RESUMEN

BACKGROUND: Non­intestinal adenocarcinoma of the nasal cavity and paranasal sinuses (non­ITAC) is a heterogeneous tumour that has rarely been reported in previous studies. We compared and analysed the symptoms, radiographic and pathological features, treatment methods, and prognosis of patients with low-grade (G1) and high-grade (G3) tumours. METHODS: This was a retrospective study included 22 patients with pathologically confirmed non-ITAC of the nasal cavity and paranasal sinuses who were treated between January 2008 and December 2021 at a single centre. Of these, 11 patients had G1 tumours, and 11 patients had G3 tumours. Clinicopathological features, treatment methods, and survival outcomes were analysed. RESULTS: The median follow-up period was 48.5 months. Nasal congestion was the most common initial symptom, and the nasal cavity was the most frequently involved site. For G1 tumours, the main treatment was simple surgery, 1 and 3­year overall survival (OS) rates were 100 and 88.9%, while the 1 and 3­year local control (LC) rates were 100 and 100%, respectively. For G3 tumours, the main treatments were surgery combined with radiotherapy and/or chemotherapy,1 and 3­year OS rates were 72.7 and 72.7%, while the 1 and 3­year LC rates were 100 and 90.91%, respectively. G3 tumours was associated with significantly shorter overall survival than G1 tumours (P = 0.035). Patients with stage III-IV showed shorter overall survival compared to stage I-II patients (P = 0.035). CONCLUSIONS: Non-ITAC of the nasal cavity and paranasal sinuses may frequently occur in the nasal cavity. The main treatment modality is surgery, supplemented by radiotherapy and chemotherapy. Pathological grade and tumour stage were poor prognostic factors for the disease.

Asunto(s)

Adenocarcinoma , Cavidad Nasal , Neoplasias Nasales , Neoplasias de los Senos Paranasales , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias de los Senos Paranasales/terapia , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/mortalidad , Neoplasias de los Senos Paranasales/diagnóstico , Neoplasias Nasales/terapia , Neoplasias Nasales/patología , Neoplasias Nasales/mortalidad , Neoplasias Nasales/diagnóstico , Anciano , Cavidad Nasal/patología , Pronóstico , Adenocarcinoma/terapia , Adenocarcinoma/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/diagnóstico , Adulto , Tasa de Supervivencia , Clasificación del Tumor , Estadificación de Neoplasias

RESUMEN

Sinonasal intestinal-type adenocarcinoma (ITAC) is a very rare, closely occupational-related tumor with strong histological similarities to colorectal cancer (CRC). In the latter, tumor budding (TB) is widely recognized as a negative prognostic parameter. The aim of this study was to evaluate the prognostic role of TB in ITAC and to correlate it with other established or emerging biomarkers of the disease, such as p53 and deficient DNA mismatch repair (MMR) system status/microsatellite instability (MSI). We retrospectively analyzed 32 consecutive specimens of patients with ITAC diagnosis treated in two institutions in Northern Italy. We reviewed surgical specimens for TB evaluation (low-intermediate/high); p53 expression and MMR proteins were evaluated via immunohistochemistry. Results were retrospectively stratified using clinical data and patients' outcomes. According to bud counts, patients were stratified into two groups: intermediate/high budding (>4 TB) and low budding (≤4 TB). Patients with high TB (>4) have an increased risk of recurrence and death compared to those with low TB, with a median survival of 13 and 54 months, respectively. On multivariate analysis, considering TB, therapy, and stage as covariates, TB emerged as an independent prognostic factor net of the stage of disease or type of therapy received. No impact of p53 status as a biomarker of prognosis was observed and no alterations regarding MMR proteins were identified. The results of the present work provide further significant evidence on the prognostic role of TB in ITAC and underline the need for larger multicenter studies to implement the use of TB in clinical practice.

RESUMEN

Sinonasal (SN) malignancies are rare. Within SN adenocarcinomas, the most frequent are intestinal-type adenocarcinomas (ITACs). ITAC has been associated with wood and leather dust occupational exposure and TP53 mutations. Not much information is available regarding its characterization and treatment. The aim of this study is to characterize the clinicopathologic and prognostic factors of patients with sinonasal adenocarcinomas (SNACs) treated in our tertiary-level hospital. A retrospective, consecutive study including SNAC patients diagnosed between 2004-2023 was conducted. Clinicopathological data was collected, and p53 status was assessed in the tumor specimens. The association between p53 status and clinicopathological variables, as well as their impact on survival, was evaluated. In total, 35 were included, most of them having ITAC (91.4%) with papillary subtype (37.5%); the majority were subjected to occupational risk exposure (82.9%). Overexpression of p53 was identified in 48.6% of the tumors. Papillary and colonic subtypes were associated with higher median progression-free survival (mPFS) than mucinous and solid subtypes (mPFS 37 months, 95% CI, 20.0-54.0, vs. 9 months, 95% CI, 7.15-10.85, p=0.01); the former was also associated with higher median overall survival (mOS) (mOS 64 months, 95% CI, 37.18-90.81 vs. 14 months, 95% CI, 0-41.58, p=0.02). Histologic grade 1-2 and macroscopic complete resection were associated with higher PFS (PFS of five months of 90.9% vs. 33.3%, p=0.01; mPFS of 37 months, 95% CI, 4.93-69.07 vs. 10 months, 95% CI, 6.43-13.57, p=0.04, respectively). Disease recurrence with distant metastases was associated with lower OS (11 months, 95% CI, 6.1-15.9 vs. 53 months, 95% CI, 22.70-83.30, p=0.04). This study reinforces the importance of protective occupational measures. Future studies will be important to validate the best treatment strategy in the advanced stages of this disease and also to identify new prognostic and/or therapeutic target biomarkers in SNAC.

RESUMEN

Background: Malignant tumors of the ureteric bud are not common, and cervical involvement is even rarer. So far, there have been no such cases in the literature. Case summary: A 50-year-old woman developed intermittent light bleeding in the past 7 months and lower abdominal pain in the past 2 months. The human papillomavirus 16 (HPV) DNA, P16 chemical staining, thinPrep cytology test (TCT), and cervical and cervical canal tissue biopsy were all negative. Pelvic color Doppler ultrasound exhibited incomplete mediastinal uterus and heterogeneous echo from the cervical canal to the posterior wall of the cervix. Pelvic contrast-enhanced CT showed left cervical mass, left retroperitoneal mass, absence of the left kidney, and mediastinal uterus. An increase in human epididymal protein 4 (HE4) (133.6 pmol/L) was detected, while other tumor markers were at normal levels. Based on these examination results, a diagnosis of "cervical fibroids, left retroperitoneal mass, incomplete mediastinal uterus, left kidney deficiency"[SIC] was conducted, and expanded hysterectomy, right adnexectomy, and left retroperitoneal mass resection were performed. Through intraoperative rapid pathological diagnosis, postoperative pathological diagnosis combined with the re-evaluation of laboratory, and imaging and intraoperative examination results, the patient was diagnosed with ureteric bud intestinal-type adenocarcinoma involving the cervix. The patient has been tracked and followed up for approximately 11 months. She underwent six courses of chemotherapy. At present, the medication has been discontinued for 4 months, and there is no recurrence, metastasis, or deterioration of the tumor. Conclusion: For large masses of the cervix, it is feasible for the operation to be performed, improving the prognosis. There were a few limitations. A preoperative aspiration biopsy of masses was not performed to differentiate benign from malignant. Preoperative urography was not performed to clarify the function of the malformed urinary system structure. Partial cystectomy should be performed simultaneously with the resection of the ureteric bud for intestinal-type adenocarcinoma. In this case, a partial cystectomy was not performed, which can only be compensated with postoperative chemotherapy. Moreover, this patient did not undergo genetic screening, and it is currently unclear whether there are any genetic mutations associated with ureteric bud intestinal adenocarcinoma.

RESUMEN

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 Años

RESUMEN

PURPOSE: Intestinal-type adenocarcinoma (ITAC) is a rare sinonasal malignancy. Curative treatment requires multidisciplinary approach, with surgical options consist of the endonasal endoscopic approach (EEA) and external surgery (EXTS). Here, we provide the post-operative and survival results from a single-center long-term follow-up. METHODS: We report long-term follow-up of 92 ITAC cases treated between 1998 and 2018, treated with EEA (n = 40) or EXTS (n = 52). Survival estimates, post-operative complications and duration of hospitalization were compared between surgical modalities. RESULTS: Baseline characteristics were similar. A higher number of T4b tumors (16%), and subsequently more tumoral invasion (39%), was present in patients undergoing EXTS compared to EEA (3% and 18%, respectively). No difference in Barnes histology subtypes was noticed. Patients undergoing EEA had a shorter post-operative hospitalization stay versus EXTS (4 versus 7 days). Use of EEA was associated to improved disease-specific survival (DSS; 11.4 versus 4.4 years; HREEA = 0.53), especially for patients with T3-4a tumors (11.4 versus 3.0 years; HREEA = 0.41). Patients with T3-4 stage, tumoral invasion, positive surgical margins, mucinous or mixed histology, and prolonged post-operative hospital stay showed poor local relapse-free, disease-free, overall, and DSS. CONCLUSIONS: Long-term follow-up in locally advanced ITAC demonstrates that resection by EEA is correlated with improved DSS compared to EXTS, especially for T3-4 tumors. No significant differences between both treatment modalities was observed regarding per- and post-operative complications, although hospitalization in patients undergoing EEA was shorter than for patients treated with EXTS. These results confirm that EEA should remain the preferred surgical procedure in operable cases of sinonasal ITAC.

Asunto(s)

Adenocarcinoma , Neoplasias de los Senos Paranasales , Humanos , Masculino , Femenino , Neoplasias de los Senos Paranasales/cirugía , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/mortalidad , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Adenocarcinoma/mortalidad , Persona de Mediana Edad , Anciano , Estudios de Seguimiento , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Tiempo de Internación/estadística & datos numéricos , Adulto , Endoscopía/métodos , Tasa de Supervivencia , Estadificación de Neoplasias

RESUMEN

Adenocarcinomas of the nasal/paranasal sinuses are uncommon, but intestinal-type adenocarcinomas (ITACs) are important. Due to the rarity of these tumors, their molecular profile is not well known. To further investigate the molecular profile and find potential oncogenic drivers, we compared the whole transcriptome and exome of ITACs at different anatomic locations in the head and neck. Twenty-one head and neck adenocarcinomas were used in this study, divided into 10 sinonasal adenocarcinomas (SNT) and 11 extrasinonasal (T) head and neck adenocarcinomas according to anatomic location and histology. Tumor samples along with normal mucosa were microdissected from formalin-fixed, paraffin-embedded samples, and RNA and DNA were subjected to whole-transcriptome and -exome shotgun sequencing. Analysis of ITACs at sinonasal locations showed 410 subtype-specific differentially expressed (DE) genes and noncoding transcripts compared with the group of other anatomic locations, with 2909 subtype-specific DE genes. The groups shared 872 genes, with 17 highly different or opposing DE genes. Whole-exome mutation analysis revealed the gene MLL3 (KMT2C) to be exhibiting the most frequent loss-of-function mutations in all adenocarcinomas investigated. The results suggest that the head and neck ITACs investigated were mainly caused by loss-of-function mutations in MLL3 that disabled chromatin methylation and remodeling of all MLL3-targeted enhancers in the tumors. This changed the activity of multiple genes/gene clusters, supporting oncogenicity mostly via pathways of signaling, dedifferentiation, proliferation, migration, and immune and inflammatory deregulation, indicating a truly epigenetic event as the root cause for the heterogenous diversity of these enteric types of cancer. The data of this study form the basis for understanding cell fate determination and cellular homeostasis in the normal respiratory mucosa at different anatomic sites and show the contribution of different mucosal components to the etiology/molecular pathology of ITAC.

Asunto(s)

Adenocarcinoma , Neoplasias de los Senos Paranasales , Humanos , Exoma , Transcriptoma , Biomarcadores de Tumor/análisis , Adenocarcinoma/patología , Neoplasias de los Senos Paranasales/patología

RESUMEN

Despite advances in surgery and radiotherapy, the overall prognosis of sinonasal intestinal-type adenocarcinoma (ITAC) is poor, and new treatment options are needed. Recent studies have indicated alterations in cellular signaling pathways that may serve as targets for modern inhibitors. Our aim was to evaluate the frequency of mTOR and ERK pathway upregulation in a retrospective series of 139 ITAC and to test the efficacy and mechanism of action of candidate targeted inhibitors in cell line ITAC-3. An immunohistochemical analysis on p-AKT, p-mTOR, p-S6, p-4E-BP1, and p-ERK indicated, respectively, a 68% and 57% mTOR and ERK pathway activation. In vitro studies using low doses of mTOR inhibitor everolimus and ERK inhibitor selumetinib showed significant growth inhibition as monotherapy and especially as combined therapy. This effect was accompanied by the downregulation of mTOR and ERK protein expression. Our data open a new and promising possibility for personalized treatment of ITAC patients.

Asunto(s)

Adenocarcinoma , Transducción de Señal , Humanos , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Everolimus/farmacología , Everolimus/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Estudios Retrospectivos , Serina-Treonina Quinasas TOR/metabolismo

RESUMEN

We report 2 cases of high-grade sinonasal adenocarcinoma with a distinct morphological and immunohistochemical phenotype. Albeit histologically different from secretory carcinoma of the salivary glands, both tumors presented here share an ETV6::NTRK3 fusion. The highly cellular tumors were composed of solid and dense cribriform nests, often with comedo-like necroses in the center, and minor areas with papillary, microcystic, and trabecular formations without secretions, mostly located at the periphery of the lesion. The cells displayed high-grade features, with enlarged, crowded, and often vesicular nuclei with conspicuous nucleoli and brisk mitotic activity. The tumor cells were immunonegative for mammaglobin while showing immunopositivity for p40/p63, S100, SOX10, and GATA3, as well as for cytokeratins 7, 18, and 19. For the first time, we describe 2 cases of primary high-grade non-intestinal type adenocarcinomas of the nasal cavity, distinct from secretory carcinoma by morphology and immunoprofile, harboring the ETV6::NTRK3 fusion.

Asunto(s)

Adenocarcinoma , Carcinoma , Neoplasias de las Glándulas Salivales , Humanos , Adenocarcinoma/genética , Adenocarcinoma/patología , Biomarcadores de Tumor/genética , Carcinoma/genética , Carcinoma/patología , Inmunohistoquímica , Proteínas de Fusión Oncogénica/genética , Neoplasias de las Glándulas Salivales/genética , Neoplasias de las Glándulas Salivales/patología , Proteína ETS de Variante de Translocación 6

RESUMEN

Background: Primary non-squamous cell carcinomas of the vulva are rare entities including various tumor types. Among these, primary vulvar intestinal-type adenocarcinoma (vPITA) is extremely rare. Until 2021, less than twenty-five cases have been reported in the literature. Case presentation: We report a case of vPITA in a 63 years old woman with a histopathological diagnosis of signet-ring cell intestinal type adenocarcinoma at vulvar biopsy. Accurate clinical and pathological work-up excluded secondary metastatic localization, and vPITA was diagnosed. The patient was treated with radical vulvectomy and bilateral inguinofemoral dissection. Adjuvant chemo-radiotherapy was performed because of a positive lymph node. At 20 months follow-up the patient was alive and free of disease. Conclusion:  The prognosis of this very rare disease is unclear and optimal treatment is not well established. About 40% of clinical early-stage diseases reported in literature had positive inguinal nodes, more than in vulvar squamous cell carcinomas. A proper histopathologic and clinical diagnosis is mandatory to exclude secondary disease and to recommend an adequate treatment.

RESUMEN

Sinonasal neoplasms are uncommon diseases, characterized by heterogeneous biological behavior, which frequently results in challenges in differential diagnosis and treatment choice. The aim of this review was to examine the pathogenesis and molecular mechanisms underlying the regulation of tumor initiation and growth, in order to better define diagnostic and therapeutic strategies as well as the prognostic impact of these rare neoplasms. A systematic review according to Preferred Reporting Items for Systematic Review and Meta-Analysis criteria was conducted between September and November 2022. The authors considered the three main histological patterns of sinonasal tumors, namely Squamous Cell Carcinoma, Intestinal-Type Adenocarcinoma, and Olfactory Neuroblastoma. In total, 246 articles were eventually included in the analysis. The genetic and epigenetic changes underlying the oncogenic process were discussed, through a qualitative synthesis of the included studies. The identification of a comprehensive model of carcinogenesis for each sinonasal cancer subtype is needed, in order to pave the way toward tailored treatment approaches and improve survival for this rare and challenging group of cancers.

Asunto(s)

Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Nasales , Neoplasias de los Senos Paranasales , Senos Paranasales , Humanos , Adenocarcinoma/patología , Neoplasias Nasales/diagnóstico , Neoplasias Nasales/genética , Neoplasias Nasales/terapia , Neoplasias de los Senos Paranasales/diagnóstico , Neoplasias de los Senos Paranasales/genética , Neoplasias de los Senos Paranasales/terapia

RESUMEN

Villous adenoma is a benign neoplasm with an exceptional presentation in the renal pelvis, hence very few cases have been reported. Herein we present the case of a patient who presented with left flank pain clinically suggestive of complicated pyelonephritis, culminating in simple nephrectomy with a villous adenoma in the renal pelvis as histopathological finding associated to the presence of a microscopic focus of intestinal-type adenocarcinoma.

RESUMEN

BACKGROUND: Recent guidelines advise to subtype adenocarcinoma at the ampulla and papilla of Vater (here: ampullary cancer) as intestinal, pancreatobiliary, and mixed, because this has consequences for both prognosis and treatment. This nationwide study aimed to investigate how often histopathological subtyping is performed in daily clinical practice in patients with ampullary cancer. METHODS: Pathology reports of all patients with ampullary cancer were retrieved from the Dutch nationwide pathology database (PALGA, 1991-2020). Reports were assessed for the presence and methods used for the classification of these tumors into intestinal, pancreatobiliary, and mixed subtypes. The use of immunohistochemical markers was recorded. RESULTS: Overall, 5246 patients with ampullary cancer were included. In 1030 (19.6%) patients, a distinction between intestinal, pancreatobiliary, and mixed subtypes was made. Use of subtyping increased from 3% in 1991-1993 to 37% in 2018-2020. In 274 of the 1030 (26.6%) patients, immunohistochemistry was used to make this distinction. A gradual increase in the use of various immunohistochemical markers was seen over time since 2008, with cytokeratin 7, cytokeratin 20, and CDX2 being the most common. Staining of DPC4/SMAD4 was increasingly used since 2012. CONCLUSION: Despite recent improvements in the use of subtyping in ampullary cancer, the distinction between intestinal, pancreatobiliary, and mixed subtypes is only made in a minority of patients. Nationwide efforts are required to standardize the pathological distinction of the various subtypes of ampullary cancer.

Asunto(s)

Adenocarcinoma , Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco , Humanos , Ampolla Hepatopancreática/patología , Biomarcadores de Tumor/análisis , Neoplasias del Conducto Colédoco/patología , Adenocarcinoma/patología , Pronóstico

RESUMEN

OBJECTIVES: The improvements in survival with expansion of the survivors' population, along with evolution of endoscopically-based treatment modalities, have contributed to emphasize the clinical relevance of recurrences in sinonasal cancers. However, at present, literature is scant regarding the pattern of recurrences and the therapeutic strategies available to manage long survivors who experienced single or multiple failures. The aim of the present study was to analyze sinonasal cancers recurrences to provide data regarding rates and patterns of relapse, predictors of failure and prognostic impact of the recurrence. MATERIALS AND METHODS: All patients receiving multimodal treatments including endoscopic surgery between 1995 and 2021 in three European referral centers were included. Statistical analysis of survival was performed through univariable, multivariable and unidirectional multistate models. Survival after recurrence analysis was implemented for patients experiencing at least one recurrence. RESULTS: The 5- and 10-year recurrence free survival rates were 34.1% and 38.4% for the whole population. With a mean follow-up time of 60 months, a global recurrence rate of 32.9% was observed. The 5- and 10-year survival after recurrence rates were 27.2% and 21.7%, respectively. Incidence and rates of recurrences were significantly associated with histology subtypes. CONCLUSION: This study provides valuable oncologic outcomes regarding a large homogenous cohort of patients affected by sinonasal malignances treated within a multimodal framework, emphasizing the strong correlation of histologic type with prognosis, as well as with pattern of recurrences.

Asunto(s)

Recurrencia Local de Neoplasia , Neoplasias de los Senos Paranasales , Endoscopía/métodos , Humanos , Recurrencia Local de Neoplasia/patología , Neoplasias de los Senos Paranasales/patología , Pronóstico , Estudios Retrospectivos

RESUMEN

BACKGROUND: The periurethral mass in the female is a rare clinical entity and most of the lesions are benign. We present an unusual case of a periurethral mass found to be intestinal-type adenocarcinoma which has not been previously reported in the literature. CASE PRESENTATION: A 58-year-old woman was referred to our hospital with acute urinary retention. She complained of frequency, urgency and progressive obstructive urinary symptoms for the last 3 months. A pelvic magnetic resonance imaging scan showed a soft tissue mass of 5 × 4 cm surrounding the entire urethra. A needle biopsy was done and revealed adenocarcinoma with intestinal-type features. The tumor was removed by a simultaneous laparoscopic abdominal and transperineal approach. The pathological results showed a positive surgical margin and urethra and vagina wall invasion. The neoplastic cells were positive for CK20, CDX-2, CerbB-2, MSH2, MSH6, MLH1, PMS2 and P53. The patient received adjuvant systemic chemotherapy comprising S-1 and oxaliplatin. Follow-up with pelvic MRI 6 months after surgery showed no signs of local recurrence. CONCLUSIONS: We have reported the first case of the primary periurethral adenocarcinoma of intestinal type. There are currently no standardized protocols for the diagnosis, clinical course, and treatment of this rare tumor. This case study can aid decision-making regarding the diagnosis and treatment of this tumor.

Asunto(s)

Adenocarcinoma , Retención Urinaria , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/cirugía , Quimioterapia Adyuvante , Femenino , Humanos , Persona de Mediana Edad , Uretra

RESUMEN

Sinonasal intestinal-type adenocarcinoma (sITAC) is histomorphologically indistinguishable from colorectal adenocarcinoma (CRC) leading to diagnostic challenges. Metastases from CRCs to the sinonasal tract have been reported. The aim of the study was to identify a biomarker making it possible to distinguish between sITAC and metastases of colorectal origin. Formalin-fixated paraffin-embedded (FFPE) tissue from 20 consecutive patients with sITAC treated at Rigshospitalet, Denmark from 2005 to 2017, 20 patients with CRC, and second patients with both sinonasal and colorectal carcinomas were included, and RNA-sequencing was performed on all samples. Moreover, a series of 26 samples from metastasizing CRC were included (in-house data). 3139 differentially expressed genes were identified, of these several were deemed as possible biomarkers, including CSDE1, for which immunohistochemical staining was performed. sITAC and CRC differ in genomic expression. CSDE1, previously found upregulated in CRC, was significantly differentially expressed. Using immunohistochemical staining, no sITACs displayed strong and diffuse staining for CSDE1, which represents a potential marker to use in distinguishing sITAC from a metastasis of colorectal origin. This knowledge could improve the diagnostic process and hopefully the outcome in patients with this rare tumor.

Asunto(s)

Adenocarcinoma , Neoplasias Colorrectales , Adenocarcinoma/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/patología , Expresión Génica , Humanos

RESUMEN

PURPOSE OF REVIEW: Sinonasal tumors are rare and heterogeneous diseases which pose challenges in diagnosis and treatment. Despite significant progress made in surgical, oncological, and radiotherapy fields, their prognosis still remains poor. Therefore, alternative strategies should be studied in order to refine diagnosis and improve patient care. RECENT FINDINGS: In recent years, in-depth molecular studies have identified new biological markers, such as genetic abnormalities and epigenetic variations, which have allowed to refine diagnosis and predict prognosis. As a consequence, new histological entities have been described and specific subgroup stratifications within the well-known histotypes have been made possible. These discoveries have expanded indications for immunotherapy and targeted therapies in order to reduce tumor spread, thus representing a valuable implementation of standard treatments. Recent findings in molecular biology have paved the way for better understanding and managing such rare and aggressive tumors. Although further efforts need to be made in this direction, expectations are promising.

Asunto(s)

Neoplasias de los Senos Paranasales , Biomarcadores de Tumor/genética , Diagnóstico Diferencial , Humanos , Neoplasias de los Senos Paranasales/diagnóstico , Neoplasias de los Senos Paranasales/genética , Neoplasias de los Senos Paranasales/terapia , Pronóstico

Asunto(s)

Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/genética , Neoplasias Intestinales/diagnóstico , Metaplasia/diagnóstico , Senos Paranasales/patología , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Biomarcadores de Tumor/metabolismo , Factor de Transcripción CDX2/genética , Factor de Transcripción CDX2/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Expresión Génica , Humanos , Inmunohistoquímica , Neoplasias Intestinales/genética , Neoplasias Intestinales/patología , Neoplasias Intestinales/cirugía , Intestinos/metabolismo , Intestinos/patología , Queratina-20/genética , Queratina-20/metabolismo , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Masculino , Metaplasia/genética , Metaplasia/patología , Metaplasia/cirugía , Senos Paranasales/metabolismo , Senos Paranasales/cirugía

RESUMEN

Sinonasal intestinal-type adenocarcinoma is strongly associated with hardwood dust exposure. Non-intestinal-type adenocarcinoma is a rarer and less well-known subtype considered not to be related with wood dust exposure. We determined the relative numbers of these two tumor types in 56 sinonasal adenocarcinoma patients in France and Finland, relating them with carefully assessed wood dust exposure histories. Diagnostic workup including immunohistochemistry for the intestinal markers CDX2 and CK20 indicated that the proportions of the two tumors differed significantly between France and Finland. In Finnish samples non-intestinal adenocarcinomas were more common than intestinal-type adenocarcinomas (12 non-intestinal vs. nine intestinal), while in the French samples the reverse was true (six non-intestinal vs. 29 intestinal). Such remarkably dissimilar occurrence of these tumors in France and Finland presumably reflects different pathogenetic circumstances in the two countries, and perhaps their different patterns of wood dust exposure. In France the main source of wood dust is from hardwoods. In Finland it is derived from softwoods. This is the first systematic comparison of the occurrence of intestinal-type adenocarcinoma and non-intestinal-type adenocarcinoma in two countries with different wood usage. It appears to be the first systematic study on differences in wood dust exposure between intestinal-type adenocarcinoma and non-intestinal-type adenocarcinoma.

RESUMEN

Sinonasal intestinal-type adenocarcinoma (ITAC) is strongly related to occupational exposure to wood and leather dust, however, little is known on the genetic alterations involved in tumor development and progression. The aim of this study was to identify tumorigenic signaling pathways affected by gene mutations and their relation to clinical features. We applied whole exome sequencing of 120 cancer-related genes in 50 ITACs and analyzed the signaling activity of four specific pathways frequently affected by mutations. Genes involved in DNA damage response showed somatic mutations in 30% of cases, including four tumors that also harbored germline mutations. Genes in Wnt, MAPK and PI3K pathways harbored mutations in 20%, 20% and 24% of cases, respectively. Mutations and copy number gains in receptor tyrosine kinases possibly affecting MAPK and PI3K pathways occurred in 44% of cases. Expression of key pathway proteins showed no correlation to mutations in these pathways, except for nuclear ß-catenin and APC/CTNNB1 mutation. No specific gene mutation, mutated pathway, nor pathway activity level showed correlation to clinical data or survival. In addition, a similar mutational profile was observed among histological subtypes. The wide spectrum of gene mutations suggests that ITAC is a genetically heterogeneous without specific characterizing gene mutations.