Severe Pulmonary Hypertension and Fever of Unknown Etiology in an Elderly Woman

Abstract

INTRODUCTION: The differentials for pulmonary hypertension (PHTN) with fever of unknown etiology (FUO) are extensive. Main causes include collagen vascular disease (CVD), vasculitis, sarcoidosis and malignancies. We present a unique case of intravascular lymphoma (IVL) presenting with FUO, PHTN and disseminated lymphadenopathy. CASE PRESENTATION: A 72 year-old woman, was admitted with intermittent fever of 3 years duration, fatigue and weight loss of 20 lbs in 6 months. She had vague abdominal discomfort and progressive dyspnea on exertion. Medical history included diabetes, hypertension, ESRD, chronic anemia, atrial fibrillation and diastolic heart failure. Personal, Family and Social History was noncontributory. Physical exam was significant for fever T 101 F, hypotension, axillary lymphadenopathy, systolic murmur, ascitis, and hepatosplenomegaly Laboratory revealed low cortisol, pancytopenia, elevated LDH, ACE and ANA levels. Imaging of chest/abdomen/pelvis showed mediastinal adenopathy (Fig 1). Exhaustive work up including bone marrow, subcarinal and axillary LN biopsy, ruled out any infective, granulomatous or lymphoproliferative etiology. V/Q scan was normal. Vasculitis work up was only vaguely supportive. She received hydrocortisone with resolution of hypotension. Abdominal fat pad biopsy to rule out amyloidosis showed large lymphoma cells in the lumen of small vessels (Fig 2). Immunostains were consistent with intravascular B cell lymphoma and patient was started on chemotherapy. DISCUSSION: First described in 1959, IVL is an extremely rare type of diffuse large B cell lymphoma, with aggressive behavior and postmortem diagnosis in most cases. Extranodal involvement is the hallmark of IVL. Fever is the most common presenting complaint. Brain and skin are frequently involved organs. There are sporadic reports involving almost every organ and few cases of pulmonary HTN. Histopathology shows classic appearance of large malignant lymphocytes filling small vascular lumina. IVL has been diagnosed by random skin biopsy especially in the setting of fever, but the yield of random fat pad biopsy is also described, and in our case led to assertive diagnosis. Ours is a unique presentation of severe pulmonary HTN and FUO with uncommonly reported lymphadenopathy and hepatosplenomegaly. CONCLUSIONS: Intravascular lymphoma may be an under-diagnosed entity requiring a high index of suspicion. We recommend a low threshold for random skin biopsy especially in the setting of FUO since IVL has been diagnosed in clinically uninvolved skin. Most cases of IVL are associated with a poor prognosis and timely intervention with an anthracycline-based regimen such as R-CHOP has been associated with favorable outcome.