed scattered, non-calcified, solid centrilobular nodules with mild, diffuse bronchiectasis & bilateral hilar lymphadenopathy. Bronchoscopy with biopsy revealed diffuse light chain deposits. Immunofluorescence showed diffuse alveolar septal involvement by IgG lambda (heavy/light chain) consistent with light chain lambda disease. In addition, congo red stain & AA amyloid testing was negative. amyloid P component and thioflavin T stain tested positive. On electron microscopy, specimen showed pulmonary parenchyma with expanded alveolar septae & focal nodules with amorphous material. In addition, there is deposition of fibrillary material in the alveolar septae and focally forming well nodules which obliterate the normal pulmonary architecture. The fibrils are randomly distributed, non-branching and measure 7-12 nm in diameter. Bone marrow aspiration & biopsy revealed 6- 10% plasma cells with lambda restriction consistent with monoclonal gammopathy associated with amyloidosis. FISH results of the bone marrow revealed t(11;14) commonly associated with a plasma cell dyscrasia. Serum light chains demonstrated a lambda light chain of 521 kappa 10.9 with a ratio of 0.02. M-spike was 0.23 IgG lambda and beta-2-microglobulin was 2.72. She was enrolled in clinical trial and received 4 courses of chemotherapy consisting of bortezomib and dexamethasone weekly. Discussion: Our patient's chest tomography showed multiple calcified nodules and lymphadenopathy within the mediastinum and hilum indicating diffuse alveolar septal amyloidosis. Diagnosis requires histopathological confirmation which reveals inert, proteinaceous, homogenous, eosinophilic material. When subjected to histochemical staining with Congo red, the specimen shows green birefringence when stained with Congo red under polarized light. This method remains the gold standard of diagnosis. Diffuse alveolar septal amyloidosis is commonly associated with primary systemic amyloidosis as in our patient and leads to progressive respiratory distress. (Figure Preseted).