Gen Thorac Cardiovasc Surg DOI 10.1007/s11748-013-0367-5
CASE REPORT
Epithelioid hemangioendothelioma originating from the chest wall with rib metastases Junichi Shimamura • Moriyuki Kiyoshima • Hisashi Suzuki • Miyuki Kitahara • Yuji Asato Tatsuo Iijima • Ryuta Amemiya
•
Received: 15 September 2013 / Accepted: 22 December 2013 Ó The Japanese Association for Thoracic Surgery 2014
Abstract An asymptomatic 39-year-old woman was referred to us for an abnormal nodular opacity detected on the chest X-ray. Histopathological and further examinations revealed findings consistent with epithelioid hemangioendothelioma (EHE) originating from the chest wall with metastases to the ribs. Complete excision was performed; however, adjuvant chemotherapy was not administered because of the patient’s mental disorder. There are very few reports of EHE arising from the chest wall; therefore, we present this case report with the clinicopathological features of EHE and discuss the therapeutic aspects. Keyword
Chest wall/tumor (chest wall)
Introduction Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor of intermediate malignancy grade that usually arises from the bone, liver, soft tissues or lung. Few cases of EHE originating from the chest wall have been reported; therefore, we present a report of this case of chest wall EHE that directly invaded as well as metastasized to the ribs, and was treated by excision.
J. Shimamura (&) M. Kiyoshima H. Suzuki M. Kitahara Y. Asato R. Amemiya Department of Surgery, Ibaraki Prefectural Central Hospital, 6528 Koibuchi, Kasama, Ibaraki 309-1793, Japan e-mail: [email protected] T. Iijima Department of Pathology, Ibaraki Prefectural Central Hospital, Ibaraki, Japan
Case report A 39-year-old Japanese woman was admitted to the previous hospital for uterine myoma surgery. Chest X-ray and chest computed tomography (CT) performed as a part of preoperative assessment revealed an abnormal nodular opacity. The patient, who had no related symptoms, was then referred to our hospital for further management. She was a non-smoker and had no history of asbestos exposure. Physical examination and laboratory findings were unremarkable. Chest X-ray revealed a round mass in the right upper lung field and notching on the posterior aspect of the fourth rib, along with localized thickening on the lateral aspect of the fourth and fifth ribs (Fig. 1). CT revealed a nodular mass that measured 37 9 24 mm in size and protruded into the right thoracic cavity and was attached to the fourth rib, suggesting rib invasion. The lateral aspects of the fourth and fifth ribs were thickened (Fig. 2). 18-FDG-PET/CT revealed increased FDG uptakes in the tumor, in the posterior aspect of the fourth rib and lateral aspects of the fourth and fifth ribs. The maximum standardized uptake value (SUVmax) was 4.93 in the early phase and 5.74 in the late phase. CT-guided percutaneous needle biopsy of the main tumor revealed a preliminary diagnosis of EHE. Excision of the tumor and partial resection of the fourth and fifth ribs including the intercostal chest wall was performed for final diagnosis and treatment. The tumor was a smooth soft mass measuring 35 9 24 9 15 mm in size located primarily in the intercostal soft tissues that was adherent to the fourth rib, but not to the lung. There were also tumorous lesions on the fourth and fifth ribs distant from the chest wall lesion. Microscopically, the tumor was found to have originated from the subpleural soft tissue. The tumor was composed of epithelioid cells with mild atypia containing rounded
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Gen Thorac Cardiovasc Surg
markers CD31, CD34 and factor VIII, but negative staining for CKAE 1?3, D2-40, EMA, calretinin, a-SMA and HMB45 (Fig. 3b, c). Based on the histological and immunohistochemical findings, the patient was diagnosed as having EHE invading the fourth rib and metastasizing to the fourth and fifth ribs. The postoperative course was uneventful and the patient was discharged on postoperative day 10. Unfortunately, the patient had a medical history of panic disorder and refused our recommendation of postoperative chemotherapy. At present, 6 months since the surgery, no additional hematogenous metastases have appeared, and the patient’s condition remains unchanged.
Discussion
Fig. 1 Chest radiograph showing a spherical mass in the right upper lung field with notching of the posterior side of the fourth rib (white arrow) and local thickening on the lateral sides of the fourth and fifth ribs (black arrow)
Fig. 2 Chest CT showed a nodular mass measuring 37 9 24 mm in the right chest wall adherent to the fourth rib, suggesting invasion (arrow)
nuclei and dense eosinophilic cytoplasm arranged in short strands or nests. The tumor cells were surrounded by hyalinized stroma with intracytoplasmic vascularization, and invaded the fourth rib (Fig. 3a). Biopsy of the tortuous lesions on the fourth and fifth ribs revealed bone marrow filled with epithelioid tumor cells that were thought to be metastases from the chest wall lesion. Immunohistochemistry revealed positive staining for the vascular endothelial
123
EHE was first described by Weiss et al. [1] in 1982 as a rare tumor of vascular endothelial origin and borderline malignancy, with histological and clinical features intermediate between those of benign hemangioma and angiosarcoma. In the endothelial tumors of blood and lymph vessels section of World Health Organization Classification of Tumours, Pathology and Genetics of Tumours of Soft Tissue and Bone, 2002, soft tissue tumors are classified into three entities based on the level of malignancy, as epithelioid hemangioma (EH), benign; EHE, intermediategrade malignancy with a metastatic rate of 31 %; angiosarcoma, high-grade malignancy with a metastatic rate of greater than 50 % [2]. EHE can occur at one of many sites, but most commonly arises from the soft tissues, lung, liver and bone. Chest wall origin is extremely rare, and only a few cases have been reported in the past [3]. Vascular neoplasms of the chest wall are rare and are reported to account for 3 % of all chest tumors [4]. Histologically, these tumors consist of dendritic and epithelioid cells. On immunohistochemical analysis, they show positive staining for endothelial markers such as factor VIII, CD34 and CD31, and negative staining for epithelial markers such as cytokeratin and carcinoembryonic antigen. As most patients are asymptomatic without significant elevation of the serum levels of tumor markers, EHEs are often diagnosed incidentally and are already at an advanced stage at the time of diagnosis. Although imaging findings specific to EHEs of the chest wall have not yet been reported, hepatic EHEs have been shown to have some unique characteristics: they are visualized as discrete nodules with varying echogenicity on ultrasonography, as peripheral lesions with capsular retraction on CT, and show a target appearance due to a central sclerotic zone and a peripheral region of cellular proliferation on MRI [5]. The prognosis of patients with EHE is quite variable depending on the site of origin, and cannot be predicted solely on histopathological or clinical grounds [6, 7]. Patients with
Gen Thorac Cardiovasc Surg Fig. 3 a Histological findings included epithelioid tumor cells arranged in short strands or nests. b Immunohistochemical staining was positive for the vascular endothelial marker CD31. c Immunohistochemical staining was positive for the vascular endothelial marker CD34
this tumor often pursue an aggressive clinical course with wide metastases, and have a poor prognosis. Although the clinical behavior of EHE is considered to be intermediate between that of benign EH and high-grade angiosarcoma, pathological differentiation between EHE and EH is extremely difficult because of a considerable overlap in the cytological findings. Mild atypia can be observed in both entities. Findings useful for differentiating between the two include the presence of mature vessels with open lumen formation in the case of EH and of a peculiar myxochondroid or densely sclerotic stroma in the case of EHE. We should, therefore, consider the clinical picture and the results of imaging, histological and immunohistochemical studies while making a diagnosis of EHE. This case is also unique because of its metastatic behavior. The tumor had invaded the fourth rib, with distant metastasis to the fourth and fifth ribs. Considering the location of the metastases, it appears that the tumor cells directly invaded the adjacent fourth rib, and then spread via the intercostal artery to the fourth rib and via the systemic circulation to the fifth rib. Although the metastatic sites are relatively localized, we propose to continue follow-up of
this case closely, because metastasis is believed to be systemic in nature. A standardized therapeutic regimen has yet to be established for EHE due to varying malignancy grade and rarity of this tumor. Complete surgical resection of the tumor is the most important prognostic factor for limited disease. Patients with systemic lesions should undergo postoperative chemotherapy, although our patient’s mental condition precluded such a therapeutic course. Several regimens have been tried, including carboplatine plus etoposide [8], and interferon-alpha [9]; these regimens may be beneficial for cases with systemic spread. Conflict of interest interest.
All the authors have declared no competing
References 1. Weiss SW, Enzinger FM. Epithelioid hemangioendothelioma: a vascular tumor often mistaken for carcinoma. Cancer. 1982;50:970–81.
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Gen Thorac Cardiovasc Surg 2. Fletcher CDM, Unni K, Mertens F. World health organization classification of tumours, pathology and genetics of tumours of soft tissue and bone, 2002, IARC Press. 3. Yokoi K, Igarashi S, Matsuguma H, Sawafuji M. Epithelioid hemangioendothelioma presenting as a chest wall tumor. Thorac Cardiovasc Surg. 1997;45:254–6. 4. King RM, Pairolero PC, Trastek VF, Piehler JM, Payne WS, Bernatz PE. Primary chest wall tumors: factors affecting survival. Ann Thorac Surg. 1986;41:597–601. 5. Lyburn ID, Torreggiani WC, Harris AC, Zwirewich CV, Buckley AR, Davis JE, et al. Hepatic epithelioid hemangioendothelioma: sonographic, CT, and MR imaging appearances. Am J Roentgenol. 2003;180:1359–64. 6. Weiss SW, Ishak KG, Dail DH, Sweet DE, Enzinger FM. Epithelioid hemangioendothelioma and related lesions. Semin Diagn Pathol. 1986;3:259–87.
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7. Kitaichi M, Nagai S, Nishimura K, Itoh H, Asamoto H, Izumi T, et al. Pulmonary epithelioid hemangioendothelioma in 21 patients, including three with partial spontaneous regression. Eur Respir J. 1998;12:89–96. 8. Pinet C, Magnan A, Garbe L, Payan MJ, Vervloet D. Aggressive form of pleural epithelioid hemangioendothelioma: complete response after chemotherapy. Eur Respir J. 1999;14:237–8. 9. Roudier-Pujol C, Enjolras O, Lacronique J, Guillemette J, Herbreteau D, Leibowitch M, et al. Multifocal epithelioid hemangioendothelioma with partial remission after interferon alfa-2a treatment. Ann Dermatol Venereol. 1994;121:898–904.
CASE REPORT
Epithelioid hemangioendothelioma originating from the chest wall with rib metastases Junichi Shimamura • Moriyuki Kiyoshima • Hisashi Suzuki • Miyuki Kitahara • Yuji Asato Tatsuo Iijima • Ryuta Amemiya
•
Received: 15 September 2013 / Accepted: 22 December 2013 Ó The Japanese Association for Thoracic Surgery 2014
Abstract An asymptomatic 39-year-old woman was referred to us for an abnormal nodular opacity detected on the chest X-ray. Histopathological and further examinations revealed findings consistent with epithelioid hemangioendothelioma (EHE) originating from the chest wall with metastases to the ribs. Complete excision was performed; however, adjuvant chemotherapy was not administered because of the patient’s mental disorder. There are very few reports of EHE arising from the chest wall; therefore, we present this case report with the clinicopathological features of EHE and discuss the therapeutic aspects. Keyword
Chest wall/tumor (chest wall)
Introduction Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor of intermediate malignancy grade that usually arises from the bone, liver, soft tissues or lung. Few cases of EHE originating from the chest wall have been reported; therefore, we present a report of this case of chest wall EHE that directly invaded as well as metastasized to the ribs, and was treated by excision.
J. Shimamura (&) M. Kiyoshima H. Suzuki M. Kitahara Y. Asato R. Amemiya Department of Surgery, Ibaraki Prefectural Central Hospital, 6528 Koibuchi, Kasama, Ibaraki 309-1793, Japan e-mail: [email protected] T. Iijima Department of Pathology, Ibaraki Prefectural Central Hospital, Ibaraki, Japan
Case report A 39-year-old Japanese woman was admitted to the previous hospital for uterine myoma surgery. Chest X-ray and chest computed tomography (CT) performed as a part of preoperative assessment revealed an abnormal nodular opacity. The patient, who had no related symptoms, was then referred to our hospital for further management. She was a non-smoker and had no history of asbestos exposure. Physical examination and laboratory findings were unremarkable. Chest X-ray revealed a round mass in the right upper lung field and notching on the posterior aspect of the fourth rib, along with localized thickening on the lateral aspect of the fourth and fifth ribs (Fig. 1). CT revealed a nodular mass that measured 37 9 24 mm in size and protruded into the right thoracic cavity and was attached to the fourth rib, suggesting rib invasion. The lateral aspects of the fourth and fifth ribs were thickened (Fig. 2). 18-FDG-PET/CT revealed increased FDG uptakes in the tumor, in the posterior aspect of the fourth rib and lateral aspects of the fourth and fifth ribs. The maximum standardized uptake value (SUVmax) was 4.93 in the early phase and 5.74 in the late phase. CT-guided percutaneous needle biopsy of the main tumor revealed a preliminary diagnosis of EHE. Excision of the tumor and partial resection of the fourth and fifth ribs including the intercostal chest wall was performed for final diagnosis and treatment. The tumor was a smooth soft mass measuring 35 9 24 9 15 mm in size located primarily in the intercostal soft tissues that was adherent to the fourth rib, but not to the lung. There were also tumorous lesions on the fourth and fifth ribs distant from the chest wall lesion. Microscopically, the tumor was found to have originated from the subpleural soft tissue. The tumor was composed of epithelioid cells with mild atypia containing rounded
123
Gen Thorac Cardiovasc Surg
markers CD31, CD34 and factor VIII, but negative staining for CKAE 1?3, D2-40, EMA, calretinin, a-SMA and HMB45 (Fig. 3b, c). Based on the histological and immunohistochemical findings, the patient was diagnosed as having EHE invading the fourth rib and metastasizing to the fourth and fifth ribs. The postoperative course was uneventful and the patient was discharged on postoperative day 10. Unfortunately, the patient had a medical history of panic disorder and refused our recommendation of postoperative chemotherapy. At present, 6 months since the surgery, no additional hematogenous metastases have appeared, and the patient’s condition remains unchanged.
Discussion
Fig. 1 Chest radiograph showing a spherical mass in the right upper lung field with notching of the posterior side of the fourth rib (white arrow) and local thickening on the lateral sides of the fourth and fifth ribs (black arrow)
Fig. 2 Chest CT showed a nodular mass measuring 37 9 24 mm in the right chest wall adherent to the fourth rib, suggesting invasion (arrow)
nuclei and dense eosinophilic cytoplasm arranged in short strands or nests. The tumor cells were surrounded by hyalinized stroma with intracytoplasmic vascularization, and invaded the fourth rib (Fig. 3a). Biopsy of the tortuous lesions on the fourth and fifth ribs revealed bone marrow filled with epithelioid tumor cells that were thought to be metastases from the chest wall lesion. Immunohistochemistry revealed positive staining for the vascular endothelial
123
EHE was first described by Weiss et al. [1] in 1982 as a rare tumor of vascular endothelial origin and borderline malignancy, with histological and clinical features intermediate between those of benign hemangioma and angiosarcoma. In the endothelial tumors of blood and lymph vessels section of World Health Organization Classification of Tumours, Pathology and Genetics of Tumours of Soft Tissue and Bone, 2002, soft tissue tumors are classified into three entities based on the level of malignancy, as epithelioid hemangioma (EH), benign; EHE, intermediategrade malignancy with a metastatic rate of 31 %; angiosarcoma, high-grade malignancy with a metastatic rate of greater than 50 % [2]. EHE can occur at one of many sites, but most commonly arises from the soft tissues, lung, liver and bone. Chest wall origin is extremely rare, and only a few cases have been reported in the past [3]. Vascular neoplasms of the chest wall are rare and are reported to account for 3 % of all chest tumors [4]. Histologically, these tumors consist of dendritic and epithelioid cells. On immunohistochemical analysis, they show positive staining for endothelial markers such as factor VIII, CD34 and CD31, and negative staining for epithelial markers such as cytokeratin and carcinoembryonic antigen. As most patients are asymptomatic without significant elevation of the serum levels of tumor markers, EHEs are often diagnosed incidentally and are already at an advanced stage at the time of diagnosis. Although imaging findings specific to EHEs of the chest wall have not yet been reported, hepatic EHEs have been shown to have some unique characteristics: they are visualized as discrete nodules with varying echogenicity on ultrasonography, as peripheral lesions with capsular retraction on CT, and show a target appearance due to a central sclerotic zone and a peripheral region of cellular proliferation on MRI [5]. The prognosis of patients with EHE is quite variable depending on the site of origin, and cannot be predicted solely on histopathological or clinical grounds [6, 7]. Patients with
Gen Thorac Cardiovasc Surg Fig. 3 a Histological findings included epithelioid tumor cells arranged in short strands or nests. b Immunohistochemical staining was positive for the vascular endothelial marker CD31. c Immunohistochemical staining was positive for the vascular endothelial marker CD34
this tumor often pursue an aggressive clinical course with wide metastases, and have a poor prognosis. Although the clinical behavior of EHE is considered to be intermediate between that of benign EH and high-grade angiosarcoma, pathological differentiation between EHE and EH is extremely difficult because of a considerable overlap in the cytological findings. Mild atypia can be observed in both entities. Findings useful for differentiating between the two include the presence of mature vessels with open lumen formation in the case of EH and of a peculiar myxochondroid or densely sclerotic stroma in the case of EHE. We should, therefore, consider the clinical picture and the results of imaging, histological and immunohistochemical studies while making a diagnosis of EHE. This case is also unique because of its metastatic behavior. The tumor had invaded the fourth rib, with distant metastasis to the fourth and fifth ribs. Considering the location of the metastases, it appears that the tumor cells directly invaded the adjacent fourth rib, and then spread via the intercostal artery to the fourth rib and via the systemic circulation to the fifth rib. Although the metastatic sites are relatively localized, we propose to continue follow-up of
this case closely, because metastasis is believed to be systemic in nature. A standardized therapeutic regimen has yet to be established for EHE due to varying malignancy grade and rarity of this tumor. Complete surgical resection of the tumor is the most important prognostic factor for limited disease. Patients with systemic lesions should undergo postoperative chemotherapy, although our patient’s mental condition precluded such a therapeutic course. Several regimens have been tried, including carboplatine plus etoposide [8], and interferon-alpha [9]; these regimens may be beneficial for cases with systemic spread. Conflict of interest interest.
All the authors have declared no competing
References 1. Weiss SW, Enzinger FM. Epithelioid hemangioendothelioma: a vascular tumor often mistaken for carcinoma. Cancer. 1982;50:970–81.
123
Gen Thorac Cardiovasc Surg 2. Fletcher CDM, Unni K, Mertens F. World health organization classification of tumours, pathology and genetics of tumours of soft tissue and bone, 2002, IARC Press. 3. Yokoi K, Igarashi S, Matsuguma H, Sawafuji M. Epithelioid hemangioendothelioma presenting as a chest wall tumor. Thorac Cardiovasc Surg. 1997;45:254–6. 4. King RM, Pairolero PC, Trastek VF, Piehler JM, Payne WS, Bernatz PE. Primary chest wall tumors: factors affecting survival. Ann Thorac Surg. 1986;41:597–601. 5. Lyburn ID, Torreggiani WC, Harris AC, Zwirewich CV, Buckley AR, Davis JE, et al. Hepatic epithelioid hemangioendothelioma: sonographic, CT, and MR imaging appearances. Am J Roentgenol. 2003;180:1359–64. 6. Weiss SW, Ishak KG, Dail DH, Sweet DE, Enzinger FM. Epithelioid hemangioendothelioma and related lesions. Semin Diagn Pathol. 1986;3:259–87.
123
7. Kitaichi M, Nagai S, Nishimura K, Itoh H, Asamoto H, Izumi T, et al. Pulmonary epithelioid hemangioendothelioma in 21 patients, including three with partial spontaneous regression. Eur Respir J. 1998;12:89–96. 8. Pinet C, Magnan A, Garbe L, Payan MJ, Vervloet D. Aggressive form of pleural epithelioid hemangioendothelioma: complete response after chemotherapy. Eur Respir J. 1999;14:237–8. 9. Roudier-Pujol C, Enjolras O, Lacronique J, Guillemette J, Herbreteau D, Leibowitch M, et al. Multifocal epithelioid hemangioendothelioma with partial remission after interferon alfa-2a treatment. Ann Dermatol Venereol. 1994;121:898–904.
