Lung Cancer: Global Case Report Poster - Lung Cancer |

When the JAK Fails the Pump FREE TO VIEW

Inderjit Singh, MD; Cristobal Risquez, MD; Abraham Sanders, MD
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New York Presbyterian Hospital-Weill Cornell Medical College, New York, NY

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;150(4_S):687A. doi:10.1016/j.chest.2016.08.782
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SESSION TITLE: Global Case Report Poster - Lung Cancer

SESSION TYPE: Global Case Report Poster

PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM

INTRODUCTION: Polycythemia vera is a myeloproliferative neoplasm. The JAK-2 mutation has been implicated in the pathogenesis of polycythemia vera (95% of cases), and half of the cases in essential thrombocythemia and primary myelofibrosis.

CASE PRESENTATION: 69-year-old female with history of JAK-2 positive polycythemia vera presents with a two year history of progressive exertional dyspnea. Despite treatment with conventional agents, her disease progressed with increasing splenomegaly and thrombocytopenia. A bone marrow biopsy showed changes of post-polycythemic myelofibrosis. She was continued on prednisone and was started on Ruxolitinib. Her chest CT at the time showed diffuse bilateral ground glass opacities , a broncho-alveolar lavage sample ruled out potential infection, and aTCM-labeled colloid scan had no evidence of extra-medullary hematopoiesis A surgical lung biopsy was performed. This showed an interstitial pneumonitis-like extramedullary hematopoiesis (EMH). Treatment with single fraction whole-lung radiation was initiated. However, she continued to experience progressive decline in her exercise tolerance. Repeat CT chest showed progression in the bilateral diffuse ground glass opacities. An echocardiogram study revealed a severely dilated right ventricle with severe pulmonary hypertension (PH). A VQ scan showed no evidence of chronic thrombo-embolic disease. Right heart catheterization revealed elevated PA pressures at baseline, PA 58/21/32 (mmHg) PVR 4.4 WU normal PCWP and normal CO/CI with response to iNO PA 33/10/20 (mmHg) She was then started on Sildenafil. Repeat echocardiogram demonstrated improvement in right ventricular function. The patient however succumbed to her illness one year later.

DISCUSSION: Several conditions can lead to EMH including primary / secondary myelofibrosis, thalassemia, and sickle cell anemia. The pathogenesis of EMH is poorly understood. It may represent differentiation of embryonic hematopoietic stem cells or the abnormal release of marrow precursors into the circulation. Radiology characteristics are variable and are at best suggestive of pulmonary EMH. Chest CT features are highly non-specific and include diffuse bilateral ground glass opacities, interstitial septal thickening, masses, or nodules. The colloid labeled with Technetium is taken up by macrophages and it also highlights erythopoietic activity. However, as seen in this case, false negatives do occur particularly if there is little medullary stroma present or if there is low cell activity. There are several pathophysiologic mechanisms implicated in the development of PH in patients with myeloproliferative neoplasms, including chronic thromboembolic PH (CTEPH) and pulmonary myeloid infiltration. Aberrant JAK-STAT signaling pathway may also contribute to the pathogenesis of PH in myelofibrosis by cultivating cultivating a hyper-proliferative apoptosis resistant state for pulmonary vascular endothelial cells (PAECs) and by depleting its nitric oxide (NO) stores.

CONCLUSIONS: Extramedullary hematopoiesis is seen in chronic myeloproliferative neoplasms, such as myelofibrosis.The liver and spleen are commonly implicated organs, while pulmonary involvement is rare. Chronic thrombo-embolic disease, hematopoietic infiltration of the lung parenchyma, and aberrant JAK-STAT signaling pathway are probable causes of pulmonary hypertension in patients with myelofibrosis. Treatment of JAK-2 positive myelofibrosis-associated PH should be directed towards the underlying cause. PH-specific pharmacotherapy should be reserved for patients who demonstrate an exhausted cardio-pulmonary reserve despite conventional therapies.

Reference #1: Tabarroki A, et al. Ruxolitinib leads to improvement of pulmonary hypertension in patients with myelofibrosis. Leukemia (2014); 28,1486-1493

Reference #2: Barosi G, et al. Diagnostic and clinical relevance of the number of circulating CD34+ cells in myelofibrosis with myeloid metaplasia. Blood.2001; 98(12); 3249

Reference #3: Van DD et al. Differences in distribution of erythopoietic and reticuloendothelial marrow in hematologic disease. Blood. 1967; 30:364-374

DISCLOSURE: The following authors have nothing to disclose: Inderjit Singh, Cristobal Risquez, Abraham Sanders

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