The MYD88 L265P somatic variant (MYD88) has a high prevalence in Waldenstrom’s Macroglobulinemia (WM), a form of lymphoplasmacytic lymphoma (LPL) associated with monoclonal IgM. Although the role of MYD88 in WM was initially reported in 2012, it was not until 2016 that MYD88 testing was included in the National Cancer Care Network (NCCN) Guidelines. We present a case illustrating the utility of MYD88 status in distinguishing atypical forms of WM from marginal zone lymphoma (MZL) and in selecting second-line therapy with ibrutinib. In 2012, a 64-year-old male presented with dyspnea on exertion, a hemoglobin of 5.6 g/dL, a platelet count of 86,000, and monoclonal IgM kappa on serum immunofixation but no detectable M-spike. Bone marrow biopsy revealed 95% monoclonal B-lymphocytes with lymphoplasmacytic differentiation favoring a diagnosis of LPL/WM over MZL, with a favorable response to chemotherapy. This diagnosis was called into question 3 years later following relapse, and MZL was favored based on the lack of MYD88 mutation. One year later, however, repeat bone marrow biopsy detected the MYD88 mutation and therapy with ibrutinib yielded a favorable response. The distinction between certain lymphomas can be problematic and in this case MYD88 was helpful in clarifying a diagnosis of atypical LPL/WM from MZL and in selecting effective second-line therapy.
Introduction Methamphetamine has been identified as a risk factor for the development of pulmonary hypertension (PH), though the mechanism remains unclear. We present a case of reversible, symptomatic PH in a patient consuming methamphetamine. Case Presentation A 35-year-old male smoker with a history of hypertension and active methamphetamine abuse presented to the emergency department with progressive dyspnea on exertion for 8 months, with worsening symptoms over the preceding week. He took no medications at home. At presentation, he was hypertensive (218/140 mm Hg) and tachycardic. Physical examination was unremarkable. He was found to be in acute hypoxic respiratory failure, requiring oxygen supplementation via a venturi mask. Labwork at presentation was notable for elevated nt-pro bnp (1572 pg/mL), hypoxia with respiratory alkalosis on arterial blood gas (pH: 7.49;pCO2: 30 mm Hg;pO2: 54.4 mm Hg), and amphetamines on urine toxicology. Respiratory viral panel, including testing for SARS-CoV-2, was negative. Chest imaging, including radiography and computed tomography (CT) with angiography demonstrated no acute pathology. Aggressive control of blood pressure was instituted with lisinopril, hydrochlorothiazide, and amlodipine, along with diuresis and non-invasive ventilatory support. Transthoracic echocardiography with bubble study was notable for right ventricular enlargement and systolic dysfunction, with enlarged right atrium, bidirectional shunt at the atrial level, and high pulmonary artery systolic pressure (83 mm Hg). Rheumatoid factor, anti-double stranded DNA, HIV testing, and serum protein electrophoresis were negative. One week following admission, his respiratory failure improved, and a right heart catheterization was performed, which demonstrated a mean pulmonary artery pressure of 27 mmg Hg, with normal pulmonary capillary wedge pressure (11 mm Hg) and pulmonary vascular resistance (2.5 Woods Units). Transesophageal echocardiography showed normal right ventricular size and function with a moderate right-to-left shunt through a patent foramen ovale. Discussion Methamphetamine is a sympathomimetic amine which can cause adrenergic stimulation by displacing neurotransmitters such as norepinephrine, epinephrine, and serotonin from cytoplasmic vesicles of pre-synaptic neurons. Methamphetamines are associated with a range of pulmonary complications, including PH, pulmonary hemorrhage, and edema. We present a case of transient dynamic PH in the setting of methamphetamine use, which caused severe hypoxic respiratory failure, and abated with cessation of amphetamines and aggressive control of hypertension. Methamphetamine is classified as a “likely” risk factor for PH.(1) Studies have demonstrated worse prognosis in patients with meth-PH compared to idiopathic PH.(2,3) PH should be considered as a differential when encountering respiratory failure in patients who use methamphetamines.
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