AM ER IC AN JOURNAL OF OT OLA RYNGOLOGY–H E A D A N D NE CK M E D ICI N E AN D S U RGE RY 3 5 (2 0 1 4) 8 06 –8 0 9
Available online at www.sciencedirect.com
ScienceDirect www.elsevier.com/locate/amjoto
Case reports
Angiosarcoma arising from the frontal sinus☆,☆☆ Senja Tomovic, MD a , Evelyne Kalyoussef, MD a , Neena M. Mirani, MD a, b , Soly Baredes, MD, FACS a, c , Jean Anderson Eloy, MD, FACS a, c, d,⁎ a
Department of Otolaryngology–Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey Department of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, New Jersey c Center for Skull Base and Pituitary Surgery, Neurological Institute of New Jersey, Rutgers New Jersey Medical School, Newark, New Jersey d Department of Neurological Surgery, Rutgers New Jersey Medical School, Newark, New Jersey b
ARTI CLE I NFO
A BS TRACT
Article history:
Primary sinonasal angiosarcomas are very rare tumors. They typically occur in the nasal cavity of
Received 15 July 2014
middle-aged patients. They are classically highly aggressive. Primary treatment is surgical excision when feasible. We describe a unique case of angiosarcoma in a young woman arising from the frontal sinus with distant metastasis. This case represents the first report of angiosarcoma arising from the frontal sinus in the English literature. The traditional treatment options for the advanced nature of her disease and overall poor prognosis are discussed. We further
review
the
literature
and
discuss
alternative
treatments
options.
Newer
chemotherapeutic regiments on the horizon show promise in helping to control this disease. © 2014 Elsevier Inc. All rights reserved.
1.
Introduction
Angiosarcomas are aggressive tumors of vascular endothelial origin. These tumors tend to occur in the middle-aged population and are managed with surgical excision with radiation and chemotherapy traditionally reserved for unresectable disease or positive margins. This case is unique in that it is the first reported case in the English literature of a paranasal sinus angiosarcoma 1) arising in the frontal sinus, 2) with distant metastatic spread, and 3) staged using positron emission tomography (PET). In addition, due to the extent of disease careful thought and discussion were given to the optimal treatment modality. Interestingly, with the recent advent of newer targeted treatments more consideration has been given to the role of an antibody to vascular endothelial growth factor (anti-VEGF) to help control and limit disease. ☆
2.
Illustrative case
A previously healthy 21-year-old female with no prior history of radiation exposure presented with two months of progressing left sided forehead tingling, pain and proptosis with no significant vision changes that were refractory to antibiotics. A computed tomography (CT) scan showed a calcified mass centered in the left lateral frontal sinus with evidence of cortical bone destruction and invasion of the left frontal lobe and superior left orbit with opacification of the ethmoid sinus and destruction of the cribriform plate and medial orbital wall (Fig. 1A&B). A magnetic resonance imaging (MRI) showed an enhancing heterogeneous mass centered in the left frontal sinus extending into the left superolateral aspect of the orbit with diffuse dural enhancement towards the vertex and left temporal lobe (Fig. 1C&D).
Financial Disclosures: None. Conflicts of Interest: None. ⁎ Corresponding author at: Department of Otolaryngology, Head and Neck Surgery, Rutgers New Jersey Medical School, 90 Bergen St., Suite 8100, Newark, NJ 07103. Tel.: + 973 972 4588; fax: + 973 972 3767. E-mail address: [email protected] (J.A. Eloy).
☆☆
http://dx.doi.org/10.1016/j.amjoto.2014.08.003 0196-0709/© 2014 Elsevier Inc. All rights reserved.
AM ER IC AN JOURNAL OF OT OLARYNGOLOGY–H E A D A N D NE CK M E D IC IN E A ND S U RGE RY 3 5 (2 0 1 4) 8 06–8 0 9
807
Fig. 1 – Preoperative imaging. (A) Axial CT scan showing opacification of the left frontal sinus with destruction of the posterior table and extension into the ethmoid sinuses. (B) Coronal CT scan with a lytic lesion of the left lateral frontal sinus. (C) T1-weighted gadolinium enhanced axial MRI showing enhancing lesion of the left frontal sinus extending into the left frontal lobe. (D) T1-weighted gadolinium enhanced coronal MRI showing enhancing lesion of the left frontal sinus with dural enhancement.
The patient was taken to the operating room for nasal endoscopy and biopsy, which revealed a purple friable necrotic tumor obstructing the left middle meatus (Fig. 2). Histology was consistent with a high grade angiosarcoma, invading bone with hemorrhagic necrosis (Fig. 3) Malignant endothelial cells were epithelioid type with nuclear pleomorphism and mitoses. The tumor cells were immunoreactive to vimentin and endothelial markers such as, CD31 and CD34, Fli-1 and Factor VIII. A postoperative PET/CT was performed and showed a lyticlesion of the left frontal bone extending to the superolateral aspect of the left orbit with a maximum SUV of 10.5. The ethmoid sinus had opacification with a maximum
SUV of 11.7 and the left maxillary sinus had a maximum SUV of 7.7. There was also a lesion of 1.1 cm in the apex of the right lung with an SUV of 2.5, a right level II cervical lymph node with an SUV of 2.7 and a C2 vertebral body lesion with an SUV of 3.4, all considered metastatic. Given the distant disease as well as extensive local disease, initial treatment with chemotherapy including bevicizumab and radiation was recommended with the consideration for salvage surgery. The patient was subsequently treated with docetaxel and gemcitabine for six months with regression of the tumor, however the tumor regrew and the patient was started on radiation therapy. She is currently one year out from diagnosis with full functional capacity.
Fig. 2 – (A & B) Intraoperative endoscopic view of the tumor in the left middle meatus with the asterisk labeling the necrotic friable purple tumor.
808
AM ER IC AN JOURNAL OF OT OLA RYNGOLOGY–H E A D A N D NE CK M E D ICI N E AN D S U RGE RY 3 5 (2 0 1 4) 8 06 –8 0 9
Fig. 3 – (A) Hematoxylin and eosin (H & E, 40x) stained specimen showing submucosal nests of malignant epithelioid cells with hemorrhage. (B) Proliferating vascular channels invading the bone and lined by hyperchromatic malignant endothelial cells (H & E, 400x). (C) Epithelioid tumor cells with pleomorphic nuclei and mitosis (H & E, 600x). (D) Tumor cells immunoreactive to CD31 (endothelial marker) (CD31 immunostain, 100x).
3.
Discussion
Angiosarcomas are rare high-grade malignant vascular tumors that account for less than 0.1% of all sinonasal malignancies [1]. The largest single series on sinonasal tract angiosarcomas in the English literature reports a series of 10 cases gathered from the Armed Forces Institute of Pathology between 1970 and 1995. In this series eight arose from the nasal cavity proper and two from the maxillary sinus [2]. The etiology is unclear, but exposure to radiation and vinyl chloride has been proposed to be a predisposing factor. The symptoms include epistaxis, nasal obstruction and nasal discharge. Diagnosis involves a combination of appropriate imaging, including contrast studies (CT, MRI, and/or angiography with or without embolization) to assess the degree of vascularity. PET/CT scans have shown great utility in assessing for distant spread in many different types of cancer. Interestingly, current literature contains mostly small studies and case reports of the use of PET/CT in angiosarcomas of the cardiothoracic and abdominal viscera and only two reports of its use in defining the extent of disease in cases of scalp angiosarcomas [3]. Further studies using PET/CT technology may prove to be useful for diagnosis, staging and monitoring response to treatment. Pathologic diagnosis is accomplished through nasal endoscopy and biopsy which allow for tumor mapping and the ability to control bleeding. Macroscopically the tumor is vascular, typically red to purple, soft and friable. The differential diagnosis includes granulation tissue, intravascular papillary endothelial hyperplasia, epithelioid hemangioma, glomangiopericytoma, juvenile
nasopharyngeal angiofibroma, kaposi sarcoma, and mucosal melanoma [2]. Microscopic analysis reveals anastomosing vascular channels that appear tortuous and irregular with small to large cavernous spaces. The endothelial cells have pleomorphic nuclei with irregular nuclear contours and mitotic figures. Immunohistochemistry is characterized by immunoreactivity with Factor VIII-RA, CD34, CD31 and smooth muscle actin, but non-reactive with S-100. Currently the treatment paradigm includes surgical resection with possible adjuvant radiation and chemotherapy depending on the specific case characteristics (i.e. positive margins, tumor size and distant spread). The overall 5-year survival for nasal and paranasal sinus angiosarcoma ranges from 12% to 33% [4]. Traditional chemotherapy regimens have included a combination of ifosfamide, paclitaxel and doxorubicin for soft tissue sarcomas [5]. Bevacizumab, a newer humanized monoclonal antibody against vascular endothelia growth factor (VEGF), has shown some promise in helping to control inoperable cases of angiosarcomas of the head and neck in a few case reports [5–8]. In addition there have been a couple of studies using sorafenib, a targeted multiple-kinase inhibitor, with some promising results [9,10]. Due to the rarity of the disease there is a dearth of literature on the subject. This limits our ability to extract statistically significant information on demographics and prognostic factors. Nonetheless, the present case demonstrates several unique features in terms of both location and management that should be considered when encountering nasal and paranasal sinus angiosarcomas.
AM ER IC AN JOURNAL OF OT OLARYNGOLOGY–H E A D A N D NE CK M E D IC IN E A ND S U RGE RY 3 5 (2 0 1 4) 8 06–8 0 9
4.
Conclusion
This is a rare case of an angiosarcoma arising in the frontal sinus with local extension and distant metastases. The extent of disease was determined with the aid of PET/CT, which helped to further determine treatment. The final proposal took into consideration 1) the distant spread, 2) the locally extensive and aggressive tumor which alone would necessitate a debilitating and highly morbid surgery, 3) the overall poor prognosis and 4) the young age of the patient. The patient was given a more standard treatment of chemotherapeutics followed by radiation after the chemotherapeutic response weaned. The complexity and rarity of this case emphasize the need for an interdisciplinary approach and further research into targeted medical treatments.
REFERENCES
[1] Aust MR, Olsen KD, Lewis JE, et al. Angiosarcomas of the head and neck: clinical and pathologic characteristics. Ann Otol Rhinol Laryngol 1997;106:943–51.
809
[2] Nelson BL, Thompson LD. Sinonasal tract angiosarcoma: a clinicopathologic and immunophenotypic study of 10 cases with a review of the literature. Head Neck Pathol 2007;1:1–12. [3] Vasanawala MS, Wang Y, Quon A, et al. F-18 fluorodeoxyglucose PET/CT as an imaging tool for staging and restaging cutaneous angiosarcoma of the scalp. Clin Nucl Med 2006;31:534–7. [4] Sturgis EM, Potter BO. Sarcomas of the head and neck region. Curr Opin Oncol 2003;15:239–52. [5] Yang P, Zhu Q, Jiang F. Combination therapy for scalp angiosarcoma using bevacizumab and chemotherapy: a case report and review of literature. Chin J Cancer Res 2013;25:358–61. [6] Fuller CK, Charlson JA, Dankle SK, et al. Dramatic improvement of inoperable angiosarcoma with combination paclitaxel and bevacizumab chemotherapy. J Am Acad Dermatol 2010;63:e83–4. [7] De Yao JT, Sun D, Powell AT, et al. Scalp angiosarcoma remission with bevacizumab and radiotherapy without surgery: a case report and review of the literature. Sarcoma 2011;2011:160369. [8] Koontz BF, Miles EF, Rubio MA, et al. Preoperative radiotherapy and bevacizumab for angiosarcoma of the head and neck: two case studies. Head Neck 2008;30:262–6. [9] Ono S, Tanioka M, Fujisawa A, et al. Angiosarcoma of the scalp successfully treated with a single therapy of sorafenib. Arch Dermatol 2012;148:683–5. [10] Ray-Coquard I, Italiano A, Bompas E, et al. Sorafenib for patients with advanced angiosarcoma: a phase II trial from the French Sarcoma Group (GSF/GETO). Oncologist 2012;17:260–6.
Available online at www.sciencedirect.com
ScienceDirect www.elsevier.com/locate/amjoto
Case reports
Angiosarcoma arising from the frontal sinus☆,☆☆ Senja Tomovic, MD a , Evelyne Kalyoussef, MD a , Neena M. Mirani, MD a, b , Soly Baredes, MD, FACS a, c , Jean Anderson Eloy, MD, FACS a, c, d,⁎ a
Department of Otolaryngology–Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey Department of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, New Jersey c Center for Skull Base and Pituitary Surgery, Neurological Institute of New Jersey, Rutgers New Jersey Medical School, Newark, New Jersey d Department of Neurological Surgery, Rutgers New Jersey Medical School, Newark, New Jersey b
ARTI CLE I NFO
A BS TRACT
Article history:
Primary sinonasal angiosarcomas are very rare tumors. They typically occur in the nasal cavity of
Received 15 July 2014
middle-aged patients. They are classically highly aggressive. Primary treatment is surgical excision when feasible. We describe a unique case of angiosarcoma in a young woman arising from the frontal sinus with distant metastasis. This case represents the first report of angiosarcoma arising from the frontal sinus in the English literature. The traditional treatment options for the advanced nature of her disease and overall poor prognosis are discussed. We further
review
the
literature
and
discuss
alternative
treatments
options.
Newer
chemotherapeutic regiments on the horizon show promise in helping to control this disease. © 2014 Elsevier Inc. All rights reserved.
1.
Introduction
Angiosarcomas are aggressive tumors of vascular endothelial origin. These tumors tend to occur in the middle-aged population and are managed with surgical excision with radiation and chemotherapy traditionally reserved for unresectable disease or positive margins. This case is unique in that it is the first reported case in the English literature of a paranasal sinus angiosarcoma 1) arising in the frontal sinus, 2) with distant metastatic spread, and 3) staged using positron emission tomography (PET). In addition, due to the extent of disease careful thought and discussion were given to the optimal treatment modality. Interestingly, with the recent advent of newer targeted treatments more consideration has been given to the role of an antibody to vascular endothelial growth factor (anti-VEGF) to help control and limit disease. ☆
2.
Illustrative case
A previously healthy 21-year-old female with no prior history of radiation exposure presented with two months of progressing left sided forehead tingling, pain and proptosis with no significant vision changes that were refractory to antibiotics. A computed tomography (CT) scan showed a calcified mass centered in the left lateral frontal sinus with evidence of cortical bone destruction and invasion of the left frontal lobe and superior left orbit with opacification of the ethmoid sinus and destruction of the cribriform plate and medial orbital wall (Fig. 1A&B). A magnetic resonance imaging (MRI) showed an enhancing heterogeneous mass centered in the left frontal sinus extending into the left superolateral aspect of the orbit with diffuse dural enhancement towards the vertex and left temporal lobe (Fig. 1C&D).
Financial Disclosures: None. Conflicts of Interest: None. ⁎ Corresponding author at: Department of Otolaryngology, Head and Neck Surgery, Rutgers New Jersey Medical School, 90 Bergen St., Suite 8100, Newark, NJ 07103. Tel.: + 973 972 4588; fax: + 973 972 3767. E-mail address: [email protected] (J.A. Eloy).
☆☆
http://dx.doi.org/10.1016/j.amjoto.2014.08.003 0196-0709/© 2014 Elsevier Inc. All rights reserved.
AM ER IC AN JOURNAL OF OT OLARYNGOLOGY–H E A D A N D NE CK M E D IC IN E A ND S U RGE RY 3 5 (2 0 1 4) 8 06–8 0 9
807
Fig. 1 – Preoperative imaging. (A) Axial CT scan showing opacification of the left frontal sinus with destruction of the posterior table and extension into the ethmoid sinuses. (B) Coronal CT scan with a lytic lesion of the left lateral frontal sinus. (C) T1-weighted gadolinium enhanced axial MRI showing enhancing lesion of the left frontal sinus extending into the left frontal lobe. (D) T1-weighted gadolinium enhanced coronal MRI showing enhancing lesion of the left frontal sinus with dural enhancement.
The patient was taken to the operating room for nasal endoscopy and biopsy, which revealed a purple friable necrotic tumor obstructing the left middle meatus (Fig. 2). Histology was consistent with a high grade angiosarcoma, invading bone with hemorrhagic necrosis (Fig. 3) Malignant endothelial cells were epithelioid type with nuclear pleomorphism and mitoses. The tumor cells were immunoreactive to vimentin and endothelial markers such as, CD31 and CD34, Fli-1 and Factor VIII. A postoperative PET/CT was performed and showed a lyticlesion of the left frontal bone extending to the superolateral aspect of the left orbit with a maximum SUV of 10.5. The ethmoid sinus had opacification with a maximum
SUV of 11.7 and the left maxillary sinus had a maximum SUV of 7.7. There was also a lesion of 1.1 cm in the apex of the right lung with an SUV of 2.5, a right level II cervical lymph node with an SUV of 2.7 and a C2 vertebral body lesion with an SUV of 3.4, all considered metastatic. Given the distant disease as well as extensive local disease, initial treatment with chemotherapy including bevicizumab and radiation was recommended with the consideration for salvage surgery. The patient was subsequently treated with docetaxel and gemcitabine for six months with regression of the tumor, however the tumor regrew and the patient was started on radiation therapy. She is currently one year out from diagnosis with full functional capacity.
Fig. 2 – (A & B) Intraoperative endoscopic view of the tumor in the left middle meatus with the asterisk labeling the necrotic friable purple tumor.
808
AM ER IC AN JOURNAL OF OT OLA RYNGOLOGY–H E A D A N D NE CK M E D ICI N E AN D S U RGE RY 3 5 (2 0 1 4) 8 06 –8 0 9
Fig. 3 – (A) Hematoxylin and eosin (H & E, 40x) stained specimen showing submucosal nests of malignant epithelioid cells with hemorrhage. (B) Proliferating vascular channels invading the bone and lined by hyperchromatic malignant endothelial cells (H & E, 400x). (C) Epithelioid tumor cells with pleomorphic nuclei and mitosis (H & E, 600x). (D) Tumor cells immunoreactive to CD31 (endothelial marker) (CD31 immunostain, 100x).
3.
Discussion
Angiosarcomas are rare high-grade malignant vascular tumors that account for less than 0.1% of all sinonasal malignancies [1]. The largest single series on sinonasal tract angiosarcomas in the English literature reports a series of 10 cases gathered from the Armed Forces Institute of Pathology between 1970 and 1995. In this series eight arose from the nasal cavity proper and two from the maxillary sinus [2]. The etiology is unclear, but exposure to radiation and vinyl chloride has been proposed to be a predisposing factor. The symptoms include epistaxis, nasal obstruction and nasal discharge. Diagnosis involves a combination of appropriate imaging, including contrast studies (CT, MRI, and/or angiography with or without embolization) to assess the degree of vascularity. PET/CT scans have shown great utility in assessing for distant spread in many different types of cancer. Interestingly, current literature contains mostly small studies and case reports of the use of PET/CT in angiosarcomas of the cardiothoracic and abdominal viscera and only two reports of its use in defining the extent of disease in cases of scalp angiosarcomas [3]. Further studies using PET/CT technology may prove to be useful for diagnosis, staging and monitoring response to treatment. Pathologic diagnosis is accomplished through nasal endoscopy and biopsy which allow for tumor mapping and the ability to control bleeding. Macroscopically the tumor is vascular, typically red to purple, soft and friable. The differential diagnosis includes granulation tissue, intravascular papillary endothelial hyperplasia, epithelioid hemangioma, glomangiopericytoma, juvenile
nasopharyngeal angiofibroma, kaposi sarcoma, and mucosal melanoma [2]. Microscopic analysis reveals anastomosing vascular channels that appear tortuous and irregular with small to large cavernous spaces. The endothelial cells have pleomorphic nuclei with irregular nuclear contours and mitotic figures. Immunohistochemistry is characterized by immunoreactivity with Factor VIII-RA, CD34, CD31 and smooth muscle actin, but non-reactive with S-100. Currently the treatment paradigm includes surgical resection with possible adjuvant radiation and chemotherapy depending on the specific case characteristics (i.e. positive margins, tumor size and distant spread). The overall 5-year survival for nasal and paranasal sinus angiosarcoma ranges from 12% to 33% [4]. Traditional chemotherapy regimens have included a combination of ifosfamide, paclitaxel and doxorubicin for soft tissue sarcomas [5]. Bevacizumab, a newer humanized monoclonal antibody against vascular endothelia growth factor (VEGF), has shown some promise in helping to control inoperable cases of angiosarcomas of the head and neck in a few case reports [5–8]. In addition there have been a couple of studies using sorafenib, a targeted multiple-kinase inhibitor, with some promising results [9,10]. Due to the rarity of the disease there is a dearth of literature on the subject. This limits our ability to extract statistically significant information on demographics and prognostic factors. Nonetheless, the present case demonstrates several unique features in terms of both location and management that should be considered when encountering nasal and paranasal sinus angiosarcomas.
AM ER IC AN JOURNAL OF OT OLARYNGOLOGY–H E A D A N D NE CK M E D IC IN E A ND S U RGE RY 3 5 (2 0 1 4) 8 06–8 0 9
4.
Conclusion
This is a rare case of an angiosarcoma arising in the frontal sinus with local extension and distant metastases. The extent of disease was determined with the aid of PET/CT, which helped to further determine treatment. The final proposal took into consideration 1) the distant spread, 2) the locally extensive and aggressive tumor which alone would necessitate a debilitating and highly morbid surgery, 3) the overall poor prognosis and 4) the young age of the patient. The patient was given a more standard treatment of chemotherapeutics followed by radiation after the chemotherapeutic response weaned. The complexity and rarity of this case emphasize the need for an interdisciplinary approach and further research into targeted medical treatments.
REFERENCES
[1] Aust MR, Olsen KD, Lewis JE, et al. Angiosarcomas of the head and neck: clinical and pathologic characteristics. Ann Otol Rhinol Laryngol 1997;106:943–51.
809
[2] Nelson BL, Thompson LD. Sinonasal tract angiosarcoma: a clinicopathologic and immunophenotypic study of 10 cases with a review of the literature. Head Neck Pathol 2007;1:1–12. [3] Vasanawala MS, Wang Y, Quon A, et al. F-18 fluorodeoxyglucose PET/CT as an imaging tool for staging and restaging cutaneous angiosarcoma of the scalp. Clin Nucl Med 2006;31:534–7. [4] Sturgis EM, Potter BO. Sarcomas of the head and neck region. Curr Opin Oncol 2003;15:239–52. [5] Yang P, Zhu Q, Jiang F. Combination therapy for scalp angiosarcoma using bevacizumab and chemotherapy: a case report and review of literature. Chin J Cancer Res 2013;25:358–61. [6] Fuller CK, Charlson JA, Dankle SK, et al. Dramatic improvement of inoperable angiosarcoma with combination paclitaxel and bevacizumab chemotherapy. J Am Acad Dermatol 2010;63:e83–4. [7] De Yao JT, Sun D, Powell AT, et al. Scalp angiosarcoma remission with bevacizumab and radiotherapy without surgery: a case report and review of the literature. Sarcoma 2011;2011:160369. [8] Koontz BF, Miles EF, Rubio MA, et al. Preoperative radiotherapy and bevacizumab for angiosarcoma of the head and neck: two case studies. Head Neck 2008;30:262–6. [9] Ono S, Tanioka M, Fujisawa A, et al. Angiosarcoma of the scalp successfully treated with a single therapy of sorafenib. Arch Dermatol 2012;148:683–5. [10] Ray-Coquard I, Italiano A, Bompas E, et al. Sorafenib for patients with advanced angiosarcoma: a phase II trial from the French Sarcoma Group (GSF/GETO). Oncologist 2012;17:260–6.
