Dysregulation of Translation Factors EIF2S1, EIF5A and EIF6 in Intestinal-Type Adenocarcinoma (ITAC)

Intestinal-type adenocarcinoma (ITAC) is a rare cancer of the nasal cavity and paranasal sinuses that occurs sporadically or secondary to exposure to occupational hazards, such as wood dust and leather. Eukaryotic translation initiation factors have been described as promising targets for novel cancer treatments in many cancers, but hardly anything is known about these factors in ITAC. Here we performed in silico analyses, evaluated the protein levels of EIF2S1, EIF5A and EIF6 in tumour samples and non-neoplastic tissue controls obtained from 145 patients, and correlated these results with clinical outcome data, including tumour site, stage, adjuvant radiotherapy and survival. In silico analyses revealed significant upregulation of the translation factors EIF6 (ITGB4BP), EIF5, EIF2S1 and EIF2S2 (p < 0.05) with a higher arithmetic mean expression in ITAC compared to non-neoplastic tissue (NNT). Immunohistochemical analyses using antibodies against EIF2S1 and EIF6 confirmed a significantly different expression at the protein level (p < 0.05). In conclusion, this work identifies the eukaryotic translation initiation factors EIF2S1 and EIF6 to be significantly upregulated in ITAC. As these factors have been described as promising therapeutic targets in other cancers, this work identifies candidate therapeutic targets in this rare but often deadly cancer.

Occurrence of Sinonasal Intestinal-Type Adenocarcinoma and Non-Intestinal-Type Adenocarcinoma in Two Countries with Different Patterns of Wood Dust Exposure

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.

A deep learning model for gastric diffuse-type adenocarcinoma classification in whole slide images

Gastric diffuse-type adenocarcinoma represents a disproportionately high percentage of cases of gastric cancers occurring in the young, and its relative incidence seems to be on the rise. Usually it affects the body of the stomach, and it presents shorter duration and worse prognosis compared with the differentiated (intestinal) type adenocarcinoma. The main difficulty encountered in the differential diagnosis of gastric adenocarcinomas occurs with the diffuse-type. As the cancer cells of diffuse-type adenocarcinoma are often single and inconspicuous in a background desmoplaia and inflammation, it can often be mistaken for a wide variety of non-neoplastic lesions including gastritis or reactive endothelial cells seen in granulation tissue. In this study we trained deep learning models to classify gastric diffuse-type adenocarcinoma from WSIs. We evaluated the models on five test sets obtained from distinct sources, achieving receiver operator curve (ROC) area under the curves (AUCs) in the range of 0.95–0.99. The highly promising results demonstrate the potential of AI-based computational pathology for aiding pathologists in their diagnostic workflow system.

Aberrant Signaling Pathways in Sinonasal Intestinal-Type Adenocarcinoma

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 β-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.

Imaging of Skull Base and Orbital Invasion in Sinonasal Cancer: Correlation with Histopathology

Background: Pretreatment assessment of local extension in sinonasal cancer is essential for prognostic evaluation and surgical planning. The aim of this study was to assess the diagnostic performance of two common imaging techniques (CT and MRI) for the diagnosis of skull base and orbital invasion by comparing imaging findings to histopathological data. Methods: This was a retrospective two-center study including patients with sinonasal cancer involving the skull base and/or the orbit operated on between 2000 and 2019. Patients were included only if pre-operative CT and/or MRI, operative and histopathologic reports were available. A double prospective blinded imaging review was conducted according to predefined radiological parameters. Radiologic tumor extension was compared to histopathological reports, which were considered the gold standard. The predictive positive value (PPV) for the diagnosis of skull base/orbital invasion was calculated for each parameter. Results: A total of 176 patients were included. Ethmoidal intestinal-type adenocarcinoma was the most common type of cancer (41%). The PPV for major modification of the bony skull base was 78% on the CT scan, and 89% on MRI. MRI signs of dural invasion with the highest PPVs were: contact angle over 45° between tumor and dura (86%), irregular deformation of dura adjacent to tumor (87%) and nodular dural enhancement over 2 mm in thickness (87%). Signs of orbital invasion had low PPVs (<50%). Conclusions: This retrospective study provides objective data about the diagnostic value of pretreatment imaging in patients with sinonasal cancer.

Rare case of metastatic adenocarcinoma to the maxillary sinus

Colorectal carcinoma metastases to the head and neck are exceedingly rare. Patients may present with vague symptoms that may lead to a delay in diagnosis. We report the case of a 51-year-old man with a known history of stage IIIB colorectal adenocarcinoma who presented with right-sided molar tooth bleeding and right-sided palate swelling that led to difficulty speaking, eating and weight-loss of 15 pounds. Imaging studies revealed a 3.1×4.8×3 cm mass that was centred around the posterior aspect of the maxilla. Pathology revealed moderately differentiated intestinal type adenocarcinoma of colonic subtype, immune histochemistry was positive for CDX2, CK20 and MUC2, thus confirming metastatic disease to the maxilla. The patient is undergoing chemoradiation therapy for palliation of his symptoms. Clinicians should be aware of this potentional site of metastatic disease and suspect the diagnosis in a timely manner to avoid delays in making a diagnosis.