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Squamous cell carcinoma of the oral cavity represents about 2% of all malignant neoplasms and 47% of those developing in the head and neck area. The tongue is the most common site involved, and this incidence is increasing mainly in young people, possibly related to human papilloma virus infections. Prognosis depends on the stage: the 5-year survival rate of tongue squamous cell carcinoma, whatever the T stage, is 73% in pN0 cases, 40% in patients with positive nodes without extracapsular spread (pNl ECS-), and 29% when nodes are metastatic with extracapsular spread (pNl ECS+: por = 0.0001). Nodal micrometastases (cN0 pN1) are found in up to 50% of cN0 tongue squamous cell carcinoma patients operated on the neck. At present, no clinical, imaging staging modalities or biological markers are available to diagnose nodal micrometastases. The sentinel node biopsy has been tested since 1996 in order to find a solution to this problem. The sentinel node is the first node reached by the lymphatic stream, assuming an orderly and sequential drainage from the tumour site, and should be predictive of the nodal stage. According to the literature, sentinel node biopsy is a reliable technique in selected cN0 cases, but the procedure is still experimental and should not be performed outside validation trials. Successful application of sentinel node biopsy in the head and neck region requires surgical experience and specific technical devices, including pre-operative lymphoscintigraphy and intra-operative gamma-probe. Moreover, dynamic lymphoscintigraphy seems to be able to show the lymphatic stream from the primary tumour and could allow a selective neck dissection to be tailored thus reducing the related morbidity.

Noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) are low-risk thyroid lesions most often characterised by RAS-type mutations. The histological diagnosis may be challenging, and even immunohistochemistry and molecular approaches have not yet provided conclusive solutions. This study characterises a set of NIFTPs by Matrix-Assisted Laser Desorption/Ionisation (MALDI)–Mass Spectrometry Imaging (MSI) to highlight the proteomic signatures capable of overcoming histological challenges. Archived formalin-fixed paraffin-embedded samples from 10 NIFTPs (n = 6 RAS-mutated and n = 4 RAS-wild type) were trypsin-digested and analysed by MALDI–MSI, comparing their profiles to normal tissue and synchronous benign nodules. This allowed the definition of a four-peptide signature able to distinguish RAS-mutant from wild-type cases, the latter showing proteomic similarities to hyperplastic nodules. Moreover, among the differentially expressed signals, Peptidylprolyl Isomerase A (PPIA, 1505.8 m/z), which has already demonstrated a role in the development of cancer, was found overexpressed in NIFTP RAS-mutated nodules compared to wild-type lesions. These results underlined that high-throughput proteomic approaches may add a further level of biological comprehension for NIFTPs. In the future, thanks to the powerful single-cell detail achieved by new instruments, the complementary NGS–MALDI imaging sequence might be the correct methodological approach to confirm that the current NIFTP definition encompasses heterogeneous lesions that must be further characterised.

Functional loss of E-cadherin is frequent during tumor progression and occurs through a variety of mechanisms, including proteolytic cleavage. E-cadherin downregulation leads to the conversion of a more malignant phenotype promoting Epithelial to Mesenchymal Transition (EMT). The UBC9/SUMO pathway has been also shown to be involved in the regulation of EMT in different cancers. Here we found an increased expression of UBC9 in the progression of Head and Neck Cancer (HNC) and uncovered a role for UBC9/SUMO in hampering the HPV-mediated E-cadherin cleavage in HNC.

Radiomics focuses on extracting a large number of quantitative imaging features and testing both their correlation with clinical characteristics and their prognostic and predictive values. We propose a radiomic approach using magnetic resonance imaging (MRI) to decode tumor phenotype and local recurrence in oropharyngeal squamous cell carcinoma (OPSCC). The contrast-enhanced T1-weighted sequences from baseline MRI examinations of OPSCC patients treated between 2008 and 2016 were retrospectively selected. Radiomic features were extracted using the IBEX software, and hierarchical clustering was applied to reduce features redundancy. The association of each radiomic feature with tumor grading and stage, HPV status, loco-regional recurrence within 2 years, considered as main endpoints, was assessed by univariate analysis and then corrected for multiple testing. Statistical analysis was performed with SAS/STAT® software. Thirty-two eligible cases were identified. For each patient, 1286 radiomic features were extracted, subsequently grouped into 16 clusters. Higher grading (G3 vs. G1/G2) was associated with lower values of GOH/65Percentile and GOH/85Percentile features (p = 0.04 and 0.01, respectively). Positive HPV status was associated with higher values of GOH/10Percentile (p = 0.03) and lower values of GOH/90Percentile (p = 0.03). Loco-regional recurrence within 2 years was associated with higher values of GLCM3/4-7Correlation (p = 0.04) and lower values of GLCM3/2-1InformationMeasureCorr1 (p = 0.04). Results lost the statistical significance after correction for multiple testing. T stage was significantly correlated with 9 features, 4 of which (GLCM25/180-4InformationMeasureCorr2, Shape/MeanBreadth, GLCM25/90-1InverseDiffMomentNorm and GLCM3/6-1InformationMeasureCorr1) retained statistical significance after False Discovery Rate correction. MRI-based radiomics is a feasible and promising approach for the prediction of tumor phenotype and local recurrence in OPSCC. Some radiomic features seem to be correlated with tumor characteristics and oncologic outcome however, larger collaborative studies are warranted in order to increase the statistical power and to obtain robust and validated results.

Tongue squamous cell carcinoma is the most common malignancy in the oral cavity. Despite advances in diagnosis and treatment, the prognosis of advanced states has not significantly improved. Depth of invasion, pattern of invasion such as tumor budding grade, lingual lymph node metastasis in early stages, collective cell migration and circulating tumor cells in peripheral blood are some examples of the mechanisms that are currently receiving increasing attention in the evaluation of the prognosis of tongue cancers. Anatomic-based surgery showed that it is possible to improve loco-regional control of tongue cancer. In patients with a “T-N tract involvement”, there is significantly more distant recurrence (40%) in patients undergoing a compartmental tongue surgery. In general, the neoplastic infiltration of the lingual muscles is traced back to the finding of neoplastic tissue along the course of a muscle; however, the muscle fibers, due to their spatial conformation and the organization of the extracellular matrix, could influence the movement of tumor cells through the muscle, leaving its three-dimensional structure unchanged. We need to exclude the possibility that tongue muscle fibers represent a mechanism for the diffusion of cancer cells without muscle invasion.

Aberrations in histone post-translational modifications (PTMs), as well as in the histone modifying enzymes (HMEs) that catalyze their deposition and removal, have been reported in many tumors and many epigenetic inhibitors are currently under investigation for cancer treatment. Therefore, profiling epigenetic features in cancer could have important implications for the discovery of both biomarkers for patient stratification and novel epigenetic targets. In this study, we employed mass spectrometry-based approaches to comprehensively profile histone H3 PTMs in a panel of normal and tumoral tissues for different cancer types, identifying various changes, some of which appear to be a consequence of the increased proliferation rate of tumors, while others are cell-cycle independent. Histone PTM changes found in tumors partially correlate with alterations of the gene expression profiles of HMEs obtained from publicly available data and are generally lost in culture conditions. Through this analysis, we identified tumor- and subtype-specific histone PTM changes, but also widespread changes in the levels of histone H3 K9me3 and K14ac marks. In particular, H3K14ac showed a cell-cycle independent decrease in all the seven tumor/tumor subtype models tested and could represent a novel epigenetic hallmark of cancer.

Although heart metastases are uncommon and generally a sign of disseminated disease, they are up to 40 times more frequent than primary cancers of the heart, and typically arise from melanoma or primary mediastinal cancer, but also from lymphoma, breast cancer, esophageal cancer, and leukemia. They are usually asymptomatic and found only at autopsy. Symptomatic patients generally die within a few weeks of diagnosis and usual treatments are chemotherapy, radiotherapy, or both. Surgical resection is recommended only for a single lesion, which is rare. We describe a 49-year-old man treated for squamous cell cancer of the esophagus in whom a single asymptomatic left heart metastasis was discovered incidentally during follow-up. The lesion was debulked surgically and multimodal treatment followed. The patient survived 1 year after diagnosis with good performance status during which time no other lesion was discovered. Cardiac metastasis is challenging and necessitates skilled multidisciplinary management to maximize the clinical outcome.

CD117, a trans-membrane tyrosine kinase receptor, has been immunolocalized in a large variety of human neoplasms. Little, however, is known about the prevalence and clinical implications of CD117 in stage I adenocarcinoma and squamous cell carcinoma of the lung. We evaluated 201 consecutive stage I adenocarcinoma and squamous cell carcinoma of the lung for CD117 immunoreactivity (dichotomized as negative or positive if containing less than 5% or >/=5% immunoreactive neoplastic cells, respectively), also taking into account the pattern (either membranous or cytoplasmic), and the intensity of immunostaining in comparison with intratumoral mast cells. The immunostaining results were then correlated with tumor biopathological characteristics and patients' survival. Membranous CD117 immunoreactivity was documented in 19 (22%) of 88 adenocarcinomas and 15 (13%) of 113 squamous cell carcinomas, whereas cytoplasmic labelling was seen in 28 (32%) adenocarcinomas and eight (7%) squamous cell carcinomas. In both tumor types, membranous or cytoplasmic CD117 immunoreactivity was associated with higher proliferative fraction and with features of more aggressive tumor behavior, including higher stage, size and grade, occurrence of clinical symptoms, high microvessel density and neuroendocrine differentiation. Furthermore, immunoreactive tumors exhibited increased levels of bcl-2, cyclin-E, Her-2, p27(Kip1) and fascin, the latter being a marker of tumor cell metastatization in lung cancer. Membranous but not cytoplasmic labelling emerged as an independent risk factor for death and reduced time to progression in adenocarcinoma but not in squamous cell carcinoma patients, when singly adjusted for confounding factors. CD117 immunoreactivity identifies a peculiar subset of stage I adenocarcinoma and squamous cell carcinoma of the lung with highly proliferative tumors and may have prognostic relevance in adenocarcinoma patients. Targeting the CD117 pathway could be a novel therapeutic strategy in a subset of pulmonary carcinomas.