Scientific Letter
A 60-Year-Old Male Smoker With Chronic Obstructive Pulmonary Disease and Hypereosinophilia
Varón de 60 años de edad con enfermedad pulmonar obstructiva crónica y eosinofilia
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We report a case of FIP1L1/PDGFRA-positive myeloproliferative HES diagnosed in a patient with pulmonary eosinophilia.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 60-year-old man, smoker of 50 pack-years, attended the respiratory medicine clinic with a 2-month history of worsening of his habitual cough and expectoration, and no other symptoms. He had been diagnosed 2 years previously with grade II COPD (forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s [FEV<span class="elsevierStyleInf">1</span>] 79%), well managed after giving up smoking and receiving treatment with fluticasone/salmeterol 25/250<span class="elsevierStyleHsp" style=""></span>mcg.</p><p id="par0015" class="elsevierStylePara elsevierViewall">No lymphadenopathies were observed on physical examination, and auscultation revealed some rhonchi, and a respiratory rate of 16<span class="elsevierStyleHsp" style=""></span>breaths/min and heart rate of 90<span class="elsevierStyleHsp" style=""></span>beats/min. No other significant findings were noted.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Blood tests showed leukocytosis 12<span class="elsevierStyleHsp" style=""></span>590<span class="elsevierStyleHsp" style=""></span>cells/mm with eosinophils 8560 (61%). Other blood counts, coagulation, and biochemistry results were normal. Lung function tests: FEV<span class="elsevierStyleInf">1</span> 2610<span class="elsevierStyleHsp" style=""></span>l (87%), forced vital capacity (FVC) 4090<span class="elsevierStyleHsp" style=""></span>l (109%), FEV<span class="elsevierStyleInf">1</span>/FVC 63.78%. Bronchodilator test and methacholine challenge were negative. Chest X-ray showed radiological signs of COPD. Chest and abdomen CT showed centriacinar and paraseptal emphysema, micronodules in the upper lung lobes, middle lobe and lingula, and thickening of the bladder, with suspected malignancy (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Echocardiogram was normal. Given these findings, the patient was referred to the urology department, where he was diagnosed with transitional cell carcinoma, and treated accordingly. The high number of eosinophils in blood prompted us to undertake a detailed differential diagnosis. Tests for parasites, helminths (<span class="elsevierStyleItalic">Ascaris lumbricoides</span>, <span class="elsevierStyleItalic">Taenia solium</span>, hydatidosis, <span class="elsevierStyleItalic">Toxocara canis</span>, <span class="elsevierStyleItalic">Leishmania</span>) and fungi, and stool culture were all negative. Hepatitis A, B and <span class="elsevierStyleSmallCaps">C</span> and human immunodeficiency virus serologies, and <span class="elsevierStyleItalic">Mycobacterium</span> and <span class="elsevierStyleItalic">Bordetella</span> testing were also negative. In view of these findings, fiberoptic bronchoscopy was performed, and bronchial aspirate, bronchoalveolar lavage (BAL), and transbronchial biopsy (TBB) were obtained. Bronchial aspirate was negative for malignant cells. The BAL cell count was: lymphocytes 6%, polymorphonuclear cells 69%, and eosinophils 20%. Pathology study of TBB reported bronchial mucosa and pulmonary parenchyma with eosinophil infiltration, confirming pulmonary eosinophilia. The immunological study, including antinuclear antibodies, anti-neutrophil cytoplasmic antibodies, and rheumatoid factor, was also negative.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The hematology department was consulted, in view of the patient's persistently high blood and pulmonary eosinophil levels (11.330/μl and 20%, respectively). A bone marrow biopsy was performed which showed marked eosinophilia with predominantly mature cells. Flow cytometry revealed a predominance of CD3. A genetic study was performed using fluorescence in situ hybridization (FISH), a technique which detects and locates a specific DNA sequence on a chromosome after hybridization with a fluorescent molecule. The results were positive for the 4q12 FIP1L1 gene in 20% of cells with normal karyotype. The rest of the genetic analysis was negative. These data and the immunophenotype prompted us to consider a diagnosis of tumor-derived hypereosinophilic syndrome, and allowed us to differentiate between myeloproliferative and lymphoproliferative disease. The patient was thus diagnosed with myeloproliferative hypereosinophilic syndrome with pulmonary involvement, and specific treatment was initiated.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Hypereosinophilic syndrome (HES) is a heterogeneous group of disorders, and causes range from idiopathic disease to malignancy. It mostly affects men aged 20–40 years, with eosinophilia ≥1500<span class="elsevierStyleHsp" style=""></span>cells/mm<span class="elsevierStyleSup">3</span> for more than 6 months, and signs of systemic involvement.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Lung involvement is detected in 40% of cases (cough, pulmonary infiltrates with micronodules on CT, and pleural involvement).<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Our patient presented marked peripheral eosinophilia and a 2-month history of worsening of his respiratory disease (COPD), along with radiological images of lung involvement. The differential diagnosis of this type of pathological process is complex. In patients with pulmonary involvement and eosinophilia, and no evidence of disease in other organs, the first step is to rule out infection, allergy, effects of drugs, and autoimmune diseases.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> With the collaboration of the hematology department, we were able to establish a definitive diagnosis. In this case, eosinophilia in the BAL and TBB prompted us to perform a bone marrow biopsy, which, together with the subsequent genetic assessment, confirmed the diagnosis of FIP1L1/PDGFRA-positive myeloproliferative HES.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">There are 2 variants of HES: lymphoproliferative, occurring in 90% of cases, and myeloproliferative, in 10%. This variant is due in most cases to rearrangement of the FIP1L1/PDGFRA gene, although other genetic disorders have also been observed. It is detected using the FISH technique, which can identify chromosomal abnormalities by capturing the fluorescent point on the chromosome to which each FISH probe binds. This mutation causes continuous activation of a tyrosine kinase that leads to the clonal proliferation of eosinophils.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8–10</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Although HES is a very rare entity that is still relatively unknown, we do not believe that it was associated with the transitional cell carcinoma detected in our patient, although we cannot confidently rule this out.</p><p id="par0050" class="elsevierStylePara elsevierViewall">To conclude, in the evaluation of pulmonary eosinophilia when eosinophil concentrations are very high, the possibility of rare hematological diseases, such as FIP1L1/PDGFRA-positive myeloproliferative HES, must be considered.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Sánchez-Jareño M, Yuste Jiménez V, Villasante C, Canales MÁ, Álvarez-Sala R. Varón de 60 años de edad con enfermedad pulmonar obstructiva crónica y eosinofilia. Arch Bronconeumol. 2018;54:394–395.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 950 "Ancho" => 950 "Tamanyo" => 94269 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Chest CT showing multiple micronodules.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Eosinophilia in pulmonary disorders" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K. Woolnough" 1 => "A.J. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 5 | 13 |
| 2024 October | 83 | 16 | 99 |
| 2024 September | 104 | 15 | 119 |
| 2024 August | 99 | 36 | 135 |
| 2024 July | 89 | 26 | 115 |
| 2024 June | 86 | 21 | 107 |
| 2024 May | 70 | 22 | 92 |
| 2024 April | 67 | 33 | 100 |
| 2024 March | 53 | 20 | 73 |
| 2024 February | 41 | 25 | 66 |
| 2023 March | 17 | 4 | 21 |
| 2023 February | 68 | 31 | 99 |
| 2023 January | 58 | 26 | 84 |
| 2022 December | 72 | 32 | 104 |
| 2022 November | 78 | 27 | 105 |
| 2022 October | 85 | 51 | 136 |
| 2022 September | 82 | 33 | 115 |
| 2022 August | 38 | 48 | 86 |
| 2022 July | 66 | 82 | 148 |
| 2022 June | 43 | 48 | 91 |
| 2022 May | 76 | 32 | 108 |
| 2022 April | 68 | 23 | 91 |
| 2022 March | 58 | 47 | 105 |
| 2022 February | 68 | 26 | 94 |
| 2022 January | 61 | 38 | 99 |
| 2021 December | 69 | 54 | 123 |
| 2021 November | 59 | 42 | 101 |
| 2021 October | 74 | 51 | 125 |
| 2021 September | 55 | 45 | 100 |
| 2021 August | 54 | 30 | 84 |
| 2021 July | 39 | 25 | 64 |
| 2021 June | 80 | 31 | 111 |
| 2021 May | 66 | 35 | 101 |
| 2021 April | 124 | 68 | 192 |
| 2021 March | 84 | 21 | 105 |
| 2021 February | 56 | 28 | 84 |
| 2021 January | 47 | 17 | 64 |
| 2020 December | 43 | 20 | 63 |
| 2020 November | 49 | 18 | 67 |
| 2020 October | 33 | 32 | 65 |
| 2020 September | 26 | 20 | 46 |
| 2020 August | 25 | 17 | 42 |
| 2020 July | 46 | 29 | 75 |
| 2020 March | 20 | 4 | 24 |
| 2020 February | 31 | 13 | 44 |
| 2020 January | 35 | 12 | 47 |
| 2019 December | 48 | 17 | 65 |
| 2019 November | 32 | 16 | 48 |
| 2019 October | 12 | 13 | 25 |
| 2019 September | 18 | 9 | 27 |
| 2019 August | 25 | 14 | 39 |
| 2019 July | 18 | 16 | 34 |
| 2019 June | 18 | 8 | 26 |
| 2019 May | 35 | 18 | 53 |
| 2019 April | 36 | 29 | 65 |
| 2019 March | 47 | 21 | 68 |
| 2019 February | 36 | 18 | 54 |
| 2019 January | 25 | 13 | 38 |
| 2018 December | 4 | 2 | 6 |
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