CYP1A1 immunohistochemistry is highly specific for angiofibroma of soft tissue among morphological mimics.

AIMS: Angiofibroma of soft tissue (AFST) is a benign, morphologically distinctive tumour type that harbours recurrent AHRR::NCOA2 fusions in 60-70% of cases and shows a non-specific immunophenotype, expressing EMA in roughly half of cases. The AHRR::NCOA2 fusion results in increased expression of cytochrome P450 1A1 (CYP1A1); a recent study demonstrated CYP1A1 immunohistochemistry (IHC) to be moderately sensitive and highly specific for AFST. METHODS AND RESULTS: In this study, we sought to validate these findings in a larger independent cohort of 30 AFST, as well as 215 morphological mimics, including 30 solitary fibrous tumours, 29 myxoid liposarcomas, 28 low-to-intermediate grade myxofibrosarcomas (MFS), 20 atypical spindle cell lipomatous tumours (ASCLT), 20 cellular angiofibromas, 10 cases each of spindle cell lipoma, neurofibroma, malignant peripheral nerve sheath tumour, superficial angiomyxoma, cellular myxoma, soft tissue perineurioma and deep fibrous histiocytoma, and nine cases each of low-grade fibromyxoid sarcoma and mammary-type myofibroblastoma. We found CYP1A1 IHC to be 70% sensitive for AFST, with granular cytoplasmic staining in 21 of 30 tumours, and 98% specific, with staining in only five morphological mimics: two deep fibrous histiocytomas, one MFS, one cellular angiofibroma and one ASCLT. CONCLUSIONS: These findings confirm that CYP1A1 is 70% sensitive, consistent with the prevalence of AHRR::NCOA2 fusions that up-regulate this protein, and that it is highly specific among morphological mimics.

Para testicular cellular angiofibroma (AF)/angiomyofibroblastoma (AMF)-like tumor: A case report of a rare diagnosis in an elderly male.

Cellular angiofibroma (AF)/Angiomyofibroblastoma (AMF)-like tumor is a rare benign mesenchymal neoplasm. It is very challenging to distinguish benign versus malignant mass radiologically. It is of paramount importance to distinguish Cellular Angiofibroma (CAF) microscopically from its differential diagnoses. A 64-year-old man presented with scrotal swelling. Pathological examination showed features of cellular AF/AMF- like tumor, which shows positivity for CD34, with negativity for S-100 Protein, smooth muscle actin and desmin.

FGFR3 and FGFR4 overexpression in juvenile nasopharyngeal angiofibroma: impact of smoking history and implications for personalized management.

Lifestyle factors, including smoking, have been linked to neoplastic diseases, and reports suggest an association between smoking and overexpression of FGFR (fibroblast growth factor receptor) in certain neoplasms. This study aims to assess the expression of FGFR3 and FGFR4 genes in patients with and without a history of smoking.A total of 118 participants were recruited, including 83 Juvenile Nasopharyngeal Angiofibroma (JNA) patients and 35 healthy participants, the JNA patients were further stratified as smokers and nonsmokers. Total RNA was extracted from the blood & saliva sample by using TRIzol reagent, and quantified using a Nanodrop, and then subjected to gene expression analysis of FGFR3/4 using RT-PCR. Immunohistochemistry analysis was employed using fresh biopsies of JNA to validate the findings. All experiments were performed in triplicates and analysed using the Chi-Square test (P < 0.05). Smokers exhibited significantly lower total RNA concentrations across all sample types (P < 0.001). The study revealed significant upregulation of both FGFR3/4 genes in JNA patients (P < 0.05). Moreover, FGFR3 expression was significantly higher among smokers 66% (95% CI: 53-79%) compared to non-smokers 22% (95% CI: 18-26%). Immunohistochemistry analysis demonstrated moderate to strong staining intensity for FGFR3 among smokers. The study highlights the overexpression of FGFR3/4 genes in JNA patients, with a stronger association observed among smokers. Furthermore, medical reports indicated higher rates of recurrence and bleeding intensity among smokers. These findings emphasize the potential role of FGFR3 as a key molecular factor in JNA, particularly in the context of smoking.

Tuberous Sclerosis Complex in a 17-month-old: A Case Report.

Tuberous sclerosis complex is a rare autosomal dominant genetic disorder that affects multiple organ systems, primarily affecting the central nervous system. It develops with a pathogenic mutation in tumour suppressor genes i.e. Tuberous Sclerosis Complex 1 or Tuberous Sclerosis Complex 2 which codes for protein hamartin and tuberin leading to unopposed hyperactivation of the mammalian target of the rapamycin signalling pathway. It presents with a triad of facial angiofibroma, intellectual disability, and epilepsy. We present a case of a 17-month female toddler with abnormal body movement with loss of consciousness and later developing into generalised jerky movements. On magnetic resonance imaging, a diagnosis of tuberous sclerosis was made. The patient underwent symptomatic management with anti-epileptic. As seizures in these cases are subtle, they remain undiagnosed for a long time leading to delays in management and developing refractory seizures. Keywords: angiofibroma; case reports; seizures; tuberous sclerosis; tumor suppressor gene.

Neural Crest Stem Cells in Juvenile Angiofibromas.

The etiology of juvenile angiofibroma (JA) has been a controversial topic for more than 160 years. Numerous theories have been proposed to explain this rare benign neoplasm arising predominately in adolescent males, focusing mainly on either the vascular or fibrous component. To assess our hypothesis of JA's being a malformation arising from neural crest cells/remnants of the first branchial arch plexus, we performed immunohistochemical analyses of neural crest stem cells (NCSC) and epithelial-mesenchymal transition (EMT) candidates. Immunoexpression of the NCSC marker CD271p75 was observed in all investigated JA's (n = 22), mainly around the pathological vessels. Close to CD271p75-positive cells, high MMP3-staining was also observed. Additionally, from one JA with sufficient material, RT-qPCR identified differences in the expression pattern of PDGFRß, MMP2 and MMP3 in MACS®-separated CD271p75positive vs. CD271p75 negative cell fractions. Our results, together with the consideration of the literature, provide evidence that JA's represent a malformation within the first branchial arch artery/plexus remnants deriving from NCSC. This theory would explain the typical site of tumor origin as well as the characteristic tumor blood supply, whereas the process of EMT provides an explanation for the vascular and fibrous tumor component.

Cellular angiofibroma arising in the anorectal region: clinicopathologic and immunohistochemical analysis of five cases.

Cellular angiofibroma (CA) is a rare, benign mesenchymal tumor with a predilection to the distal female and male genital tract. Extragenital examples of CA, including anorectal CAs, are exceedingly rare and documented mainly as single case reports. Herein, we analyze the clinicopathological and immunohistochemical features of 5 anorectal CAs. There were 4 males and one female ranging in age from 45 to 70 (median, 58) years at the time of surgery. Tumors arose in the superficial tissues of the anorectal (n = 3) and perianal (n = 2) regions. The tumors were well circumscribed ranging from 2 to 6.7 (median, 5.4) cm. All demonstrated a low to moderately cellular proliferation of cytologically bland spindled cells within a variably dense collagenous and focally myxocollagenous stroma and small- to medium-sized vessels featuring perivascular collagen deposition. Two cases showed degenerative and/or inflammatory changes. All 5 tumors strongly expressed CD34 and androgen receptor proteins, more variably expressed estrogen (n = 5) and progesterone (n = 4) receptor proteins and desmin (n = 3), and focally expressed alpha-smooth muscle actin (n = 3), GATA-3 (n = 2), and p16 (n = 1). Retinoblastoma protein expression was reduced (n = 4) (compared with expression in endothelial cells) or completely lost (n = 1). All patients were treated with simple surgical excision, and the 2 study members with follow-up data showed no evidence of local recurrence over a postoperative follow-up interval of 23 and 73 months. In comparison with conventional genital tract CA, our 5 anorectal CAs occurred mostly in males, were generally less cellular, and appear to follow a similar uneventful clinical course.

Validation of Postoperative Angiofibroma Radionuclide Imaging Study (PARIS) Protocol Using PSMA PET/CT-A Proof of Concept Study.

OBJECTIVES: Juvenile nasopharyngeal angiofibroma (JNA) expresses prostate-specific membrane antigen (PSMA), and PSMA PET/CT scan may be used for its imaging. Also, the precise diagnosis of residual/recurrent JNA after surgical treatment remains difficult with conventional contrast MRI and/or CT; functional imaging with PSMA PET/CT promises greater accuracy in the detection or exclusion of recurrent/residual JNA. PATIENTS AND METHODS: In this prospective study, 22 postoperative JNA patients who underwent a PSMA PET/CT scan both preoperatively and postoperatively from January 2018 to September 2020 were included. All patients underwent a low-dose head and neck spot PET/CT imaging. Abnormal postcontrast enhancement of a definite lesion was considered residual/recurrent tumor in contrast-enhanced MRI (CEMRI). In PSMA PET/CT, any abnormal uptake apart from physiological sites in the head and neck was considered as residual lesions. Radiological results were categorized as negative, suspicious for residual lesions, or definite residual/recurrent tumors. PSMA PET/CT findings were considered as the radiological standard, and patients were managed accordingly. The sensitivity, specificity, positive predictive value, and negative predictive value were separately calculated for CEMRI and PSMA PET/CT for diagnosing residual lesions. RESULTS: On postoperative CEMRI evaluation, 12 patients had residual tumors, 2 had normal suspicious scans, and 8 had normal postoperative scans. On PSMA PET/CT, only 7 patients had residual tumors and 15 had normal postoperative scans. In 1 patient with a residual tumor on both scans, a discrepancy was noted concerning tumor extent, and PSMA PET/CT accurately mapped the tumor. The sensitivity, specificity, positive predictive value, and negative predictive value of CEMRI were 100%, 53.33%, 41.67%, and 100%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of PSMA PET/CT were 100% for all parameters. CONCLUSIONS: Because CEMRI is oversensitive and less specific compared with PSMA PET/CT, Postoperative Angiofibroma Radionuclide Imaging Study (PARIS) protocol should be used always. In residual tumors, PSMA PET/CT has an outright advantage over CEMRI in the diagnosis, tumor mapping, decision making, planning stereotactic radiation, and aiding in future follow-ups.

Histopathological characteristics and CD163 immunostaining pattern in fibrous papule of the face.

BACKGROUND: Signs of inflammation including epidermal interface changes, spongiosis, and dermal inflammation as well as pagetoid dyskeratosis are rarely described in fibrous papule (FP). We aimed to describe the inflammatory parameters, the rate of pagetoid dyskeratosis, along with CD163 immunohistochemical staining as an adjunctive diagnostic tool in FP. METHODS: Histopathology samples of all biopsy-proven FP cases were retrieved from archives and investigated for inflammatory parameters, presence of pagetoid dyskeratosis, as well as CD163, CD10, and CD34 immunostaining pattern of dermal spindle/stellate or multinucleate cells (graded from 0 to 4). RESULTS: Thirty-two cases of FP were identified. A high rate of inflammatory parameters including interface changes (20/32), spongiosis (31/32), and dermal lymphocytic inflammation (31/32) were detected. Pagetoid dyskeratosis was identified in eight out of 32 cases (25%). A grade 4 staining revealing a strong dendritic pattern was confirmed in all FP cases with CD163 immunohistochemistry including atypical variants such as granular FP, compared with CD10 (11/32) and CD34 (3/32). CONCLUSION: The dendritic cellular proliferation in FP may represent an inflammatory response to various stimuli; pagetoid dyskeratosis is a relatively common and underrecognized epidermal feature and CD163 immunostaining may be used as an adjunctive diagnostic tool in unusual histopathological subtypes.

Prostate-Specific Membrane Antigen Expression in Primary Juvenile Nasal Angiofibroma-A Pilot Study.

PURPOSE: Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells and is exploited for imaging and treatment of patients with prostate cancer. Prostate-specific membrane antigen expression is also demonstrated in the tumor-associated neovasculature endothelium. Juvenile nasal angiofibroma (JNA), being a similar highly vascular tumor, may also demonstrate significant PSMA expression, which may be utilized for its imaging and treatment. METHODS: In this prospective study, 25 clinicoradiologically diagnosed primary JNA patients underwent PSMA PET/CT scan. The scan was performed after 45 to 60 minutes of intravenous injection of 2 to 3 mCi (74-111 MBq) of Ga-PSMA-HBED-CC on a dedicated PET/CT scanner. Low-dose CT scan was acquired from vertex to sternoclavicular joint (100 mA, 20 kVp, 3-mm slice thickness, 0.8 pitch). Images were reconstructed with iterative reconstruction technique (4 iterations, 24 subsets). The objective was to assess the intensity and pattern of PSMA uptake in primary JNA patients. RESULTS: All cases (n = 25) of primary JNA showed PSMA expression in the tumor (100%). The median PSMA SUVmax ratio of tumor to background was 4.57 (range, 2.08-7.27). Intracranial extension in 14 of 25 patients was prominently visualized because of absence of background uptake in the brain. Advanced stage tumors demonstrated greater uptake than early tumors (P = 0.011). A statistically nonsignificant trend was noted for decreasing uptake with increasing age after normalizing for stage (Spearman correlation coefficient r = -0.08). CONCLUSIONS: Assessment of PSMA expression in JNA by PSMA PET/CT opens up a new window of opportunity with respect to its radiological staging, vascularity assessment, and molecular characterization. A potential role in identification of the difficult residual-recurrent disease is anticipated and perhaps also in radioligand therapy for residual/recurrent JNA.Clinical Trials Registry of India (CTRI/2018/08/015479).

A concise review of angiofibroma of soft tissue: A rare newly described entity that can be encountered by dermatopathologists.

Angiofibroma of soft tissue (AFST) is a newly described, rare mesenchymal neoplasm with fibroblastic and vascular components; it can be seen in both sexes and in a broad age range. It presents as a slowly enlarging mass, most often in the deep tissues of the upper and lower extremities, but occasionally in a superficial location where it may be encountered by dermatopathologists. It has a benign clinical course with a very low probability of recurrence after complete excision. This lesion has a prominent vasculature and may have an infiltrative growth pattern. These features could lead to a misdiagnosis, such as malignant vascular tumor, by an unwary dermatopathologist. The diagnosis of AFST initially relied solely on morphology and immunohistochemistry but, more recently, molecular studies have begun to play a role. Because of the potential for misdiagnosis, we present this review to raise awareness.

The Genetic and Molecular Determinants of Juvenile Nasopharyngeal Angiofibroma: A Systematic Review.

OBJECTIVE: Juvenile nasopharyngeal angiofibroma (JNA) is a rare vascular tumor of unknown etiology. Studies investigating the molecular and genetic determinants of JNA are limited by small sample size and inconsistent approaches. The purpose of this study is to examine all eligible JNA studies in aggregate, applying qualitative analysis to highlight areas of particular relevance, including potential targets for therapeutic intervention. METHODS: The PubMed, MEDLINE, Embase, Web of Science, Cochrane, and CINAHL databases were screened with inclusion and exclusion criteria applied to all citations. Manuscripts investigating the genetic determinants, histopathogenesis, and heritability of juvenile nasopharyngeal angiofibroma were included. Non-English studies, case reports, and articles focusing on clinical management without original data were excluded. Full text articles were obtained. A qualitative synthesis of data was performed. RESULTS: A total of 59 articles met criteria for inclusion. These were divided into 6 categories based on the primary topic or target discussed, (1) steroid hormone receptors, (2) chromosomal abnormalities, (3) growth factors, (4) genetic targets, (5) molecular targets, (6) Wnt cell signaling, and (7) studies that overlapped multiple of the aforementioned categories. Although relatively low n values prevent definitive conclusions to be drawn, a predominance of certain molecular targets such as vascular endothelial growth factor (VEGF) and Wnt/ß-catenin pathway intermediaries is apparent. CONCLUSIONS: Although the etiology of JNA remains elusive, contemporary molecular genetic investigation holds promise for risk stratification and could form the basis of a modernized staging system. A multicenter clinical registry and linked tissue bank would further promote the search for JNA specific biomarkers.

Molecular interactions in juvenile nasopharyngeal angiofibroma: preliminary signature and relevant review.

BACKGROUND: The molecular profile of juvenile nasopharyngeal angiofibroma (JNA) is extremely variable. In absence of established molecular signature the molecular targeting seems difficult for this heterogeneous disease. To establish a basic molecular signature, this paper analyses the interaction of 7 markers according to their ranks as per the decreasing scale of molecular expression. MATERIALS AND METHODS: Fourteen samples of JNA were obtained following surgical excision and mRNA expressions were established through real-time polymerase chain reaction (RT-PCR) for vasculoendothelial growth factor (VEGF), fibroblastic growth factor (FGF), c-Kit, c-myc, Ras, platelet-derived growth factor (PDGF) and tumor suppressor gene p53. Nasal polyp was taken as control. The quantitative expressions for every marker were ranked on a decreasing scale and were compared by Spearman's rank correlation test to define the statistically significant interaction. An attempt was also made to overview the basic clinical parameters (age, duration of symptoms, radiological staging, intraoperative haemorrhage and tumor-volume/weight) associated with enhanced molecular expressions for every marker. RESULTS: Five significant molecular interactions were identified on the basis of rank-correlation: (1) FGF/VEGF (p < 0.01); (2) Ras/FGF (p < 0.01); (3) Ras/VEGF (p < 0.001), (4) FGF/c-Kit (p < 0.05); (5) c-Myc/p53 (p < 0.05). These basic 'molecular signatures' suggested a preliminary 'molecular classification'. The implication of the interactions between FGF, VEGF and Ras were the most outstanding observation that not only revealed a direct relationship but were also consistent with the clinical behaviour. In addition, a non-significant interaction was identified with c-Myc/PDGF and also an inverse relationship between FGF/c-Kit. CONCLUSIONS: FGF, VEGF, and Ras being significantly interrelated seemed to be the 'most soft' molecular targets for JNA. The other targets observed included FGF/c-Kit and c-Myc/p53 interactions that seemed equally important but only after VEGF/FGF/Ras complex per se. These preliminary signatures are likely to provide a background for further expansion of the molecular classification of JNA.

Clinical correlation of molecular (VEGF, FGF, PDGF, c-Myc, c-Kit, Ras, p53) expression in juvenile nasopharyngeal angiofibroma.

BACKGROUND: A molecular surrogate may exist for the clinical behaviour of juvenile nasopharyngeal angiofibroma (JNA). METHODS: In 9-14 cases, a 'correlation' of clinical behaviour with molecular expression (m-RNA expression through RT-PCR) of VEGF, FGF, PDGF, Ras, c-Myc, c-Kit and p53 was undertaken. RESULTS: A comparison of the two extremes of expressions characterized some specific clinical phenotypes for every marker except c-Myc. A higher FGF was associated with post-adolescent presentation, smaller tumour size, enhanced haemorrhage and recurrence. A higher c-Kit was associated with adolescents, rapid growth, skull base involvement and recurrence. Enhanced Ras was associated with post-adolescence, smaller tumour size, skull base involvement and recurrence. Enhanced p53 and PDGF were associated with adolescents, early presentation and rapid progression. Higher VEGF expression was associated with skull base involvement and enhanced haemorrhage. CONCLUSION: This study is currently the only evidence revealing a clinical molecular association in JNA and larger multicentric studies need to be performed to show a statistical significance.

Hypoxia-Inducible Factor-1α (HIF-1α) Expression on Endothelial Cells in Juvenile Nasopharyngeal Angiofibroma: A Review of 70 cases and Tissue Microarray Analysis.

OBJECTIVE: To examine the expression of hypoxia-inducible factor-1α (HIF-1α) and its related molecules (cellular repressor of E1A-stimulated genes [CREG], osteopontin [OPN], proto-oncogene tyrosine-protein kinase Src [c-Src], and vascular endothelial growth factor [VEGF]) in juvenile nasopharyngeal angiofibroma (JNA) and explore the correlation between clinical prognosis and HIF-1α expression. METHODS: The study performed a retrospective review of the clinical records of patients with JNA treated between 2003 and 2007. Specimens were analyzed by immunohistochemistry for HIF-1α, CREG, OPN, c-Src, and VEGF expression, and microvessel density (MVD) was assessed by tissue microarray. The correlation between expression levels and clinicopathological features including age, tumor stage, intraoperative blood loss, and recurrence was analyzed. RESULTS: HIF-1α, CREG, OPN, c-Src, and VEGF were upregulated in endothelial cells (ECs) of patients with JNA, and strong correlations in the expression of these molecules were observed. HIF-1α expression was higher in young patients ( P = .032) and in recurrent cases ( P = .01). Survival analysis showed that low HIF-1α levels in ECs predicted longer time to recurrence (log rank test P = .006). Receiver operating characteristic curve analysis showed that HIF-1α was a prognostic factor for recurrence (area under the curve = 0.690, P = .019). No correlation was found between the expression of molecules and Radkowski stage or intraoperative blood loss. CONCLUSION: In cases of JNA treated surgically, HIF-1α expression in ECs is a useful prognostic factor for tumor recurrence.

Molecular Signature of Tumors with Monoallelic 13q14 Deletion: a Case Series of Spindle Cell Lipoma and Genetically-Related Tumors Demonstrating a Link Between FOXO1 Status and p38 MAPK Pathway.

Spindle cell/pleomorphic lipomas (SCLs), cellular angiofibromas (CAFs) and mammary-type myofibroblastomas (MFBs) are rare benign mesenchymal tumors with monoallelic 13q14 deletion. They are predicted to have a common pathogenic mechanism due to shared similar histological and immunohistochemical features; however, pathological consequences of monoallelic 13q14 deletion remain unknown. We previously reported a CAF case with monoallelic 13q14 deletion in which the tumor expressed decreased levels of FOXO1 and RB1, both of which were encoded in 13q14, and increased reactive oxygen species (ROS) levels. We further demonstrated the activation of p38 mitogen-activated protein kinase (p38 MAPK) pathway induced by oxidative stress. We hypothesized that SCLs, CAFs and MFBs would share common molecular signatures involving FOXO1, ROS and p38 MAPK and that their expression patterns were different from those tumors without monoallelic 13q14 deletion such as solitary fibrous tumors (SFTs). We compared the expression levels of FOXO1, RB1, ROS markers and several signal transduction factors between SCLs and SFTs. SCLs expressed decreased levels of FOXO1 and RB1, whereas SFTs showed no change. Both tumor types exhibited increased markers of ROS; however, nuclear localization of phosphorylated p38 was significantly more frequent in SCLs than that in SFTs, suggesting p38 MAPK activation by oxidative stress. SFTs showed lower p38 MAPK activity and higher ß-catenin expression, implying that oxidative stress was caused by increased cellular proliferation stress. Finally, CAFs and MFBs showed changes similar to those observed in SCLs. Overall, tumors with monoallelic 13q14 deletion showed shared molecular signatures that might be associated with pathogenesis.

Inhibition of fibroblast growth factor receptor with AZD4547 mitigates juvenile nasopharyngeal angiofibroma.

BACKGROUND: Juvenile nasopharyngeal angiofibroma (JNA) is a benign tumor that presents in adolescent males. Although surgical excision is the mainstay of treatment, recurrences complicate treatment. There is a need to develop less invasive approaches for management. JNA tumors are composed of fibroblasts and vascular endothelial cells. We identified fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor (VEGF) expression in JNA-derived fibroblasts. FGFR influences fibroblast proliferation and VEGF is necessary for angiogenesis. We hypothesized that targeting FGFR would mitigate JNA fibroblast proliferation, invasion, and migration, and that targeting the VEGF receptor would attenuate endothelial tubule formation. METHODS: After informed consent, fibroblasts from JNA explants of 3 patients were isolated. Fibroblasts were treated with FGFR inhibitor AZD4547, 0 to 25 µg/mL for 72 hours and proliferation was quantified using CyQuant assay. Migration and invasion of JNA were assessed using 24-hour transwell assays with subsequent fixation and quantification. Mitigation of FGFR and downstream signaling was evaluated by immunoblotting. Tubule formation was assessed in human umbilical vein endothelial cells (HUVECs) treated with vehicle control (dimethylsulfoxide [DMSO]) or semaxanib (SU5416) as well as in serum-free media (SFM) or JNA conditioned media (CM). Tubule length was compared between treatment groups. RESULTS: Compared to control, AZD4547 inhibited JNA fibroblast proliferation, migration, and invasion through inhibition of FGFR and downstream signaling, specifically phosphorylation of - p44/42 mitogen activated protein kinase (p44/42 MAPK). JNA fibroblast CM significantly increased HUVEC tubule formation (p = 0.0039). CONCLUSION: AZD4547 effectively mitigates FGFR signaling and decreases JNA fibroblast proliferation, migration, and invasion. SU5416 attenuated JNA fibroblast-induced tubule formation. AZD4547 may have therapeutic potential in the treatment of JNA.

Current status and clinical association of beta-catenin with juvenile nasopharyngeal angiofibroma.

OBJECTIVE: A possible role of the APC/beta-catenin pathway in the pathogenesis of sporadic juvenile nasopharyngeal angiofibroma has been suggested. This paper presents its current status and clinical association in our patients. METHOD: A prospective observational study was conducted at King George Medical University and Central Drug Research Institute, in Lucknow, India. Western blot analysis was undertaken in 16 cases to examine beta-catenin expression. The clinical details were recorded along with follow up observations, to determine associations. RESULTS: Up-regulation of beta-catenin expression was seen in 69 per cent of cases. The clinical variables did not reveal significant differences between patients with extremes of expression (extreme under- vs over-expression). However, absent expression was shown exclusively in young adults aged over 18 years, while enhanced expression was associated with an altered facial profile. CONCLUSION: Although a beta-catenin association was seen in a subset of our sporadic juvenile nasopharyngeal angiofibroma cases, its expression was not homogeneous. This is in contrast to the Western literature that suggests a universal (homogenous) enhanced expression in the majority. Hence, further research is required to better define its molecular cascade.

Human Papilloma virus in Juvenile Nasopharyngeal Angiofibroma: possible recent trend.

BACKGROUND: Juvenile nasopharyngeal angiofibroma (JNA) has witnessed a four-fold increase in the incidence at our facility in the current decade as compared to the 1980s. With high global incidence of human pappilloma virus (HPV) related oropharyngeal cancer in India, we hypothesize its implication in JNA as it has not yet been reported. METHODS: Clinico-Surgical variables of 6 patients of JNA were included for correlation and their tissue samples were subjected to western blotting (WB), polymerase chain reaction and immunoflorescence to demonstrate a definite association with HPV. In addition 6 control samples (adenoids) underwent WB analysis. OBSERVATIONS: A universal presence of HPV with JNA is novel 'discovery' and has suggested a possibility of a definite association. Only a single case suggested weak infection. None of the controls suggested infection, thus ruling out the presence of HPV in nasopharynx of normal population. INTERPRETATION: With the dawn of this definite association, no specific conclusions can yet be drawn but a whole plethora of questions have emerged with our novel 'discovery'.

Expression of vascular endothelial growth factor in Juvenile Angiofibroma.

OBJECTIVE: To examine Juvenile Angiofibroma (JA) tissue for expression of vascular endothelial growth factor (VEGF), and to explore its relationship with puberty status, stage, recurrence and the intraoperative blood loss. METHODS: Retrospective cohort study of 36 histologically proven cases of JA. Minimum follow up period was 3 years. VEGF expression on tumor cells assessed by immunohistochemistry and graded on two criteria--percentage of cells expressing positivity and the intensity of positivity. These two parameters assessed for impact on puberty status, stage, recurrence, and blood loss. RESULTS: VEGF expression noted on the tumor endothelial cells in 36/36, and on the tumor stromal cells in 34/36. The percentage of cells expressing VEGF and the intensity of expression were not significantly related to puberty status, tumor stage, recurrence, or intra-operative blood loss (p values 0.3-1.0). CONCLUSION: VEGF expression is near universal in JA. Such expression is independent of puberty status and stage, and does not impact on intra operative blood loss and recurrence.