A 26-year-old male was admitted with history of recurrent hemoptysis and breathlessness for two months. There were no other constitutional symptoms. Three weeks earlier he was admitted in a peripheral hospital with hypotension, diffuse bilateral opacities on chest radiograph and pericardial effusion and was treated as a case of disseminated tuberculosis (Pulmonary and pericardial) with anti tubercular treatment (ATT) and oral steroids. On physical examination he was averagely built and nourished and afebrile. His blood pressure was 120/80 mm Hg, respiration 18 per minute and pulse was 80 per minute. He had grade II clubbing and few scattered crackles over both infrascapular area. Other systems were normal.
Laboratory investigations revealed hemoglobin: 13 gm/dl, total leukocyte count of 7600/mm3 with polymorphs 64%, lymphocyte 29%, monocyte 2 %, eosinophils 5 % and platelets - 210000 / mm3. His blood sugar, renal functions, liver function tests, electrolytes, urinalysis, bleeding time, clotting time and prothrombin time were normal. Sputum was repeatedly negative for acid fast bacilli. Serology for human immunodeficiency virus (HIV) was non reactor. Peripheral smear showed microcytic hypochromic blood picture. Chest radiograph showed diffuse bilateral alveolar opacities (). Contrast enhanced computerized tomographic (CECT) scan of chest showed multiple patchy ground glass opacities bilaterally with normal intervening lung parenchyma and small nodular opacities scattered in subpleural area (). Bronchoscopy revealed oozing of blood from all segmental bronchi bilaterally. Bronchoalveolar lavage showed numerous hemosiderin laden macrophages on Perl's stain. Transbronchial lung biopsy showed features of chronic inflammation. Echocardiography showed mild loculated pericardial effusion with no left ventricular dysfunction. The diagnosis of diffuse alveolar hemorrhage was made and he was investigated to rule out any secondary cause. Antinuclear antibodies, antibodies to double stranded DNA, cytoplasmic and peripheral, antineutrophil cytoplasmic antibody (ANCA), rheumatoid factor, immunoglobulin profile, complement level, ultrasound abdomen, 24 hours urinary proteins were normal, ruling out any collagen disorder or renal diseases as a cause of alveolar hemorrhage.
Chest radiograph (PA view) showing diffuse reticulonodular and alveolar opacities of varying sizes from apex to base predominantly in periphery of lung.
Computed tomographic scan of chest showing multiple patchy ground glass opacities bilaterally with normal intervening lung parenchyma and small nodular opacities scattered in subpleural area
He was managed as a case of idiopathic pulmonary hemosiderosis with prednisilone 60 mg OD for 4 weeks followed by tapering. He showed initially good response with cessation of hemoptysis but subsequently he developed progressive weakness with recurrence of hemoptysis and marked pallor. There was no other obvious source of bleeding from any other site. Repeat chest radiograph showed increase in the diffuse alveolar opacities. His hemoglobin dropped to 3.2 gm/ dl. His repeat coagulation profile and metabolic parameters were normal. He was managed with repeated blood transfusions, broad spectrum antibiotics along with continuation of prednisilone and ATT, but he did not respond. Patient showed progressive deterioration and preterminally (last 4-5 days) developed multiorgan dysfunction in the form of azotemia, deranged liver functions, abnormal coagulation profile and left sided hemiplegia with deterioration of sensorium, suggesting the possible development of septicemia which ultimately led to fatality after 2 months of hospitalization.
Post mortem showed multiple nodular and hemorrhagic areas in the lungs, liver, stomach, large and small intestines and brain and multiple brownish nodules over pericardial surface. Histopathological examination showed focal hemorrhages in alveolar spaces with many hemosiderin laden macrophages. Dysplastic spindle cells were seen infiltrating into the lung parenchyma (). Section from heart showed large dysplastic spindle shaped cells forming vascular channels. The cells showed atypical nuclei with scant cytoplasm. These cells were seen infiltrating into cardiomyocytes (). Matastatic lesions of angiosarcoma were also seen in liver, stomach and brain. Immunohistochemistry (CD 31 positivity) confirmed the diagnosis of angiosarcoma ( insert).
Sections from the lung show large dysplastic spindle cells with hyperchromatic irregular nuclei replacing the lung parenchyma. Adjacent areas of hemorrhage are seen (H&E × 400).
Section from the heart shows large dysplastic spindle cells with hyperchromatic irregular nuclei forming vascular channels and invading into the cardiomyocytes (H&E × 200). Insert: Spindle cells showing CD 31 positivity.