Recurrent USP6 rearrangement in a subset of atypical myofibroblastic tumours of the soft tissues: low-grade myofibroblastic sarcoma or atypical/malignant nodular fasciitis?

AIMS: Low-grade myofibroblastic sarcoma (LGMS) is a rarely metastasizing myofibroblastic tumour mostly affecting extremities and the head and neck of adults. Histologically, it shows long infiltrative fascicles of spindle cells with moderate nuclear atypia. By immunohistochemistry, it stains positive for smooth muscle actin (SMA) and sometimes for desmin. To date, no recurrent genetic abnormalities have been described. Ubiquitin-specific peptidase 6 (USP6) gene rearrangement is typically found in some benign bone and soft-tissue tumours including nodular fasciitis (NF), among others. Nevertheless, rare cases of USP6-rearranged tumours resembling NF with atypical features have been reported. METHODS AND RESULTS: One index case of LGMS of the deltoid in a 56-year-old man presented the THBS2::USP6 translocation by RNA sequencing (Archer FusionPlex Sarcoma v2 panel). Further screening of 11 cases of LGMS using fluorescent in situ hybridization (FISH) analysis with a USP6 break-apart probe identified two additional cases. These cases were investigated with RNA-sequencing, and a RRBP1::USP6 translocation was detected in one. The other case was not assessable because of low-quality RNA. Noteworthy, rearranged LGMSs presented distinctive features including variable multinodular/plexiform architecture, prominent vasculature with occasional wall thickening, scattered osteoclast-like multinucleated giant cells, and peripheral lymphoid aggregates. CONCLUSION: Our findings support the notion that among soft-tissue neoplasms with fibroblastic/myofibroblastic phenotype, USP6 rearrangement is not limited to benign tumours, and warrants further investigation of genetic changes in myofibroblastic sarcomas.

Role of Surgical Pathologist for Detection of Immunooncologic Predictive Factors in Head and Neck Cancer.

Immunotherapy has shown promising results in the treatment of recurrent and metastatic head and neck cancers. Antiprogrammed cell death (PD)-1 therapies have been recently approved in this setting and they are currently tested also in the treatment of locally advanced diseases and in the neoadjuvant setting. However, the clinical benefits of these treatments have been quite variable, hence the need to select those patients who may obtain the maximal efficacy through the identification of predictive biomarkers. Currently, PD-L1 immunohistochemical expression by tumor and immune cells is the most widely used predictive biomarker for immunotherapy in head and neck squamous cell carcinoma. Nevertheless, patients with PD-L1 - tumors may still respond to treatments, thereby emphasizing the need for the identification of other predictive biomarkers. In this review, we summarize the current data on histologic and molecular parameters that can be used to select patients with head and neck cancers for immunotherapy, with a focus on squamous cell carcinoma and salivary gland carcinomas.

The added value of the visual analysis of DWI in post-surgery follow-up of soft tissue sarcoma of the extremities: do we really need ADC?

INTRODUCTION: MRI has a fundamental role in the follow-up of soft tissue sarcomas (STSs). However, the differentiation of recurrences/residual disease from post-surgical changes is a complex task, with a central role for the radiologist. MATERIALS AND METHODS: We retrospectively evaluated 64 post-surgery MRI for extremities STSs. MR protocol included DWI (b = 0, 1000). Two radiologists were asked to consensually evaluate: presence/absence of tumoral nodules, lesion conspicuity, imaging diagnostic confidence, ADC values, and DWI overall image quality. The gold standard was histology or MR follow-up. RESULTS: Thirty-seven lesions in 29/64 patients were confirmed as local recurrence or residual disease (n = 16 ≤ 1 cm) with 1 MR false positive. On DWI, the conspicuity of the proved tumor lesions resulted excellent in 29/37, good in 3/37 and low in 5/37, higher than conventional imaging. A statistically significant higher diagnostic confidence of DWI compared to conventional imaging (p < 0.001) and DCE (p = 0.009) was observed. In the 37 histologically confirmed lesions, mean ADC value was 1.31 × 10-9 m2/s. Overall scar tissues mean ADC was 1.70 × 10-9 m2/s. DWI quality resulted adequate in 81% and unsatisfactory in 5%. CONCLUSIONS: In this highly heterogeneous group of tumors, the role of ADC seems to be limited. Based on our experience, looking at DWI images makes the lesions promptly and easily detectable. This technique gives less deceptive findings making the reader more confident in detecting/excluding tumoral tissue; the main drawback is the image quality and the lack of standardization.

Identification of New Potential Prognostic and Predictive Markers in High-Grade Osteosarcoma Using Whole Exome Sequencing.

Conventional high-grade osteosarcoma (OS) is the most common primary cancer of bone and it typically affects the extremities of adolescents. OS has a complex karyotype, and molecular mechanisms related to carcinogenesis, progression and resistance to therapy are still largely unknown. For this reason, the current standard of care is associated with considerable adverse effects. In this study, our aim was to identify gene alterations in OS patients using whole exome sequencing (WES) to find new potential prognostic biomarkers and therapeutic targets. We performed WES on formalin-fixed paraffin-embedded (FFPE) biopsy materials collected from 19 patients affected by conventional high-grade OS. The clinical and genetic data were analyzed according to response to therapy, presence of metastasis and disease status. By comparing good and poor responders to neoadjuvant therapy, we detected a clear prevalence of mutations in the ARID1A, CREBBP, BRCA2 and RAD50 genes in poor responders that negatively influence the progression-free survival time. Moreover, higher tumor mutational burden values correlated with worse prognosis. The identification of mutations in ARID1A, CREBBP, BRCA2 and RAD50 may support the use of a more specific therapy for tumors harboring these alterations. In particular, BRCA2 and RAD50 are involved in homologous recombination repair, and could thus be used as specific therapy targets of inhibitors of the enzyme Poly ADP Ribose Polymerase (PARP). Finally, tumor mutational burden is found to be a potential prognostic marker for OS.

Chondroblastoma-like osteosarcoma: a clinicopathological and molecular study of a rare osteosarcoma variant.

OBJECTIVE: Chondroblastoma-like osteosarcoma (CBLOS) is a rare and poorly understood variant of OS. We examined the clinicopathological, immunohistochemical and molecular features of six CBLOSs to highlight the differences with conventional high-grade OS (CHGOS) and CB, including CB with aggressive features. METHODS: We performed histone 3.3 mutation analysis by gene sequencing and/or immunohistochemistry in all cases, while whole exome sequencing (WES) was performed on two CB-like osteosarcomas and 11 conventional high-grade OS. RESULTS: CBLOSs were predominantly localised at acral sites and involved mainly male subjects with a mean age of 29 years. One patient who had metastases at presentation died of disease, while another patient who developed multiple local recurrences and lung metastases was alive with no evidence of disease (ANED) at 294 months. The remaining patients were ANED after a mean interval of 70.8 months. Histologically, all CBLOS presented aggressive features, including nuclear atypia and infiltrative growth. Immunohistochemistry with H3F3 K36M mutant antibody was negative in all CBLOSs, and none of the five tumours tested by gene sequencing had H3F3B mutations. Conversely, all CBs presented the H3F3B K36M variant and were positive for immunostaining with the H3F3 K36M antibody. Two CBLOSs analysed by WES differed in amount and type of mutation from 11 cases of CHGOS. Moreover, CBLOSs showed lower copy number alteration (CNA) score values than CHGOSs. CONCLUSIONS: CBLOS presents a different genetic background and a less aggressive clinical behaviour in comparison with CHGOS. Search of the H3F3B K36M mutation is useful in the differential diagnosis with CB.

Recurrent novel HMGA2-NCOR2 fusions characterize a subset of keratin-positive giant cell-rich soft tissue tumors.

Giant cell tumors of soft tissue (GCT-ST) are rare low-grade neoplasms that were at one time thought to represent the soft tissue counterparts of GCT of bone (GCT-B) but are now known to lack the H3F3 mutations characteristic of osseous GCT. We present six distinctive giant cell-rich soft tissue neoplasms that expressed keratins and carried a recurrent HMGA2-NCOR2 gene fusion. Patients were five females and one male aged 14-60 years (median, 29). All presented with superficial (subcutaneous) masses that were removed by conservative marginal (3) or wide (2) local excision. The tumors originated in the upper extremity (2), lower extremity (2), head/neck (1), and trunk (1). Five patients with follow-up (median, 21 months; range, 14-168) remained disease-free. Grossly, all tumors were well-demarcated but not encapsulated with variable lobulation. Histologically, they were composed of bland plump epithelioid or ovoid to spindled mononuclear cells admixed with evenly distributed multinucleated osteoclast-type giant cells. Foci of stromal hemorrhage and hemosiderin were seen in all cases. The mitotic activity ranged from 2 to 14/10 high power fields (median: 10). Foci of necrosis and vascular invasion were seen in one case each. The mononuclear cells were immunoreactive with the AE1/AE3 keratin cocktail and less frequently/less diffusely for K7 and K19 but lacked expression of other lineage-associated markers. RNA-based next-generation sequencing revealed an HMGA2-NCOR2 fusion in all tumors. None of the keratin-negative conventional GCT-ST showed the HMGA2-NCOR2 fusion (0/7). Metaplastic bone (4/9) and SATB2 expression (3/4) were frequent in keratin-negative conventional GCT-ST but were lacking in keratin-positive HMGA2-NCOR2 fusion-positive tumors. The distinctive immunophenotype and genotype of these tumors strongly suggest that they represent a discrete entity, differing from conventional GCT-ST and other osteoclast-rich morphologic mimics. Their natural history appears favorable, although a study of additional cases and longer follow-up are warranted.

MUC4 is a valuable marker for distinguishing secretory carcinoma of the salivary glands from its mimics.

AIMS: Secretory carcinoma (SC) (synonym: mammary analogue secretory carcinoma) is a low-grade salivary gland tumour that occurs in both major and minor salivary glands. SC is known for its wide morphological, architectural and immunohistochemical spectrum, which overlaps with those of several salivary gland neoplasms, including acinic cell carcinoma (AciCC) and intercalated duct-type intraductal carcinoma (IDC) in major salivary glands, and polymorphous adenocarcinoma (PAC) in minor salivary glands. These tumours share with SC some morphological features and SOX10 immunoreactivity; also, with the exception of AciCC, they all coexpress S100 and mammaglobin. METHODS AND RESULTS: We compared MUC4 and mammaglobin expression in 125 salivary gland carcinomas (54 genetically confirmed SCs, 20 AciCCs, 21 PACs, and 30 IDCs) to evaluate the potential of these two markers to differentiate these entities. Moderate to strong diffuse MUC4 positivity was detected in 49 SCs (90.7%), as compared with none of the IDCs and PACs. In contrast, mammaglobin was frequently expressed in SCs (30 of 36 cases; 83.3%), IDCs (24/28; 85.7%), and PACs (7/19; 36.8%). Two of three high-grade SCs lost MUC4 expression in the high-grade tumour component. No significant correlation was found between MUC4 expression and the fusion variant in SC (ETV6-NTRK versus non-ETV6-NTRK). CONCLUSION: The results of our study identify MUC4 as a sensitive (90.7%) and specific (100%) marker for SC, with high positive (100%) and negative (93.4%) predictive values. Thus, MUC4 may be used as a surrogate for SC in limited biopsy material and in cases with equivocal morphology.

Pleomorphic adenoma: the great mimicker of malignancy.

Pleomorphic adenoma (PA) is the most common salivary gland neoplasm, and its diagnosis is straightforward in the majority of cases. However, not infrequently, PA shows unusual and uncommon histological features that can be confused with those of malignancy. The difficulties in diagnosing PA arise from its ability to mimic invasion, show atypical or metaplastic cytomorphology, and show morphological features that overlap with those of established salivary gland carcinomas. In addition, recognising early malignant transformation to carcinoma ex-pleomorphic adenoma continues to be a frequent challenge. This review describes the diagnostic pitfalls of PA, and offers a systematic approach to avoid them by combining classic histopathology with novel immunohistochemical and molecular tests.

Papillary-cystic neoplasms of the middle ear are distinct from endolymphatic sac tumours.

AIMS: Papillary neoplasms of the middle and inner ear are rare and poorly characterised. The current World Health Organization classification divides them into two major subtypes: aggressive papillary tumours (APTs) and endolymphatic sac tumours (ELSTs). The aim of this article is to present two papillary neoplasms of the middle ear that do not fit into either the classic APT category or the classic ELST category, and compare them with three ELSTs. METHODS AND RESULTS: The patients were a 48-year-old female and a 59-year-old male without a history of other neoplasms. Histology showed papillary-cystic growth of predominantly oncocytic (Case 1) or mucinous (Case 2) cells surrounded by a p63-positive basal layer. The overall histology was reminiscent of oncocytic sinonasal papilloma (Case 1) and pancreatobiliary or salivary intraductal papillary mucinous neoplasms (Case 2). Ovarian-type stroma, invasion and malignant features were absent. Immunohistochemistry revealed expression of cytokeratin (CK) 7, but not carbonic anhydrase IX (CAIX) or paired box gene 8 (PAX8) (except for very focal PAX8 expression in Case 1). The TST15 gene panel and HRAS sequencing revealed no pathogenic mutations in BRAF, KRAS, EGFR, AKT1, or HRAS. The TruSight RNA fusion panel revealed an MKRN1-BRAF fusion in Case 1. No fusion was detected in Case 2. The three ELSTs showed classic features of the entity, expressed CK7, epithelial membrane antigen, PAX8, and CAIX, and lacked a basal cell layer. CONCLUSION: These novel cases suggest that papillary tumours of the ear represent a heterogeneous spectrum of distinct neoplasms unified by a prominent papillary-cystic pattern rather than a single entity. Future studies should clarify whether the MKRN1-BRAF fusion is a defining recurrent driver event, especially in those cases reported as sinonasal-type middle ear papillomas.

Emerging Entities and New Diagnostic Markers for Head and Neck Soft Tissue and Bone Tumors.

Bone and soft tissue tumors of the head and neck are relatively uncommon tumors that often represent a diagnostic challenge because of the wide range of entities that must be considered in the differential diagnosis. Over the past few years, classification of bone and soft tissue tumors has evolved primarily because of substantial contributions from molecular genetics, with the identification of new markers that are increasingly used to complement histopathologic findings in the routine diagnostic workup. This review focuses on the recently described mesenchymal tumors that preferentially involve the head and neck region, with a focus on the most relevant novel immunohistochemical and molecular findings, including gene fusions and mutations, that can help in the diagnosis and in the assessment of clinical behavior.

High-grade Transformation/Dedifferentiation in Salivary Gland Carcinomas: Occurrence Across Subtypes and Clinical Significance.

High-grade transformation (HGT) or dedifferentiation has been described in a variety of salivary gland carcinomas, including acinic cell carcinoma, secretory carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, polymorphous adenocarcinoma, low-grade mucoepidermoid carcinoma, and hyalinizing clear cell carcinoma. High-grade (HG) transformed tumors are composed of a conventional low-grade component characterized by specific microscopic and immunohistochemical features for the given entity, intermingled with or juxtaposed to areas of HG morphology. This is usually either poorly differentiated adenocarcinoma, carcinoma not otherwise specified, or undifferentiated carcinoma, in which the original line of differentiation is lost. The HG component is composed of solid nests of anaplastic cells with large vesicular pleomorphic nuclei, prominent nucleoli, and abundant cytoplasm. Frequent mitoses and extensive necrosis may be present. The Ki-67 labeling index is consistently higher in the HG component. The molecular genetic mechanisms responsible for HGT of salivary gland carcinomas are largely unknown, though p53 inactivation and human epidermal growth factor receptor 2 overexpression and/or gene amplification have been demonstrated in the HG component in a few examples, the frequency varies for each histologic type. Salivary gland carcinomas with HGT are more aggressive than conventional carcinomas, with a higher local recurrence rate and a poorer prognosis. They have a high propensity for cervical lymph node metastasis suggesting a need for a wider resection and neck dissection. HGT of salivary gland carcinoma can occur either at initial presentation or less commonly at the time of recurrence, sometimes following postoperative radiotherapy. The potential for HGT in almost any type of salivary gland carcinoma warrants a thorough sampling of all salivary gland malignancies to prevent oversight of a HG component.

Undifferentiated and dedifferentiated head and neck carcinomas.

Undifferentiated carcinomas arising at salivary gland and head and neck mucosal sites may originate either de novo or through a process of dedifferentiation of a differentiated carcinoma. While in the latter group the diagnosis is largely dependent on the identification of the differentiated component or recognition of a specific genotype, the classification of undifferentiated carcinomas that lack a differentiated component is mainly based on the identification of specific genetic drivers, like for example the NUTM1 fusions in NUT carcinoma. A further category is represented by virus associated carcinomas (mainly HPV and EBV), that frequently displays an undifferentiated morphology. Overall, these tumors often represent a diagnostic challenge, especially in small biopsies. This review summarizes and discuss the diagnostic approach to the main head and neck carcinoma types that frequently or occasionally display an undifferentiated appearance, with a focus on salivary gland, oropharyngeal, nasopharyngeal and sinonasal subsites.

Analysis of a Preliminary microRNA Expression Signature in a Human Telangiectatic Osteogenic Sarcoma Cancer Cell Line.

Telangiectatic osteosarcoma (TOS) is an aggressive variant of osteosarcoma (OS) with distinctive radiographic, gross, microscopic features, and prognostic implications. Despite several studies on OS, we are still far from understanding the molecular mechanisms of TOS. In recent years, many studies have demonstrated not only that microRNAs (miRNAs) are involved in OS tumorigenesis, development, and metastasis, but also that the presence in high-grade types of OS of cancer stem cells (CSCs) plays an important role in tumor progression. Despite these findings, nothing has been described previously about the expression of miRNAs and the presence of CSCs in human TOS. Therefore, we have isolated/characterized a putative CSC cell line from human TOS (TOS-CSCs) and evaluated the expression levels of several miRNAs in TOS-CSCs using real-time quantitative assays. We show, for the first time, the existence of CSCs in human TOS, highlighting the in vitro establishment of this unique stabilized cell line and an identification of a preliminary expression of the miRNA profile, characteristic of TOS-CSCs. These findings represent an important step in the study of the biology of one of the most aggressive variants of OS and the role of miRNAs in TOS-CSC behavior.

[The new national guidelines for the keeping of the Italian Sinonasal Cancer Registry (ReNaTuNS)]. / Il nuovo manuale operativo ReNaTuNS per la gestione dei casi di tumore naso-sinusale.

Sinonasal cancers (SNC) are rare tumours with predominant occupational aetiology associated with exposures to specific carcinogens. In Italy, SNC incidence has been under compulsory surveillance since 2008, through the National Sinonasal Cancer Registry (ReNaTuNS), a nationwide cancer registry coordinated by the National Institute for Insurance Against Accidents at Work (Inail). The ReNaTuNS has a regional structure with local registries, established at Regional Operating Centres (CORs). Currently, seven Italian Regions are active in SNC search and, together with Inail, have recently released a new version of the national guidelines for keeping the Registry (available on the Inail website). The aim of this text is to present the new guidelines, an updating version, and to underline the relevance of this tool in enforcing the role of the ReNaTuNS, considering the high occupational fraction of SNC and the unicity of the Italian Registry, which collects all the information available on occupational exposures of each SNC case registered. It is recommended that the active search for SNC cases and the analysis of exposure become a systematic and well-organized activity to prevent or reduce risks of exposure and to support and improve the efficiency of the compensation and welfare system.

Ameloblastic fibrosarcoma: clinicopathological and molecular analysis of seven cases highlighting frequent BRAF and occasional NRAS mutations.

AIMS: Ameloblastic fibrosarcoma (AFS) is an aggressive odontogenic neoplasm featuring malignant mesenchymal stroma in addition to an ameloblastic epithelial component, and is hence considered to be the malignant counterpart of ameloblastic fibroma (AF). AFS is exceedingly rare, with <110 cases having been reported so far. Although BRAF mutations are recognised driver mutations in ameloblastoma, the molecular pathogenesis of AFS remains elusive. METHODS AND RESULTS: We herein describe seven AFSs that were analysed, for the first time, for mutations in the BRAF-NRAS pathway. The patients were four females and three males aged 23-57 years (median, 26 years). Three tumours developed after one or multiple recurrences of AF (4-20 years after initial diagnosis), two showed transition from AF-like bland areas, and two developed de novo. All patients were treated with surgery; adjuvant chemotherapy was given to one patient. At the last follow-up, five patients were alive and well (19-344 months). The remainder were lost to follow-up. Histological examination showed variable sarcomatous overgrowth with varying degrees of atypia and increased mitotic activity. The epithelial component varied greatly according to the degree of sarcomatous overgrowth. Molecular testing revealed BRAF V600E mutations in five cases and NRAS p.Gln61Lys mutation in one case. One tumour was wild-type. CONCLUSION: To our knowledge, this is the first study on BRAF/NRAS mutations in AFS. Given the activity of RAF and MEK inhibitors across different cancers harbouring V600E mutations, our data strongly suggest that all AFS cases should be genetically tested, and that targeted treatment approaches for this extremely rare sarcoma subtype should be clinically investigated.

Synovial chondrosarcoma: a single-institution experience with molecular investigations and review of the literature.

AIMS: To evaluate the available diagnostic histological criteria for synovial chondrosarcoma and to screen for the presence of IDH1/IDH2 mutations in a series of cases of this malignant cartilaginous neoplasm. METHODS AND RESULTS: Ten cases of synovial chondrosarcoma diagnosed at our institute were reviewed. At presentation, all tumours occurred in adults (median age, 62 years). The most common location was the knee joint (five cases), and the size at diagnosis ranged from 30 mm to 170 mm. Eight patients had secondary synovial chondrosarcomas associated with pre-existing/recurrent or concomitant synovial chondromatosis. Five patients had local recurrences and three had lung metastases. All patients with intralesional excisions developed local recurrences, whereas those who underwent wide resections did not. At last follow-up (mean, 91 months), available for nine patients, seven patients were alive and disease-free, one patient had died of disease, and one was alive with paravertebral metastases. Frequent histological features observed included loss of clustering of chondrocytes (nine cases), the presence of variable amounts of myxoid matrix (eight cases), peripheral hypercellularity (eight cases), tumour necrosis (six cases), and spindling of chondrocytes (four cases). Of the seven cases for which it was possible to evaluate bone permeation, six showed infiltration of bone marrow. All seven cases screened for mutations of exon 4 of IDH1 and IDH2 were found to be wild-type. CONCLUSIONS: Histological criteria in correlation with clinical and radiological features allow the recognition of synovial chondrosarcoma. IDH1/IDH2 mutations were not present in synovial chondrosarcoma. Adequate surgical margins are important for disease control.

Sinonasal Undifferentiated Carcinoma (SNUC): From an Entity to Morphologic Pattern and Back Again-A Historical Perspective.

Since the first description of sinonasal undifferentiated carcinoma (SNUC) as a distinctive highly aggressive sinonasal neoplasm with probable origin from the sinonasal mucosa (Schneiderian epithelium), SNUC has been the subject of ongoing study and controversy. In particular, the SNUC category gradually became a "wastebasket" for any undifferentiated or unclassifiable sinonasal malignancy of definite or probable epithelial origin. However, with the availability of more specific and sensitive immunohistochemical antibodies and increasing implementation of novel genetic tools, the historical SNUC category became the subject of progressive subdivision leading to recognition of specific genetically defined, reproducible subtypes. These recently recognized entities are characterized by distinctive genetic aberrations including NUTM1-rearranged carcinoma (NUT carcinoma) and carcinomas associated with inactivation of different members of the SWI/SNF chromatin-remodeling gene complex such as SMARCB1-deficient and less frequently SMARCA4-deficient carcinoma. The ring became almost closed, with recent studies highlighting frequent oncogenic IDH2 mutations in the vast majority of histologically defined SNUCs, with a frequency of 82%. A review of these cases suggests the possibility that "true SNUC" probably represents a distinctive neoplastic disease entity, morphologically, phenotypically, and genetically. This review addresses this topic from a historical perspective, with a focus on recently recognized genetically defined subsets within the SNUC spectrum.

Diffuse bone and soft tissue angiomatosis with GNAQ mutation.

We describe a unique case of skeletal and extraskeletal angiomatosis complicated by Kasabach-Merritt syndrome. The patient was a 3-year-old boy, who presented with involvement of both femurs and left tibia, as well as with soft tissue lesions of the left thigh. At birth, multiple hemangiomas of the soft tissues of the frontal and parietal scalp had been identified, together with a space-occupying lesion of the lung. Histologically, the skeletal and soft tissue lesions consisted of a proliferation of thin-walled, dilated blood vessels, with an endothelial lining devoid of atypia and exhibiting immunoreactivity for CD31 and CD34, while podoplanin and GLUT1 were negative. Whole exome sequencing performed on samples from the lesion of the femur, the tibia and the skin of the thigh, showed a GNAQ (c.286A>T:p.T96S) variant in all specimens, that was confirmed with digital droplet PCR. This case expands the clinical and pathologic spectrum of vascular proliferations showing similar molecular biology, characterized by GNAQ, GNA11 or GNA14 mutations.

[The new ReNaTuNS operating manual for nasal sinus tumor case management].

SUMMARY: No abstract available.