Chromosomal Alterations and Gene Expression Changes Associated with the Progression of Leukoplakia to Advanced Gingivobuccal Cancer

We present an integrative genome-wide analysis that can be used to predict the risk of progression from leukoplakia to oral squamous cell carcinoma (OSCC) arising in the gingivobuccal complex (GBC). We find that the genomic and transcriptomic profiles of leukoplakia resemble those observed in later stages of OSCC and that several changes are associated with this progression, including amplification of 8q24.3, deletion of 8p23.2, and dysregulation of DERL3, EIF5A2, ECT2, HOXC9, HOXC13, MAL, MFAP5 and NELL2. Comparing copy number profiles of primary tumors with and without lymph-node metastasis, we identify alterations associated with metastasis, including amplifications of 3p26.3, 8q24.21, 11q22.1, 11q22.3 and deletion of 8p23.2. Integrative analysis reveals several biomarkers that have never or rarely been reported in previous OSCC studies, including amplifications of 1p36.33 (attributable to MXRA8), 3q26.31 (EIF5A2), 9p24.1 (CD274), and 12q13.2 (HOXC9 and HOXC13). Additionally, we find that amplifications of 1p36.33 and 11q22.1 are strongly correlated with poor clinical outcome. Overall, our findings delineate genomic changes that can be used in treatment management for patients with potentially malignant leukoplakia and OSCC patients with higher risk of lymph-node metastasis

Role of imaging in the management of thyroglossal duct cyst carcinomas (TGC-TIRADS): a single centre retrospective study over 16 years

IntroductionThyroglossal duct cyst (TGDC) is the most frequently encountered developmental anomaly in thyroid genesis with a reported incidence of 7% in the adult population. The cyst is known to develop anywhere along the pathway of thyroid descent but is more frequently seen in the infrahyoid neck in the midline. The incidence of malignancy in a TGDC is approximately 1%; a majority of these are papillary carcinomas. This study was conducted at a single tertiary care centre which spanned over a decade which adds practice changing evidence-based knowledge to existing literature on this rare entity. A comprehensive study which conclusively establishes the imaging features predictive of malignancy in TGDC carcinomas (TGDCa), the protocol for optimal management, clinical outcome and long-term survival of these patients is not available. Although TGDC carcinoma is thought to have an excellent prognosis, there is not enough data available on the long-term survival of these patients. The aim of this study was to identify whether neck ultrasound (US) can serve as an accurate imaging tool for the preoperative diagnosis of TGDC carcinomas.MethodsWe accessed the electronic medical records of 86 patients with TGDC between January 2005 to December 2021. Of these, 22 patients were detected with TGDC papillary carcinoma on histopathologic examination. Relevant imaging, treatment and follow up information for all cases of TGDC carcinoma were retrospectively reviewed. We compared US characteristics predictive of malignancy across outcomes groups; malignant vs benign using the Chi-square test. Based on the results, a TGC-TIRADS classification was proposed with calculation of the percentage likelihood of malignancy for each category.ResultsCompared to benign TGDCs, malignant TGDCs were more likely to present with following US characteristics: irregular or lobulated margins (90.40 vs. 38.10%), solid-cystic composition (61.90 vs. 17.07%), internal vascularity (47.62 vs. 4.88 %), internal calcification (76.19 vs. 7.32 %) (each p value < 0.005). Calcifications and internal vascularity were the most specific while irregular/lobulated margins were the most sensitive feature for malignancy. AUC under the ROC curve was 0.88. Allpatients were operated and were disease free at the end of 5 years or till the recent follow up.DiscussionUS is the imaging modality of choice for pre-operative diagnosis of TGDC carcinoma. Thepre-operative diagnosis and risk stratification of thyroglossal lesions will be aided by the application of the proposed TGC-TIRADS classification, for which the percentage likelihood of malignancy correlated well with the results in our study. Sistrunk procedure is adequate for isolated TGDC carcinoma; suspicious neck nodes on imaging also necessitates selective nodal dissection. Papillary carcinomas have an excellent prognosis with low incidence of disease recurrence

Nasal mucosal metastasis in a case of carcinoma esophagus: Case report and review of literature

A 60-year-old male, chronic alcoholic and smoker with decompensated cirrhosis was diagnosed with adenocarcinoma lower-third esophagus with multiple liver metastasis. While on palliative chemotherapy, the patient presented with a lesion at the tip of the nose. Excision of the lesion was performed suspecting mucormycosis. Histopathological examination revealed a poorly differentiated adenocarcinoma esophagus, similar to the initial disease. The nasal lesion recurred in 2 months, which was palliated with external radiotherapy given to the nasal lesion as well as the primary. The aim of this article is to present this rare case and review literature related to metastatic carcinoma of the esophagus with focus on nasal metastasis

Cytopathological features of scar endometriosis mimicking an adenocarcinoma: A diagnostic pitfall

Scar endometriosis can be a diagnostic challenge in fine-needle aspiration cytology (FNAC) smears that at times, is the first diagnostic modality in such cases. The challenge is amplified when the clinical details are limited and cytopathological features reveal nuclear atypia. A 33-year-old lady presented with an abdominal swelling that she noticed after she met with a scald. Clinically, the swelling was located lateral to her 3-year-old pfannenstiel incision scar. The initial diagnosis on FNAC was metastatic adenocarcinoma. On review, smears were hypercellular, comprising epithelial cells in groups and focally, regular glandular arrangements, imperceptibly admixed with numerous, relatively smaller, short spindly cells. Epithelial cells exhibited mild to focally, moderate nuclear enlargement/atypia. Subsequent biopsy and excision revealed endometrial glands exhibiting focal nuclear atypia with adjacent stroma. Diagnosis of endometriosis was offered. The results were reinforced with positive estrogen receptor staining in the glands and stroma, along with CD10 positivity in the stroma. The patient was recommended gonadotropin releasing hormone analogs and is presently free of disease a year after her diagnosis. FNAC can be a pitfall in the diagnosis of endometriosis. Correct diagnosis has significant therapeutic implications. Although presence of atypia in such cases should not delude the diagnosing cytopathologist for consideration of endometriosis, it should be documented. The value of clinical history in such cases cannot be overemphasized

Immunoglobulin G4-related disease (IgG4-RD) manifestations in the head-and-neck: A narrative review with a focus on imaging

Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune fibrosclerotic inflammatory condition with distinctive histopathological findings affecting various organ systems. The disease can be tumefactive or “mass-like” in morphology, or less commonly, infiltrative. Many historic and well-known disease entities are manifestations of IgG4-RD in different organs. Radiologists need to be aware of this multifaceted disorder and its systemic nature. We searched Pubmed and Embase using the keywords “head and neck,” “IgG4-related disease,” and “imaging.” We included the relevant review articles published in the English language from 1997 to 2021, whose major area of discussion was IgG4-RD manifestations in the head-and-neck. Filters applied for inclusion were: “full text,” “humans,” “English,” “cancer,” article type: “review,” “meta-analysis,” “systematic review,” and “guideline.” In this review article, we have discussed the wide spectrum of manifestations of this disease at different head-and-neck subsites to familiarize radiologists with this interesting disease entity

Recurring Amplification at 11q22.1-q22.2 Locus Plays an Important Role in Lymph Node Metastasis and Radioresistance in OSCC

A key feature in the pathogenesis of OSCC is genetic instability, which results in altered expression of genes located in amplified/deleted chromosomal regions. In a previous study we have shown that the amplification of the 11q22.1-q22.2 region, encoding cIAP1 and cIAP2, is associated with lymph node metastasis and poor clinical outcome in OSCC. Here, we validate the aCGH results by nuc ish and detect a weak amplification at the 11q22.1-q22.2 locus in 37% of the 182 samples tested. We find positive correlation of 11q22.1-q22.2 amplification with lymph node metastasis, reduced survival, and increased cancer recurrence, and we observe that patients with 11q22.1-q22.2 amplification fail to respond to radiotherapy. We confirm the concurrent overexpression of cIAP1 and cIAP2 and observe differential subcellular localization of the two proteins in OSCC. To ascertain the roles of cIAP1/cIAP2 in lymph node metastasis and radioresistance, we use an in vitro pre-clinical model and confirm the role of cIAP1 in invasion and the role of cIAP2 in invasion and migration. Studies of other tumor types in which cIAP1 is overexpressed suggest that multi-regimen treatments including SMAC mimetics may be effective. Thus, the evaluation of 11q22.1-q22.2 amplifications in OSCC patients may help choose the most effective treatment

Genome-wide DNA methylation profiling of HPV-negative leukoplakia and gingivobuccal complex cancers

Background Gingivobuccal complex oral squamous cell carcinoma (GBC-OSCC) is an aggressive malignancy with high mortality often preceded by premalignant lesions, including leukoplakia. Previous studies have reported genomic drivers in OSCC, but much remains to be elucidated about DNA methylation patterns across different stages of oral carcinogenesis. Results There is a serious lack of biomarkers and clinical application of biomarkers for early detection and prognosis of gingivobuccal complex cancers. Hence, in search of novel biomarkers, we measured genome-wide DNA methylation in 22 normal oral tissues, 22 leukoplakia, and 74 GBC-OSCC tissue samples. Both leukoplakia and GBC-OSCC had distinct methylation profiles as compared to normal oral tissue samples. Aberrant DNA methylation increases during the different stages of oral carcinogenesis, from premalignant lesions to carcinoma. We identified 846 and 5111 differentially methylated promoters in leukoplakia and GBC-OSCC, respectively, with a sizable fraction shared between the two sets. Further, we identified potential biomarkers from integrative analysis in gingivobuccal complex cancers and validated them in an independent cohort. Integration of genome, epigenome, and transcriptome data revealed candidate genes with gene expression synergistically regulated by copy number and DNA methylation changes. Regularised Cox regression identified 32 genes associated with patient survival. In an independent set of samples, we validated eight genes (FAT1, GLDC, HOXB13, CST7, CYB5A, MLLT11, GHR, LY75) from the integrative analysis and 30 genes from previously published reports. Bisulfite pyrosequencing validated GLDC (P = 0.036), HOXB13 (P < 0.0001) promoter hypermethylation, and FAT1 (P < 0.0001) hypomethylation in GBC-OSCC compared to normal controls. Conclusions Our findings identified methylation signatures associated with leukoplakia and gingivobuccal complex cancers. The integrative analysis in GBC-OSCC identified putative biomarkers that enhance existing knowledge of oral carcinogenesis and may potentially help in risk stratification and prognosis of GBC-OSCC.ISSN:1868-7075ISSN:1868-708