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The spindle cell neoplasms include sinonasal tract angiofibroma (STA), glomangiopericytoma (GPC), and biphenotypic sinonasal sarcoma (BSNS). These entities share some clinical, histomorphologic, immunohistochemical, and even molecular characteristics. Nevertheless, there are features that are unique to each tumor type. STA shows heavily collagenized and vascular stroma, with apparent relationship to underlying hormonal changes. GPC consistently exhibits monomorphic, ovoid cytologic appearance with the constant feature of Beta-catenin nuclear accumulation by IHC. Lastly, BSNS is a deceptively bland and neural-like neoplasm featuring consistent co-expression of S100 and smooth muscle markers with specific genetic rearrangements serving to uniquely characterize this entity., Competing Interests: Disclosures The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The molecular basis and mechanisms of juvenile nasopharyngeal angiofibromas (JNA) pathogenesis are still unknown. Despite being a rare and benign neoplasm, JNA is a locally aggressive and potentially destructive head and neck neoplasm, typically found in young males. The advancement of genome technologies and analytical tools has provided an unparalleled opportunity to explore the intricacy of JNA. The present study provides the first evidence of the involvement of Y-chromosome genes in JNA., Methods: A total of 13 JNA patients at an advanced disease stage and five age-matched male controls were registered for this study. Whole-exome sequencing (WES) analysis was conducted followed by functional analysis to understand the molecular mechanism of the JNA., Results: WES analysis revealed a high prevalence of mutations in 14 genes within the protein-coding, male-specific region of the Y-chromosome of young males (mean age: 13.8 ± 2.4) with JNA. These mutations, occurring at 28 distinct positions, were characterized as moderate to high impact and were prevalent in nine JNA patients but not in the control group. The most frequently mutated genes were USP9Y and UTY, followed by KDM5D, DDX3Y, and TSPY4. The expression of USP9Y, UTY, and DDX3Y was found to be co-modulated, implying their coordinated regulation as a complex. Furthermore, somatic mutations were detected in genes previously linked to JNA., Conclusion: The wide array of genetic mutations in the Y-chromosome male-specific region, along with the somatic alterations identified in JNA, provides novel insights into JNA pathophysiology., (© 2024 Wiley Periodicals LLC.)

Background: Cellular angiofibroma, a rare benign mesenchymal neoplasm, is classified within the 13q/RB1 family of tumors due to morphological, immunohistochemical, and genetic similarities with spindle cell lipoma. Here, genetic data reveal pathogenetic heterogeneity in cellular angiofibroma., Methods: Three cellular angiofibromas were studied using G-banding/Karyotyping, array comparative genomic hybridization, RNA sequencing, and direct cycling sequencing., Results: The first tumor carried a del(13)(q12) together with heterozygous loss and minimal expression of the RB1 gene. Tumors two and three displayed chromosome 8 abnormalities associated with chimeras of the pleomorphic adenoma gene 1 (PLAG1). In tumor 2, the cathepsin B (CTSB) fused to PLAG1 (CTSB::PLAG1) while in tumor 3, the mir-99a-let-7c cluster host gene (MIR99AHG) fused to PLAG1 (MIR99AHG::PLAG1), both leading to elevated expression of PLAG1 and insulin growth factor 2., Conclusion: This study uncovers two genetic pathways contributing to the pathogenetic heterogeneity within cellular angiofibromas. The first aligns with the 13q/RB1 family of tumors and the second involves PLAG1-chimeras. These findings highlight the diverse genetic landscape of cellular angiofibromas, providing insights into potential diagnostic strategies., (© 2024 The Author(s). Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.)

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., (© 2023 John Wiley & Sons Ltd.)

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., (© 2023. The Author(s), under exclusive licence to Institute of Plant Genetics Polish Academy of Sciences.)

Aims: Angiofibroma of soft tissue is a benign soft tissue tumour characterised by bland spindle cells and a distinct branching vascular network. The majority of soft tissue angiofibromas harbour AHRR::NCOA2 gene fusions. Here we present three cases of EWSR1::GFI1B-fused soft tissue tumours that are morphologically most reminiscent of soft tissue angiofibroma., Methods and Results: All three cases presented in male patients with an age range of 35-78 years (median = 54 years). Two cases presented as subcutaneous nodules on the trunk (posterior neck and chest wall); one was an intramuscular foot mass. The tumours were unencapsulated nodules with infiltrative margins ranging from 2.2 to 3.4 cm in greatest dimension. Histologically, the tumours contained uniformly bland fibroblastic spindle cells with ovoid to fusiform nuclei and delicate cytoplasmic processes embedded in a myxoid to myxocollagenous stroma. All three cases were characterised by a thin-walled, branching vascular network evenly distributed throughout the tumour. Overt cytological atypia or conspicuous mitotic activity was absent. The spindle cells had an essentially null immunophenotype. By targeted RNA sequencing, an in-frame gene fusion between EWSR1 exons 1-7 and GFI1B exons 6-11 or 7-11 was detected in all three cases. The tumours were marginally excised. For all three cases, there were no documented local recurrence or distant metastases during a limited follow-up period of 6-10 months., Conclusions: We propose that EWSR1::GFI1B may represent a novel fusion variant of soft tissue angiofibroma., (© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Background: Multiple Endocrine Neoplasia type 1 is a rare genetic syndrome mainly caused by mutations of MEN1 gene and characterized by a combination of several endocrine and non-endocrine manifestations. The objective of this study was to describe cutaneous lesions and other non-endocrine manifestations of MEN1 in a cohort of patients with familial (F) and sporadic (S) MEN1 , compare the prevalence of these manifestations between the two cohorts, and investigate the correlation with MEN1 mutation status., Methods: We collected phenotypic and genotypic data of 185 patients with F- MEN1 and S- MEN1 followed from 1997 to 2022. The associations between F- MEN1 and S- MEN1 or MEN1 mutation-positive and mutation-negative patients and non-endocrine manifestations were determined using chi-square or Fisher's exact tests or multivariate exact logistic regression analyses., Results: The prevalence of angiofibromas was significantly higher in F- MEN1 than in S- MEN1 in both the whole (p < 0.001) and index case (p = 0.003) cohorts. The prevalence of lipomas was also significantly higher in F- MEN1 than in S- MEN1 (p = 0.009) and in MEN1 mutation-positive than in MEN1 mutation-negative (p = 0.01) index cases. In the whole cohort, the prevalence of lipomas was significantly higher in MEN1 mutation-positive compared to MEN1 mutation-negative patients (OR = 2.7, p = 0.02) and in F- MEN1 than in S- MEN1 (p = 0.03), only after adjustment for age. No significant differences were observed for the other non-endocrine manifestations between the two cohorts. Hibernoma and collagenoma were each present in one patient (0.5%) and meningioma and neuroblastoma in 2.7% and 0.5%, respectively. Gastric leiomyoma was present in 1.1% of the patients and uterine leiomyoma in 14% of women. Thyroid cancer, breast cancer, lung cancer, basal cell carcinoma, melanoma, and colorectal cancer were present in 4.9%, 2.7%, 1.6%, 1.6%, 2.2%, and 0.5% of the whole series, respectively., Conclusions: We found a significantly higher prevalence of angiofibromas and lipomas in F- MEN1 compared with S- MEN1 and in MEN1 mutation-positive compared to MEN1 mutation-negative patients. In patients with one major endocrine manifestation of MEN1 , the presence of cutaneous lesions might suggest the diagnosis of MEN1 and a possible indication for genetic screening., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pierotti, Pardi, Dinoi, Piaggi, Borsari, Della Valentina, Sardella, Michelucci, Caligo, Bogazzi, Marcocci and Cetani.)

Aims: Angiofibroma of soft tissue (AFST) is a benign tumour characterised by prominent arborizing blood vessels throughout the lesion. Approximately two-thirds of AFST cases were reported to have AHRR::NCOA2 fusion, and only two cases have been reported to have other gene fusions: GTF2I::NCOA2 or GAB1::ABL1. Although AFST is included in fibroblastic and myofibroblastic tumours in the World Health Organization's 2020 classification, histiocytic markers, especially CD163, have been reported to be positive in almost all examined cases, and it still remains the possibility of a fibrohistiocytic nature of the tumour. Therefore, we aimed to clarify the genetic and pathological spectrum of AFST and identify whether histiocytic marker-positive cells were true neoplastic cells., Methods and Results: We evaluated 12 AFST cases, which included 10 cases with AHRR::NCOA2 and two with AHRR::NCOA3 fusions. Pathologically, nuclear palisading, which has not been reported in AFST, was detected in two cases. Furthermore, one tumour resected by additional wide resection revealed severe infiltrative growth. Immunohistochemical analysis indicated varying levels of desmin-positive cells in nine cases, whereas CD163- and CD68-positive cells were diffusely distributed in all 12 cases. We also performed double immunofluorescence staining and immunofluorescence in situ hybridisation in four resected cases with >10% desmin-positive tumour cells. The results suggested that the CD163-positive cells differed from desmin-positive cells with AHRR::NCOA2 fusion in all four cases., Conclusion: Our findings suggested that AHRR::NCOA3 could be the second most frequent fusion gene, and histiocytic marker-positive cells are not genuine neoplastic cells in AFST., (© 2023 John Wiley & Sons Ltd.)

Angiofibroma of soft tissue (AFST) is a recently described benign fibroblastic neoplasm composed of uniform bland spindle cell proliferation in fibrous and fibromyxoid stroma with prominent thin-walled small branching vessels. A major recurrent genetic abnormality in AFST is t(5;8)(p15;q13), which results in the rearrangement of AHRR and NCOA2 . Owing to a lack of discriminatory IHC markers and potential overlap with other mesenchymal neoplasms, it may be difficult to confirm the diagnosis of AFST in some cases. Triggered by a recent gene expression profile study of AFST, which showed the significant upregulation of AhR/AHRR/ARNT downstream genes (including CYP1A1 ), we used a mouse monoclonal antibody to explore the diagnostic significance of CYP1A1 expression in histologically confirmed AFST cases along with 224 control cases, consisting of 221 neoplastic mimickers and 3 non-neoplastic lesions. We found moderate to strong cytoplasmic expression of CYP1A1 in 13 of 16 AFST cases (sensitivity, 81.3%). In contrast, the vast majority of other examined histologic mimickers exhibited no expression of CYP1A1 (specificity, 97.3%), except for 3 myxofibrosarcomas (3/31), 2 solitary fibrous tumors (2/22), and 2 neurofibroma (1/27). Our results indicate that CYP1A1 immunohistochemistry may aid in the diagnosis of AFST by distinguishing among various kinds of tumors, particularly those harboring prominent vasculature., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Tuberous sclerosis complex (TSC) is a genetic syndrome due to mutations in either TSC1 or TSC2 , leading to the development of hamartomatous tumours at multiple body sites, including facial skin (facial angiofibroma (FAF)), brain (cortical tubers) and kidney (angiomyolipoma (AML)). In this report, we describe an individual with minimal TSC clinical features, who had 'no mutation identified' (NMI) by prior genetic testing in a clinical laboratory. Our massively parallel sequencing (MPS) analysis of multiple samples from different body sites and tumours (including blood, saliva, normal skin, AML and FAF) revealed an extraordinary situation in which FAF and AML had completely independent inactivating biallelic variants in TSC2, not present in other matched samples. This suggests that the two different lesions (AML and FAF) are not due to the same underlying germline or mosaic mutation, rather both are likely sporadic events. This case demonstrates the relevance of thorough clinical examination, high-coverage MPS of multiple tumours and matched normal tissues, and appropriate genetic counselling for individuals with marginal TSC features and possible TSC1 or TSC2 mosaicism., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Angiofibroma of soft tissue (AFST) is a new soft tissue tumor entity described in the 2020 World Health Organization Classification of Soft Tissue and Bone Tumors. It most often arises in the lower extremities of middle-aged adults and pursues a benign clinical course with a low rate of non-destructive local recurrence. Histologically, the lesion consists of uniform bland spindle cells in a fibromyxoid stroma with a prominent vascular network. The vascular component forms a complex arrangement of small, thin-walled branching blood vessels. By immunohistochemistry, AFST is variably positive for epithelial membrane antigen, desmin, smooth muscle actin, CD34, CD68, CD163 and estrogen receptor. The exact etiology of AFST remains unknown, but it appears genetically distinct, with a balanced t(5;8)(p15;q13) translocation resulting in a fusion of aryl hydrocarbon receptor repressor (AHRR) and nuclear receptor coactivator 2 (NCOA2). Knowledge of this recently described entity is important because it can mimic a variety of intermediate and malignant soft tissue tumors, including solitary fibrous tumor, low-grade fibromyxoid sarcoma, myxoid liposarcoma and low-grade myxofibrosarcoma. We review AFST, with an emphasis on the diagnostic spectrum, recent molecular genetic features and the differential diagnosis.

Angiomyofibroblastoma and superficial myofibroblastoma are distinctive benign mesenchymal tumors occurring in the female lower genital tract. Despite their significant overlapping clinicopathologic features, including the presence of bland-looking spindle or oval cells with myofibroblastic or myoid differentiation, the tumors have been regarded as separate entities. Although subepithelial, hormone-sensitive mesenchymal cells of the female lower genital tract are considered as their potential common progenitor cells, their potential kinship or pathogenetic similarities remain elusive. Based on the identification of a novel RNA sequencing-based MTG1-CYP2E1 fusion transcript in an angiomyofibroblastoma index case, we investigated an additional ten samples of the tumor and its site-specific histological mimics, including eight superficial myofibroblastomas, four deep angiomyxomas, four cellular angiofibromas, three fibroepithelial stromal polyps, and eight non-site-specific mesenchymal tumors occurring in the female lower genital tract. Using reverse transcription-polymerase chain reaction, we showed that the MTG1-CYP2E1 fusion transcripts were consistently detectable in angiomyofibroblastomas (5/5, 100%) and often in superficial myofibroblastomas (3/5, 60%) but were not detected in the other examined site-specific or non-site-specific mesenchymal tumors. Our immunohistochemical experiments showed that CYP2E1, an isoenzyme belonging to the cytochrome P450 superfamily, exhibited increased positivity in tumors with MTG1-CYP2E1 than was observed in fusion-negative tumors (RR = 6.56, p = 0.001). The results of our study provide further evidence supporting the assertion that angiomyofibroblastoma and superficial myofibroblastoma represent phenotypic variants of site-specific mesenchymal tumors and share a common oncogenic mechanism., (© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Tuberous sclerosis is a rare autosomal dominant genetic disorder. It is characterized by the appearance of benign tumors, known as hamartomas, which can affect multiple organs, including the skin. Cutaneous manifestations are present in almost all patients; therefore, the dermatologist has a fundamental role in the history and evolution of the disease in spite of being a multisystemic disorder. Two tumor suppressor genes, CET1 and CET2 , involved in tissue growth and cell proliferation, show mutation in this disease, which leads to the appearance of various benign tumors, hamartomas. Clinical characteristics are more than three hypomelanotic macules, more than three angiofibromas or face or scalp cephalic fibrotic plaque, more than two ungual fibromas, shagreen plaque, multiple retinal hamartomas, etc. Treatment is basically symptomatic, and genetic counseling is very important. This is an autosomal dominant disorder, although there is spontaneous mutation and no familial history in 65% of patients. When one of the parents is affected, genetic study is useful for prenatal diagnosis.

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/β-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.

Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome characterized by mostly benign tumors of the brain, skin, heart, kidney, and eye. Aberrations in the genes TSC1 and TSC2 which encode hamartin and tuberin, respectively, cause TSC. Because disease manifestations develop over time, early diagnosis and intervention are imperative for patients. TSC is not well described in patients from sub-Saharan Africa or of black African ancestry. Here, we report on a 4-year-old Nigerian boy with skin lesions and cardiac anomalies associated with TSC. Furthermore, we note that in areas with limited resources for genetic diagnoses, the common skin manifestations found in TSC may be especially useful clinical markers., (© 2019 Wiley Periodicals, Inc.)

Juvenile nasopharyngeal angiofibroma (JNA) is a histopathologically benign and highly vascular neoplasm, which is mainly seen in young adolescent men. It is a rare tumor, accounting for 0.05% of all head and neck neoplasms. The etiology of JNA has always been a controversial topic. Some researchers believe that it is a genuine tumor. Others consider that it is the result of vascular malformation caused by the non-absorption of artery residues in the first branchial arch during development, and that hormone and genetic effects are also related to its etiology. In addition, the JNA was so called because it was previously thought to originate from the nasopharynx. However, the origin site of JNA is not completely clear. Several studies emphasized that it originated from the upper lip of the sphenopalatine foramen at the junction of the sphenoid process of the palate and the pterygoid process, while others stressed that it originated from the pterygoid canal. Thus, further studies are needed for identifying the ultimate origin.

A 27-year-old Hispanic man presented with multiple papules and nodules measuring up to 10 cm in diameter. These lesions were widespread (Figure 1), but not on mucosal epithelium. At birth, the patient had had multiple hypopigmented macules that had progressed to papules and nodules over time. Dermatoscopic examination of these papules and nodules showed prominent capillaries. New lesions were constantly developing but were slow-growing. Other family members had similar lesions, including the patient's three brothers, father, paternal aunt, and a 3-year-old niece (daughter of the 2nd eldest brother), although not as extensively as in this patient. The paternal grandparents were not affected (Figure 2). As the patient had been raised in rural Mexico with limited financial resources, access to health care was limited, so the condition had been left undiagnosed and untreated for most of the patient's life.

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 β-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.

Juvenile nasopharyngeal angiofibroma (JNA) is a highly vascularized and locally aggressive tumor that typically presents in adolescent males. The molecular biology of this tumor remains understudied. We sought to identify differentially expressed genes in the JNA transcriptome through messenger RNA sequencing of primary fibroblasts from 2 tumor explants and tonsil tissue from tumor-free subjects. In total, 1088 significant, differentially expressed genes were identified with 749 upregulated and 339 downregulated. Pathway analysis identified a number of activated signaling pathways, most notably, the vascular endothelial growth factor (VEGF) pathway (adjusted overlap P = .03). VEGF-A showed a 4.4-fold upregulation in JNA samples. In addition, the angiogenic receptor, fibroblast growth factor receptor 2 (FGFR2), was not present in tumor-free samples but increased in JNA. We validate these findings with immunohistochemistry, demonstrating upregulation of VEGF and FGFR2 in patient sections. Inhibition of the VEGF or FGFR signaling axes may have therapeutic potential in the treatment of JNA.

Objective: To investigate the clinicopathologic and genetic features, pathologic diagnosis and differential diagnosis of angiofibroma of soft tissue(AFST). Methods: The clinicopathologic characteristics of 24 cases diagnosed at Fudan University Shanghai Cancer Center from 2011 to 2017 were analyzed; immunohistochemical staining and interphase fluorescence in situ hybridization (FISH) were performed, and the literatures were also reviewed. Results: There were 15 male and 9 female (male∶female=1.7∶1.0) patients with age of onset ranging from 8 to 68 years (mean, 45 years). Fourteen cases occurred in extremities, including upper limbs ( n =3) and lower limbs ( n =11); seven cases were in the trunk, and 1 case each was in the temporal region, retroperitoneum and liver, respectively. Clinically, the tumors usually presented as a slowly growing painless mass. Tumor sizes ranged from 0.8 to 14 cm (mean 4.6 cm). Microscopically, most lesions were well-circumscribed, with fibrous capsules. Few cases infiltrated the surrounding fibrofatty tissue focally. The tumors were mainly composed of sparse short spindle cells and numerous small, branching, thin-walled blood vessels distributed in amyxoid, fibromyxoid or collagenous matrix, often accompanied by medium-sized, round or irregular and ecstatic vessels at the tumor periphery.By immunohistochemistry, all tested cases expressed vimentin (5/5), and showed variable positivity for EMA (2/4), ER (1/2), PR (2/3), α-SMA (1/18)and desmin (1/10). Ki-67 proliferation index were all less than 5%. CD34, CD31 and ERG staining clearly outlined the contours of blood vessels in the stroma. Four cases were tested for NCOA2 gene rearrangement by FISH, of which three were positive. Follow-up data was available in 17 patients (range, 3 to 69 months; mean, 30 months) were all free of disease. Conclusions: Soft tissue angiofibroma is a benign fibroblastic neoplasm characterized by a prominent and complex vasculature set in a myxoid-to-collagenous stroma, and cytogenetically a distinctive NCOA2 gene rearrangement. Caution should be exercised for the possibility of potentially misinterpretation of AFST as vascular tumors and other myxoid soft tissue tumors.

Soft tissue angiofibroma is rare and has characteristic histomorphological and genetic features. For diagnostic purposes, there are no specific antibodies available. Fourteen lesions (6 females, 8 males; age range 7-67 years) of the lower extremities (12) and trunk (2) were investigated by immunohistochemistry, including for the first time NCOA2. NCOA2 was also tested in a control group of other spindle cell lesions. The known fusion-genes (AHRR-NCOA2 and GTF2I-NCOA2) were examined using RT-PCR in order to evaluate their diagnostic value. Cases in which no fusion gene was detected were additionally analysed by RNA sequencing. All cases tested showed nuclear expression of NCOA2. However, this was not specific since other spindle cell neoplasms also expressed this marker in a high percentage of cases. Other variably positive markers were EMA, SMA, desmin and CD34. STAT6 was negative in the cases tested. By RT-PCR for the most frequently observed fusions, an AHRR-NCOA2 fusion transcript was found in 9/14 cases. GTF2I-NCOA2 was not detected in the remaining cases (n = 3). RNA sequencing revealed three additional positive cases; two harbored a AHRR-NCOA2 fusion and one case a novel GAB1-ABL1 fusion. Two cases failed molecular analysis due to poor RNA quality. In conclusion, the AHRR-NCOA2 fusion is a frequent finding in soft tissue angiofibroma, while GTF2I-NCOA2 seems to be a rare genetic event. For the first time, we report a GAB1-ABL1 fusion in a soft tissue angiofibroma of a child. Nuclear expression of NCOA2 is not discriminating when compared with other spindle cell neoplasms., (© 2017 Wiley Periodicals, Inc.)

Background: Molecular categorisation may explain the wide variation in the clinical characteristics of juvenile nasopharyngeal angiofibroma., Methods: Variations in molecular markers in juvenile nasopharyngeal angiofibroma in an Indian population were investigated and compared with global reports., Results: Variable molecular marker expression was demonstrated at the regional and global levels. A wide variation in molecular characteristics is evident. Molecular data have been reported for only 11 countries, indicating a clear geographical bias. Only 58 markers have been studied, and most are yet to be validated., Conclusion: Research into the molecular epidemiology of juvenile nasopharyngeal angiofibroma is still in its infancy. Although the molecular variation is not well understood, data obtained so far have prompted important research questions. Hence, multicentre collaborative molecular studies are needed to establish the aetiopathogenesis and establish molecular surrogates for clinical characteristics.

Objective: An attempt is made to analyze the molecular behavior of juvenile nasopharyngeal angiofibroma (JNA)., Study Design: Case Series METHODS: Quantification of mRNAs expression was undertaken through real-time polymerase chain reaction in JNA (9-24) samples for VEGF-A, basic fibroblast growth factor (b-FGF), platelet-derived growth factor PDGF-A, KIT proto-oncogene receptor tyrosine kinase (c-Kit), Avian myelomatosis viral oncogene homolog (c-Myc), Harvey rat sarcoma viral oncogene homolog (H-Ras), tumor suppressor gene TP53, and androgen receptor and interleukin 6 (IL-6). The β-catenin expression was evaluated by western blot in 16 samples. Nasal polyp was taken as control., Results: A significantly increased (P < 0.01) expression of c-myc, VEGFA, bFGF, PDGFA, c-kit, and TP53 was seen, along with enhanced expression of β-catenin. A massive enhancement of H-Ras expression was seen for the first time. Androgen receptor expression was no different, whereas IL-6 despite showing upregulation trend was not significant., Conclusion: The enhanced expressions of various markers suggest their potential role in JNA. Although the biological significance of c-kit, c-myc, and one of the novel markers H-Ras has yet to be defined, their significant expression may have a therapeutic importance., Level of Evidence: NA. Laryngoscope, 127:E100-E106, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Cellular angiofibroma is a rare benign mesenchymal neoplasm with morphological and immunohistochemical similarities to spindle cell lipoma. Karyotypic information on cellular angiofibroma is restricted to one case only which showed loss of material from chromosomes 13 and 16. A few other studies using fluorescence in situ hybridization showed deletions of the RB1 and FOXO1 loci, both of which are located in chromosome band 13q14. We present here cytogenetic data on two cellular angiofibromas with an abnormal karyotype., Methods: G-banding and fluorescence in situ hybridization (FISH) analyses were done on two cellular angiofibromas., Results: In both tumors, a rearrangement leading to loss of chromosome 13 material was seen, together with other structural chromosome abnormalities. FISH analysis showed heterozygous deletion of the RB1 locus (13q14) in both cases., Conclusion: Our results demonstrate loss of chromosome 13 material in cellular angiofibroma, though not as the sole cytogenetic change, confirming the (cyto)genetic similarity of these tumors with spindle cell lipomas.

Tuberous Sclerosis Complex (TSC) is an autosomal dominant tumor suppressor gene syndrome in which patients develop several types of tumors, including facial angiofibroma, subungual fibroma, Shagreen patch, angiomyolipomas, and lymphangioleiomyomatosis. It is due to inactivating mutations in TSC1 or TSC2. We sought to generate a mouse model of one or more of these tumor types by targeting deletion of the Tsc1 gene to fibroblasts using the Fsp-Cre allele. Mutant, Tsc1ccFsp-Cre+ mice survived a median of nearly a year, and developed tumors in multiple sites but did not develop angiomyolipoma or lymphangioleiomyomatosis. They did develop a prominent skin phenotype with marked thickening of the dermis with accumulation of mast cells, that was minimally responsive to systemic rapamycin therapy, and was quite different from the pathology seen in human TSC skin lesions. Recombination and loss of Tsc1 was demonstrated in skin fibroblasts in vivo and in cultured skin fibroblasts. Loss of Tsc1 in fibroblasts in mice does not lead to a model of angiomyolipoma or lymphangioleiomyomatosis., Competing Interests: The authors have declared that no competing interests exist.

We present an angiofibroma of soft tissue with the karyotype 46,XY,t(4;5)(q24;q31),t(5;8;17)(p15;q13;q21)[8]/46,XY,t(1;14)(p31;q32)[2]/46,XY[3]. RNA‑sequencing showed that the t(4;5)(q24;q31) resulted in recombination of the genes TBCK on 4q24 and P4HA2 on 5q31.1 with generation of an in‑frame TBCK‑P4HA2 and the reciprocal but out‑of‑frame P4HA2‑TBCK fusion transcripts. The putative TBCK‑P4HA2 protein would contain the kinase, the rhodanese‑like domain, and the Tre‑2/Bub2/Cdc16 (TBC) domains of TBCK together with the P4HA2 protein which is a component of the prolyl 4‑hydroxylase. The t(5;8;17)(p15;q13;q21) three‑way chromosomal translocation targeted AHRR (on 5p15), NCOA2 (on 8q13), and ETV4 (on 17q21) generating the in‑frame fusions AHRR‑NCOA2 and NCOA2‑ETV4 as well as an out‑of‑frame ETV4‑AHRR transcript. In the AHRR‑NCOA2 protein, the C‑terminal part of AHRR is replaced by the C‑terminal part of NCOA2 which contains two activation domains. The NCOA2‑ETV4 protein would contain the helix‑loop‑helix, PAS&#95;9 and PAS&#95;11, CITED domains, the SRC‑1 domain of NCOA2 and the ETS DNA‑binding domain of ETV4. No fusion gene corresponding to t(1;14)(p31;q32) was found. Our findings indicate that, in spite of the recurrence of AHRR‑NCOA2 in angiofibroma of soft tissue, additional genetic events (or fusion genes) might be required for the development of this tumor.

Aims: Angiofibroma of soft tissue (AFST) is a rare soft tissue neoplasm characterized by a fibroblastic cytomorphology and a prominent vascular structure. AFSTs possess a novel fusion gene, i.e. NCOA2-AHRR/AHRR-NCOA2 or GTF2I-NCOA2, providing a useful approach to diagnosing AFST. Morphologically, AFSTs span a wide spectrum, making diagnosis a challenge. The aim of this study was to review AFST cases and to report previously unknown histological features, which we confirmed by genetic analysis., Methods and Results: We reviewed 276 cases diagnosed as solitary fibrous tumours/haemangiopericytomas (232 cases), unclassified tumours of fibroblastic differentiation (36 cases), and recently diagnosed AFSTs (eight cases), and retrieved 13 cases compatible with AFST. Immunohistochemical staining was performed for these cases, all 13 of which were analysed by reverse transcription polymerase chain reaction and fluorescence in-situ hybridization. The histological findings were as follows: amianthoid fibres, extravasation of red blood cells, haemosiderin deposition, aggregates of foamy histiocytes, cystic change, necrosis, and haemorrhage. Immunohistochemically, the tumour cells were positive for epithelial membrane antigen (four of 13 cases), desmin (six of 13 cases), CD163 (13 of 13 cases), CD68 (seven of 13 cases), oestrogen receptor (13 of 13 cases), progesterone receptor (three of 13 cases), and STAT6 (one of 13 cases, weak nuclear staining), but they were negative for CD34, α-smooth muscle actin, muscle-specific actin, S100, pan-cytokeratin, MDM2, and CDK4. The AHRR-NCOA2 fusion gene was detected in eight cases, and NCOA2 gene rearrangement in nine cases., Conclusion: We revealed the previously unreported histological variation and immunohistochemical findings of AFST, and confirmed them by using genetic methods. The results suggested that AFST should be considered in the diagnosis of fibrous or fibrohistiocytic tumours with the above histological features., (© 2016 John Wiley & Sons Ltd.)

Juvenile angiofibromas (JAs) are benign fibro-vascular tumors occurring nearly exclusively in adolescent males. Even less is known about this rare tumor entity, alterations affecting the Wnt-pathway seem to play a pivotal role in tumor biology as activating CTNNB1 mutations have been detected. However, the knowledge of Wnt-pathway changes is still limited. Therefore, we aimed to determine in JAs further insight into Wnt/β-catenin pathway components. In our present study, genetic alterations of the Wnt-pathway members CTNNB1, APC, GSK3β, and Axin2 detected by metaphase comparative genomic hybridization (CGH) were shown to result in elevated transcript levels in the majority of JA samples compared to nasal mucosa stroma (p < 0.001, p = 0.001, p = 0.046, and p = 0.006, respectively). Additionally, amplifications of CTNNB1 were validated by fluorescence in situ hybridization (FISH) and genomic qPCR. Moreover, our mutation analysis detected already known mutations as well as, to the best of our knowledge, mutations and an interstitial deletion of CTNNB1 not described in JAs before. Additionally, a so far unknown transcribed Axin2 splice variant was found, but no further Axin2 mutations. Taken together, our current study supports the importance of aberrant Wnt-signaling as a common event in JAs, most likely by the observed genetic alterations driven by mutations, interstitial deletions but also amplifications of CTNNB1 contributing to the stabilization of β-catenin.

Cellular angiofibroma (CAF) is a rare soft tissue tumor characterized by random arrangement of spindle tumor cells in the stroma with short collagen bundles and thick- and hyalinized small vessels. CAFs share histological characteristics with spindle cell lipomas and mammary type myofibroblastomas. Because these tumors harbor monoallelic 13q14, common genetic and molecular mechanism for tumorigenesis is presumed. In this study, we reported a case of CAF in a 69-year-old man with monoallelic 13q14. Immunohistochemical analysis revealed that FOXO1, which is located in chromosome 13q14, was not expressed in the tumor. We also detected oxidative stress markers and found p38 MAPK activation, which is often induced by cellular stressors such as reactive oxygen species (ROS). Because FOXO1 induces the expression of genes encoding enzymes that generate antioxidants, oxidative stress induced by loss of FOXO1 expression may be common among CAFs, spindle cell lipomas, and mammary type myofibroblastomas.

Angiomyofibroblastoma (AMFB) is a benign tumor that belongs to the category of the "stromal tumors of the lower female genital tract," together with cellular angiofibroma and myofibroblastoma. Previous studies have shown overlapping morphologic and immunohistochemical features between these tumors and spindle cell lipoma, mammary-type myofibroblastoma, and vulvovaginal cellular angiofibroma and myofibroblastoma. In addition, typical loss of genetic material from the 13q14 region has been documented in all the above-mentioned tumors, suggesting that they are histogenetically related. We report the clinicopathologic features of 11 new cases of vulvovaginal AMFBs. Histologically, the basic common theme was a proliferation of bland-looking spindle to round-to-epithelioid cells set in an edematous to fibrous stroma, frequently arranged around thin-walled blood vessels. Two cases were composed of a prominent mature fatty component closely admixed with typical areas of AMFB, and thus, they were designated as "lipomatous AMFBs." Notably, 1 case was closely reminiscent of Sertoli cell tumor, sclerosing type, because of its predominant cord-like arrangement. Immunohistochemically, all tumors were diffusely positive for vimentin, whereas desmin and α-smooth muscle actin were expressed in a minority of cases, suggesting a fibroblastic rather than myofibroblastic differentiation. Most cases of AMFBs coexpressed Bcl-2 protein and CD99. Interestingly, all 5 cases of AMFB with evaluable signals failed to show monoallelic loss of FOXO1 loci (13q14) by fluorescence in situ hybridization. These cytogenetic findings suggest that vulvovaginal AMFB is not genetically related to cellular angiofibroma and myofibroblastoma of the lower female genital tract., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Soft tissue angiofibroma (STA), a recently suggested new histologic entity, is a benign fibrovascular soft tissue tumor composed of bland spindle-shaped tumor cells with abundant collagenous to myxoid stroma and branching small vessels. The lesion has a characteristic AHRR-NCOA2 fusion gene derived from chromosomal translocation of t(5;8)(p15;q13). However, morphologically similar tumors containing abundant fibrovascular and myxoid stroma can complicate diagnosis. We designed an original DNA probe for detecting NCOA2 split signals on fluorescence in situ hybridization (FISH) and estimated its utility with 20 fibrovascular tumors: 4 each of STAs, solitary fibrous tumors (SFTs), and cellular angiofibromas and 3 each of low-grade myxofibrosarcomas, myxoid liposarcomas, and low-grade fibromyxoid sarcomas. We also performed FISH for 13q14 deletion and immunohistochemistry (IHC) staining for estrogen receptor, progesterone receptor, retinoblastoma protein, and MUC-4 expression. Furthermore, IHC for Stat6 was conducted in the 20 cases analyzed by FISH and in an additional 26 SFTs. We found moderate to strong nuclear Stat6 expression in all SFTs but no expression in the other tumors. Both estrogen receptor and progesterone receptor expressions were observed in STAs, SFTs, and cellular angiofibromas. Expression of retinoblastoma protein was found in less than 10% of cells in all tumor types except myxoid liposarcoma. The low-grade fibromyxoid sarcomas were strongly positive for MUC-4. All STAs showed NCOA2 split signals on FISH. All tumors, regardless of histologic type, had 13q14 deletion. The NCOA2 FISH technique is a practical method for confirming STA diagnosis. The combination of NCOA2 FISH and Stat6 IHC proved effective for the differential diagnosis of STA, even when using small biopsy specimens., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Angiofibroma of soft tissue is a recently described soft tissue tumor that is characterized by fibroblastic spindle tumor cells with arborizing capillary proliferation. Cytogenetically, it harbors a specific fusion gene involving the nuclear receptor coactivator 2 (NCOA2) gene. We report here additional new pathological and cytogenetic features. A soft tissue tumor in the left thigh of 73-year-old female was investigated. Microscopically, histiocytoid tumor cells were scattered in an edematous background with branching capillary proliferation. Immunohistochemically, we identified that the tumor cells were positive for histiocytic markers such as CD68 and CD163. Rearrangement of the NCOA2 gene was detected successfully by chromogenic in situ hybridization; however, abnormal signal patterns were observed in only a small subset of tumor cells. Unlike typical tumors with bland spindle cells, the present tumor needs to be distinguished from myxoid, dendritic and clear cell tumors. This case may suggest that angiofibroma of soft tissue is not in the center of the fibroblastic/myofibroblastic tumor group, but rather shows a fibrohistiocytic nature. We also found intratumor genetic heterogeneity, which is uncommon for a translocation-associated tumor. Therefore, careful evaluation is required to detect the gene rearrangement in this tumor entity., (© 2014 The Authors. Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.)

Background: The clinical phenotypes and their severity in patients with tuberous sclerosis complex can be quite variable and are sometimes never determined simply by the primary mutation. These make clinically selecting appropriate treatments and predicting disease outcome difficult. In this report, the prognostic ominous sequence was evaluated in association with clinical manifestations and gene mutations., Methods: The patients were classified by each renal lesion of angiomyolipomas and polycystic disease. The other clinical manifestations and outcomes of epilepsy, mental retardation, facial angiofibromas, subependymal giant cell astrocytoma, cortical tubers were reviewed and each gene mutations were analyzed in seven unrelated patients., Results: Two patients with multiple and large proliferative renal angiomyolipoma showed poor clinical outcome than the patients with other renal lesions. These patients presented with progressively proliferative facial angiofibroma, West syndrome, Lennox-Gastaut syndrome, severe mental retardation, subependymal giant cell astrocytoma and they were affected by TSC2 gene mutations., Conclusion: The sequence of progressively proliferative renal angiomyolipoma, facial angiofibroma, West syndrome and TSC2 gene mutations might be prognostic ominous factors., (Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Solitary fibrous tumour (SFT) is quite a rare neoplasm involving the eye and the orbit. It is described as showing benign behaviour in adults, but malignant cases are exceptionally reported in this location. This report describes four new cases of SFT/giant cell angiofibroma (GCA) of the eyelid and orbit, one in a 5-year-old child, and one with sarcomatous dedifferentiated transformation occurring 9 years after radiotherapy., Methods: Four cases of ocular SFT/GCA were retrieved from the database of the Pathological Anatomy Unit, University of Padova; immunohistochemistry and RT-PCR were used to identify COL1A1-PDBGF fusion gene transcripts in all cases., Results: In case 1, late relapse 9 years later was characterised by abrupt transition into a high-grade component, associated with a non-distinctive high-grade sarcomatous area. The latter component was CD34, CD99 and Bcl2 negative and smooth muscle actin positive. Molecular characterisation showed the absence of COL1A1-PDGFB fusion transcripts in cases 1, 3 and 4, excluded diagnosis of giant cell fibroblastoma in all cases. Analysis could not be performed in case 2., Conclusions: An eyelid SFT/GCA in a 5-year-old child is the youngest case reported in the literature, indicating that the tumour is not exclusive to adults. The case with sarcomatous transformation, with dedifferentiated features occurring 9 years after radiotherapy, raises some questions about the choice of treatment for ocular SFT, in which excision is sometimes difficult without devastating surgery.

Juvenile nasopharyngeal angiofibroma (JNA) is a vascular tumor of the nasopharynx that accounts for 0.5% of all cancers of the head and neck. It primarily affects males aged 14-25 years. Of the many genes that mediate the development of JNA, GSTM1 has been most frequently associated with this vascular tumor. The loss of expression of GSTM1 (null genotype) is linked to the development of these tumors. The aim of this cross-sectional case study was to examine the prevalence of the GSTM1-null genotype in Brazilian patients with JNA. DNA was extracted from the leukocytes of blood samples from 10 patients. GSTM1 genotypes were analyzed using a PCR-based assay that was designed to identify the wild-type allele of GSTM1. All 10 patients (100%) were males, with a mean age of 17.8 years. The null genotype for GSTM1 was noted in 4 patients (40%)-1 (10%) at Fisch stage I, 1 (10%) at stage III, and 2 (20%) at stage II. No patient with this genotype had stage IV disease. There was no correlation between Fisch classification and GSTM1 genotype (P = .5695). The correlation between age at diagnosis and GSTM1 genotype was not significant (P = .728). The present findings indicate that there is evidence of an association between the GSTM1-null genotype and JNA in this studied Brazilian population.

Tuberous sclerosis is a genetic multisystem disorder characterized by widespread hamartomas in several organs. Clinically, more than 90% of affected patients have skin lesions including facial angiofibromas, periungual fibromas, hypomelanotic macule, etc. Periungual fibroma is one of the major diagnostic criteria of tuberous sclerosis and has the same pathology (angiofibroma) as the facial papules. We herein describe an interesting histologic variant of angiofibromas coupled with multiple epidermoid cysts in a 33-year-old patient with tuberous sclerosis., (Copyright © 2013 John Wiley & Sons A/S.)

Several soft tissue tumors are characterized by fibrous stroma with a conspicuous vascular component including cellular angiofibroma, nasopharyngeal angiofibroma, and solitary fibrous tumor. Recently, a distinctive fibroblastic tumor composed of bland spindle cells and a complex vascular network has been characterized morphologically and shown to harbor a recurrent t(5;8) translocation with AHRR-NCOA2 gene fusion. We report our recent experience with 2 examples of this benign tumor, the diagnosis for one of which was supported by fluorescence in situ hybridization for NCOA2 rearrangement. Identification of this tumor is important to prevent misdiagnosis as a low-grade sarcoma., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives/hypothesis: To explore the molecular genetic background of juvenile nasopharyngeal angiofibromas and to identify biological processes and putative factors determining the different growth patterns of these tumors., Study Design: By comparing copy number and gene expression level changes of two clinically different phenotypes of juvenile nasopharyngeal angiofibromas, we aimed to find processes essential in the growth and development of these tumors. Based on the results and prior knowledge of the proteins significance for growth, we studied the expression of tyrosine kinase SYK in 27 tumor samples., Methods: Comparative genomic hybridization and gene expression analyses were performed for the two tumor samples, and protein expression of SYK was studied in 27 samples by immunohistochemical staining., Results: Between low- and high-stage juvenile nasopharyngeal angiofibromas, 1,245 genes showed at least a two-fold change in expression. The corresponding proteins of these transcripts were enriched in different biological processes. Protein kinase SYK was expressed in all 27 samples, and its intensity significantly correlated with tumor stage., Conclusions: Because the molecular genetic background of juvenile nasopharyngeal angiofibroma is unknown, our aim was to investigate genomic alterations that could associate to low- and high-stage tumors. We were able to identify gene expression changes that relate to particular biological processes, but assessing clinically relevant molecular profiles still requires further characterization. Due to the low incidence of juvenile angiofibroma, in the future a combination of molecular profiling data from several studies would be useful in understanding the molecular background of the disease., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Partial monosomy 13q, a chromosomal alteration originally reported in spindle cell lipoma, has also been documented in a few cases of mammary myofibroblastoma. Subsequently, a monoallelic loss of RB1 and FOXO1, located on 13q14, was identified in some cases of cellular angiofibroma, a benign stromal tumor of the lower female genital tract. This cytogenetic finding and the overlapping morphologic and immunohistochemical features shared by spindle cell lipoma, mammary myofibroblastoma, and cellular angiofibroma strongly suggest a histogenetic link among these tumors. Recently, we have emphasized morphologic and immunohistochemical similarities between mammary and vulvovaginal myofibroblastoma. The aim of the present study was to asses if these 2 tumors share the same chromosomal alteration. We studied the chromosome 13q14 region by fluorescence in situ hybridization analysis in a series of mammary and vaginal myofibroblastomas, with a readable signal in 7 of 13 mammary myofibroblastomas and 5 of 7 cases of vaginal myofibroblastomas. Despite histologic variation, most of the mammary (5/7) and vaginal (3/5) myofibroblastomas showed monoallelic deletion of FOXO1 in more than 22% of the cell populations. Our findings confirm that mammary myofibroblastoma is a tumor that exhibits chromosome abnormalities associated with the loss of the 13q14 region. In addition, we show for the first time that myofibroblastoma of the lower female genital tract also exhibits the same chromosomal abnormality, supporting the hypothesis that both tumors are in the spectrum of a single entity, likely arising from a common precursor cell., (Copyright © 2012 Elsevier Inc. All rights reserved.)