- Email: [email protected]
Asymptomatic inflammatory myofibroblastic tumor of the heart: immunohistochemical profile, differential diagnosis, and review of the literature
Cardiovascular Pathology 18 (2009) 187 – 190
Case Report
Asymptomatic inflammatory myofibroblastic tumor of the heart: immunohistochemical profile, differential diagnosis, and review of the literature Angela Pucci a,⁎, Andrea Valori b , Maruska Muscio a , Luca Garofalo a , Francesca Ferroni a , Pietro Angelo Abbruzzese b a
Department of Pathology, Regina Margherita Hospital, ASO OIRM-S.Anna, 94-10126 Turin, Italy Department of Cardiovascular Surgery, Regina Margherita Hospital, ASO OIRM-S.Anna, Turin, Italy
b
Received 10 November 2007; received in revised form 8 January 2008; accepted 4 March 2008
Abstract Background: Inflammatory myofibroblastic tumor (IMT) is an uncommon lesion, mainly occurring in children and young adults and extremely rare in the heart. IMTs are composed of differentiated myofibroblastic cells accompanied by inflammatory cells. Cardiac IMTs are considered biologically benign, but they may have fatal consequences depending upon the peculiarity of site. Because of their rarity in the heart, most knowledge is based on extracardiac lesions that have uncertain behaviour. Methods and results: We investigated the morphologic features and the immunohistochemical profile of an intracardiac IMT, arising in the right outflow tract of an asymptomatic 11month-old boy, by using a large panel of antibodies, many of them previously reported in extracardiac IMTs only. Results were compared with data of literature. After complete surgical excision of the tumor, the patient is disease-free at 1 year of follow-up. Conclusions: The present case showed morphologic and immunohistochemical features characteristic of IMT. Immunohistochemistry was helpful for characterization and differential diagnosis. The immunoreactivity pattern (including calponin expression) was similar to that of extracardiac IMTs except for anaplastic lymphoma kinase 1 immunoreactivity, lacking in this benign intracardiac IMT but usually associated to favourable prognosis in extracardiac IMTs. © 2009 Elsevier Inc. All rights reserved. Keywords: Cardiac tumors; Inflammatory myofibroblastic tumor; Immunohistochemistry; Childhood
1. Introduction Primary heart tumors in infancy are exceedingly rare, and the majority of these lesions are benign proliferations represented by rhabdomyoma, fibroma, myxoma, and teratoma [1]. A very rare, potentially intracardiac mass is the inflammatory myofibroblastic tumor (IMT), which, in the past, has also been termed plasma cell granuloma or inflammatory pseudotumor [2]. It is composed of differentiated myofibroblastic cells accompanied by inflammatory cells, and it mainly occurs in children and young adults. The ⁎ Corresponding author. Anatomia Patologica - Ospedale Infantile Regina Margherita - ASO OIRM-S.Anna - P.zza Polonia, 94-10126 Torino, Italy. Tel.: +39011 3131988; fax: +39011 3135412. E-mail address: [email protected] (A. Pucci). 1054-8807/08/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.carpath.2008.03.002
most common site is represented by the lung, but it has been described in various other sites (abdomen, pelvis, retroperitoneum, liver, head/neck, extremities) [2,3] and exceptionally in the heart [4]. Its true neoplastic nature and/or possible relationship with inflammatory events are still debated: most cases behave as true neoplasms, but exceptionally spontaneous or steroid-induced regression has been recorded in cardiac IMTs [5,6]. Cardiac IMT is diagnostically troublesome because of its rarity, few cardiac IMTs having been so far reported [4–16]. Cardiac IMT does not generally recur following complete surgical resection, but it may have severe hemodynamic consequences and even cause sudden death because of its location [4,10]. We describe an asymptomatic cardiac IMT, characterize its immunoreactivity pattern using a large panel of antibodies, review the aggregated information
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A. Pucci et al. / Cardiovascular Pathology 18 (2009) 187–190
on cardiac IMT, and discuss the most relevant features for differential diagnosis.
2. Case report An 11-month-old boy underwent echocardiography because of an occasionally detected heart murmur. By imaging, a solitary 2×2.5-cm mass attached to the infundibular septum was evidenced, immediately below the posterior cusp of the pulmonary valve, penetrating into the valvular ostium during systole and generating a 30-mmHg gradient. No other lesion was appreciated. At surgery, the whitish and firm mass spontaneously protruded through the pulmonary valve after opening the pulmonary trunk and was attached to the interventricular septum and to the posterior pulmonary cusp (Fig. 1A). On gross examination, the completely resected tumor measured 2.3×2.5×1.5 cm. It was glistening, white, circumscribed, and polypoid with a short, broad
pedicle of 0.4×0.3 cm, showed a firm, tan-white, whorled cut surface with myxoid areas, focal punctuate haemorrhage, and centrally located softer, yellow, necrotic-appearing foci. Microscopically, the lesion was composed of a mixture of spindle cells with an irregular network of small blood vessels and with numerous acute and chronic inflammatory cells including plasma cells, lymphocytes, neutrophils, and histiocytes. The spindle cells were plump, with an eosinophilic cytoplasm and a vesicular nucleus containing prominent nucleoli (Fig. 1B). These cells exhibited variable density from area to area, arranged loosely and rather randomly or in small interlacing fascicles, in a variable amount of myxoid background or in a collagenized stroma. The tumor demonstrated mitotic activity, but no more than two mitoses in 10 high-powered fields and no atypical mitotic figure. The softer yellow areas corresponded to collections of macrophages and/or coagulative necrosis, presumably due to torsion. A panel of immunohistochemical stains revealed diffuse positivity for smooth muscle actin
Fig. 1. (A) Intraoperative view of the cardiac mass with smooth, glistening surface. (B) Spindle cell proliferation in a stromal background with an irregular network of small blood vessels and associated inflammatory infiltrates (haematoxylin and eosin, original magnification ×10). (C) Proliferating spindle cells show intense and diffuse immunostaining for smooth muscle actin in the peripheral, highly cellular area of the tumor. (D) the spindle cells are also plurifocally positive for Calponin [immunoperoxidase, haematoxylin counterstaining; original magnification ×10 (C) and ×20 (D)].
A. Pucci et al. / Cardiovascular Pathology 18 (2009) 187–190
(Fig. 1C) and vimentin and plurifocal immunoreactivity for calponin (Fig. 1D) in the spindle cells. These cells were negative for desmin, myogenin, caldesmon, S-100, synaptophysin, cytokeratin AE1/AE3, CD34, CD56, CD117, bcl-2 and anaplastic lymphoma kinase (ALK)-1. Spindle cells displayed also low proliferating index Ki-67 (≤2%), and rare (b1%) p53 immunoreactive nuclei. CD138-positive plasma cells and CD68-immunoreactive macrophages were variably distributed within tumor. The patient is well and disease-free at 1 year of follow-up.
3. Discussion IMT of the heart is an extremely uncommon tumor and represents a challenging diagnosis for pathologist, cardiologist, and cardiac surgeon. The exact incidence of cardiac IMT is unknown, lacking uniform diagnostic criteria and existing a multiciplity of terms used to designate the lesion (i.e., IMT, inflammatory pseudotumor, plasma cell granuloma). Tian et al. [9] have recognized 11 reported intracardiac IMTs in childhood. Recently, other two cases have been reported [7,8], and a consultation series (from the Armed Force Institute of Pathology and CVPath Gaithesburg Institute) including 10 IMTs in children or young adults has been studied [4]. As far as we know, three other cardiac IMTs have been reported in older adults [11–13]. Cardiac IMTs occur primarily as an endocardial-based cavitary mass, nonluminal mass being exceptionally described [10], and does not show a right or left side predominance [4]. In the heart, it has unpredictable clinical expression, unknown etiology, but favourable prognosis after complete surgical excision, only one reported case showing recurrence so far [14]. Spontaneous or steroidinduced regression of this tumor has also been reported in two cases [5,6]. Nevertheless cardiac IMTs may even cause death because of their peculiar site [4,10]. The intracardiac tumor of the present report was characterized by the distinct histologic features of cardiac IMTs: it was an endocardial-based polypoid mass consisting of proliferating myofibroblastic cells with slight atypias in a myxoid or poorly collagenized background. The lack of prominent pleomorphism, of atypical mitosis, and of locally aggressive behaviour, together with a low proliferating index (MIB-1) and very rare expression of p53, suggested a benign nature of the tumor. The observed necrosis was considered as ischemic, presumably due to torsion of the tumor pedicle and therefore distinct from tumor necrosis of malignant tumors [4]. The cardiac IMT of this report could be differentiated from myxoma, fibroma, or papillary fibroelastoma because of the presence of large myofibroblasts with slight atypias, associated with inflammatory cells, irregular vascular network, and of the absence of elastosis. The differential diagnosis from low-grade sarcoma with myofibroblastic differentiation was based on lacking features of significant
189
pleomorphism and atypical mitotic figures; macroscopic features were not helpful because, in the heart, both IMT and low-grade sarcoma are endocardial-based [4]. The immunoreactivity pattern of spindle cells, i.e., immunostaining for alpha-smooth-muscle actin, vimentin, and calponin, together with desmin and caldesmon negativity, was consistent with myofibroblastic differentiation. Calponin is expressed by myofibroblasts and, as far as we know, calponin immunoreactivity has been previously reported in extracardiac IMTs only [17]. In the present case, the proliferating spindle cells were negative for CD56, CD117, bcl-2, myogenin, and synaptophysin; these markers have been previously investigated in extracardiac IMTs with similar results, CD56 and bcl-2 reactivity only having been reported in a minority of cases [3]. Cardiac and extracardiac IMTs share many features, but a few differences do exist. Cardiac IMTs are usually biologically benign tumors, lacking metastatic potential, whereas atypical and aggressive cases of extracardiac IMTs have been described, particularly in abdominopelvic tumors [3]. As to gross findings, cardiac IMTs are mainly pedunculated endocardial-based tumors, whereas extracardiac IMTs may have variable macroscopic presentation, i.e., polypoid or verrucoid mass, intraparenchimal focal or multifocal noncontiguous lesions [2,3]. Also, ALK expression appears different in extracardiac and cardiac IMTs. So far, ALK reactivity does not show any diagnostic or prognostic role in intracardiac IMT: ALK-1 immunostaining was negative in the present case, and there is little or no evidence of ALK expression in previously reported cardiac IMTs [4,9,15,16]. Conversely, approximately half of extracardiac IMTs harbour a clonal cytogenetic aberration that activates the ALK receptor tyrosine kinase gene on the short arm of chromosome 2 at 2p23, leading to ALK protein overexpression and detectable by immunohistochemistry with a relatively specific cytoplasmic reactivity [3]. Moreover, in extracardiac IMTs, absent ALK expression has been associated with a higher age, subtle histologic differences, and death from disease or distant metastases, suggesting that ALK reactivity may be a favourable prognostic indicator [3,4]. No other specific cytogenetic abnormality has been identified in IMTs so far [3]. In conclusion, the cardiac IMT we report is an extremely rare tumor; in the heart, IMT has histological and biological characteristics of benignity, although it may have fatal consequences because of the peculiarity of site; the immunohistochemical features we have shown (including calponin-immunoreactivity) are helpful for characterization and diagnosis and are largely similar to those of the extracardiac counterpart, except for ALK-1 expression (usually negative in benign cardiac IMTs, whereas extracardiac ALK-1 negative IMTs may show an unfavourable course); differential diagnosis from other cardiac lesions; and particularly from low-grade sarcomas has important prognostic implications and relies on careful histological examination.
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Acknowledgments The authors wish to thank Dr. Riccardo Arisio for his photographic assistance. References [1] Becker AE. Primary heart tumors in the pediatric age group: a review of salient pathologic features relevant for clinicians. Pediatr Cardiol 2000;21:317–23. [2] Yousem SA, Tazelaar HD, Manabe T, Dehner LP. Tumors of the lung— mesenchymal tumours: inflammatory myofibroblastic tumor. In: Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC, editors. WHO Classification of Tumours- Pathology and Genetics- Tumours of the lung, pleura, thymus and Heart. Lyon: IARC Press, 2004. pp. 105–6. [3] Coffin CM, Hornick JL, Fletcher CDM. Inflammatory myofibroblastic tumor. Comparison of clinicopathologic, histologic and immunohistochemical features including ALK expression in atypical and aggressive cases. Am J Surg Pathol 2007;31:509–19. [4] Burke A, Li L, Kling E, Kutys R, Virmani R, Miettinen M. Cardiac inflammatory myofibroblastic tumor: a “benign” neoplasm that may result in syncope, myocardial infarction, and sudden death. Am J Surg Pathol 2007;31:1115–22. [5] Ferbend P, Abramson LP, Backer CL, Mavroudis C, Webb CL, Doll JA, et al. Cardiac plasma cell granulomas: response to oral steroid treatment. Pediatr Cardiol 2004;25:406–10. [6] Pearson PJ, Smithson WA, Driscoll DJ, Banks PM, Ehman RE. Inoperable plasma cell granuloma of the heart: spontaneous decrease in size during an 11-month period. Mayo Clin Proc 1988;63:1022–5.
[7] Gandy KL, Burtelow MA, Reddy M, Silverman NH. Myofibroblastic tumor of the heart: A rare intracardiac tumor. J Thorac Cardiovasc Surg 2005;130:888–9. [8] Murdison KA, Septimus S, Garola RE, Pizarro C. Intracardiac inflammatory myofibroblastic tumor: a unique presentation. Eur J Cardiothorac Surg 2007;31:750–2. [9] Tian JTT, Cheng LC, Yung TCY. Multiple cardiac inflammatory myofibroblastic tumors in the right ventricle in an infant. Ann Thorac Surg 2006;82:1531–5. [10] Rose AG, McCormick S, Cooper K, Titus JL. Inflammatory pseudotumor (plasma cell granuloma) of the heart. Report of two cases and literature review. Arch Pathol Lab Med 1996;120:549–54. [11] Kelly SJ, Lambie NK, Singh HP. Inflammatory myofibroblastic tumor of the left ventricle in an older adult. Ann Thorac Surg 2003;75:1971–3. [12] Krishna L, Ng WL, Chachlani N. Inflammatory pseudotumor of the heart causing aortic regurgitation. Ann Thorac Surg 2001;71:1361–3. [13] Su JW, Caleb MG, Tan RS, Hoe Low AF, Lim CH. Cardiac inflammatory myofibroblastic tumor as a rare cause of aortic regurgitation: a case report. J Thorac Cardiovasc Surg 2006;132:150–1. [14] Hartyanszky IL, Kadar K, Hubay M. Rapid recurrence of an inflammatory myofibroblastic tumor in the right ventricular outflow tract. Cardiol Young 2000;10:271–4. [15] Butany J, Dixit V, Leong SW, Daniel LB, Mezody M, David TE. Inflammatory myofibroblastic tumour with valvular involvement: a case report and review of the literature. Cardiovasc Pathol 2007;16:359–64. [16] Li L, Cerilli LA, Wick MR. Inflammatory pseudotumor (myofibroblastic tumor of the heart). Ann Diagn Pathol 2002;6:116–21. [17] Yamamoto H, Oda Y, Saito T, Sakamoto A, Miyajima K, Tamiya S, et al. p53 Mutation and MDM2 amplification in inflammatory myofibroblastic tumours. Histopathology 2003;42:431–9.
Case Report
Asymptomatic inflammatory myofibroblastic tumor of the heart: immunohistochemical profile, differential diagnosis, and review of the literature Angela Pucci a,⁎, Andrea Valori b , Maruska Muscio a , Luca Garofalo a , Francesca Ferroni a , Pietro Angelo Abbruzzese b a
Department of Pathology, Regina Margherita Hospital, ASO OIRM-S.Anna, 94-10126 Turin, Italy Department of Cardiovascular Surgery, Regina Margherita Hospital, ASO OIRM-S.Anna, Turin, Italy
b
Received 10 November 2007; received in revised form 8 January 2008; accepted 4 March 2008
Abstract Background: Inflammatory myofibroblastic tumor (IMT) is an uncommon lesion, mainly occurring in children and young adults and extremely rare in the heart. IMTs are composed of differentiated myofibroblastic cells accompanied by inflammatory cells. Cardiac IMTs are considered biologically benign, but they may have fatal consequences depending upon the peculiarity of site. Because of their rarity in the heart, most knowledge is based on extracardiac lesions that have uncertain behaviour. Methods and results: We investigated the morphologic features and the immunohistochemical profile of an intracardiac IMT, arising in the right outflow tract of an asymptomatic 11month-old boy, by using a large panel of antibodies, many of them previously reported in extracardiac IMTs only. Results were compared with data of literature. After complete surgical excision of the tumor, the patient is disease-free at 1 year of follow-up. Conclusions: The present case showed morphologic and immunohistochemical features characteristic of IMT. Immunohistochemistry was helpful for characterization and differential diagnosis. The immunoreactivity pattern (including calponin expression) was similar to that of extracardiac IMTs except for anaplastic lymphoma kinase 1 immunoreactivity, lacking in this benign intracardiac IMT but usually associated to favourable prognosis in extracardiac IMTs. © 2009 Elsevier Inc. All rights reserved. Keywords: Cardiac tumors; Inflammatory myofibroblastic tumor; Immunohistochemistry; Childhood
1. Introduction Primary heart tumors in infancy are exceedingly rare, and the majority of these lesions are benign proliferations represented by rhabdomyoma, fibroma, myxoma, and teratoma [1]. A very rare, potentially intracardiac mass is the inflammatory myofibroblastic tumor (IMT), which, in the past, has also been termed plasma cell granuloma or inflammatory pseudotumor [2]. It is composed of differentiated myofibroblastic cells accompanied by inflammatory cells, and it mainly occurs in children and young adults. The ⁎ Corresponding author. Anatomia Patologica - Ospedale Infantile Regina Margherita - ASO OIRM-S.Anna - P.zza Polonia, 94-10126 Torino, Italy. Tel.: +39011 3131988; fax: +39011 3135412. E-mail address: [email protected] (A. Pucci). 1054-8807/08/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.carpath.2008.03.002
most common site is represented by the lung, but it has been described in various other sites (abdomen, pelvis, retroperitoneum, liver, head/neck, extremities) [2,3] and exceptionally in the heart [4]. Its true neoplastic nature and/or possible relationship with inflammatory events are still debated: most cases behave as true neoplasms, but exceptionally spontaneous or steroid-induced regression has been recorded in cardiac IMTs [5,6]. Cardiac IMT is diagnostically troublesome because of its rarity, few cardiac IMTs having been so far reported [4–16]. Cardiac IMT does not generally recur following complete surgical resection, but it may have severe hemodynamic consequences and even cause sudden death because of its location [4,10]. We describe an asymptomatic cardiac IMT, characterize its immunoreactivity pattern using a large panel of antibodies, review the aggregated information
188
A. Pucci et al. / Cardiovascular Pathology 18 (2009) 187–190
on cardiac IMT, and discuss the most relevant features for differential diagnosis.
2. Case report An 11-month-old boy underwent echocardiography because of an occasionally detected heart murmur. By imaging, a solitary 2×2.5-cm mass attached to the infundibular septum was evidenced, immediately below the posterior cusp of the pulmonary valve, penetrating into the valvular ostium during systole and generating a 30-mmHg gradient. No other lesion was appreciated. At surgery, the whitish and firm mass spontaneously protruded through the pulmonary valve after opening the pulmonary trunk and was attached to the interventricular septum and to the posterior pulmonary cusp (Fig. 1A). On gross examination, the completely resected tumor measured 2.3×2.5×1.5 cm. It was glistening, white, circumscribed, and polypoid with a short, broad
pedicle of 0.4×0.3 cm, showed a firm, tan-white, whorled cut surface with myxoid areas, focal punctuate haemorrhage, and centrally located softer, yellow, necrotic-appearing foci. Microscopically, the lesion was composed of a mixture of spindle cells with an irregular network of small blood vessels and with numerous acute and chronic inflammatory cells including plasma cells, lymphocytes, neutrophils, and histiocytes. The spindle cells were plump, with an eosinophilic cytoplasm and a vesicular nucleus containing prominent nucleoli (Fig. 1B). These cells exhibited variable density from area to area, arranged loosely and rather randomly or in small interlacing fascicles, in a variable amount of myxoid background or in a collagenized stroma. The tumor demonstrated mitotic activity, but no more than two mitoses in 10 high-powered fields and no atypical mitotic figure. The softer yellow areas corresponded to collections of macrophages and/or coagulative necrosis, presumably due to torsion. A panel of immunohistochemical stains revealed diffuse positivity for smooth muscle actin
Fig. 1. (A) Intraoperative view of the cardiac mass with smooth, glistening surface. (B) Spindle cell proliferation in a stromal background with an irregular network of small blood vessels and associated inflammatory infiltrates (haematoxylin and eosin, original magnification ×10). (C) Proliferating spindle cells show intense and diffuse immunostaining for smooth muscle actin in the peripheral, highly cellular area of the tumor. (D) the spindle cells are also plurifocally positive for Calponin [immunoperoxidase, haematoxylin counterstaining; original magnification ×10 (C) and ×20 (D)].
A. Pucci et al. / Cardiovascular Pathology 18 (2009) 187–190
(Fig. 1C) and vimentin and plurifocal immunoreactivity for calponin (Fig. 1D) in the spindle cells. These cells were negative for desmin, myogenin, caldesmon, S-100, synaptophysin, cytokeratin AE1/AE3, CD34, CD56, CD117, bcl-2 and anaplastic lymphoma kinase (ALK)-1. Spindle cells displayed also low proliferating index Ki-67 (≤2%), and rare (b1%) p53 immunoreactive nuclei. CD138-positive plasma cells and CD68-immunoreactive macrophages were variably distributed within tumor. The patient is well and disease-free at 1 year of follow-up.
3. Discussion IMT of the heart is an extremely uncommon tumor and represents a challenging diagnosis for pathologist, cardiologist, and cardiac surgeon. The exact incidence of cardiac IMT is unknown, lacking uniform diagnostic criteria and existing a multiciplity of terms used to designate the lesion (i.e., IMT, inflammatory pseudotumor, plasma cell granuloma). Tian et al. [9] have recognized 11 reported intracardiac IMTs in childhood. Recently, other two cases have been reported [7,8], and a consultation series (from the Armed Force Institute of Pathology and CVPath Gaithesburg Institute) including 10 IMTs in children or young adults has been studied [4]. As far as we know, three other cardiac IMTs have been reported in older adults [11–13]. Cardiac IMTs occur primarily as an endocardial-based cavitary mass, nonluminal mass being exceptionally described [10], and does not show a right or left side predominance [4]. In the heart, it has unpredictable clinical expression, unknown etiology, but favourable prognosis after complete surgical excision, only one reported case showing recurrence so far [14]. Spontaneous or steroidinduced regression of this tumor has also been reported in two cases [5,6]. Nevertheless cardiac IMTs may even cause death because of their peculiar site [4,10]. The intracardiac tumor of the present report was characterized by the distinct histologic features of cardiac IMTs: it was an endocardial-based polypoid mass consisting of proliferating myofibroblastic cells with slight atypias in a myxoid or poorly collagenized background. The lack of prominent pleomorphism, of atypical mitosis, and of locally aggressive behaviour, together with a low proliferating index (MIB-1) and very rare expression of p53, suggested a benign nature of the tumor. The observed necrosis was considered as ischemic, presumably due to torsion of the tumor pedicle and therefore distinct from tumor necrosis of malignant tumors [4]. The cardiac IMT of this report could be differentiated from myxoma, fibroma, or papillary fibroelastoma because of the presence of large myofibroblasts with slight atypias, associated with inflammatory cells, irregular vascular network, and of the absence of elastosis. The differential diagnosis from low-grade sarcoma with myofibroblastic differentiation was based on lacking features of significant
189
pleomorphism and atypical mitotic figures; macroscopic features were not helpful because, in the heart, both IMT and low-grade sarcoma are endocardial-based [4]. The immunoreactivity pattern of spindle cells, i.e., immunostaining for alpha-smooth-muscle actin, vimentin, and calponin, together with desmin and caldesmon negativity, was consistent with myofibroblastic differentiation. Calponin is expressed by myofibroblasts and, as far as we know, calponin immunoreactivity has been previously reported in extracardiac IMTs only [17]. In the present case, the proliferating spindle cells were negative for CD56, CD117, bcl-2, myogenin, and synaptophysin; these markers have been previously investigated in extracardiac IMTs with similar results, CD56 and bcl-2 reactivity only having been reported in a minority of cases [3]. Cardiac and extracardiac IMTs share many features, but a few differences do exist. Cardiac IMTs are usually biologically benign tumors, lacking metastatic potential, whereas atypical and aggressive cases of extracardiac IMTs have been described, particularly in abdominopelvic tumors [3]. As to gross findings, cardiac IMTs are mainly pedunculated endocardial-based tumors, whereas extracardiac IMTs may have variable macroscopic presentation, i.e., polypoid or verrucoid mass, intraparenchimal focal or multifocal noncontiguous lesions [2,3]. Also, ALK expression appears different in extracardiac and cardiac IMTs. So far, ALK reactivity does not show any diagnostic or prognostic role in intracardiac IMT: ALK-1 immunostaining was negative in the present case, and there is little or no evidence of ALK expression in previously reported cardiac IMTs [4,9,15,16]. Conversely, approximately half of extracardiac IMTs harbour a clonal cytogenetic aberration that activates the ALK receptor tyrosine kinase gene on the short arm of chromosome 2 at 2p23, leading to ALK protein overexpression and detectable by immunohistochemistry with a relatively specific cytoplasmic reactivity [3]. Moreover, in extracardiac IMTs, absent ALK expression has been associated with a higher age, subtle histologic differences, and death from disease or distant metastases, suggesting that ALK reactivity may be a favourable prognostic indicator [3,4]. No other specific cytogenetic abnormality has been identified in IMTs so far [3]. In conclusion, the cardiac IMT we report is an extremely rare tumor; in the heart, IMT has histological and biological characteristics of benignity, although it may have fatal consequences because of the peculiarity of site; the immunohistochemical features we have shown (including calponin-immunoreactivity) are helpful for characterization and diagnosis and are largely similar to those of the extracardiac counterpart, except for ALK-1 expression (usually negative in benign cardiac IMTs, whereas extracardiac ALK-1 negative IMTs may show an unfavourable course); differential diagnosis from other cardiac lesions; and particularly from low-grade sarcomas has important prognostic implications and relies on careful histological examination.
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A. Pucci et al. / Cardiovascular Pathology 18 (2009) 187–190
Acknowledgments The authors wish to thank Dr. Riccardo Arisio for his photographic assistance. References [1] Becker AE. Primary heart tumors in the pediatric age group: a review of salient pathologic features relevant for clinicians. Pediatr Cardiol 2000;21:317–23. [2] Yousem SA, Tazelaar HD, Manabe T, Dehner LP. Tumors of the lung— mesenchymal tumours: inflammatory myofibroblastic tumor. In: Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC, editors. WHO Classification of Tumours- Pathology and Genetics- Tumours of the lung, pleura, thymus and Heart. Lyon: IARC Press, 2004. pp. 105–6. [3] Coffin CM, Hornick JL, Fletcher CDM. Inflammatory myofibroblastic tumor. Comparison of clinicopathologic, histologic and immunohistochemical features including ALK expression in atypical and aggressive cases. Am J Surg Pathol 2007;31:509–19. [4] Burke A, Li L, Kling E, Kutys R, Virmani R, Miettinen M. Cardiac inflammatory myofibroblastic tumor: a “benign” neoplasm that may result in syncope, myocardial infarction, and sudden death. Am J Surg Pathol 2007;31:1115–22. [5] Ferbend P, Abramson LP, Backer CL, Mavroudis C, Webb CL, Doll JA, et al. Cardiac plasma cell granulomas: response to oral steroid treatment. Pediatr Cardiol 2004;25:406–10. [6] Pearson PJ, Smithson WA, Driscoll DJ, Banks PM, Ehman RE. Inoperable plasma cell granuloma of the heart: spontaneous decrease in size during an 11-month period. Mayo Clin Proc 1988;63:1022–5.
[7] Gandy KL, Burtelow MA, Reddy M, Silverman NH. Myofibroblastic tumor of the heart: A rare intracardiac tumor. J Thorac Cardiovasc Surg 2005;130:888–9. [8] Murdison KA, Septimus S, Garola RE, Pizarro C. Intracardiac inflammatory myofibroblastic tumor: a unique presentation. Eur J Cardiothorac Surg 2007;31:750–2. [9] Tian JTT, Cheng LC, Yung TCY. Multiple cardiac inflammatory myofibroblastic tumors in the right ventricle in an infant. Ann Thorac Surg 2006;82:1531–5. [10] Rose AG, McCormick S, Cooper K, Titus JL. Inflammatory pseudotumor (plasma cell granuloma) of the heart. Report of two cases and literature review. Arch Pathol Lab Med 1996;120:549–54. [11] Kelly SJ, Lambie NK, Singh HP. Inflammatory myofibroblastic tumor of the left ventricle in an older adult. Ann Thorac Surg 2003;75:1971–3. [12] Krishna L, Ng WL, Chachlani N. Inflammatory pseudotumor of the heart causing aortic regurgitation. Ann Thorac Surg 2001;71:1361–3. [13] Su JW, Caleb MG, Tan RS, Hoe Low AF, Lim CH. Cardiac inflammatory myofibroblastic tumor as a rare cause of aortic regurgitation: a case report. J Thorac Cardiovasc Surg 2006;132:150–1. [14] Hartyanszky IL, Kadar K, Hubay M. Rapid recurrence of an inflammatory myofibroblastic tumor in the right ventricular outflow tract. Cardiol Young 2000;10:271–4. [15] Butany J, Dixit V, Leong SW, Daniel LB, Mezody M, David TE. Inflammatory myofibroblastic tumour with valvular involvement: a case report and review of the literature. Cardiovasc Pathol 2007;16:359–64. [16] Li L, Cerilli LA, Wick MR. Inflammatory pseudotumor (myofibroblastic tumor of the heart). Ann Diagn Pathol 2002;6:116–21. [17] Yamamoto H, Oda Y, Saito T, Sakamoto A, Miyajima K, Tamiya S, et al. p53 Mutation and MDM2 amplification in inflammatory myofibroblastic tumours. Histopathology 2003;42:431–9.