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Background
This tumor occurs in several locations. Most commonly, it is a tumor of males. It presents with nasal obstruction and nose bleeds and is located in the lateral nasopharynx or posterior nasal cavity. It is most common in adolescents (peak 15 yrs) and thus is sometimes referred to as a juvenile nasopharyngeal angiofibroma. Although benign, tumors may cause complications by growth into the adjacent sinuses or orbit. Complete surgical resection is curative. These tumors do contain testosterone receptors and may grow during testosterone administration. There are no estrogen or progesterone receptors. The characteristic clinical triad is a nasopharyngeal mass, nasal obstruction, and episodic epistaxis (nosebleeding).
Under the microscope, these tumors are well-circumscribed but unencapsulated and composed of collagenized fibrous stroma with vessels ranging from small slit-like spaces to dilated lumens. No significant cytologic atypia is observed. Occasional multinucleated stromal cells are present. The vascular nature is highlighted by angiograms showing a rich supply.
However, non-head and neck cases may occur.
OUTLINE
DISEASE ASSOCIATIONS CHARACTERIZATION Familial adenomatous polyposis coli (Gardner's syndrome) Gastroenterology 1993;105:1550-1552
There is a 25x higher frequency of this tumor in patients with this polyposis syndromeJuvenile nasopharyngeal
angiofibroma and
familial adenomatous polyposis: an association?Ferouz AS, Mohr RM, Paul P.
Department of Otorhinolaryngology/
Bronchoesophagology, Temple University Health Sciences Center, Philadelphia, Pennsylvania, USAOtolaryngol Head Neck Surg 1995 Oct;113(4):435-9 Abstract quote
Juvenile nasopharyngeal angiofibroma is a benign neoplasm affecting the nasopharynx of male adolescents. Two patients treated at Temple University Hospital for this condition were also diagnosed with familial adenomatous polyposis. Familial adenomatous polyposis results from the inheritance of a mutated adenomatous polyposis coli gene in an autosomal dominant pattern. The development of colorectal carcinoma in middle age is seen almost invariably in familial adenomatous polyposis, if a prophylactic colectomy is not performed.
To identify a possible association between juvenile nasopharyngeal angiofibroma and familial adenomatous polyposis, chart reviews and patient interviews were carried out for all patients treated for juvenile nasopharyngeal angiofibroma at Temple University Hospital between 1985 and 1993.
Single-strand conformational polymorphism was performed to detect the presence of certain adenomatous polyposis coli gene mutations within the germline DNA of those juvenile nasopharyngeal angiofibroma patients not previously found to have familial adenomatous polyposis. Although no more patients with both juvenile nasopharyngeal angiofibroma and familial adenomatous polyposis were found by these methods, the two patients with both disorders previously identified constitute 22% of our juvenile nasopharyngeal angiofibroma series. The implications of these findings are discussed.
PATHOGENESIS CHARACTERIZATION GROWTH FACTORS
Growth factors and receptors in juvenile nasopharyngeal angiofibroma and nasal polyps: an immunohistochemical study.
Zhang PJ, Weber R, Liang HH, Pasha TL, LiVolsi VA.
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, USA.
Arch Pathol Lab Med. 2003 Nov;127(11):1480-4. Abstract quote
BACKGROUND: Juvenile nasopharyngeal angiofibroma is a rare nasopharyngeal tumor that occurs exclusively in adolescent boys. It is a histologically benign but locally persistent growth of stromal and vascular tissue. Although male hormones and some growth factors, such as transforming growth factor beta1 (TGF-beta1), insulin-like growth factor II (IGF-II), and, lately, the proto-oncogene beta-catenin, have been implicated in the histogenesis of the tumor, the biologic signaling pathways that drive this peculiar fibrovascular proliferation are still nuclear.OBJECTIVE: To evaluate immunoexpressions of beta-catenin, c-Kit, p130Cas, TGF-beta3, bone morphogenic protein 4, nerve growth factor (NGF), and the IGF receptor (IGF-1R) in a series of juvenile nasopharyngeal angiofibromas and to compare to that of a group of nasal polyps.
DESIGN: A standard immunohistochemical technique was used on paraffin sections of 12 sporadic juvenile nasopharyngeal angiofibromas and 15 nasal polyps with microwave or steam antigen retrieval. Immunoreactivity was analyzed semiquantitatively in stromal cells and endothelial cells of each case.
RESULTS: The expressions of beta-catenin (nuclear), c-Kit (cytoplasmic), and NGF (cytoplasmic) were higher and more frequent in stromal cells of juvenile nasopharyngeal angiofibromas than those of nasal polyps. Both juvenile nasopharyngeal angiofibromas and nasal polyps showed similarly frequent and strong immunoreactivity for p130Cas and TGF-beta3 and weak immunoreactivity for bone morphogenic protein 4 in both stromal cells and endothelial cells. No IGF-1R immunoreactivity was detected in any case of either group.
CONCLUSIONS: Our results support the role of beta-catenin in juvenile nasopharyngeal angiofibromas and suggest a potential involvement of c-Kit and NGF signaling pathways in the juvenile nasopharyngeal angiofibromas. Although the biologic significance of c-Kit in juvenile nasopharyngeal angiofibromas has yet to be defined, the finding of frequent and high c-Kit expression might have therapeutic importance for patients with juvenile nasopharyngeal angiofibromas.
Expression of growth factors, proto-oncogenes, and p53 in nasopharyngeal angiofibromas.
Nagai MA, Butugan O, Logullo A, Brentani MM.
Departmento de Radiologia, Faculdade de Medicina, Universidade de Sao Paulo, Brazil.
Laryngoscope 1996 Feb;106(2 Pt 1):190-5 Abstract quote
Biopsies from 25 juvenile nasopharyngeal angiofibromas (JNAs) and respective normal inferior turbinates were examined and compared. The expression patterns of the messenger RNAs (mRNAs) for various growth factors possibly involved in the growth of mesenchymal cells, as well as angiogenesis and fibrosis, were also compared.
These growth factors included insulin-like growth factor II (IGF-II), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), transforming growth factors-beta1 (TGF-beta1) and platelet-derived growth factors (PDGF-A and PDGF-B). Quantification of mRNA coding for proto-oncogenes and suppressor genes related to proliferation (i.e., c-myc, c-fos, p53) was also undertaken. Tumor and turbinates expressed similar levels of bFGF, VEGF, TGF-beta1, c-myc, c-fos, and PDGF-A mRNAs. The presence of TGF-beta1 protein was confirmed by immunohistochemistry in several structures that characterize the lesions of JNA, which suggests that TGF-beta1 may play a role in the development of the fibrous component of this tumor. PDGF-B and p53 were overexpressed (i.e., twice the mean level found in turbinates) in 50% and 32% of JNAs, respectively but there was no statistical significance when compared with controls.
Statistically significant increased expression of IGF-II mRNA was observed in JNA (P = .04). IGF-II mRNA levels were correlated to p53 (P = .05) and PDGF-B (P = .034), indicating a possible synergistic action of such factors in JNA. The results of this study suggest that IGF-II might be a potential growth regulator of nasopharyngeal angiofibromas.
Nasopharyngeal angiofibroma: true neoplasm or vascular malformation?
Beham A, Beham-Schmid C, Regauer S, Aubock L, Stammberger H.
Institute of Pathology, University of Graz Medical School, Austria.
Adv Anat Pathol 2000 Jan;7(1):36-46 Abstract quote
Nasopharyngeal angiofibromas (NA) are rare tumor-like lesions characterized by architecturally irregular vessels set in a fibrous stroma. The unique morphology, the strong predilection for male adolescents, and the uncertainty about its etiology contributes to significant confusion regarding the classification of NA, which still has not been solved today.
Based on immunohistochemical and electron microscopic examinations, we demonstrate in detail the various unusual vascular architectural features of NA. They represent discontinuous vascular basal laminae, focal lack of pericytes, and pronounced irregularity of the smooth muscle layers. In thick smooth muscle layers and pads, the orientation of muscle cells is frequently disturbed, and the individual cells differ in size and shape. Occasionally, the muscle layers disperse peripherally into individual cells, creating the impression of vessel-independent smooth muscle cells within the stroma.
The summation of all morphological irregularities demonstrated in this paper allows the conclusion that NA represent vascular malformations.
Nasopharyngeal angiofibroma: an APC-gene-associated tumor?
Guertl B, Beham A, Zechner R, Stammberger H, Hoefler G.
Department of Pathology, University of Graz, Austria.
Hum Pathol 2000 Nov;31(11):1411-3 Abstract quote
Nasopharyngeal angiofibromas are extremely rare, locally invasive tumors of unknown cause exclusively occurring in male adolescents. Recently, 6 cases have been reported in patients with familial adenomatous polyposis coli (Gardners syndrome). Mutations or allelic loss of the adenomatous polyposis coli (APC) gene have therefore been implied in the pathogenesis of nasopharyngeal angiofibroma.
The authors analyzed 11 cases of nasopharyngeal angiofibromas from 9 male patients for mutations in the mutation cluster region and allelic loss of the APC gene. Six were primary tumors; 2 first recurrences; and 1, primary tumor with 2 recurrences. Direct sequence analysis was performed on several overlapping polymerase chain reaction (PCR) products. Detection of allelic loss was performed by restriction length polymorphism analysis at a polymorphic locus. No mutation was detected in 11 tumors of 9 different patients. None of the 9 informative (heterozygous) cases carried an allelic loss.
We conclude that alterations of the APC gene do not play a major role in the development of nasopharyngeal angiofibroma. The coincidence of nasopharyngeal angiofibromas and adenomatous polyposis coli in some families implies the possibility that another gene in this region might be responsible for the development of nasopharyngeal angiofibromas.
Frequent beta-catenin mutations in juvenile nasopharyngeal angiofibromas.
Abraham SC, Montgomery EA, Giardiello FM, Wu TT.
Department of Pathology, Division of Gastroenterology, The Johns Hopkins University School of Medicine, 720 Rutland Ave., Baltimore, MD 21205-2196, USA.
Am J Pathol 2001 Mar;158(3):1073-8 Abstract quote
Juvenile nasopharyngeal angiofibromas (JNAs) are locally aggressive vascular tumors occurring predominantly in adolescent males. The pathogenesis of JNAs is unknown. Recently, JNAs have been reported to occur at increased frequency among patients with familial adenomatous polyposis, suggesting that alterations of the adenomatous polyposis coli (APC)/beta-catenin pathway might also be involved in the pathogenesis of sporadic JNAs.
We analyzed somatic beta-catenin and APC gene mutations in 16 sporadic JNAs from nonfamilial adenomatous polyposis patients using immunohistochemistry for beta-catenin, and direct DNA sequencing for exon 3 of the beta-catenin gene and the mutation cluster region of the APC gene. Nuclear accumulation of beta-catenin was diffusely present in the stromal cells but not in the endothelial cells of all 16 JNAs. Activating beta-catenin gene mutations were present in 75% (12 of 16) of JNAs. Six JNA patients also had recurrent tumors after surgery, and in all cases the beta-catenin gene status of the recurrent JNA was identical to the initial tumor. No mutations in the mutation cluster region of the APC gene were detected in the four JNAs without beta-catenin mutations. The high frequency of beta-catenin mutations in sporadic JNAs and the presence of identical beta-catenin gene mutations in recurrent tumors indicates that activating beta-catenin gene mutations are important in the pathogenesis of JNAs.
The immunohistochemical localization of beta-catenin only to the nuclei of stromal cells further suggests that the stromal cells, rather than endothelial cells, are the neoplastic cells of JNAs.
LABORATORY/
RADIOLOGIC/OTHERCHARACTERIZATION Postoperative follow-up of juvenile nasopharyngeal angiofibromas: assessment by CT scan and MR imaging.
Chagnaud C, Petit P, Bartoli J, Champsaur P, Gaubert J, Dessi P, Zanaret M, Cannoni M, Moulin G.
Department of Radiology, Groupe Hospitalier de la Timone, Centre Hospitalier et Universitaire de Marseille, F-13385 Marseille Cedex 5, France.
Eur Radiol 1998;8(5):756-64 Abstract quote
The purpose of this study was to assess the radiological findings after surgical removal of juvenile nasopharyngeal angiofibromas (JNA).
The postoperative CT and MRI scans of ten patients were reviewed. The cured group included six patients. The non-controlled group included six patients with eight recurrences. Two patients belonged to both groups as they were also followed and cured after surgery for relapse. Four recurrences were asymptomatic and diagnosed by imaging. The imaging patterns were matched to the patients clinical status and endoscopic findings. In the cured group, non-enhanced residual soft tissue masses were seen in all cases. In the non-controlled group, recurrence was always demonstrated on early postoperative CT or MR as a dramatically enhanced mass. The recurrence was located in the lateral or superior aspect of the nasopharynx (n = 3), deep to the fossa of Rosenmuller (n = 4) or out of the nasopharynx (n = 1). In two cases a remaining enhanced mass disappeared spontaneously on iterated examinations.
Because of numerous asymptomatic relapses, a radiological workup is recommended four months after surgery, even in patients with normal endoscopy, to rule out posterolateral or extranasopharyngeal recurrences. Spontaneous evolution of residual masses must be appreciated on iterated imaging examinations.
Juvenile angiofibroma: the lessons of 20 years of modern imaging.
Lloyd G, Howard D, Phelps P, Cheesman A.
Royal National Throat, Nose and Ear Hospital, London, UK.
J Laryngol Otol 1999 Feb;113(2):127-34 Abstract quote
Seventy-two patients with juvenile angiofibroma have been investigated by computerized tomography (CT) and/or magnetic resonance imaging (MRI) over a period of 20 years. The evidence from these studies indicates that angiofibroma takes origin in the pterygo-palatine fossa at the aperture of the pterygoid (vidian) canal. An important extension of the tumour is posteriorly along the pterygoid canal with invasion of the cancellous bone of the pterygoid base, and greater wing of the sphenoid (60 per cent of patients). Distinctive features of angiofibroma are the high recurrence rate, and the rapidity with which many tumours recur. It is postulated that the principal determinant of recurrence is a high tumour growth rate at the time of surgery coupled with incomplete surgical excision.
The inability to remove the tumour in toto is principally due to deep invasion of the sphenoid, as described above. In this series 93 per cent of recurrences occurred with this type of tumour extension. A contributory cause in these patients is the use of pre-operative embolization. The treatment implications of these findings are examined.
CLINICAL VARIANTS/GROSS DISEASE CHARACTERIZATION Juvenile nasopharyngeal angiofibroma--a rare case of primary orbital development.
Moschos M, Demetra A, Kontogeorgos G.
Ophthalmology Department, University of Athens, Greece.
Acta Ophthalmol Scand 1998 Aug;76(4):506-8 Abstract quote
PURPOSE: To present a rare case of juvenile nasopharyngeal angiofibroma invading the ophthalmic orbit.
METHODS: The CT scan examination and the ultrasound tomography revealed the existence of a homogeneous solid mass causing distention and erosion of the nasal wall as well as dislocation of the ocular bulbus.
RESULT: The patient was operated, the mass was carefully liberated from its synechiae and it was totally excised with its capsule.
CONCLUSION: A rare case of juvenile nasopharyngeal angiofibroma invading the orbit is presented. The tumor was totally excized and the patient is five years after the operation in good general health without recurrence of the tumor.
EXTRANASAL Extranasopharyngeal angiofibroma.
Huang RY, Damrose EJ, Blackwell KE, Cohen AN, Calcaterra TC.
Department of Surgery, Division of Head and Neck Surgery, UCLA School of Medicine, 10833 Le Conte Avenue, Room 62-132, Los Angeles, CA 90095-1624, USA.
Int J Pediatr Otorhinolaryngol 2000 Nov 30;56(1):59-64 Abstract quote
Juvenile nasopharyngeal angiofibromas are vascular neoplasms, which originate characteristically in the posterior lateral wall of the nasopharynx. Although angiofibromas extend beyond the nasopharynx commonly, they rarely originate outside the nasopharynx. Reports of primary extranasopharyngeal angiofibromas have appeared sporadically in the literature.
We present an unusual case of an angiofibroma arising from the middle turbinate. The clinical characteristics of extranasopharyngeal angiofibromas do not conform to that of nasopharyngeal angiofibromas. Therefore, they can present diagnostic challenges. A methodic evaluation and a high index of suspicion are essential in establishing the proper diagnosis and treatment.
Extranasopharyngeal angiofibroma arising from the nasal septum.
Handa KK, Kumar A, Singh MK, Chhabra AH.
Department of Otorhinolaryngology, All India Institute of Medical Sciences, New Delhi, 110029 India
Int J Pediatr Otorhinolaryngol 2001 Apr 27;58(2):163-6 Abstract quote
Extra nasopharyngeal origin of angiofibroma is very rare. The nasal septum is a very rare site of extra nasopharyngeal angiofibroma with only two cases reported in the medical literature.
We report here a case of a vascular mass arising from the nasal septum of an 8 year old boy. Histopathology confirmed it to be a case of angiofibroma.
A review is also made of the other reported cases of angiofibroma arising from the nasal cavity. The likely theory of origin of the tumor and the management is also discussed.
VULVA
Cellular angiofibroma of the vulva: a clinicopathological study of two cases with documentation of some unusual features and review of the literature.Dargent JL, De Saint Aubain N, Galdon MG, Valaeys V, Cornut P, Noel JC.
Department of Pathology, CHU Saint-Pierre/Institut Jules Bordet, Department of Dermatology, ULB-Hopital Erasme, Brussels, Department of Pathology, CHU de Charleroi, Charleroi, and Department of Pathology, ULB-Hopital Erasme, Brussels, Belgium.
J Cutan Pathol. 2003 Jul;30(6):405-11. Abstract quote BACKGROUND: Cellular angiofibroma (CA) of the vulva is a recently described condition, whose clinical and pathological features are poorly known.
METHODS: We have encountered two cases of this very unusual tumor. Their clinical and pathological features were analyzed and compared to those reported in the literature.
RESULTS: Both patients were middle-aged women. In each case, the lesion had the clinical appearance of a vulvar cyst, located in the lateral aspect of the clitoris and the right labium majus, respectively. Microscopically, the lesions were well circumscribed but not truly encapsulated. Both were composed of small spindle cells arranged in short fascicles and mixed up with relatively abundant small- or medium-sized rounded vessels. While mitotic activity was perceptible in both cases, no cellular atypia could be demonstrated. A striking feature seen in one case was the presence of pseudoangiomatous changes in the stroma, similar to those occasionally found in spindle cell lipoma. Phenotypically, the tumor cells consistently expressed vimentin, CD99, and both estrogen and progesterone receptors. A discrete CD34 or smooth muscle actin immunoreactivity was also found in one case. No expression of S-100 protein, Bcl-2 protein, CD117 (c-kit gene product), epithelial membrane antigen, desmin, or h-caldesmon could be demonstrated.
CONCLUSION: This study further illustrates that CA of the vulva has distinct clinical and pathologic features that set it apart from the other soft tissue conditions involving this area. However, like many soft tissue neoplasms, this tumor also exhibits some variation in its histological or immunohistochemical features.
HISTOPATHOLOGY CHARACTERIZATION CELLULAR
- Cellular Angiofibroma: Clinicopathologic and Immunohistochemical Analysis of 51 Cases.
Iwasa Y, Fletcher CD.
From the daggerDepartment of Pathology, Brigham and Women's Hospital and Harvard University Medical School, Boston, Massachusetts, U.S.A.; and *Kyoto University Hospital, Kyoto University, Kyoto, Japan.
Am J Surg Pathol. 2004 Nov;28(11):1426-1435. Abstract quote
Cellular angiofibroma is a recently described histologically distinctive benign mesenchymal neoplasm composed of 2 principal components, the cellular spindle cell component and prominent stromal blood vessels. Cases in males have sometimes been called "angiomyofibroblastoma-like tumor."
We describe a series of 51 cases of cellular angiofibroma to further characterize its clinicopathologic and immunohistochemical features. There were 26 women and 25 men, ranging in age from 22 to 78 years (mean 53.5, median 52 years). Men tended to be older than women. Tumor size ranged from 0.6 to 25.0 cm (overall median size 3.9 cm, median in women 2.7 cm, median in men 6.7 cm). Most common sites were the vulvovaginal region (22 cases) and the inguinoscrotal region (19 cases). Preoperative duration (known for 25 patients) ranged from 1 week to 5 years, with presentation as a painless mass, except for 1 case each with intermittent genital bleeding and a painful mass. Most lesions were located primarily in subcutaneous tissue. Most cases were grossly well marginated. Two cases showed foci of hemorrhage and 1 case showed foci of necrosis.
Microscopically, 41 tumors were well circumscribed, and 2 tumors infiltrated into the surrounding tissue. All tumors consisted of bland, spindle-shaped cells, short bundles of wispy collagen and numerous small- to medium-sized thick-walled vessels. Intralesional fat was present in 12 cases (6 female and 6 male cases). Mild cytologic atypia (5 cases) and frequent mitoses (3 cases) were infrequent; significant nuclear atypia and abnormal mitoses were absent.
By immunohistochemistry, 29 of 48 tumors (60%) expressed CD34, 10 of 48 (21%) SMA, 4 of 48 (8%) desmin, but none expressed S-100 protein.
Follow-up information was available for 40 patients (range 4-168 months; mean 31.2 months) and no patient has developed recurrence or metastasis to date.
SPECIAL STAINS/
IMMUNO-HISTOCHEMISTRYCHARACTERIZATION Nasopharyngeal angiofibroma: an immunohistochemical study of 32 cases.
Beham A, Fletcher CD, Kainz J, Schmid C, Humer U.
Institute of Pathology, University of Graz Medical School, Austria.
Virchows Arch A Pathol Anat Histopathol 1993;423(4):281-5 Abstract quote
Thirty-two cases of nasopharyngeal angiofibroma, including 2 recurrences, all of which had been excised from males between 7 and 25 years, were subjected to systematic immunohistochemical study.
Most of the tumour vessels, which lacked elastic laminae, were characterized by vascular walls of irregular thickness and variable muscle content. In places endothelial cells were only separated from the stroma by a single attenuated layer of contractile cells, whereas elsewhere the same vessel walls showed pad-like thickenings of their muscle coat. All cells of the vessel walls showed immunoreactivity for vimentin and smooth muscle actin, whereas desmin-positive cells were present only in small numbers in some vessels, generally those with thicker muscle coats.
The stromal cells were decorated by vimentin antibodies only; however, in some more fibrotic hyaline areas the stromal cells displayed also reactivity for smooth muscle actin. In most cases S-100 protein-staining disclosed many nerves, and this accentuated their parital distortion by tumour tissue.
Our findings provide an extended insight to the morphology of angiofibromas at this site, particularly highlighting the irregularity of their vascular walls, which, taken together with the lack of elastic laminae and elastic stromal fibres, can be held responsible for the typical pronounced tendency for haemorrhage in these lesions.
Expression of CD34-antigen in nasopharyngeal angiofibromas.
Beham A, Regauer S, Beham-Schmid C, Kainz J, Stammberger H.
Institute of Pathology, University of Graz Medical School, Austria.
Int J Pediatr Otorhinolaryngol 1998 Aug 1O;44(3):245-50 Abstract quote
Formalin-fixed, paraffin-embedded and frozen tissues of 24 patients with primary nasopharyngeal angiofibroma, of whom seven had recurrences, were studied immunohistochemically for the expression of CD34 antigen using two different antibodies (HPCA-1 and QBEND 10).
In all cases, there was an exclusive staining of endothelial cells, while pericytes, smooth muscle cells and stromal fibroblasts were not reactive. The staining intensity, however, was more pronounced in small tumor vessels of capillary- and sinusoidal-type than in larger vessels, which were usually characterized by an irregular smooth muscle coat. This differential staining indicates an increased proliferative potential of the endothelium of the small vessel component of nasopharyngeal angiofibroma (neoangiogenesis) and an inhibitory influence of vascular smooth muscle cells on endothelial cell growth. Moreover, the positive immunoreaction of all endothelial cells for CD34 is indicative of the absence of lymphatic vessels, which confirms previous ultrastructural observations. No differences in the staining pattern were observed between primary versus recurrent tumors, formalin fixed, paraffin embedded versus snap-frozen acetone fixed material, or between both CD34 antibodies.
Our findings indicate that nasopharyngeal angiofibroma is a vasoproliferative malformation.
Expression of androgen receptors in nasopharyngeal angiofibroma: an immunohistochemical study of 24 cases.
Hwang HC, Mills SE, Patterson K, Gown AM.
Department of Pathology, University of Washington, Seattle, USA.
Mod Pathol 1998 Nov;11(11):1122-6 Abstract quote
Angiofibromas are uncommon benign tumors that typically occur in the lateral portion of the nasopharynx of adolescent boys. Numerous reports showed indirect evidence for the presence of sex-hormone receptors, i.e., androgen (AR), estrogen (ER), and progesterone (PR) receptors, in these tumors.
The goal of the current study was to show direct evidence of sex hormone receptor expression in angiofibromas with use of sensitive immunocytochemical techniques and to document which cell populations express the receptor. Twenty-four nasopharyngeal angiofibromas were obtained from archived tissue, and immunocytochemical studies were performed with antibodies to AR, PR, and ER. Positive stromal and endothelial nuclear immunostaining, implying the presence of ARs, was seen in 18 (75%) of 24 cases, whereas 2 (8.3%) of 24 cases were positive with antibodies to PR. None of the 24 cases examined was positive with antibodies to ER.
These results provide the first direct evidence for the presence of ARs in angiofibromas, which might help to explain the unique clinicopathologic features of these tumors.
ELECTRON MICROSCOPY Immunohistochemical and electron microscopical characterization of stromal cells in nasopharyngeal angiofibromas.
Beham A, Kainz J, Stammberger H, Aubock L, Beham-Schmid C.
Institute of Pathology, University of Graz Medical School, Austria.
Eur Arch Otorhinolaryngol 1997;254(4):196-9 Abstract quote
Twenty-eight cases of nasopharyngeal angiofibroma were studied immunohistochemically for cytoskeletal phenotyping of stromal cells.
Electron microscopy was also used to study the ultrastructure of five of the tumors. All typical stromal cells showed intensive immunostaining for vimentin, but were negative for smooth muscle actin and desmin.
Ultrastructurally, most of these cells appeared to be exclusively fibroblasts. However, in some areas stromal cells were seen that morphologically resembled myofibroblasts by their shapes and arrangement, and were characterized by the coexpression of vimentin and smooth muscle actin. Electron microscopy confirmed their myofibroblastic nature. The present study showed that the typical stromal cells in nasopharyngeal angiofibromas were fibroblasts and not myofibroblasts. In these tumors myofibroblasts occurred only focally, in connection with fibrotic areas and exclusively as a vimentin+/actin+cytoskeletal phenotype.
This indicates that myofibroblasts are not primary stromal tumor cells in nasopharyngeal angiofibromas, but occur due to regressive changes.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES Fibrosed nasal polyp Uncommon in patients <20 years
Do not produce anterior bowing of the posterior wall of the maxillary sinus
No prominent vascularity on angiographic examination
Muscular vessels in stromaAngiectatic nasal polyps that clinically simulate a malignant process: report of 2 cases and review of the literature.
Yfantis HG, Drachenberg CB, Gray W, Papadimitriou JC.
Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.
Arch Pathol Lab Med 2000 Mar;124(3):406-10 Abstract quote
BACKGROUND: Approximately 5% of inflammatory or allergic sinonasal polyps develop extensive vascular proliferation and ectasia with deposition of pseudoamyloid. These so-called angiectatic nasal polyps (ANPs) can grow rapidly and exhibit an aggressive clinical behavior that could simulate malignancy preoperatively.
OBJECTIVE: To systematically address the differential histologic diagnosis of ANPs.
METHODS: We evaluated by light microscopy, immunohistochemistry, and electron microscopy biopsy and resection specimens from 2 large ANPs (8 and 10 cm in diameter) that presented in 2 adult men with life-threatening epistaxis and facial deformity, respectively.
RESULTS: The tumors were firm, lobulated, and covered by smooth, partially ulcerated mucosa. Histologically, clusters of dilated, thin-walled blood vessels embedded in pools of Congo red-negative eosinophilic material, associated with patchy necrosis and atypical stromal spindle cells, were seen. Electron microscopy and immunohistochemistry (CD34, factor VIII) confirmed the endothelial nature of the cells lining the spaces, whereas the atypical stromal cells were classified as myofibroblasts.
CONCLUSIONS: These 2 cases represent extreme examples of ANPs that clinically simulate a malignant process. Awareness of the histological features of ANPs should prevent confusion of such lesions with other vascular or spindle cell lesions of the nasopharynx that would require different treatment and carry a different prognosis.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS Staging and treatment of nasopharyngeal angiofibroma.
Ochoa-Carrillo FJ, Carrillo JF, Frias M.
Division of Surgery, Instituto Nacional de Cancerologia, Mexico City, Mexico.
Eur Arch Otorhinolaryngol 1997;254(4):200-4 Abstract quote
To analyze the prognostic value of clinical-radiologic staging, morbidity, mortality and results of treatment used in the Instituto Nacional de Cancerologia, Mexico, a retrospective study of angiofibroma was performed.
Charts were reviewed from patients who attended the institute from 1977 to 1993. History and physical examination, rhinoscopy and fiber-optic nasopharyngolaryngoscopy were done in every patient. Radiologic evaluation was done with computed tomography, after which Chandler's staging system was used. Disease-free interval curves were estimated for patients who had presented with stage III or IV tumors. Thirty-one patients were treated with surgery and/or radiotherapy. Most of the patients had stage III (70.9%) or stage JV (25.8%) disease. Surgical procedures included lateral rhinotomies (15 cases), transpalatal dissections (11 cases), transantral degloving (3 cases), median rhinotomies (2 cases), infratemporal transzygomatic dissections (2 cases), frontotemporal craniotomy (1 case) and suprahyoid pharyngotomy (1 case). Radiotherapy (as 3000-5500 cGy) was administered to 16 patients: 7 patients with stage III persistent or recurrent tumor and 8 patients as initial treatment for stage IV disease. The disease-free interval of patients with stage III and IV disease was 80.3% and 19%, respectively, after 36 months of follow-up.
Findings demonstrated that surgery was the treatment chosen in patients with stage II and III disease, with low morbidity and mortality, and good results in disease control. In contrast, radiotherapy was usually the treatment in stage IV disease, but had low effectiveness, indicating the need to carefully investigate the value of craniofacial approaches in these tumors.
RECURRENCE Long-term follow-up of juvenile nasopharyngeal angiofibromas: analysis of recurrences.
Herman P, Lot G, Chapot R, Salvan D, Huy PT.
Department of Ear, Nose, and Throat Medicine, Hopital Lariboisiere, Paris, France.
Laryngoscope 1999 Jan;109(1):140-7 Abstract quote
OBJECTIVES: Juvenile nasopharyngeal angiofibroma often recurs if the tumor is large. This report is a long-term follow-up of these cases. It establishes the prognostic values of tumor extensions, analyzes the anatomic factors involved in recurrences, describes the spontaneous evolution of remnants based on a radiographic follow-up, and evaluates the pertinence of complex combined surgical approaches for invasive tumors and the value of complementary endoscopy.
STUDY DESIGN: Retrospective review of 44 cases treated between 1985 and 1996.
METHODS: Statistical analysis of the correlation between recurrence and tumor extension as evaluated by systematic analysis of 18 putative tumor extensions on preoperative computed tomography scans.
RESULTS: Invasion of the skull base affected two-thirds of the patients, and the rate of recurrence was 27.5%. Extensions to the infratemporal fossa, sphenoid sinus, base of pterygoids and clivus, the cavernous sinus (medial), foramen lacerum, and anterior fossa were correlated with more frequent recurrence. Long-term radiographic follow-up revealed putative residual disease in nine asymptomatic patients: these remnants gradually involuted.
CONCLUSIONS: The data in the current study emphasize the prognostic value of skull base invasion and the difficulty of complete resection of extended lesions. Tumor remnants detected in symptom-free patients should be kept under surveillance by repeated computed tomography scan, since involution may occur. Recurrent symptoms may be treated by radiotherapy (30 Gy) rather than by extended combined procedures. Endoscopic surgery should be combined with surgery for better control of skull base extensions.
Recurrence and its avoidance in juvenile angiofibroma.
Howard DJ, Lloyd G, Lund V.
Institute of Laryngology & Otology, University College London, UK.
Laryngoscope 2001 Sep;111(9):1509-11 Abstract quote
OBJECTIVE: Angiofibroma is a highly vascular lesion for which a wide range of surgical approaches has been recommended. Irrespective of the approach, a significant and often rapid recurrence rate is reported in all major series.
AIM: To consider the impact of lessons learned from imaging on the recurrence rate of angiofibroma.
MATERIAL AND METHODS: From a cohort of 90 male patients with histologically proven angiofibroma, 40 individuals were studied. The recurrence rate in 20 cases treated before March 1998 was compared with that in 19 cases treated thereafter. In the latter group, an additional exploration of the basisphenoid had been undertaken.
RESULTS: The two cohorts were comparable in age range (7-27 y and 11-24 years, respectively), and all had been treated by midfacial degloving. In the first group, 8 recurrences occurred which were multiple in 1 patient. In the next 19 patients, the area of the pterygoid canal was meticulously explored and the basisphenoid drilled to remove all residual tumor. No recurrences have occurred in this group during a follow-up of between 6 months to 3 years.
CONCLUSION: Meticulous removal of angiofibroma infiltrating the pterygoid canal and basisphenoid is paramount to avoid "recurrence."
TREATMENT
- Endoscopic Resection of a Juvenile Angiofibroma: The Role of the XPS Microdebrider.
Thornton M, Mahesh BN, Lang J.
Department of Otolaryngology, University College Hospital Galway, Galway, Ireland.
J Laparoendosc Adv Surg Tech A. 2005 Apr;15(2):194-6. Abstract quote
Juvenile angiofibromas are vascular tumors found almost exclusively in the adolescent male. Although benign, their clinical course can be aggressive and can result in major morbidity and mortality.
Endoscopic transnasal resection of juvenile angiofibromas, confined to the nose, paranasal sinuses, pterygopalatine fossa, and medial infratemporal fossa, has been a significant advance in their management, eliminating or reducing the need for extensive soft tissue and bony dissection of traditional surgical approaches.
We discuss a case of a juvenile angiofibroma resected transnasally using the XPS microdebrider (Medtonic Xomed, Jacksonville, Florida) and outline the role of this instrument in this surgery.Endoscopic treatment of juvenile nasopharyngeal angiofibroma.
Newlands SD, Weymuller EA Jr.
Department of Surgery, University of Mississippi Medical Center, Jackson 39216-4505, USA
Am J Rhinol 1999 May-Jun;13(3):213-9 Abstract quote
Traditional treatment of juvenile nasopharyngeal angiofibromas (JNAs) has included open surgical approaches for the majority of tumors. At the University of Washington Medical Center (UWMC), endoscopic techniques have been used for the removal of some small JNAs.
This report describes the institutional experience in treating these tumors. The medical records of 15 patients at UWMC treated over a 15-year period for JNA were reviewed. Three patients were treated only by an endoscopic approach, and one patient had a combined endoscopic and open procedure. All three of the patients treated only by the endoscopic approach were disease free with a minimum of 24 months follow up. The one patient treated with a combined endoscopic and open approach had recurrence of disease.
Endoscopic removal after embolization effectively treated three patients with early stage JNAs. Indications for this procedure are discussed.
Diagnosis and treatment of juvenile nasopharyngeal angiofibroma.
Paris J, Guelfucci B, Moulin G, Zanaret M, Triglia JM.
Department of Oto-Laryngology, Head and Neck Surgery, La Timone University Hospital Center, Boulevard Jean Moulin, 13385 Marseille, France.
Eur Arch Otorhinolaryngol 2001 Mar;258(3):120-4 Abstract quote
The aim of this retrospective study was to compare clinical and radiological findings and discuss optimal surgical approach in patients with juvenile nasopharyngeal angiofibroma (JNA).
Forty-three cases of JNA were treated at our institution from 1975 to 1999. Thirty-three male patients aged between 8 and 25 years (mean 15.3) were included. Twenty-nine patients underwent primary surgical treatment at our institution and four were treated for recurrence following primary surgery elsewhere. Tumors were staged according to Fisch's staging. Preoperative embolization was performed in 22 cases. Surgical techniques consisted of the transantral approach, lateral rhinotomy approach, transmaxillary via midfacial degloving approach, and the subtemporal preauricular infratemporal fossa approach. Tumors were classified stage I in seven cases, stage II in 11, stage III in 13 and stage IV in two. The mean delay between the initial symptom and surgery was 14 months overall, 18 months for stage I, 14 for stage II, 13 for stage III and 12 for stage IV. The transantral approach was used in 11 patients, lateral rhinotomy approach in 11 cases, transmaxillary via midfacial degloving approach in three patients, and pre-auricular infra-temporal approach in eight patients. Mean follow-up after surgery was 56 months. Six patients had recurrent tumors. Surgery is the gold standard for treatment of JNA. Modern imaging techniques allow accurate diagnosis and staging of JNA.
Our experience and a review of the literature shows that the surgical approach should be selected according to tumor stage.
Long-term results of radiation therapy for juvenile nasopharyngeal angiofibroma.
Reddy KA, Mendenhall WM, Amdur RJ, Stringer SP, Cassisi NJ.
Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL, USA.
Am J Otolaryngol 2001 May-Jun;22(3):172-5 Abstract quote
PURPOSE: To analyze 15 patients treated with radiation therapy for juvenile nasopharyngeal angiofibroma (JNA) between June 1975 and March 1996.
MATERIALS AND METHODS: All patients had a 2.5-year minimum follow-up. All patients had advanced disease (Chandler stage III or stage IV); two thirds of the patients had intracranial extension.
RESULTS: Local control after radiotherapy was obtained in 13 of 15 patients (85%). Two patients had local recurrences, and both were salvaged with surgery for an ultimate local control rate of 100%. Late complications included cataracts in 3 patients, delayed transient central nervous system (CNS) syndrome in 1 patient, and a basal cell carcinoma of the skin in 1 patient. Of 15 patients, 13 (85%) had a complete response (CR) on physical examination following radiation therapy. The median time to CR was 13 months (range, 1 to 39 months). Of 6 patients with residual disease in more than 24 months, 2 (33%) had a recurrence, whereas no patient achieving CR in less than 24 months experienced a recurrence.
CONCLUSIONS: Radiotherapy is an effective treatment for advanced JNA. Tumor regression usually occurs slowly over several months. JNAs that are slow to regress (greater than 2 years) may have an increased risk of recurrence.
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