- Email: [email protected]
Intracardiac leiomyomatosis presenting as an intraoperative consultation
Accepted Manuscript Title: Intracardiac leiomyomatosis presenting as an intraoperative consultation Author: Ant´onio Joaquim Teixeira Alves Marco Ant´onio Ferreira Javier Gallego-Poveda Ana Matos Artur Costa-Silva ˆ Angelo Nobre Ant´onio Lopez-Beltran PII: DOI: Reference:
S0344-0338(16)30042-5 http://dx.doi.org/doi:10.1016/j.prp.2016.03.007 PRP 51557
To appear in: Received date: Revised date: Accepted date:
3-11-2015 7-3-2016 18-3-2016
Please cite this article as: Ant´onio Joaquim Teixeira Alves, Marco Ant´onio Ferreira, ˆ Javier Gallego-Poveda, Ana Matos, Artur Costa-Silva, Angelo Nobre, Ant´onio LopezBeltran, Intracardiac leiomyomatosis presenting as an intraoperative consultation, Pathology - Research and Practice http://dx.doi.org/10.1016/j.prp.2016.03.007 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Title Page Title: Intracardiac leiomyomatosis presenting as an intraoperative consultation Author names and affiliations: António Joaquim Teixeira Alves a ([email protected]) Marco António Ferreira b ([email protected]) Javier Gallego-Poveda c ([email protected]) Ana Matos c ([email protected]) Artur Costa-Silva a ([email protected]) Ângelo Nobre c ([email protected]) António Lopez-Beltran d ([email protected]) a
Department of Anatomic Pathology, Centro Hospitalar Lisboa Norte (CHLN)-EPE
Avenida Professor Egas Moniz 1649-035 Lisbon, Portugal b
Department of Anatomic Pathology, Hospital Prof. Doutor Fernando Fonseca, EPE
IC19, 2720-276 Amadora, Portugal c
Department of Cardiothoracic Surgery, Hospital de Santa Maria, Centro Hospitalar
Lisboa Norte (CHLN)-EPE Avenida Professor Egas Moniz 1649-035 Lisbon, Portugal d
Champalimaud Clinical Centre, Department of Pathology
Avenida Brasilia 1400-038 Lisbon, Portugal Corresponding author: António Joaquim Teixeira Alves Address: Avenida Professor Egas Moniz, Hospital de Santa Maria – Serviço de Anatomia Patológica, 1649-035 Lisbon, Portugal Telephone: 00351 936007535 Email: [email protected]
1
Abstract Intravenous leiomyomatosis (IVL) is an extremely rare variant of leiomyoma in which nodular masses of tumor grow within venous channels. Rarely, the tumor can reach the vena cava and right heart. We present a case of a 45-year-old woman, admitted with rapidly evolving exertional dyspnea. Cardiac ultrasonography revealed a “mass in the right chambers”. She was submitted to right atriotomy plus tumorectomy, with intraoperative consultation requested. Grossly, the tumor was polypoid, firm, with a smooth surface. The frozen section showed a lesion composed of tortuous vessels and some areas with a fibrillar eosinophil extracellular matrix and others with spindle cells, without significant atypia, mitosis or necrosis. The diagnosis was deferred for definitive paraffin sections. In the definitive H&E and immunohistochemical stains, the case was diagnosed as an IVL and confirmed in the hysterectomy specimen. This is the first case report describing an intraoperative consultation of an intracardiac leiomyomatosis. Clinical information and pathologist awareness to this entity are essential for the correct diagnosis in frozen section.
Keywords: Cardiac tumor; frozen section; intracardiac leiomyomatosis; intravenous leiomyomatosis
2
INTRODUCTION Primary cardiac tumors are rare entities with an autopsy frequency of 0.001-0.030% [1]. Three-quarters of these tumors are histologically benign, mostly myxomas, followed by papillary fibroelastoma. Metastasis to the heart and pericardium, which are much more frequent than primary cardiac tumors, may reach the heart by direct or transvenous extension. The most common extracardiac tumors that reach the atria and other heart chambers through the vena cava inferior are renal cell carcinoma, hepatocellular carcinoma, leiomyoma of the uterus, nephroblastoma, pheochromocytoma and carcinoma of the adrenal cortex [2]. Cardiac tumors, when found incidentally during surgery and/or at unusual locations, may require intraoperative frozen section diagnosis to decide on further management [3]. We present an unusual case of a patient with rapidly evolving exertional dyspnea in whom a cardiac tumor was detected. The patient was submitted to cardiac surgery, and an intraoperative consultation was requested.
CASE-REPORT A 45-year-old woman presented in the emergency room with a 3-week history of easy fatigue and rapidly evolving exertional dyspnea. A cardiac ultrasonography was performed, revealing a solid, hipoecogenic intracavitary mass, which was mobile, apparently friable, starting in the vena cava inferior and progressing to the right heart atrium, through the tricuspid valve to the entry chamber of the ventricle, with no other significant cardiac findings. The possibility of embolization was raised, and an urgent chest, abdominal and pelvic computed tomography CT scan was performed. This exam revealed a heart mass in the right atrium, having 4.5 x 3 cm, with extension to the iliac/ femoral vein, and no evidence of pulmonary thromboembolism or lung infarction was found. The patient was submitted to an emergent right atriotomy and resection of part of the tumor. For intraoperative consultation, two fragments of the tumor were received in our laboratory, the larger one with 1 cm, with the only clinical information given to the pathologist of “right heart tumor”. The frozen section examination revealed a cellular proliferation with medium to large caliber vessels and areas of variable cellularity with elongated cells with scant eosinophilic cytoplasm and poorly defined cellular 3
membranes and other areas with fibrillar eosinophilic extracellular matrix. No atypia, mitosis or necrosis were observed (Fig. 01). The intraoperative consultation was signedout as “tumor with histological features of benignity” with a definitive diagnosis being deferred to paraffin sections. Later on, the heart mass was received (Fig. 02), fixed in 10% buffered formalin and routinely processed. Immunohistochemistry was performed on representative sections with antibodies to smooth muscle actin (Dako, clone 1A4, diluted 1:800, no antigen retrieval), desmin (Leica, clone DERII, diluted 1:60, 15 minutes heat-induced epitope retrieval solution 1 - Bond), estrogen (Leica, clone 6F11, diluted 1:80, 15 minutes heat-induced epitope retrieval solution 1 - Bond) and progesterone receptors (Leica, clone LPGR312, diluted 1:300, 15 minutes heat-induced epitope retrieval solution 1 - Bond). Macroscopically, it was a 10.5 x 4 x 2.5 cm greyish-white elastic tumor with a polypoid, smooth surface and fasciculate appearance in section. Histologically, the tumor was formed by interlacing bundles of smooth muscle with areas of fibrosis and no significant atypia. There was no mitosis or necrosis. Immunohistochemically, the tumor cells stained for smooth muscle actin, desmin, estrogen and progesterone receptors. The diagnosis was of intravenous leiomyomatosis (IVL), given the appropriate clinical context. Later on, a post-operative CT scan was performed (Fig. 03) that showed a vascularized solid mass extending from the renal vein bifurcation of the inferior vena cava to the bifurcation of the common iliac veins and an uterus with multiple solid masses (from a few millimeters to 9 cm) with endovascular extension. Two months later, the patient was submitted to hysterectomy plus adnexectomy. In the uterine body, there were multiple leiomyomas, the largest one with 7 cm. Microscopically, in the external 1/3 of the myometrium, multiple leiomyomas with intravenous extensions were found. These had the same microscopic features as the intracardiac tumor. There were no other significant pathological findings (Fig. 04). DISCUSSION Intraoperative consultation for heart tumors, despite being able to provide valuable information to the surgeon, is rarely performed [4]. Therefore, beside the limitations inherent to the frozen section technique, there is a lack of experience among pathologists in this particular area of intraoperative consultation [5,6,7]. As far as we know, this is the first case report describing an intraoperative consultation in a case of IVL, with extension to the heart. 4
IVL is a rare uterine neoplasm first described in German by Dürck and Hörmann, and the first English case report was by Mandelbaum, et al in 1974 [8,9,10]. There are two main theories regarding IVL pathogenesis. One refers to an origin in the smooth muscle cells of uterine veins; another theory supports an origin in a uterine leiomyoma with subsequent advancement through the vascular wall [11,12]. Cytogenetic analysis has shown the presence of a derivative chromosome - der(14)t(12;14)(q15;q24) - frequently found in uterine leiomyomas, supporting this last theory [13]. IVL has been reported exclusively in women, with a median age of 44 (20-81 years), the majority presenting with symptoms of uterine leiomyoma and rarely with initial cardiac symptoms, as in this case. The correct preoperative diagnosis of IVL, namely with intracardiac extension, is difficult and is usually made during postoperative pathological examination. Although the tumor may resemble a typical leiomyoma, histological appearance may be quite variable with areas of fibrosis, hyalinization or hydropic change [14,15]. As in this case, the intravenous growth may be highly vascular with small to large caliber vessels, mimicking a vascular tumor [16]. Any type of variant that occurs in a leiomyoma may be present in IVL, showing the same behavior and prognosis [15,17]. This tumor and its histological variants should be differentiated from other tumors, particularly endometrial stromal sarcoma (ESS) and leiomyosarcoma. ESS generally features endometrial involvement and extravascular myometrial penetration. Histologically, ESS contains a diffuse network of small arterioles (in contrast to the characteristic thick walled vessels in IVL), and a diffuse proliferation of round or oval cells, resembling cells of the proliferative phase of the endometrium. In contrast to IVL, leiomyosarcoma is characterized by tumor cell necrosis, cytological atypia and high mitotic rates [15]. In addition to primary cardiac and metastatic tumors, thrombus-in-transit should also be considered in the differential diagnosis [14]. The most common primary tumor of the heart, cardiac myxoma, may present some difficulty due to its considerable histological variability, sometimes in different areas of the same tumor. Cardiac myxomas show variable cellularity with stellate and ovoid to plump cells in a myxoid stroma that may occur singly, in cords or surrounding small vessles. The tumor may show an intense inflammatory infiltrate (macrophages, lymphocytes, and others), hemorrhage, thrombi or other degenerative changes that may overshadow its myxomatous nature [6,18]. Cardiac myxomas are more frequent in left atrium, in 5
contrast to IVL that more commonly presents in the right heart chambers. Differentiating IVL from other carcinomas reaching the heart should be straightforward due to the epithelioid versus spindled nature of the cells. Diagnosis of intracardiac leiomyomatosis should be considered in middle aged woman with previous hysterectomy or history of leiomyomas. In the intraoperative consultation, the pathologist should be aware of this possibility, considering the adequate clinical background. The histological appearance of the frozen sections, which is similar to that of paraffin sections, is of a spindle cell neoplasm, with fibrous bands, and variable vascularity in the absence of cytologic atypia or necrosis. The clinical suspicion of IVL is highly important to suggest a correct diagnosis in the intraoperative consultation. Conflict of Interest The present case report was presented as a poster in the 24th European Congress of Pathology, and the abstract was published in Virchows Arch (2012) 461 (Suppl 1):S1– S332DOI 10.1007/s00428-012-1284-1
Acknowledgements The manuscript that we are sending you is original, all participants were active in the course of the patients treatment, diagnosis and the building of the manuscript. This manuscript is not currently under consideration for publication in another journal. All costs were supported by the authors and their institutions.
6
References
[1] Butany J, Nair V, Naseemuddin A, Nair GM, Catton C, Yau T, Cardiac tumours: diagnosis and management. Lancet Oncol. 6 (2005) 219-28. DOI: 10.1016/S1470-2045(05)70093-0 [2] Reynen K, Köckeritz U, Strasser RH, Metastases to the heart. Ann Oncol 15 (2004) 375-381. doi: 10.1093/annonc/mdh086 [3] Bagwan IN, Sheppard MN, Pitfall in frozen section diagnosis of unusually located gelatinous cardiac tumour. J Clin Pathol 62 (2009) 573. doi: 10.1136/jcp.2008.063974 [4] Turhan N, Özgüler Z, Çagli K, Cagli K, Gölbasi Z, Primary cardiac undifferentiated sarcoma: role of intraoperative imprint cytology and frozen section of two cases. Cardiovasc Pathol 20 (2011) 232237. doi: 10.1016/j.carpath.2010.06.008 [5] Jaafar H, Intra-operative frozen section consultation: concepts, applications and limitations. Malays J Med Sci 13 (2006) 4-12 [6] Bagwan I, Sheppard M, Pitfall in frozen section diagnosis of unusually located gelatinous cardiac tumour. J Clin Pathol 62 (2008) 573. doi: 10.1136/jcp.2008.063974 [7] Meir K, Maly A, Doviner V, Maly B, Intraoperative Cytologic Diagnosis of unsuspected cardiac myxoma. Acta Cytol 48 (2004) 565-568. [8] Dürck H, Ueber ein kontinvierlich durch die learned Hohlvene in das Herz vorwachsendes Fibromyom des Uterus. München Med Wochenschr. 54 (1907) 1154. [9] Hörmann K. Über einen Fall von myomatosem Uterus Tumor. Zentralbl Gynakol. 51 (1907) 1604–5.
[10] Mandelbaum I, Pauletto FJ, Nasser WK, Resection of a leiomyoma of the inferior vena cava that produced tricuspid valvular obstruction. J Thorac Cardiovasc Surg. 67 (1974) 561 –7 [11] Norris H, Parmley T, Mesenchymal tumors of the uterus. V. Intravenous leiomyomatosis. A clinical and pathologic study of 14 cases. Cancer. 36 (1975) 2164-78. [12] Fukuyama A, Yokoyama Y, Futagami M, Shigeto T, Wada R, Mizunuma H, A case of uterine leiomyoma with intravenous leiomyomatosis – Histological investigation of the pathological condition. Pathol Oncol Res. 17 (2011) 171-174. doi: 10.1007/s12253-010-9265-7 [13] Dal Cin P, Quade B, Neskey DM, Kleinman MS, Weremowicz S, Morton CC (2002) Intravenous leiomyomatosis is characterized by a der(14)t(12;14)(q15;q24). Genes Chromosomes Cancer. 36 (2003) 205-6. DOI 10.1002/gcc.10159 [14] Li B, Chen X, Chu YD, Li RY, Li WD, Ni YM, Intracardiac leiomyomatosis: a comprehensive analysis of 194 cases. Interact Cardiovasc Thorac Surg. 17 (2013) 132-8. doi: 10.1093/icvts/ivt117 [15] P.B. Clement, Intravenous leiomyomatosis of uterus: a clinicopathological analysis of 16 cases with unusual histologic features. Am J Surg Pathol 12 (1988) 932–945. [16] Kurman RJ, Mesenchymal Tumors of the Uterus. In Blaustein’s Pathology of the Female Genital Tract, sixth ed., Springer, New York, 2011, pp. 468-469.
[17] Vural C, Özen Ö, Demirhan B, Intravenous lipoleiomyomatosis of uterus with cardiac extension: A case report. Pathol Res Pract. 15 (2011) 131-4. doi: 10.1016/j.prp.2010.10.004
7
[18] Pucci A, Gagliardotto P, Zanini C, Pansini S, di Summa M, Mollo F, Histopathologic and clinical characterization of cardiac myxoma: review of 53 cases from a single institution. Am Heart J. 140 (2000) 134-8. DOI: http://dx.doi.org/10.1067/mhj.2000.107176
8
Figure captions Fig. 01 Frozen section of the intracardiac leiomyoma. (Hematoxylin and eosin, a - x40; b – x200)
9
Fig. 02 Gross appearance of the intracardiac leiomyoma. a. Polypoid with smooth contours and elastic consistency. b. Fasciculate appearance in cross-section
10
Fig. 03 Computer tomography scan that shows a vascularized solid mass (red arrow) extending from the renal vein bifurcation of the inferior vena cava to the bifurcation of the common iliac veins. Uterus with multiple solid masses with endovascular extension. a. coronal plane b. sagittal plane
Fig. 04 Histologic appearance of the uterine leiomyoma with intravenous extension (Hematoxylin and eosin, x40)
11
S0344-0338(16)30042-5 http://dx.doi.org/doi:10.1016/j.prp.2016.03.007 PRP 51557
To appear in: Received date: Revised date: Accepted date:
3-11-2015 7-3-2016 18-3-2016
Please cite this article as: Ant´onio Joaquim Teixeira Alves, Marco Ant´onio Ferreira, ˆ Javier Gallego-Poveda, Ana Matos, Artur Costa-Silva, Angelo Nobre, Ant´onio LopezBeltran, Intracardiac leiomyomatosis presenting as an intraoperative consultation, Pathology - Research and Practice http://dx.doi.org/10.1016/j.prp.2016.03.007 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Title Page Title: Intracardiac leiomyomatosis presenting as an intraoperative consultation Author names and affiliations: António Joaquim Teixeira Alves a ([email protected]) Marco António Ferreira b ([email protected]) Javier Gallego-Poveda c ([email protected]) Ana Matos c ([email protected]) Artur Costa-Silva a ([email protected]) Ângelo Nobre c ([email protected]) António Lopez-Beltran d ([email protected]) a
Department of Anatomic Pathology, Centro Hospitalar Lisboa Norte (CHLN)-EPE
Avenida Professor Egas Moniz 1649-035 Lisbon, Portugal b
Department of Anatomic Pathology, Hospital Prof. Doutor Fernando Fonseca, EPE
IC19, 2720-276 Amadora, Portugal c
Department of Cardiothoracic Surgery, Hospital de Santa Maria, Centro Hospitalar
Lisboa Norte (CHLN)-EPE Avenida Professor Egas Moniz 1649-035 Lisbon, Portugal d
Champalimaud Clinical Centre, Department of Pathology
Avenida Brasilia 1400-038 Lisbon, Portugal Corresponding author: António Joaquim Teixeira Alves Address: Avenida Professor Egas Moniz, Hospital de Santa Maria – Serviço de Anatomia Patológica, 1649-035 Lisbon, Portugal Telephone: 00351 936007535 Email: [email protected]
1
Abstract Intravenous leiomyomatosis (IVL) is an extremely rare variant of leiomyoma in which nodular masses of tumor grow within venous channels. Rarely, the tumor can reach the vena cava and right heart. We present a case of a 45-year-old woman, admitted with rapidly evolving exertional dyspnea. Cardiac ultrasonography revealed a “mass in the right chambers”. She was submitted to right atriotomy plus tumorectomy, with intraoperative consultation requested. Grossly, the tumor was polypoid, firm, with a smooth surface. The frozen section showed a lesion composed of tortuous vessels and some areas with a fibrillar eosinophil extracellular matrix and others with spindle cells, without significant atypia, mitosis or necrosis. The diagnosis was deferred for definitive paraffin sections. In the definitive H&E and immunohistochemical stains, the case was diagnosed as an IVL and confirmed in the hysterectomy specimen. This is the first case report describing an intraoperative consultation of an intracardiac leiomyomatosis. Clinical information and pathologist awareness to this entity are essential for the correct diagnosis in frozen section.
Keywords: Cardiac tumor; frozen section; intracardiac leiomyomatosis; intravenous leiomyomatosis
2
INTRODUCTION Primary cardiac tumors are rare entities with an autopsy frequency of 0.001-0.030% [1]. Three-quarters of these tumors are histologically benign, mostly myxomas, followed by papillary fibroelastoma. Metastasis to the heart and pericardium, which are much more frequent than primary cardiac tumors, may reach the heart by direct or transvenous extension. The most common extracardiac tumors that reach the atria and other heart chambers through the vena cava inferior are renal cell carcinoma, hepatocellular carcinoma, leiomyoma of the uterus, nephroblastoma, pheochromocytoma and carcinoma of the adrenal cortex [2]. Cardiac tumors, when found incidentally during surgery and/or at unusual locations, may require intraoperative frozen section diagnosis to decide on further management [3]. We present an unusual case of a patient with rapidly evolving exertional dyspnea in whom a cardiac tumor was detected. The patient was submitted to cardiac surgery, and an intraoperative consultation was requested.
CASE-REPORT A 45-year-old woman presented in the emergency room with a 3-week history of easy fatigue and rapidly evolving exertional dyspnea. A cardiac ultrasonography was performed, revealing a solid, hipoecogenic intracavitary mass, which was mobile, apparently friable, starting in the vena cava inferior and progressing to the right heart atrium, through the tricuspid valve to the entry chamber of the ventricle, with no other significant cardiac findings. The possibility of embolization was raised, and an urgent chest, abdominal and pelvic computed tomography CT scan was performed. This exam revealed a heart mass in the right atrium, having 4.5 x 3 cm, with extension to the iliac/ femoral vein, and no evidence of pulmonary thromboembolism or lung infarction was found. The patient was submitted to an emergent right atriotomy and resection of part of the tumor. For intraoperative consultation, two fragments of the tumor were received in our laboratory, the larger one with 1 cm, with the only clinical information given to the pathologist of “right heart tumor”. The frozen section examination revealed a cellular proliferation with medium to large caliber vessels and areas of variable cellularity with elongated cells with scant eosinophilic cytoplasm and poorly defined cellular 3
membranes and other areas with fibrillar eosinophilic extracellular matrix. No atypia, mitosis or necrosis were observed (Fig. 01). The intraoperative consultation was signedout as “tumor with histological features of benignity” with a definitive diagnosis being deferred to paraffin sections. Later on, the heart mass was received (Fig. 02), fixed in 10% buffered formalin and routinely processed. Immunohistochemistry was performed on representative sections with antibodies to smooth muscle actin (Dako, clone 1A4, diluted 1:800, no antigen retrieval), desmin (Leica, clone DERII, diluted 1:60, 15 minutes heat-induced epitope retrieval solution 1 - Bond), estrogen (Leica, clone 6F11, diluted 1:80, 15 minutes heat-induced epitope retrieval solution 1 - Bond) and progesterone receptors (Leica, clone LPGR312, diluted 1:300, 15 minutes heat-induced epitope retrieval solution 1 - Bond). Macroscopically, it was a 10.5 x 4 x 2.5 cm greyish-white elastic tumor with a polypoid, smooth surface and fasciculate appearance in section. Histologically, the tumor was formed by interlacing bundles of smooth muscle with areas of fibrosis and no significant atypia. There was no mitosis or necrosis. Immunohistochemically, the tumor cells stained for smooth muscle actin, desmin, estrogen and progesterone receptors. The diagnosis was of intravenous leiomyomatosis (IVL), given the appropriate clinical context. Later on, a post-operative CT scan was performed (Fig. 03) that showed a vascularized solid mass extending from the renal vein bifurcation of the inferior vena cava to the bifurcation of the common iliac veins and an uterus with multiple solid masses (from a few millimeters to 9 cm) with endovascular extension. Two months later, the patient was submitted to hysterectomy plus adnexectomy. In the uterine body, there were multiple leiomyomas, the largest one with 7 cm. Microscopically, in the external 1/3 of the myometrium, multiple leiomyomas with intravenous extensions were found. These had the same microscopic features as the intracardiac tumor. There were no other significant pathological findings (Fig. 04). DISCUSSION Intraoperative consultation for heart tumors, despite being able to provide valuable information to the surgeon, is rarely performed [4]. Therefore, beside the limitations inherent to the frozen section technique, there is a lack of experience among pathologists in this particular area of intraoperative consultation [5,6,7]. As far as we know, this is the first case report describing an intraoperative consultation in a case of IVL, with extension to the heart. 4
IVL is a rare uterine neoplasm first described in German by Dürck and Hörmann, and the first English case report was by Mandelbaum, et al in 1974 [8,9,10]. There are two main theories regarding IVL pathogenesis. One refers to an origin in the smooth muscle cells of uterine veins; another theory supports an origin in a uterine leiomyoma with subsequent advancement through the vascular wall [11,12]. Cytogenetic analysis has shown the presence of a derivative chromosome - der(14)t(12;14)(q15;q24) - frequently found in uterine leiomyomas, supporting this last theory [13]. IVL has been reported exclusively in women, with a median age of 44 (20-81 years), the majority presenting with symptoms of uterine leiomyoma and rarely with initial cardiac symptoms, as in this case. The correct preoperative diagnosis of IVL, namely with intracardiac extension, is difficult and is usually made during postoperative pathological examination. Although the tumor may resemble a typical leiomyoma, histological appearance may be quite variable with areas of fibrosis, hyalinization or hydropic change [14,15]. As in this case, the intravenous growth may be highly vascular with small to large caliber vessels, mimicking a vascular tumor [16]. Any type of variant that occurs in a leiomyoma may be present in IVL, showing the same behavior and prognosis [15,17]. This tumor and its histological variants should be differentiated from other tumors, particularly endometrial stromal sarcoma (ESS) and leiomyosarcoma. ESS generally features endometrial involvement and extravascular myometrial penetration. Histologically, ESS contains a diffuse network of small arterioles (in contrast to the characteristic thick walled vessels in IVL), and a diffuse proliferation of round or oval cells, resembling cells of the proliferative phase of the endometrium. In contrast to IVL, leiomyosarcoma is characterized by tumor cell necrosis, cytological atypia and high mitotic rates [15]. In addition to primary cardiac and metastatic tumors, thrombus-in-transit should also be considered in the differential diagnosis [14]. The most common primary tumor of the heart, cardiac myxoma, may present some difficulty due to its considerable histological variability, sometimes in different areas of the same tumor. Cardiac myxomas show variable cellularity with stellate and ovoid to plump cells in a myxoid stroma that may occur singly, in cords or surrounding small vessles. The tumor may show an intense inflammatory infiltrate (macrophages, lymphocytes, and others), hemorrhage, thrombi or other degenerative changes that may overshadow its myxomatous nature [6,18]. Cardiac myxomas are more frequent in left atrium, in 5
contrast to IVL that more commonly presents in the right heart chambers. Differentiating IVL from other carcinomas reaching the heart should be straightforward due to the epithelioid versus spindled nature of the cells. Diagnosis of intracardiac leiomyomatosis should be considered in middle aged woman with previous hysterectomy or history of leiomyomas. In the intraoperative consultation, the pathologist should be aware of this possibility, considering the adequate clinical background. The histological appearance of the frozen sections, which is similar to that of paraffin sections, is of a spindle cell neoplasm, with fibrous bands, and variable vascularity in the absence of cytologic atypia or necrosis. The clinical suspicion of IVL is highly important to suggest a correct diagnosis in the intraoperative consultation. Conflict of Interest The present case report was presented as a poster in the 24th European Congress of Pathology, and the abstract was published in Virchows Arch (2012) 461 (Suppl 1):S1– S332DOI 10.1007/s00428-012-1284-1
Acknowledgements The manuscript that we are sending you is original, all participants were active in the course of the patients treatment, diagnosis and the building of the manuscript. This manuscript is not currently under consideration for publication in another journal. All costs were supported by the authors and their institutions.
6
References
[1] Butany J, Nair V, Naseemuddin A, Nair GM, Catton C, Yau T, Cardiac tumours: diagnosis and management. Lancet Oncol. 6 (2005) 219-28. DOI: 10.1016/S1470-2045(05)70093-0 [2] Reynen K, Köckeritz U, Strasser RH, Metastases to the heart. Ann Oncol 15 (2004) 375-381. doi: 10.1093/annonc/mdh086 [3] Bagwan IN, Sheppard MN, Pitfall in frozen section diagnosis of unusually located gelatinous cardiac tumour. J Clin Pathol 62 (2009) 573. doi: 10.1136/jcp.2008.063974 [4] Turhan N, Özgüler Z, Çagli K, Cagli K, Gölbasi Z, Primary cardiac undifferentiated sarcoma: role of intraoperative imprint cytology and frozen section of two cases. Cardiovasc Pathol 20 (2011) 232237. doi: 10.1016/j.carpath.2010.06.008 [5] Jaafar H, Intra-operative frozen section consultation: concepts, applications and limitations. Malays J Med Sci 13 (2006) 4-12 [6] Bagwan I, Sheppard M, Pitfall in frozen section diagnosis of unusually located gelatinous cardiac tumour. J Clin Pathol 62 (2008) 573. doi: 10.1136/jcp.2008.063974 [7] Meir K, Maly A, Doviner V, Maly B, Intraoperative Cytologic Diagnosis of unsuspected cardiac myxoma. Acta Cytol 48 (2004) 565-568. [8] Dürck H, Ueber ein kontinvierlich durch die learned Hohlvene in das Herz vorwachsendes Fibromyom des Uterus. München Med Wochenschr. 54 (1907) 1154. [9] Hörmann K. Über einen Fall von myomatosem Uterus Tumor. Zentralbl Gynakol. 51 (1907) 1604–5.
[10] Mandelbaum I, Pauletto FJ, Nasser WK, Resection of a leiomyoma of the inferior vena cava that produced tricuspid valvular obstruction. J Thorac Cardiovasc Surg. 67 (1974) 561 –7 [11] Norris H, Parmley T, Mesenchymal tumors of the uterus. V. Intravenous leiomyomatosis. A clinical and pathologic study of 14 cases. Cancer. 36 (1975) 2164-78. [12] Fukuyama A, Yokoyama Y, Futagami M, Shigeto T, Wada R, Mizunuma H, A case of uterine leiomyoma with intravenous leiomyomatosis – Histological investigation of the pathological condition. Pathol Oncol Res. 17 (2011) 171-174. doi: 10.1007/s12253-010-9265-7 [13] Dal Cin P, Quade B, Neskey DM, Kleinman MS, Weremowicz S, Morton CC (2002) Intravenous leiomyomatosis is characterized by a der(14)t(12;14)(q15;q24). Genes Chromosomes Cancer. 36 (2003) 205-6. DOI 10.1002/gcc.10159 [14] Li B, Chen X, Chu YD, Li RY, Li WD, Ni YM, Intracardiac leiomyomatosis: a comprehensive analysis of 194 cases. Interact Cardiovasc Thorac Surg. 17 (2013) 132-8. doi: 10.1093/icvts/ivt117 [15] P.B. Clement, Intravenous leiomyomatosis of uterus: a clinicopathological analysis of 16 cases with unusual histologic features. Am J Surg Pathol 12 (1988) 932–945. [16] Kurman RJ, Mesenchymal Tumors of the Uterus. In Blaustein’s Pathology of the Female Genital Tract, sixth ed., Springer, New York, 2011, pp. 468-469.
[17] Vural C, Özen Ö, Demirhan B, Intravenous lipoleiomyomatosis of uterus with cardiac extension: A case report. Pathol Res Pract. 15 (2011) 131-4. doi: 10.1016/j.prp.2010.10.004
7
[18] Pucci A, Gagliardotto P, Zanini C, Pansini S, di Summa M, Mollo F, Histopathologic and clinical characterization of cardiac myxoma: review of 53 cases from a single institution. Am Heart J. 140 (2000) 134-8. DOI: http://dx.doi.org/10.1067/mhj.2000.107176
8
Figure captions Fig. 01 Frozen section of the intracardiac leiomyoma. (Hematoxylin and eosin, a - x40; b – x200)
9
Fig. 02 Gross appearance of the intracardiac leiomyoma. a. Polypoid with smooth contours and elastic consistency. b. Fasciculate appearance in cross-section
10
Fig. 03 Computer tomography scan that shows a vascularized solid mass (red arrow) extending from the renal vein bifurcation of the inferior vena cava to the bifurcation of the common iliac veins. Uterus with multiple solid masses with endovascular extension. a. coronal plane b. sagittal plane
Fig. 04 Histologic appearance of the uterine leiomyoma with intravenous extension (Hematoxylin and eosin, x40)
11