RESUMEN
Adenoid cystic carcinoma (AdCC) is a salivary gland neoplasm that infrequently appears in the sinonasal region. The aim of this study was to evaluate the outcome and clinicopathological parameters of sinonasal AdCC. A retrospective analysis was conducted on all cases of AdCC affecting the nasal cavity or paranasal sinuses between 2000 and 2018 at the University Hospital Zurich. Tumor material was examined for morphological features and analyzed for molecular alterations. A total of 14 patients were included. Mean age at presentation was 57.7 years. Sequencing revealed MYB::NFIB gene fusion in 11/12 analyzable cases. Poor prognostic factors were solid variant (p < 0.001), histopathological high-grade transformation (p < 0.001), and tumor involvement of the sphenoid sinus (p = 0.02). The median recurrence-free survival (RFS) and OS were 5.2 years and 11.3 years. The RFS rates at 1-, 5-, and 10-year were 100%, 53.8%, and 23.1%. The OS rates at 1-, 5-, and 10- years were 100%, 91.7%, and 62.9%, respectively. In Conclusion, the solid variant (solid portion > 30%), high-grade transformation, and sphenoid sinus involvement are negative prognostic factors for sinonasal AdCC. A high prevalence of MYB::NFIB gene fusion may help to correctly classify diagnostically challenging (e.g. metatypical) cases.
Asunto(s)
Carcinoma Adenoide Quístico , Neoplasias de los Senos Paranasales , Humanos , Carcinoma Adenoide Quístico/genética , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/mortalidad , Carcinoma Adenoide Quístico/epidemiología , Persona de Mediana Edad , Masculino , Femenino , Anciano , Estudios Retrospectivos , Adulto , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/genética , Neoplasias de los Senos Paranasales/epidemiología , Pronóstico , Factores de Transcripción NFI/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Proto-Oncogénicas c-myb/genética , PrevalenciaRESUMEN
Sinonasal squamous cell carcinomas (SNSCCs) are uncommon and they are associated with adverse prognosis. HPV-associated SNSCCs and fusion-driven SNSCCs are particularly rare. A case of an HPV-associated SNSCC with a FGFR3::TACC3 fusion is thus presented; a brief review of the pertinent literature is also provided.
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Carcinoma de Células Escamosas , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos , Humanos , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Carcinoma de Células Escamosas/virología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Proteínas Asociadas a Microtúbulos/genética , Masculino , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Neoplasias de los Senos Paranasales/virología , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/genética , Persona de Mediana Edad , FemeninoAsunto(s)
Infecciones por Papillomavirus , Neoplasias de los Senos Paranasales , Humanos , Femenino , Infecciones por Papillomavirus/virología , Neoplasias de los Senos Paranasales/virología , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/genética , Anciano de 80 o más Años , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/virología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Papillomaviridae/genética , Factores de Transcripción SOXERESUMEN
ALK-positive anaplastic large cell lymphoma is a rare T-cell lymphoma with ALK gene rearrangement that develops in children and young adults. The disease almost always affects the lymph nodes, and extranodal areas are also frequently involved. This article describes two cases of atypical localization of ALK-positive anaplastic large cell lymphoma with involvement of the paranasal sinuses.
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Quinasa de Linfoma Anaplásico , Linfoma Anaplásico de Células Grandes , Humanos , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/patología , Linfoma Anaplásico de Células Grandes/diagnóstico , Quinasa de Linfoma Anaplásico/genética , Masculino , Femenino , Adulto , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/genética , Neoplasias de los Senos Paranasales/metabolismo , Neoplasias de los Senos Paranasales/diagnóstico , Reordenamiento GénicoAsunto(s)
Células Dendríticas , Neoplasias Nasales , Proteína EWS de Unión a ARN , Translocación Genética , Humanos , Proteína EWS de Unión a ARN/genética , Células Dendríticas/patología , Femenino , Adulto , Neoplasias Nasales/genética , Neoplasias Nasales/patología , Neoplasias Nasales/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Neoplasias de los Senos Paranasales/genética , Neoplasias de los Senos Paranasales/patología , Cromosomas Humanos Par 22/genética , Proteínas de Unión a Calmodulina/genética , Proteínas de Unión a Calmodulina/metabolismoRESUMEN
BACKGROUND: We report a nasal cavity unusual perivascular epithelioid cell tumor (PEComa) mimicking mucosal melanoma. METHODS: Immunohistochemistry was performed using BenchMark Ultra and panel of antibodies. The Ion Torrent platform and Ion AmpliSeq cancer hotspot panel were utilized for DNA genotyping. Target-specific RNA libraries for the detection of fusion transcripts were constructed using Archer Universal RNA Reagent Kit v2 and Archer FusionPlex Solid Tumor panel and sequenced on the MiSeqDx instrument. RESULTS: The tumor, diagnosed in 46-year-old female, was composed of spindle cells, and lacked pigmentation. Immunohistochemically, it showed a patchy HMB-45 positivity. Other melanocytic markers (S100 protein, Melan-A, SOX10) were negative. The tumor cells were weakly positive for KIT (CD117) while negative for smooth muscle actin, pancytokeratin cocktail (AE1/AE3), and synaptophysin. Diagnosis of primary sinonasal tract mucosal melanoma was favored. Additional molecular studies detected PRCC :: TFE3 fusion as the sole genetic change, and suggested the diagnosis of unusual PEComa. Previously, TFE3 fusions were reported in a subset of PEComas but not in melanomas, while PRCC involvement has only been documented once in an ocular PEComa. Immunohistochemistry revealed strong nuclear TFE3 expression concordant with the molecular findings. CONCLUSIONS: This report emphasis the importance of molecular testing in the differential diagnosis between PEComa and melanoma, especially when the tumor arises in a site typical of melanoma but showing an unusual morphology and immunophenotype. The detection of TFE3 fusion transcripts suggested the diagnosis of SNT PEComa, although it cannot be excluded that this and similar tumors represent a distinct diagnostic category.
Asunto(s)
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Melanoma , Neoplasias de Células Epitelioides Perivasculares , Humanos , Femenino , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Neoplasias de Células Epitelioides Perivasculares/patología , Neoplasias de Células Epitelioides Perivasculares/metabolismo , Neoplasias de Células Epitelioides Perivasculares/genética , Melanoma/diagnóstico , Melanoma/metabolismo , Melanoma/patología , Melanoma/genética , Persona de Mediana Edad , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Diagnóstico Diferencial , Inmunohistoquímica , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Neoplasias de los Senos Paranasales/diagnóstico , Neoplasias de los Senos Paranasales/genética , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/metabolismo , Neoplasias Nasales/diagnóstico , Neoplasias Nasales/patología , Neoplasias Nasales/genética , Neoplasias Nasales/metabolismoRESUMEN
The mechanism and predictive biomarkers of sinonasal inverted papilloma (IP) transformation into squamous cell carcinoma (SCC) are still unclear. We investigated the genetic mutations involved and the predictive biomarkers. Fourteen patients with SCC arising from IP and six patients with IPs without malignant transformation (sIP) were included. DNA was extracted separately from areas of normal tissue, IP, dysplasia, and SCC. Whole exome sequencing and immunohistochemistry was performed. Major oncogenic mutations were observed in the progression from IP to SCC. The most frequently mutated genes were TP53 (39%) and CDKN2A (27%). Mutations in TP53 and/or CDKN2A were observed in three of six IPs with malignant transformation (cIP); none were observed in sIPs. Tumor mutational burden (TMB) increased from IP to SCC (0.64/Mb, 1.11/Mb, and 1.25 for IP, dysplasia, and SCC, respectively). TMB was higher in the cIPs than in the sIPs (0.64/Mb vs 0.3/Mb). Three cIPs showed a diffuse strong or null pattern in p53, and one showed a total loss of p16, a distinct pattern from sIPs. Our result suggests that TP53 and CDKN2A status can be predictive markers of malignant transformation of IP. Furthermore, immunohistochemistry of p53 and p16 expression can be surrogate markers for TP53 and CDKN2A status.
Asunto(s)
Biomarcadores de Tumor , Transformación Celular Neoplásica , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Papiloma Invertido , Proteína p53 Supresora de Tumor , Humanos , Papiloma Invertido/genética , Papiloma Invertido/patología , Papiloma Invertido/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Masculino , Femenino , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Anciano , Neoplasias de los Senos Paranasales/genética , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/metabolismo , Mutación , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Adulto , Anciano de 80 o más Años , Secuenciación del Exoma , InmunohistoquímicaAsunto(s)
Proteína EWS de Unión a ARN , Sarcoma , Humanos , Proteína EWS de Unión a ARN/genética , Sarcoma/genética , Sarcoma/patología , Proteínas de Fusión Oncogénica/genética , Neoplasias de los Senos Paranasales/genética , Neoplasias de los Senos Paranasales/patología , Masculino , Femenino , Biomarcadores de Tumor/genéticaRESUMEN
OBJECTIVES: Sinonasal inverted papilloma (SNIP) is a noncancerous tumor that develops in the mucous membrane of the nasal sinuses. Many malignancies are tightly linked to autophagy, an intracellular self-degradation mechanism. HMGB1 has demonstrated its ability to modulate autophagy in many pathological conditions. This work investigates how HMGB1 and other genes involved in autophagy contribute to SNIP. MATERIAL AND METHODS: The study included 45 patients with SNIP and a control group consisting of 28 individuals. In each group, qPCR was employed to examine the mRNA expression levels of genes correlated with autophagy and HMGB1. HMGB1 and genes associated with autophagy were examined for protein expression levels via Western Blot and immunohistochemical staining assays. At the same time, the association between HMGB1 and genes involved in autophagy was discovered through correlation analysis. Furthermore, Krouse staging was utilized for investigating the expression levels of HMGB1 and other autophagy-related genes at various stages in clinically staged SNIP patients. RESULTS: LC3B, ATG5, and Beclin1 autophagy-related genes and HMGB1 were substantially expressed in SNIP. Additionally, there was a positive correlation between HMGB1 and these genes. During various phases of SNIP, the levels of HMGB1 expression and autophagy-related genes were notably elevated at stage T4 compared with stage T2. CONCLUSION: Clinical staging in SNIP is correlated with HMGB1 expression in conjunction with autophagy-related genes LC3B, ATG5, and Beclin1, suggesting the possibility of novel prognostic indicators. LEVEL OF EVIDENCE: NA Laryngoscope, 134:3941-3946, 2024.
Asunto(s)
Proteína 5 Relacionada con la Autofagia , Autofagia , Beclina-1 , Proteína HMGB1 , Papiloma Invertido , Neoplasias de los Senos Paranasales , Humanos , Papiloma Invertido/genética , Papiloma Invertido/patología , Papiloma Invertido/metabolismo , Autofagia/genética , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de los Senos Paranasales/genética , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/metabolismo , Proteína 5 Relacionada con la Autofagia/genética , Proteína 5 Relacionada con la Autofagia/metabolismo , Beclina-1/genética , Beclina-1/metabolismo , Adulto , Anciano , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Estadificación de Neoplasias , Estudios de Casos y Controles , Regulación Neoplásica de la Expresión Génica , Relevancia ClínicaRESUMEN
Classification of tumors of the head and neck has evolved in recent decades including a widespread application of molecular testing in tumors of the sinonasal tract, salivary glands, and soft tissues with a predilection for the head and neck. The availability of new molecular techniques has allowed for the definition of multiple novel tumor types unique to head and neck sites. Moreover, an expanding spectrum of immunohistochemical markers specific to genetic alterations facilitates rapid identification of diagnostic molecular abnormalities. As such, it is currently possible for head and neck pathologists to benefit from a molecularly defined tumor classification while making diagnoses that are still based largely on histopathology and immunohistochemistry. This review covers the principal molecular alterations in sinonasal malignancies, such as alterations in DEK, AFF2, NUTM1, IDH1-2, and SWI/SNF genes in particular, that are important from a practical standpoint for diagnosis, prognosis, and prediction of response to treatment.
Asunto(s)
Biomarcadores de Tumor , Neoplasias de los Senos Paranasales , Humanos , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/genética , Neoplasias de los Senos Paranasales/clasificación , Neoplasias de los Senos Paranasales/diagnóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Organización Mundial de la SaludRESUMEN
BACKGROUND: Recurrent intestinal-type sinonasal adenocarcinoma (ITAC) can occur several years after primary treatment and with different histology. We aimed to clarify if such recurrences could be second primary tumors and to identify actionable mutations as targets for personalized treatment of recurrent ITAC. METHODS: Twelve pairs of primary and recurrent ITAC were histologically examined and analyzed by next-generation sequencing. RESULTS: Histological differences between primary and recurrent tumor pairs were observed in five cases. Frequent mutations included TP53, APC, TSC2, ATM, EPHA2, BRCA2, LRP1B, KRAS, and KMT2B. There was 86% concordance of somatic mutations between the tumor pairs, while four cases carried additional mutations in the recurrence. CONCLUSIONS: We found all cases to be clonal recurrences and not second primary tumors. Moreover, tumor pairs showed a remarkable genomic stability, suggesting that personalized treatment of a recurrence may be based on actionable molecular genetic targets observed in the primary tumor.
Asunto(s)
Adenocarcinoma , Secuenciación de Nucleótidos de Alto Rendimiento , Recurrencia Local de Neoplasia , Neoplasias de los Senos Paranasales , Humanos , Masculino , Recurrencia Local de Neoplasia/genética , Adenocarcinoma/genética , Adenocarcinoma/patología , Femenino , Neoplasias de los Senos Paranasales/genética , Neoplasias de los Senos Paranasales/patología , Persona de Mediana Edad , Anciano , Mutación , Inestabilidad Genómica , Anciano de 80 o más AñosRESUMEN
Sinonasal tumors with neuroepithelial differentiation, defined by neuroectodermal elements reminiscent of olfactory neuroblastoma (ONB) and epithelial features such as keratin expression or gland formation, are a diagnostically challenging group that has never been formally included in sinonasal tumor classifications. Recently, we documented that most of these neuroepithelial neoplasms have distinctive histologic and immunohistochemical findings and proposed the term "olfactory carcinoma" to describe these tumors. However, the molecular characteristics of olfactory carcinoma have not yet been evaluated. In this study, we performed targeted molecular profiling of 23 sinonasal olfactory carcinomas to further clarify their pathogenesis and classification. All tumors included in this study were composed of high-grade neuroectodermal cells that were positive for pankeratin and at least 1 specific neuroendocrine marker. A significant subset of cases also displayed rosettes and neurofibrillary matrix, intermixed glands with variable cilia, peripheral p63/p40 expression, and S100 protein-positive sustentacular cells. Recurrent oncogenic molecular alterations were identified in 20 tumors, including Wnt pathway alterations affecting CTNNB1 (n = 8) and PPP2R1A (n = 2), ARID1A inactivation (n = 5), RUNX1 mutations (n = 3), and IDH2 hotspot mutations (n = 2). Overall, these findings do demonstrate the presence of recurrent molecular alterations in olfactory carcinoma, although this group of tumors does not appear to be defined by any single mutation. Minimal overlap with alterations previously reported in ONB also adds to histologic and immunohistochemical separation between ONB and olfactory carcinoma. Conversely, these molecular findings enhance the overlap between olfactory carcinoma and sinonasal neuroendocrine carcinomas. A small subset of neuroepithelial tumors might better fit into the superseding molecular category of IDH2-mutant sinonasal carcinoma. At this point, sinonasal neuroendocrine and neuroepithelial tumors may best be regarded as a histologic and molecular spectrum that includes core groups of ONB, olfactory carcinoma, neuroendocrine carcinoma, and IDH2-mutant sinonasal carcinoma.
Asunto(s)
Biomarcadores de Tumor , Proteínas de Unión al ADN , Estesioneuroblastoma Olfatorio , Neoplasias de los Senos Paranasales , Factores de Transcripción , Vía de Señalización Wnt , Humanos , Anciano , Persona de Mediana Edad , Masculino , Factores de Transcripción/genética , Femenino , Vía de Señalización Wnt/genética , Proteínas de Unión al ADN/genética , Estesioneuroblastoma Olfatorio/patología , Estesioneuroblastoma Olfatorio/genética , Estesioneuroblastoma Olfatorio/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/genética , Neoplasias de los Senos Paranasales/metabolismo , Adulto , Proteínas Nucleares/genética , Mutación , Anciano de 80 o más Años , Neoplasias Nasales/patología , Neoplasias Nasales/genética , Neoplasias Nasales/metabolismo , InmunohistoquímicaRESUMEN
PURPOSE: Sinonasal nuclear protein in testis carcinoma (SNUTC) is a rare, aggressive malignancy caused by genetic rearrangements in the NUTM1 gene. The prognosis of SNUTC ranks among the most unfavorable within the naso-sinusal district, with an overall survival of 9.7 months. This systematic review aimed to determine the best therapeutic strategy for SNUTC. METHODS: We reviewed eligible articles for patient demographics, TNM and stage at presentation, best response after primary treatment, disease-free survival and overall survival (OS) times, other following therapy lines, and final outcomes. RESULTS: Among 472 unique citations, 17 studies were considered eligible, with reported treatment data for 25 patients. Most studies (n = 12) were case reports. The most frequently administered treatment regimen was surgery as primary treatment and combined radiochemotherapy as second-line or adjuvant treatment. Four patients were alive at follow-up. CONCLUSION: Basing on the existing literature, a standardized line in the treatment of SNUTC is not yet well delineated. A self-personalized strategy of therapy should be drawn on each patient affected by SNUTC.
Asunto(s)
Proteínas Nucleares , Humanos , Carcinoma/terapia , Carcinoma/genética , Carcinoma/patología , Terapia Combinada , Proteínas de Neoplasias/genética , Estadificación de Neoplasias , Proteínas Nucleares/genética , Proteínas Oncogénicas/genética , Neoplasias de los Senos Paranasales/terapia , Neoplasias de los Senos Paranasales/genética , Neoplasias de los Senos Paranasales/patologíaRESUMEN
Sinonasal carcinomas represent a rare and diverse group of tumors, presenting diagnostic complexities due to their varied histological and molecular features. To ensure accurate differentiation among these malignancies, a systematic and stepwise approach is paramount. Even with the morphological similarities between poorly differentiated (non) keratinizing sinonasal squamous cell carcinoma (SNSCC) and DEK::AFF2 SNSCC, the two lesions are distinguishable using the surrogate immunohistochemical marker AFF2 or molecular testing for DEK::AFF2 mutation. We report a rare case of SMARCB1-retained DEK::AFF2 papillary non-keratinizing SNSCC in a 53-year-old female, who presented with a polypoid mass corresponding to the left middle turbinate. Following the surgical resection of the tumor and locoregional lymph nodes, adjuvant radiotherapy was administered to eradicate any residual cancer cells that may have remained after surgery.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de los Senos Paranasales , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de los Senos Paranasales/diagnóstico , Neoplasias de los Senos Paranasales/genética , Diferenciación Celular , Ganglios Linfáticos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Algoritmos , Proteínas NuclearesRESUMEN
OBJECTIVE: Mucosal melanoma is a rare malignancy; however, the reported incidence rate of mucosal melanoma is higher in Asians than in Caucasians. Sinonasal mucosal melanoma (SNMM) is an aggressive malignancy with a poor prognosis due to distant metastasis. Systemic therapy with BRAF inhibitor and MEK inhibitor is one of the standards of care for cutaneous melanoma patients with BRAF V600 mutations. However, no molecular targeted therapy for patients with mucosal melanoma has been established. Relatively few studies have described the genetic mutations associated with mucosal melanoma because of its low frequency. Furthermore, to the best of our knowledge, the genetic mutations among Japanese patients have not been reported. Therefore, in the current study, we evaluated the genetic and clinicopathological characteristics of patients with SNMM. METHODS: A total of 18 tissue samples obtained from patients with SNMM were analyzed for genetic mutations based on targeted next-generation sequencing to investigate the driver of tumorigenesis and/or candidate genes for predicting clinical outcomes in SNMM. We also performed immunohistochemistry for patients identified with CTNNB1 mutations. RESULTS: Eight of the 18 (44 %) patients had genetic mutations. The most frequent mutation was NRAS (6/18, 33 %), followed by CTNNB1 (2/18, 11 %) and BRAF (1/18, 5.6 %). One patient had both NRAS and CTNNB1 mutations. Clinical outcomes did not differ significantly between those with and without genetic mutations. NRAS mutations were associated with relatively higher T classification and worse survival rates, although the differences were not significant. The nuclear translocation of ß-catenin was detected in both tumors with CTNNB1 mutations. The amino acid change in the BRAF mutation was K601R in exon 15. In the current study, no BRAF V600 mutations were detected. CONCLUSION: Genetic mutations were not significantly associated with clinical outcomes. However, NRAS mutations may be a prognostic predictor and CTNNB1 mutation may be a treatment effector for immune check inhibitors. A larger prospective study is required to clarify the clinical importance of genetic mutations in patients with SNMM.
Asunto(s)
Melanoma , Neoplasias de los Senos Paranasales , Neoplasias Cutáneas , Humanos , beta Catenina/genética , GTP Fosfohidrolasas/genética , GTP Fosfohidrolasas/metabolismo , Secuenciación de Nucleótidos de Alto Rendimiento , Japón , Melanoma/genética , Melanoma/patología , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Mutación , Neoplasias de los Senos Paranasales/genética , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/patologíaRESUMEN
AIMS: Oncogenic FGFR1/2/3 rearrangements are found in various cancers. Reported cases in head and neck (HN) are mainly squamous cell carcinomas (SCCs) with FGFR3::TACC3 fusions, a subset of which also harbour high-risk human papillomavirus (HPV). However, the knowledge of the clinicopathological spectrum of FGFR-rearranged head and neck carcinomas (FHNC) is limited. METHODS AND RESULTS: A retrospective MSK-fusion clinical sequencing cohort 2016-23 was searched to identify malignant tumours in the HN region harbouring FGFR1/2/3 fusion. FHNC were characterised by histological examination, immunohistochemistry and molecular analysis. Electronic medical records were reviewed. Three FHNC were identified. Two cases (cases 1 and 2) involved sinonasal tract and were high-grade carcinomas with squamous, basaloid, glandular and/or ductal-myoepithelial features. Case 1 arose in a 79-year-old man and harboured FGFR2::KIF1A fusion. Case 2 arose in a 58-year-old man, appeared as HPV-related multiphenotypic sinonasal carcinoma (HMSC), and was positive for FGFR2::TACC2 fusion and concurrent high-risk HPV, non-type 16/18. Case 3 was FGFR3::TACC3 fusion-positive keratinising SCCs arising in the parotid of a 60-year-old man. All three cases presented at stage T4. Clinical follow-up was available in two cases; case 1 remained disease-free for 41 months post-treatment and case 3 died of disease 2 months after the diagnosis. CONCLUSIONS: FHNC include a morphological spectrum of carcinomas with squamous features and may occur in different HN locations, such as parotid gland and the sinonasal tract. Sinonasal cases can harbour FGFR2 rearrangement with or without associated high-risk HPV. Timely recognition of FHNC could help select patients potentially amenable to targeted therapy with FGFR inhibitors. Further studies are needed (1) to determine if FGFR2 rearranged/HPV-positive sinonasal carcinomas are biologically distinct from HMSC, and (2) to elucidate the biological and clinical significance of FGFR2 rearrangement in the context of high-risk HPV.
Asunto(s)
Carcinoma de Células Escamosas , Infecciones por Papillomavirus , Neoplasias de los Senos Paranasales , Senos Paranasales , Masculino , Humanos , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Carcinoma de Células Escamosas/patología , Senos Paranasales/patología , Neoplasias de los Senos Paranasales/genética , Neoplasias de los Senos Paranasales/patología , Proteínas Asociadas a Microtúbulos , Cinesinas , Receptor Tipo 1 de Factor de Crecimiento de FibroblastosRESUMEN
Sinonasal glomangiopericytoma is an uncommon mesenchymal tumor with a perivascular myoid phenotype, which is categorized as a borderline/low-grade malignant soft tissue tumor by the current World Health Organization Classification of Head and Neck tumors. Here, we present the case of a 53-year-old woman with an unusual spindle cell morphology of sinonasal glomangiopericytoma arising in the nasal cavity, mimicking solitary fibrous tumor. Microscopically, the tumor showed a cellular proliferation of spindle cells in fascicles including a focal long sweeping arrangement or whorls, or with a storiform growth pattern, associated with hemangiopericytoma-like gaping blood vessels embedded in a fibrous stroma. This arrangement of the spindle cells faintly indicated a solitary fibrous tumor rather than sinonasal glomangiopericytoma. Immunohistochemically, the tumor was positively reactive to not only beta-catenin (in the nuclei) but also CD34, although signal transducers and activators of transcription 6 was negative. Mutational analysis using Sanger sequencing detected a CTNNB1 mutation. We finally diagnosed the tumor as a sinonasal glomangiopericytoma, showing an unusual spindle cell variant. Such unusual spindle cell morphology with CD34-immunoreactivity potentially leads to an incorrect diagnosis of solitary fibrous tumor because such prominent fascicles including long sweeping structures, reminiscent of desmoid-type fibromatosis, have scarcely been described in the literature. Hence, careful morphological scrutiny using appropriate diagnostic adjuncts is necessary for correct diagnosis.
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Neoplasias de los Senos Paranasales , Neoplasias de los Tejidos Blandos , Tumores Fibrosos Solitarios , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de los Senos Paranasales/diagnóstico , Neoplasias de los Senos Paranasales/genética , Núcleo Celular , Tumores Fibrosos Solitarios/diagnóstico , Tumores Fibrosos Solitarios/genética , Antígenos CD34 , Mutación , beta Catenina/genéticaRESUMEN
BACKGROUND: Sinonasal carcinomas represent a rare group of malignancies, accounting for less than 5% of all head and neck cancers and a worldwide incidence of less than 1 case per 100 000 inhabitants annually. Despite the restricted anatomical location, sinonasal carcinomas harbor some of the most histologically and molecularly diverse groups of tumors. SMARCB1 (INI1)-deficient sinonasal carcinomas are locally aggressive tumors commonly detected late, leading to devastating morbidity and mortality. CASE REPORT: We present two cases of SMARCB1-deficient sinonasal carcinoma involving the oral cavity and presenting as progressive radiolucent lesions with local swelling associated with maxillary dentition and alveolar bone. Both cases were initially considered odontogenic in origin and involved the destruction of the left anterior maxilla. CONCLUSION: Given the rarity and the variable presentation of these tumors, they pose a challenge for head and neck surgeons, dentists, and pathologists due to the potential overlapping features with odontogenic and non-odontogenic inflammatory and neoplastic lesions. These cases highlight the importance of a multidisciplinary team and include SMARCB1-deficient sinonasal carcinomas in the differential diagnosis of destructive lesions of the maxilla.
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Carcinoma , Neoplasias de los Senos Paranasales , Humanos , Biomarcadores de Tumor , Neoplasias de los Senos Paranasales/diagnóstico por imagen , Neoplasias de los Senos Paranasales/genética , Neoplasias de los Senos Paranasales/cirugía , Carcinoma/genética , Carcinoma/patología , Proteína SMARCB1/genéticaRESUMEN
This case report describes a novel gene fusion of PAX3::INO80D in a biphenotypic sinonasal carcinoma in a woman in her 40s.
Asunto(s)
Neoplasias de los Senos Paranasales , Sarcoma , Humanos , Adulto , Factores de Transcripción , Neoplasias de los Senos Paranasales/diagnóstico por imagen , Neoplasias de los Senos Paranasales/genética , Sarcoma/genética , Factor de Transcripción PAX3RESUMEN
PURPOSE: Local failure and distant metastases occur frequently in sinonasal mucosal melanoma (SNMM). Response rates to chemotherapy are low and targetable mutations are rarely detected. However, there is increasing data indicating efficacy of immune checkpoint inhibition (ICI). The aim of this retrospective monocenter study was to assess the mutational landscape and to evaluate the outcome of surgical treatment and ICI in SNMM in a real-world setting. METHODS: Thirty-eight SNMM patients being treated between 1999 and 2020 at our institution were retrospectively reviewed. Survival curves were generated according to Kaplan-Meier and compared by the log-rank test. RESULTS: Local failure was seen in 60% of patients treated in a curative intent. Overall, 24% of all patients suffered from regional and 66% from distant metastases. Next generation sequencing revealed mutations of BRAF, NRAS and KRAS. One out of three patients treated with a primary ICI showed a complete response (CR) and two showed progressive disease. Eleven patients received ICI as a palliative treatment. CR could be observed in three patients and stable disease in one patient. In the whole study population, the 5-year overall survival rate (OS) was 26%. OS was better for patients who received ICI during the course of disease. CONCLUSIONS: Recurrences and distant metastases are frequent in SNMM. Durable CR could be observed after primary and palliative ICI. Therefore, ICI in a palliative, adjuvant or even neoadjuvant setting might play a promising role in SNMM therapy while targetable mutations are rarely detected.