SOLVING CLINICAL PROBLEMS IN BLOOD DISEASES
AJH Educational Material
A JH
A physician or group of physicians considers presentation and evolution of a real clinical case, reacting to clinical information and data (boldface type). This is followed by a discussion/commentary.
Pulmonary masses in a patient with dyspnea: Apply Occam’s razor or Hickam’s dictum? Nelson Leung,1,2* Martha Grogan,3 Geoffrey B. Johnson,4,5 Mary E. Klecka,6 and Angela Dispenzeiri2
A 74-year-old white male, lifetime nonsmoker underwent evaluation for a 3 year history of dyspnea. Patient was a former professional athlete who was still working full time. He had remained physically fit and was able to perform his regular exercise routine which included 25 min on the elliptical machine plus weights. However, he would develop dyspnea when he walked up inclines/ramps or if there was a temperature change. Cardiac workup was negative. Cardiac computed tomography (CT) showed a coronary calcium score of zero. Exercise myocardial perfusion test showed a left ventricular ejection fraction (LVEF) of 59% at rest and 55% at peak exercise with no perfusion defects. Echocardiogram showed normal left ventricular size but mild hyperdynamic function of 71%. Pulmonary function test was normal with an FEV1 of 2.62 (112% predicted), diffusing capacity of the lung for carbon monoxide (DLCO) of 99% predicted and VO2 max of 20 ml/min/kg (96% predicted). Chest CT revealed pulmonary nodules in the right upper and lower lobes which were previously present on prior chest X-rays. A transbronchial biopsy of the lower nodule lesion found amorphous material within the alveolar septae. Congo red stain was positive for amyloid. Immunohistochemistry studies were focally positive for immunoglobulin kappa light chain, focally positive for lambda light chain and diffusely positive for transthyretin. Patient was given the diagnosis of transthyretin amyloidosis (ATTR) and was recommended to undergo testing for heart and liver transplantation. He presented for second opinion. Amyloidosis is a group of diseases resulting from misfolding of proteins [1]. Transthyretin (aka prealbumin) is a protein carrier of thyroxine and retinol-binding protein bound to retinol which is made predominantly in the liver. Currently, two types of ATTR are recognized. The most common is the wild type (ATTRwt) also known as “senile ATTR” that occurs without any mutation. The true prevalence of ATTRwt is unknown as it is suspected to be markedly underdiagnosed. Most of these patients are male (88% in one series) and older (median age 73) [2]. The most common presentation is dyspnea (>50%) with neuropathy present in
AJH Educational Material
A JH
A physician or group of physicians considers presentation and evolution of a real clinical case, reacting to clinical information and data (boldface type). This is followed by a discussion/commentary.
Pulmonary masses in a patient with dyspnea: Apply Occam’s razor or Hickam’s dictum? Nelson Leung,1,2* Martha Grogan,3 Geoffrey B. Johnson,4,5 Mary E. Klecka,6 and Angela Dispenzeiri2
A 74-year-old white male, lifetime nonsmoker underwent evaluation for a 3 year history of dyspnea. Patient was a former professional athlete who was still working full time. He had remained physically fit and was able to perform his regular exercise routine which included 25 min on the elliptical machine plus weights. However, he would develop dyspnea when he walked up inclines/ramps or if there was a temperature change. Cardiac workup was negative. Cardiac computed tomography (CT) showed a coronary calcium score of zero. Exercise myocardial perfusion test showed a left ventricular ejection fraction (LVEF) of 59% at rest and 55% at peak exercise with no perfusion defects. Echocardiogram showed normal left ventricular size but mild hyperdynamic function of 71%. Pulmonary function test was normal with an FEV1 of 2.62 (112% predicted), diffusing capacity of the lung for carbon monoxide (DLCO) of 99% predicted and VO2 max of 20 ml/min/kg (96% predicted). Chest CT revealed pulmonary nodules in the right upper and lower lobes which were previously present on prior chest X-rays. A transbronchial biopsy of the lower nodule lesion found amorphous material within the alveolar septae. Congo red stain was positive for amyloid. Immunohistochemistry studies were focally positive for immunoglobulin kappa light chain, focally positive for lambda light chain and diffusely positive for transthyretin. Patient was given the diagnosis of transthyretin amyloidosis (ATTR) and was recommended to undergo testing for heart and liver transplantation. He presented for second opinion. Amyloidosis is a group of diseases resulting from misfolding of proteins [1]. Transthyretin (aka prealbumin) is a protein carrier of thyroxine and retinol-binding protein bound to retinol which is made predominantly in the liver. Currently, two types of ATTR are recognized. The most common is the wild type (ATTRwt) also known as “senile ATTR” that occurs without any mutation. The true prevalence of ATTRwt is unknown as it is suspected to be markedly underdiagnosed. Most of these patients are male (88% in one series) and older (median age 73) [2]. The most common presentation is dyspnea (>50%) with neuropathy present in
