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A case of angiosarcoma arising from internal jugular vein
Auris Nasus Larynx 42 (2015) 68–71
Contents lists available at ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
A case of angiosarcoma arising from internal jugular vein Ippei Kishimoto a,*, Masahiro Kikuchi a, Shogo Shinohara a, Keizo Fujiwara a, Yuji Kanazawa b, Risa Tona c, Hiroyuki Harada a, Yu Usami d, Yasushi Naito a a
Department of Otolaryngology – Head and Neck Surgery, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan b Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan c Institute of Biomedical Research and Innovation, 2-2 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan d Department of Clinical Pathology, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 19 May 2014 Accepted 30 August 2014 Available online 14 January 2015
Primary angiosarcoma is a rare disease with a poor prognosis. It most commonly arises in the head and neck region; localization in the deep soft tissue of the neck is extremely rare. We herein present a case of angiosarcoma derived from the right internal jugular vein. A 79-year-old man presented with a 1-month history of a growing right neck mass. Computed tomography, magnetic resonance imaging, positron emission tomography-computed tomography, and fine-needle aspiration cytology revealed a malignant tumor of unknown origin. Right neck dissection was performed for both diagnosis and therapy. Immunostaining of the resected tumor cells revealed positivity for CD31, CD34, factor VIII-related antigen, and D2–40, which allowed for a definitive diagnosis of angiosarcoma. Postoperative radiotherapy (66 Gy) was performed on the right neck, including the surgical bed and upper mediastinum. The patient was followed up for 10 months with no recurrence. Only six cases of angiosarcoma arising in the deep soft tissue of the neck have been reported in the English-language literature. The present report is the first to describe angiosarcoma arising from the internal jugular vein. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Angiosarcoma Deep neck Jugular vein Surgery Postoperative radiotherapy
1. Introduction Primary angiosarcoma is a rare disease with a poor prognosis. Treatment is challenging in many cases, and the overall survival rate is about 35% [1]. Angiosarcoma can arise in any soft tissue structure or viscera [1]. The head and neck is the most common primary site (27.0% of all cases), followed by the extremities (15.3%), trunk (9.5%), liver, heart, bone, spleen, and other locations [1]. The scalp is the most common site for development of cutaneous angiosarcoma within the head and neck region. Development of angiosarcoma in the deep neck tissues, however, is extremely rare. We herein report an extremely rare case of angiosarcoma that occurred in the deep part of the neck. 2. Case report A 79-year-old man presented with a 1-month history of a growing right neck mass. Physical examination revealed a soft,
* Corresponding author. Tel.: +81 78 302 4321; fax: +81 78 302 7537. E-mail address: [email protected] (I. Kishimoto). http://dx.doi.org/10.1016/j.anl.2014.08.018 0385-8146/ß 2014 Elsevier Ireland Ltd. All rights reserved.
mobile, nontender mass that measured about 60 mm in diameter. No other lesions were apparent anywhere on his body, including the skin. Enhanced computed tomography showed a relatively well-defined and heterogeneous mass between the internal jugular vein and common carotid artery with a maximum diameter of 60 mm (Fig. 1). Magnetic resonance imaging also demonstrated a mass of heterogeneous density on both T1- and T2-weighted images. Although fine-needle aspiration cytology of the mass suggested an adenocarcinoma, screening examinations such as thyroid ultrasound, laryngopharyngeal fiberscopy, upper gastrointestinal endoscopy, and colon fiberscopy showed no apparent primary lesions. The tumor was thought to be a cancer of unknown primary origin, and positron-emission tomography (PET) was performed to identify the primary tumor. Localized fluorodeoxyglucose accumulation (maximum standardized uptake value of 14.1) was seen within the right neck mass; however, no other abnormal accumulation was detected. A right neck dissection was performed under a diagnosis of metastatic cervical carcinoma of unknown primary origin. The tumor was firmly adhered to the right internal jugular vein and sternocleidomastoid muscle; both of these structures were
I. Kishimoto et al. / Auris Nasus Larynx 42 (2015) 68–71
69
Fig. 1. An enhanced mass (arrow) with a diameter of 60 mm was found between the common carotid artery (black arrowhead) and internal jugular vein (white arrowhead). The internal jugular vein was displaced anteriorly by the mass. The mass contained several necrotic low-density areas and mildly enhanced solid areas. Invasion to surrounding areas was not apparent.
These findings suggested a cancer arising from both epithelial cells and soft tissues (Fig. 3A). The lumen of the internal jugular vein was patent and the tumor did not appear within it; however, the tumor was adjacent and fixed to the internal jugular vein. No lymph node tissue was seen within the tumor on histological examination. Immunostaining of the tumor cells revealed positivity for CD31, CD34, factor VIII-related antigen, and D2–40 and negativity for epithelial markers such as cytokeratin MNF116, CK7, CK20, and EMA. These pathological findings led to a diagnosis of angiosarcoma (Fig. 3B). The margin of the specimen and all excised lymph nodes were tumor-free. According to the American Joint Committee on Cancer and Union for International Cancer Control (AJCC/UICC) staging system for soft tissue sarcomas, the pathological stage of the tumor was III (T2bN0M0). Postoperative radiotherapy (66 Gy) was performed on the right neck, including the surgical bed and upper mediastinum. The patient was followed up for 10 months with no recurrences. 3. Discussion
Fig. 2. The dissected specimen of the right neck. The mass contained yellow-brown solid components and multiple cystic components with dusky red fluid (arrowheads).
resected together. The common carotid artery and vagus nerve were not adhered to the lesion and were thus preserved. The largest diameter of tumor was 60 mm, and the cut surface showed yellow-brown solid components and multiple cystic components containing dusky red fluid (Fig. 2). Hematoxylin–eosin staining of the excised specimens showed marked proliferation of spindle cells with irregularly shaped cell bodies and enlarged, irregular nuclei with prominent nucleoli.
Angiosarcoma arising in the deep soft tissue of the neck is extremely rare; only six cases have been reported in the Englishlanguage literature (Table 1). Additionally, angiosarcomas rarely arise from major vessels. In the present case, the tumor was adjacent and fixed to the internal jugular vein on both surgical and pathological examinations, although there was no transformation zone from the tissue of the internal jugular vein. Thus, the tumor was most likely to have been an angiosarcoma derived from the right internal jugular vein. To the best of our knowledge, no other previous reports have described angiosarcoma arising from the internal jugular vein. It seems unlikely that the tumor was a metastatic lymph node because no apparent primary lesions on the patient’s skin or other body parts were found on physical examination or PET. Moreover, the pathological examination showed no lymph node tissue within the tumor. Four of the six previously reported cases of angiosarcoma arising from the deep soft tissue of the neck involved malignant transformation of a vagus nerve schwannoma to an angiosarcoma. Such angiosarcomas arise directly from the tumor vasculature as opposed to schwannoma cells [2]. The main histological feature of the angiosarcoma in the present case was dense growth of spindle cells with irregularly shaped cell bodies and irregular nuclei with prominent nucleoli. Vasoformation was not evident. An established histological pattern
I. Kishimoto et al. / Auris Nasus Larynx 42 (2015) 68–71
70
Fig. 3. (A) Hematoxylin–eosin staining of the excised specimens showed marked proliferation of spindle cells with irregularly shaped cell bodies and enlarged, irregular nuclei with prominent nucleoli. (B) Immunostaining of the tumor cells revealed positivity for CD31, CD34, factor VIII-related antigen, and D2–40.
Table 1 Reported cases of Angiosarcoma arising in the deep soft tissue of the neck. Case
Age
Sex
Diameter (mm)
Origin
Treatment
Local recurrence
Metastasis
Outcome
Study
Year
1 2 3 4 5 6
46 60 73 63 50 47
M F F M M M
50 40 55 40 45 60
Carotid body Internal carotid artery Vagus nerve schwannoma Vagus nerve schwannoma Vagus nerve schwannoma Vagus nerve schwannoma
S S S S, R S S, R, C
– – – + – –
– – – Unknown Thumb of left hand Lung
NED (36 months) DWD (6 months) NED (43 months) DWD (5 months) NED (27 months) DWD (9 months)
Topuzlu et al. Whyte et al. Mentzel, T and Kantenkamp, D Mentzel, T and Kantenkamp, D Ruckert et al. Ogawa et al.
1969 1988 1999 1999 2000 2014
S: surgery; R: radiation therapy; C: chemotherapy; NED: no evidence of disease; DWD: died with disease.
of some angiosarcomas is spindle cell proliferation, and such angiosarcomas are described as spindle cell angiosarcomas [3]. However, this type of angiosarcoma is typically seen in the liver and spleen, while angiosarcomas occurring in the deep soft tissue commonly have an epithelioid appearance [4]. Therefore, definitive diagnosis of angiosarcoma based solely on the histological features was difficult in the present case because the histological features were not typical of angiosarcoma in the deep soft tissue. Hematoxylin and eosin staining suggested that the tumor was a soft tissue sarcoma and did not directly lead to the diagnosis. Immunohistochemistry is important for the confirmation of a diagnosis of angiosarcoma [1]. Immunostaining of the tumor in the present case was positive for CD31, CD34, factor VIII, and D2–40. Positivity of the three former antigens indicated the presence of a vascular tumor, and positivity of the last antigen indicated a lymphoid tumor. CD31 is a sensitive and specific antigen for endothelial differentiation and is the most reliable marker for diagnosis of almost all angiosarcomas [3,4]. CD34 is expressed in approximately 50% of angiosarcomas [3] and is also seen in Kaposi sarcoma and other soft tissue sarcomas [4]. Factor VIII-related antigen can be demonstrated in well-differentiated angiosarcomas, but usually only focally (if at all) in less differentiated tumors [3]. The immunostaining results in the present case strongly suggested that the tumor was derived from endothelial cells, and the diagnosis of angiosarcoma was finally confirmed. The stage of soft tissue sarcomas is usually determined by the AJCC/UICC staging system, which is based on the TNM staging system with additional information on the histological grade. Angiosarcomas are high-grade tumors by definition; thus, histological findings are not used in staging [1]. As mentioned above, angiosarcomas are associated with a poor prognosis,
especially when the largest tumor diameter is 5 cm or the patient’s age is >50 years; these characteristics are also consistent with other soft tissue sarcomas [5]. Other negative prognostic factors that might predict a poor outcome include metastatic disease at the time of presentation, a poor patient performance status, and the liver, heart, or retroperitoneal space as the primary disease site [1]. Radical surgery involving complete resection is the primary treatment of choice for local angiosarcomas [1,6]. In the present case, we first thought that the lesion may be an occult primary cancer and thus performed neck dissection for both diagnosis and treatment. The surgery resulted in complete resection of the angiosarcoma with adequate margins. High-dose adjuvant radiotherapy (>50 Gy) with a wide treatment field is recommended because of the high risk of local recurrence of angiosarcoma. Some retrospective studies have suggested that such treatment may improve local control and overall survival, although randomized prospective trials of radiotherapy have not yet been performed [1]. There is no convincing evidence that the administration of cytotoxic chemotherapy (e.g., taxanes, anthracycline, ifosfamide) after the performance of definitive surgery and radiotherapy improves the survival rate [1]. However, molecular-targeted agents such as pazopanib, bevacizumab, sorafenib, and sunitinib were recently reported to be effective treatments for angiosarcoma [1,7]. Pazopanib is a multikinase inhibitor that potently inhibits the activity of major receptor tyrosine kinases, including vascular endothelial growth factor receptor 1, 2, and 3; platelet-derived growth factor receptor-a and -b; and c-kit [7]. Several cases involving successful treatment of angiosarcomas with pazopanib have been reported [8,9], but no randomized trials have indicated that pazopanib is an effective adjuvant therapy. In the present case, we decided to perform surgery and postoperative radiotherapy as
I. Kishimoto et al. / Auris Nasus Larynx 42 (2015) 68–71
the initial treatment; neither adjuvant chemotherapy nor biotherapy was performed, although such use of new molecular-targeted agents in this case may have been effective as adjuvant treatment. 4. Conclusion We have presented a case of angiosarcoma arising from the internal jugular vein. A 79-year-old man presented with a 1-month history of a growing right neck mass. Imaging and fine-needle aspiration cytology findings showed a malignant tumor of unknown origin; therefore, a right neck dissection was performed for both diagnosis and therapy. The histological, immunohistochemical, and surgical findings established the diagnosis of angiosarcoma derived from the internal jugular vein. Postoperative radiotherapy was performed, and no relapse occurred during a 10month follow-up period. Conflict of interest None.
71
References [1] Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ. Angiosarcoma. Lancet Oncol 2010;11:983–91. [2] Ruckert RI, Fleige B, Rogalla P, Woodruff JM. Schwannoma with angiosarcoma. Report of a case and comparison with other types of nerve tumors with angiosarcoma. Cancer 2000;89:1577–85. [3] Miettinen M. Modern soft tissue pathology: tumors and non-neoplastic conditions. Cambridge/New York: Cambridge University Press; 2010. [4] Goldblum JR, Folpe AL, Weiss SW, Enzinger FM, Weiss SW, Enzinger. Weiss’s soft tissue tumors. Philadelphia, PA: Saunders/Elsevier; 2014. [5] Naka N, Ohsawa M, Tomita Y, Kanno H, Uchida A, Myoui A, et al. Prognostic factors in angiosarcoma: a multivariate analysis of 55 cases. J Craniofac Surg 1996;61:170–6. [6] McIntosh BC, Narayan D. Head and neck angiosarcomas. J Craniofac Surg 2005;16:699–703. [7] Heudel P, Cassier P, Derbel O, Dufresne A, Meeus P, Thiesse P, et al. Pazopanib for the treatment of soft-tissue sarcoma. Clin Pharmacol: Adv Appl 2012;4:65–70. [8] Tomita H, Koike Y, Asai M, Ogawa F, Abe K, Tanioka M, et al. Angiosarcoma of the scalp successfully treated with pazopanib. J Am Acad Dermatol 2014;70: e19–21. [9] Ong P, Greulich S, Schumm J, Backes M, Kaufmann M, Bode-Erdmann S, et al. Favorable course of pericardial angiosarcoma under paclitaxel followed by pazopanib treatment documented by cardiovascular magnetic resonance imaging. Circulation 2012;126:e279–81.
Contents lists available at ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
A case of angiosarcoma arising from internal jugular vein Ippei Kishimoto a,*, Masahiro Kikuchi a, Shogo Shinohara a, Keizo Fujiwara a, Yuji Kanazawa b, Risa Tona c, Hiroyuki Harada a, Yu Usami d, Yasushi Naito a a
Department of Otolaryngology – Head and Neck Surgery, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan b Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan c Institute of Biomedical Research and Innovation, 2-2 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan d Department of Clinical Pathology, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 19 May 2014 Accepted 30 August 2014 Available online 14 January 2015
Primary angiosarcoma is a rare disease with a poor prognosis. It most commonly arises in the head and neck region; localization in the deep soft tissue of the neck is extremely rare. We herein present a case of angiosarcoma derived from the right internal jugular vein. A 79-year-old man presented with a 1-month history of a growing right neck mass. Computed tomography, magnetic resonance imaging, positron emission tomography-computed tomography, and fine-needle aspiration cytology revealed a malignant tumor of unknown origin. Right neck dissection was performed for both diagnosis and therapy. Immunostaining of the resected tumor cells revealed positivity for CD31, CD34, factor VIII-related antigen, and D2–40, which allowed for a definitive diagnosis of angiosarcoma. Postoperative radiotherapy (66 Gy) was performed on the right neck, including the surgical bed and upper mediastinum. The patient was followed up for 10 months with no recurrence. Only six cases of angiosarcoma arising in the deep soft tissue of the neck have been reported in the English-language literature. The present report is the first to describe angiosarcoma arising from the internal jugular vein. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Angiosarcoma Deep neck Jugular vein Surgery Postoperative radiotherapy
1. Introduction Primary angiosarcoma is a rare disease with a poor prognosis. Treatment is challenging in many cases, and the overall survival rate is about 35% [1]. Angiosarcoma can arise in any soft tissue structure or viscera [1]. The head and neck is the most common primary site (27.0% of all cases), followed by the extremities (15.3%), trunk (9.5%), liver, heart, bone, spleen, and other locations [1]. The scalp is the most common site for development of cutaneous angiosarcoma within the head and neck region. Development of angiosarcoma in the deep neck tissues, however, is extremely rare. We herein report an extremely rare case of angiosarcoma that occurred in the deep part of the neck. 2. Case report A 79-year-old man presented with a 1-month history of a growing right neck mass. Physical examination revealed a soft,
* Corresponding author. Tel.: +81 78 302 4321; fax: +81 78 302 7537. E-mail address: [email protected] (I. Kishimoto). http://dx.doi.org/10.1016/j.anl.2014.08.018 0385-8146/ß 2014 Elsevier Ireland Ltd. All rights reserved.
mobile, nontender mass that measured about 60 mm in diameter. No other lesions were apparent anywhere on his body, including the skin. Enhanced computed tomography showed a relatively well-defined and heterogeneous mass between the internal jugular vein and common carotid artery with a maximum diameter of 60 mm (Fig. 1). Magnetic resonance imaging also demonstrated a mass of heterogeneous density on both T1- and T2-weighted images. Although fine-needle aspiration cytology of the mass suggested an adenocarcinoma, screening examinations such as thyroid ultrasound, laryngopharyngeal fiberscopy, upper gastrointestinal endoscopy, and colon fiberscopy showed no apparent primary lesions. The tumor was thought to be a cancer of unknown primary origin, and positron-emission tomography (PET) was performed to identify the primary tumor. Localized fluorodeoxyglucose accumulation (maximum standardized uptake value of 14.1) was seen within the right neck mass; however, no other abnormal accumulation was detected. A right neck dissection was performed under a diagnosis of metastatic cervical carcinoma of unknown primary origin. The tumor was firmly adhered to the right internal jugular vein and sternocleidomastoid muscle; both of these structures were
I. Kishimoto et al. / Auris Nasus Larynx 42 (2015) 68–71
69
Fig. 1. An enhanced mass (arrow) with a diameter of 60 mm was found between the common carotid artery (black arrowhead) and internal jugular vein (white arrowhead). The internal jugular vein was displaced anteriorly by the mass. The mass contained several necrotic low-density areas and mildly enhanced solid areas. Invasion to surrounding areas was not apparent.
These findings suggested a cancer arising from both epithelial cells and soft tissues (Fig. 3A). The lumen of the internal jugular vein was patent and the tumor did not appear within it; however, the tumor was adjacent and fixed to the internal jugular vein. No lymph node tissue was seen within the tumor on histological examination. Immunostaining of the tumor cells revealed positivity for CD31, CD34, factor VIII-related antigen, and D2–40 and negativity for epithelial markers such as cytokeratin MNF116, CK7, CK20, and EMA. These pathological findings led to a diagnosis of angiosarcoma (Fig. 3B). The margin of the specimen and all excised lymph nodes were tumor-free. According to the American Joint Committee on Cancer and Union for International Cancer Control (AJCC/UICC) staging system for soft tissue sarcomas, the pathological stage of the tumor was III (T2bN0M0). Postoperative radiotherapy (66 Gy) was performed on the right neck, including the surgical bed and upper mediastinum. The patient was followed up for 10 months with no recurrences. 3. Discussion
Fig. 2. The dissected specimen of the right neck. The mass contained yellow-brown solid components and multiple cystic components with dusky red fluid (arrowheads).
resected together. The common carotid artery and vagus nerve were not adhered to the lesion and were thus preserved. The largest diameter of tumor was 60 mm, and the cut surface showed yellow-brown solid components and multiple cystic components containing dusky red fluid (Fig. 2). Hematoxylin–eosin staining of the excised specimens showed marked proliferation of spindle cells with irregularly shaped cell bodies and enlarged, irregular nuclei with prominent nucleoli.
Angiosarcoma arising in the deep soft tissue of the neck is extremely rare; only six cases have been reported in the Englishlanguage literature (Table 1). Additionally, angiosarcomas rarely arise from major vessels. In the present case, the tumor was adjacent and fixed to the internal jugular vein on both surgical and pathological examinations, although there was no transformation zone from the tissue of the internal jugular vein. Thus, the tumor was most likely to have been an angiosarcoma derived from the right internal jugular vein. To the best of our knowledge, no other previous reports have described angiosarcoma arising from the internal jugular vein. It seems unlikely that the tumor was a metastatic lymph node because no apparent primary lesions on the patient’s skin or other body parts were found on physical examination or PET. Moreover, the pathological examination showed no lymph node tissue within the tumor. Four of the six previously reported cases of angiosarcoma arising from the deep soft tissue of the neck involved malignant transformation of a vagus nerve schwannoma to an angiosarcoma. Such angiosarcomas arise directly from the tumor vasculature as opposed to schwannoma cells [2]. The main histological feature of the angiosarcoma in the present case was dense growth of spindle cells with irregularly shaped cell bodies and irregular nuclei with prominent nucleoli. Vasoformation was not evident. An established histological pattern
I. Kishimoto et al. / Auris Nasus Larynx 42 (2015) 68–71
70
Fig. 3. (A) Hematoxylin–eosin staining of the excised specimens showed marked proliferation of spindle cells with irregularly shaped cell bodies and enlarged, irregular nuclei with prominent nucleoli. (B) Immunostaining of the tumor cells revealed positivity for CD31, CD34, factor VIII-related antigen, and D2–40.
Table 1 Reported cases of Angiosarcoma arising in the deep soft tissue of the neck. Case
Age
Sex
Diameter (mm)
Origin
Treatment
Local recurrence
Metastasis
Outcome
Study
Year
1 2 3 4 5 6
46 60 73 63 50 47
M F F M M M
50 40 55 40 45 60
Carotid body Internal carotid artery Vagus nerve schwannoma Vagus nerve schwannoma Vagus nerve schwannoma Vagus nerve schwannoma
S S S S, R S S, R, C
– – – + – –
– – – Unknown Thumb of left hand Lung
NED (36 months) DWD (6 months) NED (43 months) DWD (5 months) NED (27 months) DWD (9 months)
Topuzlu et al. Whyte et al. Mentzel, T and Kantenkamp, D Mentzel, T and Kantenkamp, D Ruckert et al. Ogawa et al.
1969 1988 1999 1999 2000 2014
S: surgery; R: radiation therapy; C: chemotherapy; NED: no evidence of disease; DWD: died with disease.
of some angiosarcomas is spindle cell proliferation, and such angiosarcomas are described as spindle cell angiosarcomas [3]. However, this type of angiosarcoma is typically seen in the liver and spleen, while angiosarcomas occurring in the deep soft tissue commonly have an epithelioid appearance [4]. Therefore, definitive diagnosis of angiosarcoma based solely on the histological features was difficult in the present case because the histological features were not typical of angiosarcoma in the deep soft tissue. Hematoxylin and eosin staining suggested that the tumor was a soft tissue sarcoma and did not directly lead to the diagnosis. Immunohistochemistry is important for the confirmation of a diagnosis of angiosarcoma [1]. Immunostaining of the tumor in the present case was positive for CD31, CD34, factor VIII, and D2–40. Positivity of the three former antigens indicated the presence of a vascular tumor, and positivity of the last antigen indicated a lymphoid tumor. CD31 is a sensitive and specific antigen for endothelial differentiation and is the most reliable marker for diagnosis of almost all angiosarcomas [3,4]. CD34 is expressed in approximately 50% of angiosarcomas [3] and is also seen in Kaposi sarcoma and other soft tissue sarcomas [4]. Factor VIII-related antigen can be demonstrated in well-differentiated angiosarcomas, but usually only focally (if at all) in less differentiated tumors [3]. The immunostaining results in the present case strongly suggested that the tumor was derived from endothelial cells, and the diagnosis of angiosarcoma was finally confirmed. The stage of soft tissue sarcomas is usually determined by the AJCC/UICC staging system, which is based on the TNM staging system with additional information on the histological grade. Angiosarcomas are high-grade tumors by definition; thus, histological findings are not used in staging [1]. As mentioned above, angiosarcomas are associated with a poor prognosis,
especially when the largest tumor diameter is 5 cm or the patient’s age is >50 years; these characteristics are also consistent with other soft tissue sarcomas [5]. Other negative prognostic factors that might predict a poor outcome include metastatic disease at the time of presentation, a poor patient performance status, and the liver, heart, or retroperitoneal space as the primary disease site [1]. Radical surgery involving complete resection is the primary treatment of choice for local angiosarcomas [1,6]. In the present case, we first thought that the lesion may be an occult primary cancer and thus performed neck dissection for both diagnosis and treatment. The surgery resulted in complete resection of the angiosarcoma with adequate margins. High-dose adjuvant radiotherapy (>50 Gy) with a wide treatment field is recommended because of the high risk of local recurrence of angiosarcoma. Some retrospective studies have suggested that such treatment may improve local control and overall survival, although randomized prospective trials of radiotherapy have not yet been performed [1]. There is no convincing evidence that the administration of cytotoxic chemotherapy (e.g., taxanes, anthracycline, ifosfamide) after the performance of definitive surgery and radiotherapy improves the survival rate [1]. However, molecular-targeted agents such as pazopanib, bevacizumab, sorafenib, and sunitinib were recently reported to be effective treatments for angiosarcoma [1,7]. Pazopanib is a multikinase inhibitor that potently inhibits the activity of major receptor tyrosine kinases, including vascular endothelial growth factor receptor 1, 2, and 3; platelet-derived growth factor receptor-a and -b; and c-kit [7]. Several cases involving successful treatment of angiosarcomas with pazopanib have been reported [8,9], but no randomized trials have indicated that pazopanib is an effective adjuvant therapy. In the present case, we decided to perform surgery and postoperative radiotherapy as
I. Kishimoto et al. / Auris Nasus Larynx 42 (2015) 68–71
the initial treatment; neither adjuvant chemotherapy nor biotherapy was performed, although such use of new molecular-targeted agents in this case may have been effective as adjuvant treatment. 4. Conclusion We have presented a case of angiosarcoma arising from the internal jugular vein. A 79-year-old man presented with a 1-month history of a growing right neck mass. Imaging and fine-needle aspiration cytology findings showed a malignant tumor of unknown origin; therefore, a right neck dissection was performed for both diagnosis and therapy. The histological, immunohistochemical, and surgical findings established the diagnosis of angiosarcoma derived from the internal jugular vein. Postoperative radiotherapy was performed, and no relapse occurred during a 10month follow-up period. Conflict of interest None.
71
References [1] Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ. Angiosarcoma. Lancet Oncol 2010;11:983–91. [2] Ruckert RI, Fleige B, Rogalla P, Woodruff JM. Schwannoma with angiosarcoma. Report of a case and comparison with other types of nerve tumors with angiosarcoma. Cancer 2000;89:1577–85. [3] Miettinen M. Modern soft tissue pathology: tumors and non-neoplastic conditions. Cambridge/New York: Cambridge University Press; 2010. [4] Goldblum JR, Folpe AL, Weiss SW, Enzinger FM, Weiss SW, Enzinger. Weiss’s soft tissue tumors. Philadelphia, PA: Saunders/Elsevier; 2014. [5] Naka N, Ohsawa M, Tomita Y, Kanno H, Uchida A, Myoui A, et al. Prognostic factors in angiosarcoma: a multivariate analysis of 55 cases. J Craniofac Surg 1996;61:170–6. [6] McIntosh BC, Narayan D. Head and neck angiosarcomas. J Craniofac Surg 2005;16:699–703. [7] Heudel P, Cassier P, Derbel O, Dufresne A, Meeus P, Thiesse P, et al. Pazopanib for the treatment of soft-tissue sarcoma. Clin Pharmacol: Adv Appl 2012;4:65–70. [8] Tomita H, Koike Y, Asai M, Ogawa F, Abe K, Tanioka M, et al. Angiosarcoma of the scalp successfully treated with pazopanib. J Am Acad Dermatol 2014;70: e19–21. [9] Ong P, Greulich S, Schumm J, Backes M, Kaufmann M, Bode-Erdmann S, et al. Favorable course of pericardial angiosarcoma under paclitaxel followed by pazopanib treatment documented by cardiovascular magnetic resonance imaging. Circulation 2012;126:e279–81.