Radiofrequency-induced thermotherapy of nasopharyngeal angiofibroma and immunohistochemical analysis of vessel proliferation: a case report
© Krstulja et al; licensee BioMed Central Ltd. 2008
Received: 30 December 2007
Accepted: 16 August 2008
Published: 16 August 2008
Nasopharyngeal angiofibroma presents with symptoms of nasal obstruction and epistaxis. The treatment of choice is embolization followed by surgery.
A 52-year-old man underwent surgery for nasopharyngeal angiofibroma after adjuvant radiofrequency-induced thermotherapy. To the best of the authors' knowledge, this is the first case of angiofibroma with clinical follow-up after thermocoagulation therapy supported by quantitative, double immunohistochemistry. We found this case of angiofibroma to be of interest owing to the presentation of symptoms leading to biopsy, the pathohistological observations obtained with synchronous Ki67/cluster of differentiation 34 and Ki67/smooth muscle actin immunohistochemistry and high pericyte proliferation.
Coagulation of angiofibroma vessels followed by acquisition of a thick mantle of pericytes in a patient with a nasopharyngeal growth suggests that radiofrequency-induced thermotherapy could be a useful, palliative therapy for bleeding nasopharyngeal angiofibroma, supporting vessel maturation prior to surgical tumor removal.
Nasopharyngeal angiofibroma is considered to be a reactive, malformed, benign but aggressive neoplasm. Clinical staging and tumor embolization reduce surgical morbidity. The therapy protocol is influenced by hospital-related factors. Radiofrequency-induced thermotherapy (RFITT) is a minimally invasive surgical procedure that causes thermal ablation through coagulation and is used in the treatment of both head and neck diseases. We were unable to find reported cases of angiofibroma that were treated with RFITT, subjected to follow-up evaluation and had documented histological changes with time.
We present an unusual case of a 52-year-old man with nasopharyngeal angiofibroma that first appeared as a nasal polyp. Coagulation, thrombosis, sclerosis and pericyte proliferation occurred after RFITT. We looked for a change in angiofibroma cell proliferation through biopsies obtained before and after RFITT when the patient was free of bleeding episodes. The cell origin of vessel formation after thermocoagulation therapy was investigated. Our results are of interest for surgeons applying pre-operative thermal ablation therapy.
A third biopsy 10 months after RFITT provided 0.075 cm3 of residual tumor with an overall Ki67 proliferation index of 10%. Plump SMA-positive and predominantly Ki67-negative cells were detached from the vessel wall and formed sheets resembling angiomyofibroblastoma after H&E staining. The second and third biopsies respected the recovery time from RFITT and were not complicated by hemorrhage.
One year after RFITT, angiography found no arteries feeding the residual tumor. The patient underwent surgery at another institution without prior embolization (no hypertrophic feeding arteries were found at repeated angiography before the operation).
Variables of cell proliferation and vessel proliferation in angiofibroma with time
proliferation index (%)
density per mm2
Order of biopsy
Double immunohistochemical staining revealed higher proliferation indices for cells of the vessel compartment compared with single Ki67 staining of each routine biopsy. The EPI slightly decreased while the PEPI increased 10 months after RFITT. The third biopsy contained a large number of detached SMA-positive cells. There were scattered Ki67-positive nuclei of cells outside the vessel wall that were defined by neither CD34 nor SMA in all three biopsies. The MVD increased 20 days after RFITT and further increased with time. The PCI also increased with time. Measurements and images were obtained using a BX-40 Olympus microscope, Sony CCD-Iris color video camera and ISSA 3.1 software (Vamstec, Zagreb).
Nasopharyngeal angiofibroma is considered a malformation in juveniles [1–3], but does not exclude the unusual presentation of the disease in mature patients, as confirmed by this report and occasional reports from other authors . While nasal polyps are not subjected routinely to CT or magnetic resonance imaging, these are established pre-operative diagnostic tools for nasopharyngeal angiofibroma.
The case presented here is of interest from both the clinical and the pathological points of view. The nasopharyngeal and sinonasal tracts are sites of different pathologies prone to epistaxis, such as the angiofibroma, angiectatic nasal polyp , and necrotizing angiocentric lesion. The stroma is different in these lesions and quite typical in angiofibroma. SMA decorates the stromal cells in certain nasal polyps. It is strongly positive in the vessel wall (pericytes) and occasionally in the stroma of angiofibromas [1, 6], which may help in differential diagnosis.
In our case, two pathologies were present synchronously, a mucosal nasal polyp and an angiofibroma, making the diagnosis more complex as noticed by other authors . The association between inflammatory nasal polyps and angiofibroma is not routinely expected, but once a biopsy is obtained, there are criteria to distinguish between nasal polyps arising through different pathogenic processes . Nasopharyngeal angiofibroma is a rare event and biopsy is not advised. The first biopsy of our patient resulted from atypical extension of the tumor into the nasal cavity. The dates for the second and third biopsy were chosen with regards to the recovery period after RFITT. Although not a new disease, nasopharyngeal angiofibroma remains a clinical and scientific challenge. Thermocoagulation should be considered as a possible pre-operative protocol when embolization is not available.
The origin of angiofibroma is still under investigation. Zhang et al.  presented arguments for primary stromal change at the molecular level of angiofibroma organization. However, the origin of vessel formation is uncertain [8, 9] and pericyte behavior in angiofibroma may be of interest. We were unable to find reports on pericyte proliferation in nasopharyngeal angiofibroma treated with RFITT. We find our observations of importance for the investigation of angiogenesis, angiofibroma and post-RFITT control biopsies. Our observations are in accordance with the purpose of the therapy, that is, to impede circulation and produce coagulation, thus reducing growth. The lesion was successfully treated surgically without pre-operative embolization, suggesting that RFITT might function as a pre-operative adjuvant therapy. Two years after RFITT, our patient is without symptoms or nasopharyngeal growth.
Histologically, both endothelial cell and pericyte proliferation were more accurately expressed with double immunohistochemistry compared with routine Ki67 staining. Pericyte proliferation was stronger than endothelial cell proliferation prior to therapy (PEPI 16.04%, EPI 8.34%). While the PEPI increased upon coagulation and progressed with time, the EPI did not. These results support the theory of angiofibroma as a maturing vasoformative lesion. Vessel formation is observed in inflammation, malformation, neovascularization of neoplasia and as a neoplastic event. Proliferation in vascular malformations has been studied previously [10, 11]. Vessel formation in inflammation is diffuse except in granulomas. Malformations and neoplasias, including angiofibromas, behave as a 'body' in that they are fed and can be embolized, and angiofibromas are not considered neoplastic events. Malformations occurring with age are unusual but not unexpected. Zhang et al.  showed that angiofibroma stromal cells might be neoplastic. Our investigation of angiofibroma using double immunohistochemistry showed negligible proliferation outside the vascular compartment.
We have presented a rare case of angiofibroma in a 52-year-old man with pericyte proliferation, supporting the maturation of the vessel compartment and revealing active angiogenic machinery (cooperation between endothelial cells and pericytes). We observed the divergent behavior of endothelial cells and pericytes after RFITT adjuvant therapy prior to surgery. Further studies of RFITT related to vessel behavior are needed. We found thrombosis and coagulation resulting from RFITT to function as equivalent to embolization prior to surgical therapy for angiofibroma. An analysis of vessel cell proliferation in tissues treated with thermal ablation might have broader clinical impact across medicine.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Cluster of differentiation
Endothelial cell proliferation index
Hematoxylin and eosin
Proliferating capillary index
Pericyte proliferation index
Smooth muscle actin.
- Liang J, Yi Z, Lianq P: The nature of juvenile nasopharyngeal angiofibroma. Otolaryngol Head Neck Surg. 2000, 123: 475-481. 10.1067/mhn.2000.105061.View ArticlePubMedGoogle Scholar
- Zhang PJ, Weber R, Liang HH, Pasha TL, LiVolsi VA: Growth factors and receptors in juvenile nasopharyngeal angiofibroma and nasal polyps: an immunohistochemical study. Arch Pathol Lab Med. 2003, 127: 1480-1484.PubMedGoogle Scholar
- Beham A, Beham-Schmid C, Regauer S, Auböck L, Stammberger H: Nasopharyngeal angiofibroma: true neoplasm or vascular malformation?. Adv Anat Pathol. 2000, 7: 36-46.View ArticlePubMedGoogle Scholar
- Celik B, Erisen L, Saraydaroglu O, Coskun H: Atypical angiofibromas: a report of four cases. Int J Pediatr Otorhinolaryngol. 2005, 69: 415-421. 10.1016/j.ijporl.2004.10.007.View ArticlePubMedGoogle Scholar
- Yfantis HG, Drachenberg CB, Gray W, Papadimitriou JC: Angiectatic nasal polyps that clinically simulate a malignant process: report of 2 cases and review of the literature. Arch Pathol Lab Med. 2000, 124: 406-410.PubMedGoogle Scholar
- Wang QP, Escudier E, Roudot-Thoraval F, Abd-Al Samad I, Peynegre R, Coste A: Myofibroblast accumulation induced by transforming growth factor-beta is involved in the pathogenesis of nasal polyps. Laryngoscope. 1997, 107: 926-931. 10.1097/00005537-199707000-00018.View ArticlePubMedGoogle Scholar
- Baumgarten C, Kunkel G, Rudolph R, Staud RD, Sperner I, Gelderblom H: Histopathological examinations of nasal polyps of different etiology. Arch Otorhinolaryngol. 1980, 226: 187-197. 10.1007/BF00455133.View ArticlePubMedGoogle Scholar
- Minasi MG, Riminucci M, De Angelis L, Borello U, Berarducci B, Innocenzi A, Caprioli A, Sirabella D, Baiocchi M, De Maria R, Boratto R, Jaffredo T, Broccoli V, Bianco P, Cossu G: The meso-angioblast: a multipotent, self-renewing cell that originates from the dorsal aorta and differentiates into most mesodermal tissues. Development. 2002, 129: 2773-2783.PubMedGoogle Scholar
- DeRuiter MC, Poelmann RE, VanMunsteren JC, Mironov V, Markwald RR, Gittenberger-de Groot AC: Embryonic endothelial cells transdifferentiate into mesenchymal cells expressing smooth muscle actins in vivo and in vitro. Circ Res. 1997, 80: 444-451.View ArticlePubMedGoogle Scholar
- Meijer-Jorna LB, Loos van der CM, de Boer OJ, Horst van der CM, Wal van der AC: Microvascular proliferation in congenital vascular malformations of skin and soft tissue. J Clin Pathol. 2007, 60: 798-803. 10.1136/jcp.2006.038885.View ArticlePubMedGoogle Scholar
- Vargel I, Cil BE, Er N, Ruacan S, Akarsu AN, Erk Y: Hereditary intraosseous vascular malformation of the craniofacial region: an apparently novel disorder. Am J Med Genet. 2002, 109: 22-35. 10.1002/ajmg.10282.View ArticlePubMedGoogle Scholar
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