Case Report
Splenic Littoral Cell Hemangioendothelioma: Report of a Case with Hepatic Metastases and Review of the Literature Ping He, MD,1 Xi-De Yan, MD,2 Jin-Rui Wang, MD,1,3,4 Run-Cai Guo,5 Hua-Bin Zhang, MD1 1
Department of Ultrasound, Peking University Third Hospital, Beijing, China Department of Function, People’s Hospital of Datong Country of Qinghai Province, China 3 Department of Ultrasound, Erdos Center’s Hospital, Inner Mongolia, China 4 Inner Mongolia Medical College, Hohhot, Inner Mongolia, China 5 Department of Radiology, Peking University Third Hospital, Beijing, China 2
Received 5 February 2013; accepted 18 October 2013
ABSTRACT: Littoral cell tumors are unique to the spleen and are different from all other primary splenic tumors. These tumors may be divided into three types: “littoral cell angioma,” “littoral cell hemangioendothelioma,” and “littoral cell angiosarcoma.” We present a patient with splenic littoral cell hemangioendothlioma accomC 2014 Wiley Periodicals, panied by hepatic metastases. V Inc. J Clin Ultrasound 42:308–312, 2014; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jcu.22120 Keywords: splenic littoral cell hemangioendothelioma; hepatic metastases; spleen; sonography; contrast medium
L
ittoral cell tumors are vascular tumors unique to the spleen and are different from all other primary splenic tumors.1,2 These tumors may also be divided into three types, including “littoral cell angioma (LCA),” which is benign, “littoral cell hemangioendothelioma,” which has intermediate malignant potential, and “littoral cell angiosarcoma,” which is malignant. Splenic littoral cell tumors with hepatic metastases are very rare. Besides, there are few reports describing the radiologic features of littoral cell tumors. We present a patient with splenic and hepatic tumors. In view of its atypical but not fully malignant histologic features, the presence of hepatic metastasis, and necrosis, a
Correspondence to: H. B. Zhang C 2014 Wiley Periodicals, Inc. V
308
diagnosis of splenic littoral cell hemangioendothlioma was made.
CASE REPORT
A 28-year-old woman presented with a 1-month history of hepatic and splenic masses. Routine laboratory results were within normal limits, and tumor markers, including CA-199, AFP, and CEA, were also within normal limits. The patient underwent sonographic examination of the abdomen performed with an iU 22 scanner (Philips Ultrasound, Bothell, WA) equipped with C5–2 convex array transducers. Sonographic examination showed splenomegaly with multiple hyperechoic masses. The largest of these masses was approximately 4.0 3 3.0 cm. Most of the lesions were well demarcated from the surrounding splenic parenchyma and were surrounded by an irregular peripheral hypoechoic rim. In addition, some lesions had an internal anechoic region, which represented necrosis (Figure 1A). With color Doppler imaging, a rich blood flow signal was seen in the solid-appearing portion of the tumors. No blood flow was found in the anechoic region (Figure 1B). The patient then underwent low-mechanicalindex real-time contrast-enhanced ultrasonography (CEUS). A sulfur hexafluoride--based microbubble contrast medium (Sonovue) was injected intravenously in 2 seconds. A volume of 1.5 ml was administered, followed by a 5-ml saline flush immediately after contrast medium injection. JOURNAL OF CLINICAL ULTRASOUND
SPLENIC LITTORAL CELL HEMANGIOENDOTHELIOMA
FIGURE 1. (A) Ultrasound of the abdomen showed a round hyperechoic mass, approximately 4.0 3 3.0 cm in greatest dimension. The lesion was well demarcated from the surrounding splenic parenchyma, with an irregular peripheral hypoechoic rim. In addition, the lesion had an internal anechoic region, representing necrosis, which was mildly enhanced through transmission. (B) Color Doppler sonography demonstrates rich blood flow signal in the solid-appearing portion of the tumor. No blood flow was found in the anechoic region. (C, D) The lesion in the liver shows the similar imaging features as that in the spleen.
CEUS showed marked enhancement in the early arterial phase, which appeared hypervascular in comparison to the normal splenic parenchyma. This enhancement persisted through the parenchymal phase and after 6 minutes had not faded away. No enhancement was apparent in the central anechoic region, consistent with necrosis (Figure 2A–2C). A CT scan showed the spleen was enlarged with multiple focal hypodense lesions, which were illdefined borders. The lesions also showed irregularly contoured areas of even lower density in the centers. After intravenous administration of iodinated contrast medium, a strong peripheral nodular or rim-like arterial enhancement was seen, and the lesions showed centripetal filling during the venous and delayed phases. The enhancement of these lesions was hyperdense in comparison with that of the surrounding splenic tissue. Central necrosis was better seen without enhancement. CT angiography showed blood supply to these lesions was via branches of the hepatic and splenic arteries. VOL. 42, NO. 5, JUNE 2014
The unenhanced T1-weighted MRI showed a markedly hypointense signal, and hyperintensity was seen on unenhanced T2-weighted MRI. The MR enhancement pattern was similar to that seen with CT (Figure 3). The lesions in the liver had the same appearance under US (Figure 1C and 1D), CEUS, CT, and MRI (Figure 3) as the splenic lesions. Whole body bone scanning showed no evidence of metastases. Grossly, the spleen was enlarged to 16 3 12 cm and contained four scattered red-brown nodules. The diameter of these nodules ranged from 0.4 to 2.0 cm. All nodules showed intact encapsulation. Nuclear atypia was mild to moderate, and no mitoses were found. Necrosis was seen in the center of solid regions. The largest liver mass was surgically excised and measured approximately 4.0 cm in greatest dimension. The histopathologic features of this mass were similar to that of the splenic lesions (Figure 4). Immunohistochemically, tumor cells in both the 309
HE ET AL
FIGURE 3. (A) The T1-weighted MRI showed a markedly hypointense signal and (B) they exhibited hyperintensity on the T2-weighted MRI. The enhancement pattern of MR was similar to that of CT.
FIGURE 2. (A) CEUS showed marked enhancement in the early arterial phase (13 seconds), which appeared hypervascular in comparison with the normal splenic parenchyma. (B) Enhancement persisted though the parenchymal phase (85 seconds). (C) Enhancement did not fade after 6 minutes. No enhancement was apparent in the central anechoic region, which is consistent with necrosis.
spleen and the liver expressed CD31, CD68, CD8, and CD34, without F8, representing both endothelial and histiocytic antigens.
DISCUSSION
Patients with littoral cell tumors are often asymptomatic and these lesions are discovered 310
FIGURE 4. The capsule of all nodules was intact. Central necrosis was seen in the solid regions. The largest mass in liver was resected and was 4.0 cm in diameter. The histopathologic features of this mass were similar to those of the splenic lesions.
incidentally at physical examination or when splenectomy is carried out for an unrelated reason, or at autopsy. In some cases of littoral cell tumor, patients may exhibit splenomegaly JOURNAL OF CLINICAL ULTRASOUND
SPLENIC LITTORAL CELL HEMANGIOENDOTHELIOMA
accompanied by hypersplenism or may simply seek medical attention for abdominal pain, weakness, or weight loss.1,3–7 The patient described here did not experience discomfort, and only splenomegaly was found at physical examination. There was no evidence of hypersplenism. In short, clinical symptoms are not specific for littoral cell tumors. Littoral cell tumors have characteristic morphologic and immunophenotypic features, which distinguish them from other vascular splenic tumors. Morphologically LCA consists of multiple nodules composed of vascular channels of red pulp and in general involves the spleen in a diffuse manner. However, a solitary form has been reported.2 LCA cells express both endothelial and histiocytic antigens. Typically, LCA cells express CD31, CD68, F8, CD21, and cathepsin D, and CD34 is negative.2 In this case CD34 was positive, and F8 was negative. In addition, CD8 was positive in this case, as sinus lining cells were found to express CD8. However, whether CD8 is typically positive in LCA is still controversial,2,3,8 and CD8 staining may be seen in splenic hamartomas and some angiosarcomas.2 Littoral cell hemangioendotheliomas and littoral cell angiosarcoma are morphologically and immunophenotypically similar to LCA. However, in contrast to LCAs, littoral cell hemangioendotheliomas may have necrosis, solid clear cell areas, nuclear atypia of low degree, hepatic metastasis, and an indolent clinical course.3,4 Littoral cell angiosarcoma shows a high degree of malignancy and usually has a rapidly progressive clinical course. Histologic features of this tumor include anaplasia, brisk mitotic activity, and necrosis.1,2,6 Because the prognosis of tumors in this family is closely related to the specific pathologic type, longer follow-up of our patient is essential, especially as atypical histology, necrosis, and metastasis were found. There are few reports describing the radiologic features of littoral cell tumors. Given the fairly complete radiologic information obtained in this case, we will summarize as follows. With ultrasound, these tumors involve the spleen in a diffuse manner that appears hyperechoic. The lesions may have clear boundaries with an irregular peripheral surrounding the hypoechoic rim. This is in accordance with pathologic findings, which showed that the capsule of these nodules was intact. Where necrosis or hemorrhage was found, there was an anechoic region in the center of the neoplasm. The solidVOL. 42, NO. 5, JUNE 2014
appearing portions of the tumor had rich blood flow, but the anechoic regions showed no flow signal with color Doppler. CEUS, contrastenhanced CT, and contrast-enhanced MR showed analogous appearances. There was marked enhancement in the early arterial phase that appeared hypervascular in comparison with the normal splenic parenchyma. Enhancement persisted through the parenchymal phase. No enhancement was found in the central anechoic region, which was consistent with necrosis in these areas. Oliver-Goldaracena et al7 suggested that the neoplastic cells of LCA have a hemophagocytic capacity, and hemosiderin therefore accumulates in the cytoplasm. This finding is specific for LCA on MRI as there are no other neoplasms that are associated with such an extensive degree of siderosis.7 The T1- and T2weighted MRIs showed a hypointense signal. With respect to the cell of origin, we believe littoral cell hemangioendothelioma and littoral cell angiosarcoma should also have this same specific appearance on MRI. The T1-weighted MRI in our case showed a hypointense signal, but they exhibited hyperintensity on the T2weighted MRI. This most likely is due to the fact that tumor cells in our case had little siderosis. Splenic neoplasms that diffusely involve the spleen may mimic splenic littoral cell tumors on imaging. Such tumors may include primary splenic tumors, metastatic tumors, and lymphoma, and infections that cause microabscesses may also mimic littoral cell tumors. However, clinical information and the associated involvement of other organs may help point to the correct diagnosis. The final diagnosis, however, must depend on pathologic results. REFERENCES 1. Falk S, Stutte HJ, Frizzera G. Littoral cell angioma. A novel splenic vascular lesion demonstrating histiocytic differentiation. Am J Surg Pathol 1991;15:1023. 2. Arber DA, Strickler JG, Chen YY, et al. Splenic vascular tumors: a histologic, immunophenotypic, and virologic study. Am J Surg Pathol 1997;21: 827. 3. Ben-Izhak O, Bejar J, Ben-Eliezer S, et al. Splenic littoral cell haemangioendothelioma: a new lowgrade variant of malignant littoral cell tumour. Histopathology 2001;39:469. 4. Fernandez S, Cook GW, Arber DA. Metastasizing splenic littoral cell hemangioendothelioma. Am J Surg Pathol 2006;30:1036.
311
HE ET AL 5. Kinoshita LL, Yee J, Nash SR. Littoral cell angioma of the spleen: imaging features. AJR Am J Roentgenol 2000;174:467. 6. Neuhauser TS, Derringer GA, Thompson LD, et al. Splenic angiosarcoma: a clinicopathologic and immunophenotypic study of 28 cases. Mod Pathol 2000;13:978.
312
7. Oliver-Goldaracena JM, Blanco A, Miralles M, et al. Littoral cell angioma of the spleen: US and MR imaging findings. Abdom Imaging 1998;23:636. 8. Rosso R, Gianelli U, Chan JK. Further evidence supporting the sinus lining cell nature of splenic littoral cell angiosarcoma. Am J Surg Pathol 1996; 20:1531.
JOURNAL OF CLINICAL ULTRASOUND
Splenic Littoral Cell Hemangioendothelioma: Report of a Case with Hepatic Metastases and Review of the Literature Ping He, MD,1 Xi-De Yan, MD,2 Jin-Rui Wang, MD,1,3,4 Run-Cai Guo,5 Hua-Bin Zhang, MD1 1
Department of Ultrasound, Peking University Third Hospital, Beijing, China Department of Function, People’s Hospital of Datong Country of Qinghai Province, China 3 Department of Ultrasound, Erdos Center’s Hospital, Inner Mongolia, China 4 Inner Mongolia Medical College, Hohhot, Inner Mongolia, China 5 Department of Radiology, Peking University Third Hospital, Beijing, China 2
Received 5 February 2013; accepted 18 October 2013
ABSTRACT: Littoral cell tumors are unique to the spleen and are different from all other primary splenic tumors. These tumors may be divided into three types: “littoral cell angioma,” “littoral cell hemangioendothelioma,” and “littoral cell angiosarcoma.” We present a patient with splenic littoral cell hemangioendothlioma accomC 2014 Wiley Periodicals, panied by hepatic metastases. V Inc. J Clin Ultrasound 42:308–312, 2014; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jcu.22120 Keywords: splenic littoral cell hemangioendothelioma; hepatic metastases; spleen; sonography; contrast medium
L
ittoral cell tumors are vascular tumors unique to the spleen and are different from all other primary splenic tumors.1,2 These tumors may also be divided into three types, including “littoral cell angioma (LCA),” which is benign, “littoral cell hemangioendothelioma,” which has intermediate malignant potential, and “littoral cell angiosarcoma,” which is malignant. Splenic littoral cell tumors with hepatic metastases are very rare. Besides, there are few reports describing the radiologic features of littoral cell tumors. We present a patient with splenic and hepatic tumors. In view of its atypical but not fully malignant histologic features, the presence of hepatic metastasis, and necrosis, a
Correspondence to: H. B. Zhang C 2014 Wiley Periodicals, Inc. V
308
diagnosis of splenic littoral cell hemangioendothlioma was made.
CASE REPORT
A 28-year-old woman presented with a 1-month history of hepatic and splenic masses. Routine laboratory results were within normal limits, and tumor markers, including CA-199, AFP, and CEA, were also within normal limits. The patient underwent sonographic examination of the abdomen performed with an iU 22 scanner (Philips Ultrasound, Bothell, WA) equipped with C5–2 convex array transducers. Sonographic examination showed splenomegaly with multiple hyperechoic masses. The largest of these masses was approximately 4.0 3 3.0 cm. Most of the lesions were well demarcated from the surrounding splenic parenchyma and were surrounded by an irregular peripheral hypoechoic rim. In addition, some lesions had an internal anechoic region, which represented necrosis (Figure 1A). With color Doppler imaging, a rich blood flow signal was seen in the solid-appearing portion of the tumors. No blood flow was found in the anechoic region (Figure 1B). The patient then underwent low-mechanicalindex real-time contrast-enhanced ultrasonography (CEUS). A sulfur hexafluoride--based microbubble contrast medium (Sonovue) was injected intravenously in 2 seconds. A volume of 1.5 ml was administered, followed by a 5-ml saline flush immediately after contrast medium injection. JOURNAL OF CLINICAL ULTRASOUND
SPLENIC LITTORAL CELL HEMANGIOENDOTHELIOMA
FIGURE 1. (A) Ultrasound of the abdomen showed a round hyperechoic mass, approximately 4.0 3 3.0 cm in greatest dimension. The lesion was well demarcated from the surrounding splenic parenchyma, with an irregular peripheral hypoechoic rim. In addition, the lesion had an internal anechoic region, representing necrosis, which was mildly enhanced through transmission. (B) Color Doppler sonography demonstrates rich blood flow signal in the solid-appearing portion of the tumor. No blood flow was found in the anechoic region. (C, D) The lesion in the liver shows the similar imaging features as that in the spleen.
CEUS showed marked enhancement in the early arterial phase, which appeared hypervascular in comparison to the normal splenic parenchyma. This enhancement persisted through the parenchymal phase and after 6 minutes had not faded away. No enhancement was apparent in the central anechoic region, consistent with necrosis (Figure 2A–2C). A CT scan showed the spleen was enlarged with multiple focal hypodense lesions, which were illdefined borders. The lesions also showed irregularly contoured areas of even lower density in the centers. After intravenous administration of iodinated contrast medium, a strong peripheral nodular or rim-like arterial enhancement was seen, and the lesions showed centripetal filling during the venous and delayed phases. The enhancement of these lesions was hyperdense in comparison with that of the surrounding splenic tissue. Central necrosis was better seen without enhancement. CT angiography showed blood supply to these lesions was via branches of the hepatic and splenic arteries. VOL. 42, NO. 5, JUNE 2014
The unenhanced T1-weighted MRI showed a markedly hypointense signal, and hyperintensity was seen on unenhanced T2-weighted MRI. The MR enhancement pattern was similar to that seen with CT (Figure 3). The lesions in the liver had the same appearance under US (Figure 1C and 1D), CEUS, CT, and MRI (Figure 3) as the splenic lesions. Whole body bone scanning showed no evidence of metastases. Grossly, the spleen was enlarged to 16 3 12 cm and contained four scattered red-brown nodules. The diameter of these nodules ranged from 0.4 to 2.0 cm. All nodules showed intact encapsulation. Nuclear atypia was mild to moderate, and no mitoses were found. Necrosis was seen in the center of solid regions. The largest liver mass was surgically excised and measured approximately 4.0 cm in greatest dimension. The histopathologic features of this mass were similar to that of the splenic lesions (Figure 4). Immunohistochemically, tumor cells in both the 309
HE ET AL
FIGURE 3. (A) The T1-weighted MRI showed a markedly hypointense signal and (B) they exhibited hyperintensity on the T2-weighted MRI. The enhancement pattern of MR was similar to that of CT.
FIGURE 2. (A) CEUS showed marked enhancement in the early arterial phase (13 seconds), which appeared hypervascular in comparison with the normal splenic parenchyma. (B) Enhancement persisted though the parenchymal phase (85 seconds). (C) Enhancement did not fade after 6 minutes. No enhancement was apparent in the central anechoic region, which is consistent with necrosis.
spleen and the liver expressed CD31, CD68, CD8, and CD34, without F8, representing both endothelial and histiocytic antigens.
DISCUSSION
Patients with littoral cell tumors are often asymptomatic and these lesions are discovered 310
FIGURE 4. The capsule of all nodules was intact. Central necrosis was seen in the solid regions. The largest mass in liver was resected and was 4.0 cm in diameter. The histopathologic features of this mass were similar to those of the splenic lesions.
incidentally at physical examination or when splenectomy is carried out for an unrelated reason, or at autopsy. In some cases of littoral cell tumor, patients may exhibit splenomegaly JOURNAL OF CLINICAL ULTRASOUND
SPLENIC LITTORAL CELL HEMANGIOENDOTHELIOMA
accompanied by hypersplenism or may simply seek medical attention for abdominal pain, weakness, or weight loss.1,3–7 The patient described here did not experience discomfort, and only splenomegaly was found at physical examination. There was no evidence of hypersplenism. In short, clinical symptoms are not specific for littoral cell tumors. Littoral cell tumors have characteristic morphologic and immunophenotypic features, which distinguish them from other vascular splenic tumors. Morphologically LCA consists of multiple nodules composed of vascular channels of red pulp and in general involves the spleen in a diffuse manner. However, a solitary form has been reported.2 LCA cells express both endothelial and histiocytic antigens. Typically, LCA cells express CD31, CD68, F8, CD21, and cathepsin D, and CD34 is negative.2 In this case CD34 was positive, and F8 was negative. In addition, CD8 was positive in this case, as sinus lining cells were found to express CD8. However, whether CD8 is typically positive in LCA is still controversial,2,3,8 and CD8 staining may be seen in splenic hamartomas and some angiosarcomas.2 Littoral cell hemangioendotheliomas and littoral cell angiosarcoma are morphologically and immunophenotypically similar to LCA. However, in contrast to LCAs, littoral cell hemangioendotheliomas may have necrosis, solid clear cell areas, nuclear atypia of low degree, hepatic metastasis, and an indolent clinical course.3,4 Littoral cell angiosarcoma shows a high degree of malignancy and usually has a rapidly progressive clinical course. Histologic features of this tumor include anaplasia, brisk mitotic activity, and necrosis.1,2,6 Because the prognosis of tumors in this family is closely related to the specific pathologic type, longer follow-up of our patient is essential, especially as atypical histology, necrosis, and metastasis were found. There are few reports describing the radiologic features of littoral cell tumors. Given the fairly complete radiologic information obtained in this case, we will summarize as follows. With ultrasound, these tumors involve the spleen in a diffuse manner that appears hyperechoic. The lesions may have clear boundaries with an irregular peripheral surrounding the hypoechoic rim. This is in accordance with pathologic findings, which showed that the capsule of these nodules was intact. Where necrosis or hemorrhage was found, there was an anechoic region in the center of the neoplasm. The solidVOL. 42, NO. 5, JUNE 2014
appearing portions of the tumor had rich blood flow, but the anechoic regions showed no flow signal with color Doppler. CEUS, contrastenhanced CT, and contrast-enhanced MR showed analogous appearances. There was marked enhancement in the early arterial phase that appeared hypervascular in comparison with the normal splenic parenchyma. Enhancement persisted through the parenchymal phase. No enhancement was found in the central anechoic region, which was consistent with necrosis in these areas. Oliver-Goldaracena et al7 suggested that the neoplastic cells of LCA have a hemophagocytic capacity, and hemosiderin therefore accumulates in the cytoplasm. This finding is specific for LCA on MRI as there are no other neoplasms that are associated with such an extensive degree of siderosis.7 The T1- and T2weighted MRIs showed a hypointense signal. With respect to the cell of origin, we believe littoral cell hemangioendothelioma and littoral cell angiosarcoma should also have this same specific appearance on MRI. The T1-weighted MRI in our case showed a hypointense signal, but they exhibited hyperintensity on the T2weighted MRI. This most likely is due to the fact that tumor cells in our case had little siderosis. Splenic neoplasms that diffusely involve the spleen may mimic splenic littoral cell tumors on imaging. Such tumors may include primary splenic tumors, metastatic tumors, and lymphoma, and infections that cause microabscesses may also mimic littoral cell tumors. However, clinical information and the associated involvement of other organs may help point to the correct diagnosis. The final diagnosis, however, must depend on pathologic results. REFERENCES 1. Falk S, Stutte HJ, Frizzera G. Littoral cell angioma. A novel splenic vascular lesion demonstrating histiocytic differentiation. Am J Surg Pathol 1991;15:1023. 2. Arber DA, Strickler JG, Chen YY, et al. Splenic vascular tumors: a histologic, immunophenotypic, and virologic study. Am J Surg Pathol 1997;21: 827. 3. Ben-Izhak O, Bejar J, Ben-Eliezer S, et al. Splenic littoral cell haemangioendothelioma: a new lowgrade variant of malignant littoral cell tumour. Histopathology 2001;39:469. 4. Fernandez S, Cook GW, Arber DA. Metastasizing splenic littoral cell hemangioendothelioma. Am J Surg Pathol 2006;30:1036.
311
HE ET AL 5. Kinoshita LL, Yee J, Nash SR. Littoral cell angioma of the spleen: imaging features. AJR Am J Roentgenol 2000;174:467. 6. Neuhauser TS, Derringer GA, Thompson LD, et al. Splenic angiosarcoma: a clinicopathologic and immunophenotypic study of 28 cases. Mod Pathol 2000;13:978.
312
7. Oliver-Goldaracena JM, Blanco A, Miralles M, et al. Littoral cell angioma of the spleen: US and MR imaging findings. Abdom Imaging 1998;23:636. 8. Rosso R, Gianelli U, Chan JK. Further evidence supporting the sinus lining cell nature of splenic littoral cell angiosarcoma. Am J Surg Pathol 1996; 20:1531.
JOURNAL OF CLINICAL ULTRASOUND
