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Aortic and Mitral Valve Replacement Due to Extensive Inflammatory Immunoglobulin G4–Related Pseudotumor

2015; Elsevier BV; Volume: 100; Issue: 4 Linguagem: Inglês

10.1016/j.athoracsur.2014.12.051

1552-6259

Josef Bešík, Jan Pirk, Ivan Netuka, Ondřej Szárszoi, Tomáš Marek, Marian Urban, Eva Honsová, Ján Laco,

Amyloidosis: Diagnosis, Treatment, Outcomes

A 64-year-old woman with extensive tumorous infiltration of the mitral and aortic valves underwent partial resection of a tumor of the left ventricular outflow tract and replacement of both affected valves. Histology revealed an inflammatory pseudotumor with a significant number of immunoglobulin-G4–positive plasma cells. The histologic and clinical findings suggested immunoglobulin-G4–related disease of the heart. A 64-year-old woman with extensive tumorous infiltration of the mitral and aortic valves underwent partial resection of a tumor of the left ventricular outflow tract and replacement of both affected valves. Histology revealed an inflammatory pseudotumor with a significant number of immunoglobulin-G4–positive plasma cells. The histologic and clinical findings suggested immunoglobulin-G4–related disease of the heart. Immunoglobulin-G4–related disease is a novel clinicopathologic entity. It is a systemic inflammatory disease characterized by a tissue infiltration by plasma cells that produce IgG4 [1Kamisawa T. Okamoto A. IgG4-related sclerosing disease.World J Gastroenterol. 2008; 14: 3948-3955Crossref PubMed Scopus (370) Google Scholar]. IgG4-related disease can involve almost any organ, but rarely affects the heart [2Stone J.H. Zen Y. Deshpande V. IgG4-related disease.N Engl J Med. 2012; 366: 539-551Crossref PubMed Scopus (1805) Google Scholar]. A 64-year-old woman was admitted with dyspnea on exertion, with New York Heart Association (NYHA) functional class III. Her medical history included fibrosclerosis affecting the right orbit. Chest radiography showed incipient pulmonary edema. Transesophageal echocardiography revealed severe aortic regurgitation and moderate mitral stenosis and regurgitation. Pathologic infiltration of the anterior leaflet was the cause of the mitral defect; the anterior leaflet of the mitral valve was thickened to up to 10 mm at the A1 and A2 scallops. Thickening continued through the anterolateral commissure on the posterior leaflet to the P1 scallop. From the mitral valve, the pathologic mass expanded to the left ventricular outflow tract (LVOT) and to the left coronary cusp of the aortic valve (Fig 1). The left coronary cusp "adhered" to the aortic wall. This resulted in massive aortic insufficiency. The left ventricle was dilated, with normal systolic function. The coronary angiogram was normal. Inasmuch as the patient's clinical condition did not improve despite aggressive conservative therapy, we recommended a cardiac operation. After a median sternotomy was performed, extracorporeal circulation was established with bicaval cannulation. After performance of an aortotomy, the heart was arrested with cold blood cardioplegia. We observed that the left coronary cusp of the aortic valve was infiltrated with a tumor, and the remaining two cusps were entirely normal. After removing the aortic valve, we extirpated the tumor from the LVOT. The tumor was yellowish white and very dense. We subsequently opened the left atrium. Especially in the area around the anterolateral commissure, the same tumor had proliferated through the mitral valve, including the subvalvular apparatus. Complete excision of the tumorous lesion could not be performed. After excising the part of the valve that was infiltrated by the tumor, we implanted an SJM 25-mm bioprosthesis in the mitral position (St. Jude Medical Inc, Minneapolis, MN) and subsequently implanted a Sorin Mitroflow 19-mm bioprosthesis in the aortic position (Sorin Group, Milan, Italy). The excised cusps of both valves and pieces of the tumor removed from the LVOT were sent for histopathologic examination. Microscopically, there was a mixture of hypocellular fibrotic tissue and areas with dense infiltration by inflammatory cells, mainly lymphocytes and polyclonal plasma cells. There were 450 IgG-positive and 320 IgG4-positive plasma cells in one high-power field with an IgG4/IgG ratio of 0.71 (Fig 2, Fig 3). The features were consistent with the diagnosis of inflammatory pseudotumor. Special stains for common microorganisms gave negative results.Fig 3Immunostaining for immunoglobulin-4–positive cells showing a significant number of IgG4-positive plasma cells (original magnification ×400).View Large Image Figure ViewerDownload (PPT) The patient tolerated the procedure well, and the postoperative course was uneventful. Predischarge transesophageal echocardiography showed good function of the left ventricle and both bioprostheses. There was persisting infiltration in the aortomitral intervalvular fibrosa region (11 × 17 mm) and thickening of the aortic root toward the left atrium (10 mm). Corticoid therapy was proposed, but the patient refused because of her fear of side effects. An echocardiogram 6 months after the operation showed good function of the left ventricle and both bioprostheses. Growth of the tumorous mass was not observed. The patient was asymptomatic (NYHA functional class I). Immunoglobulin-G4–related disease is a newly recognized systemic inflammatory disorder. Tissue infiltration by plasma cells producing IgG4 and extensive fibrosis lead to the development of mass formation, which enters the differential diagnosis of various tumors, especially in imaging methods. Clinical manifestations of IgG4-related disease include autoimmune pancreatitis, sclerosing sialoadenitis of the submandibular gland, Riedel's thyroiditis, mediastinal fibrosis, retroperitoneal fibrosis, and inflammatory pseudotumors affecting the orbits, lungs, kidneys, and other organs [2Stone J.H. Zen Y. Deshpande V. IgG4-related disease.N Engl J Med. 2012; 366: 539-551Crossref PubMed Scopus (1805) Google Scholar]. The diagnosis of IgG4-related disease is mainly based on the histopathologic finding that includes fibrosis, dense lymphoplasmacytic infiltration, and significant IgG4-positive plasma cell infiltration with IgG4/IgG ratio >40% [3Tajima M. Nagai R. Hiroi Y. IgG4-related cardiovascular disorders.Int Heart J. 2014; 55: 287-295Crossref PubMed Scopus (64) Google Scholar]. In our case, the IgG4/IgG ratio was 71%; we found 320 IgG4-positive plasma cells in one high-power field. In patients with IgG4-related disease, elevated serum IgG4 concentrations are often found (>135 mg/dL), but approximately 30% of patients have normal IgG4 levels [2Stone J.H. Zen Y. Deshpande V. IgG4-related disease.N Engl J Med. 2012; 366: 539-551Crossref PubMed Scopus (1805) Google Scholar]. Positron emission tomography scan is an effective imaging method in the clinical examination of IgG4-related disease, and it may also help identify involvement of the heart [4Carbajal H. Waters L. Popovich J. et al.IgG4-related cardiac disease.Methodist Debakey Cardiovasc J. 2013; 9: 230-232Crossref PubMed Scopus (18) Google Scholar]. Glucocorticoids are usually the first-line therapy [2Stone J.H. Zen Y. Deshpande V. IgG4-related disease.N Engl J Med. 2012; 366: 539-551Crossref PubMed Scopus (1805) Google Scholar] and the majority of patients with IgG4-related disease respond positively [1Kamisawa T. Okamoto A. IgG4-related sclerosing disease.World J Gastroenterol. 2008; 14: 3948-3955Crossref PubMed Scopus (370) Google Scholar]. The heart is rarely affected in IgG4-related disease. Song and colleagues [5Song C. Koh M.J. Yoon Y.N. Joung B. Kim S.H. IgG4-related sclerosing disease involving the superior vena cava and the atrial septum of the heart.Yonsei Med J. 2013; 54: 1285-1288Crossref PubMed Scopus (13) Google Scholar] described a case in which immunostaining proved an IgG4-related pseudotumor in the heart. In this patient, a tumorous mass affected the superior vena cava and the atrial septum, resulting in first-degree atrioventricular nodal block with sinus pauses and syncope. A pacemaker was implanted; the cardiac mass was inoperable. Carbajal and associates [4Carbajal H. Waters L. Popovich J. et al.IgG4-related cardiac disease.Methodist Debakey Cardiovasc J. 2013; 9: 230-232Crossref PubMed Scopus (18) Google Scholar] described another case of an intracardiac IgG4-related pseudotumor with infiltration of the myocardium and sinoatrial node, requiring implantation of a pacemaker. Multifocal IgG4-related periarteritis, clinically presenting as a tumorous lesion of the coronary artery and abdominal aortic aneurysm, has been also described [3Tajima M. Nagai R. Hiroi Y. IgG4-related cardiovascular disorders.Int Heart J. 2014; 55: 287-295Crossref PubMed Scopus (64) Google Scholar]. IgG4-positive plasma cell infiltration of the pericardium may cause IgG4-related pericarditis with subsequent heart failure [6Sugimoto T. Morita Y. Isshiki K. et al.Constrictive pericarditis as an emerging manifestation of hyper-IgG4 disease.Int J Cardiol. 2008; 130: e100-e101Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar]. Thus far, the only case of a surgical procedure for an IgG4-related pseudotumor of the heart has been reported by Yamauchi and colleagues [7Yamauchi H. Satoh H. Yamashita T. et al.Immunoglobulin-G4-related disease of the heart causing aortic regurgitation and heart block.Ann Thorac Surg. 2013; 95: e151-e153Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar]. In this case, the aortic valve was replaced because of significant aortic regurgitation, requiring a redo operation because of major perivalvular leakage 8 months after the first operation. Those authors believed that perivalvular leakage might have resulted from loosening of the suture placed in the aortic annulus during the first operation as a result of a reduction in the inflammatory mass after steroid therapy. Although the tumor was only partially resected (identical to our case), it is likely that the operation was successful because of the concomitant effect of steroid therapy. We believe it is crucial to establish a preoperative diagnosis, especially when there are reports of resolution of IgG4-related intracardiac masses without a surgical procedure [3Tajima M. Nagai R. Hiroi Y. IgG4-related cardiovascular disorders.Int Heart J. 2014; 55: 287-295Crossref PubMed Scopus (64) Google Scholar]. Elevated IgG4 serum concentration may be one way to select patients suspected of having IgG4-related disease before an operation is performed. A second test that may be a better biomarker is blood plasmablast concentration, which can be determined by peripheral blood flow cytometry. Circulating plasmablasts are elevated in active IgG4-related disease, even in patients with normal serum IgG4 concentrations [8Wallace Z.S. Mattoo H. Carruthers M. et al.Plasmablasts as a biomarker for IgG4-related disease, independent of serum IgG4 concentrations.Ann Rheum Dis. 2015; 74: 190-195Crossref PubMed Scopus (306) Google Scholar]. The establishment of a preoperative diagnosis is crucial for the treatment strategy. It would be possible to try to achieve adequate regression of these inflammatory masses using steroid treatment without a surgical procedure. Only if conservative therapy fails, resection should be performed. This resection does not necessarily have to be extensive to achieve the desired result. As far as we know, ours is the first case of a double-valve operation with partial resection of the IgG4-related intracardiac inflammatory pseudotumor. The operation was necessitated by heart failure that was refractory to conservative treatment. The short-term result is very good. Supported by the PRVOUK P37/11 program.