A-66-year-old male, who was exsmoker, presented to the ER for a change in mental status. As per the family, the patient who had a normal mental status in the past was noticed to be progressively worsening for the last couple of months, with disorientation mainly found over phone discussions. At the time of presentation he was awake and alert, but disoriented to time and place. He denied any pain and was unable to provide any history. Physical exam was normal except for the presence of facial ecchymosis. The neurological part showed a normal motor, sensory, and cranial nerve exam. Also, his gait was stable.
Past medical history was significant for hypertension, hypercholesterolemia, aortic valve replacement (nonmetallic), atrial fibrillation (on warfarin), incomplete heart block, pacemaker, and IgG- IgA, kappa type Monoclonal Gammopathy of Undetermined Significance (MGUS). Family history was not relevant.
MGUS was diagnosed 9 months ago on serum protein electrophoresis (SPEP) as patient was referred to our institution's center for cancer and blood related diseases for hyperglobulinemia on routine blood work. At that time the patient underwent extensive work up to rule out any plasma cell dyscrasias. The Urine protein electrophoresis (UPEP) was negative for M spike. Immunohistochemistry and flow cytometry from peripheral smear as well as from bone marrow biopsy were negative for a clonal plasma cell or malignant B-cell. Chromosomal analysis and cytogenetics were also normal.
In the ER, a head CT scan revealed multiple parenchymal hemorrhagic lesions suspicious for metastases mainly in the frontal part bilaterally and in the left parieto-temporal region, with edema and compression mainly on the left lateral ventricle. Also, an interventricular lesion at the foramen of Monro causing mild hydrocephalus was seen. CT chest, abdomen and pelvis was done to find a possible primary malignancy and revealed numerous ground-glass and solid nodules in the lungs. Warfarin was discontinued and the international normalized ratio (INR) of 2.2 was reversed with fresh frozen plasma. Patient was started on steroids and phenytoin. Lower extremity duplex was negative.
The clinical status continued to deteriorate with cold, cyanotic fingers developing on day twelve of hospitalization. At this point he was seen by a vascular surgeon in order to rule out arterial emboli. A transesophageal echocardiogram was done for possible vegetations causing infectious emboli. All results were negative, and no infiltrative cardiomyopathy was found. Bronchoscopy and broncho-alveolar lavage with cultures (including nocardia) was also negative. CT guided lung biopsy showed H&E (hematoxylin and eosin) and PAS (periodic acid-schiff) positive amorphous eosinophilic material suspicious for amyloid (). Initial staining with congo red was negative. However, it stained positively with Thioflavin T stain and had weak green birefringence under polarized light. Immunostains for kappa and lambda chains showed stronger staining for kappa subtype. Brain biopsy was positive for eosinophilic material (similar to the lungs) but negative for congo red and thioflavin T stain (). Later, the patient had a respiratory failure secondary to health care acquired pneumonia (HCAP) and was intubated. Serial blood cultures and serologies for Cryptococcus and histoplasmosis, serology for antineutrophil cytoplasmic antibody (ANCA), antinuclear antibody (ANA), rheumatoid factor (RF), cryoglobulin, and Antiglomerular basement membrane antibodies (antiGBM) were all negative. Only seen was a positive blood culture for candida on day eighteen.
Figure 1 CT guided lung biopsy showed H&E (hematoxylin and eosin) and PAS (periodic acid-schiff) positive amorphous eosinophilic material suspicious for amyloid. Initial staining with congo red was negative. However, it stained positively with Thioflavin (more ...)
Brain biopsy was positive for eosinophilic material (similar to the lungs) but negative for congo red and thioflavin T stain.
Patient was initially treated with ampicillin and gentamycin for possible endocarditis. Later, he was switched to vancomycin, meropenem, and ciprofloxacin for possible health care acquired pneumonia. Also, he was started on amphotericin B after blood cultures revealed candida. Whether a more diffuse disease such as systemic amyloidosis is present was not confirmed, as the family refused any further diagnostic procedures that are not relevant to the acute care of the patient in a context of a deteriorating clinical picture. Despite all antifungals and supportive measures, he failed weaning trials and remained on ventilator support. A tracheostomy was suggested. However, after extensive discussions, the family refused. On day 29, health care proxy decided to withdraw all life support measures based on the patient's previous wishes who did not want to be kept alive on a ventilator. Finally, the patient had a terminal wean after these events, and the family refused any autopsies.