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Biomarkers of Oral Cancer

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A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 35330

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Prof. Dr. Paweł Golusiński

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Poznan University of Medical Sciences, Poznan, Poland

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Dear Colleagues,

Oral cancer is the 11th most common malignancy in the world, with 354,864 new cases and 177,384 deaths worldwide (GLOBOCAN, 2018) The highest incidence of these cancers has mainly been reported in South and Southeast Asia and some countries in southern Europe.

The most important risk factors for oral cancer development are tobacco use and extensive alcohol consumption. Moreover, infection with oncogenic types of human papillomavirus (HPV) has been identified as a significant risk factor for a subset of oral cancer.

The main reasons for failure in oral cancer treatment, and the strongest adverse factors for prognosis, are the spread to the regional lymph nodes and early development of local recurrence or second primary tumors. Modern head and neck oncology can offer a plethora of treatment modalities including surgical resection with reconstructive options, radiotherapy (including proton therapy), conventional and targeted systemic treatment, and also, as of late, immunotherapy. The success rates of treatments can significantly vary between particular patients. Thus, one of the biggest future challenges is to tailor multidisciplinary treatments such that they are based not only on clinical assessment of disease advancement determined by stage, but also on the biological factors of the tumor.

Advances in genetics and molecular biology have improved our knowledge of cellular mechanisms, which provide insights into the pathophysiological processes that turn healthy epithelial cells into cancer. Potential biomarkers and therapeutic targets can be investigated to identify genetic signatures that could potentially be used for early diagnosis, treatment personalization, and finally, determination of prognosis for individual patients.

Prof. Dr. Paweł Golusiński
Guest Editor

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Keywords

Oral cancer
Head and neck squamous cell carcinoma
Biomarkers
Molecular diagnostics
Risk factors
Treatment strategies

Related Special Issue

Biomarkers of Oral Cancer 2.0 in Diagnostics (17 articles)

Published Papers (13 papers)

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Research

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14 pages, 1163 KiB

Open AccessArticle

CYP26A1 Is a Novel Biomarker for Betel Quid-Related Oral and Pharyngeal Cancers

by Ping-Ho Chen, Chia-Min Chung, Yen-Yun Wang, Hurng-Wern Huang, Bin Huang, Ka-Wo Lee, Shyng-Shiou Yuan, Che-Wei Wu, Lee-Shuan Lin and Leong-Perng Chan

Diagnostics 2020, 10(11), 982; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10110982 - 21 Nov 2020

Cited by 2 | Viewed by 1969

Abstract

Betel quid (BQ) has been classified as a Group I human carcinogen in light of evidence demonstrating an association with an elevated risk of oral and pharyngeal cancers. To date, the incidence rate of oral and pharynx cancers among Taiwanese men ranks the highest worldwide. However, no study has yet confirmed variants of CYP26A1 was associated with the risks of oral and pharyngeal cancers. A case-control study was conducted (n = 339). CYP26A1 polymorphism was performed using SNP assay. Real-time qRT-PCR and Western blotting were used to determine the levels of CYP26A1 expression. The cancer cell model involved treatment with arecoline. Our findings showed that the downregulation of CYP26A1 mRNA and protein expression are more frequently observed in cancerous tissues than adjacent normal tissues in patients with oral and pharynx cancers (p < 0.01). We found that CYP26A1 was downregulated as the arecoline dose increased. We hypothesized that lower levels of CYP26A1 mRNA expression can be utilized a clinically biomarker causes oral and pharynx cancers. Arecoline appears to modulate CYP26A1 expression through specific pathways. Carriers of CYP26A1 SNP, rs2068888 (G/G)/rs4418728 (G/G) and who have lower levels of CYP26A1 expression are associated with an increased risk of oral and pharyngeal cancers. Full article

(This article belongs to the Special Issue Biomarkers of Oral Cancer)

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14 pages, 1398 KiB

Open AccessArticle

The AST/ALT (De Ritis) Ratio Predicts Survival in Patients with Oral and Oropharyngeal Cancer

by Olivia Knittelfelder, Daniela Delago, Gabi Jakse, Sabine Reinisch, Richard Partl, Heidi Stranzl-Lawatsch, Wilfried Renner and Tanja Langsenlehner

Diagnostics 2020, 10(11), 973; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10110973 - 19 Nov 2020

Cited by 27 | Viewed by 3241

Abstract

Aminotransaminases, including aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT), are strongly involved in cancer cell metabolism and have been associated with prognosis in different types of cancer. The purpose of the present study was to evaluate the prognostic significance of the pre-treatment AST/ALT ratio in a large European cohort of patients with oral and oropharyngeal squamous cell cancer (OOSCC). Data from 515 patients treated for OOSCC at a tertiary academic center from 2000–2017 were retrospectively analyzed. Levels of AST and ALT were measured prior to the start of treatment. Uni- and multivariate Cox regression analyses were applied to evaluate the prognostic value of the AST/ALT ratio for cancer-specific survival (CSS) and overall survival (OS), survival rates were calculated. Univariate analyses showed a significant association of the AST/ALT ratio with CSS (hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.38–2.12; p < 0.001) and OS (HR 1.69, 95% CI 1.41–2.02; p < 0.001). In multivariate analysis, the AST/ALT ratio remained an independent prognostic factor for CSS and OS (HR 1.45, 95% CI 1.12–1.88, p = 0.005 and HR 1.42, 95% CI 1.14–1.77, p = 0.002). Applying receiver operating characteristics (ROC) curve analysis, the optimal cut-off level for the AST/ALT ratio was 1.44, respectively. In multivariate analysis, an AST/ALT ratio > 1.44 was an independent prognostic factor for poor CSS and OS (HR 1.64, 95% CI 1.10–2.43, p = 0.014 and HR 1.55, 95% CI 1.12–2.15; p = 0.008). We conclude that the AST/ALT ratio is a prognostic marker for survival in OOSCC patients and could contribute to a better risk stratification and improved oncological therapy decisions. Full article

(This article belongs to the Special Issue Biomarkers of Oral Cancer)

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13 pages, 2210 KiB

Open AccessArticle

Initial and Delayed Metabolic Activity of Palatine Tonsils Measured with the PET/CT-Dedicated Parameters

by Agata Pietrzak, Andrzej Marszalek, Malgorzata Paterska, Pawel Golusinski, Julitta Narozna and Witold Cholewinski

Diagnostics 2020, 10(10), 836; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10100836 - 17 Oct 2020

Cited by 4 | Viewed by 3193

Abstract

One of the most critical elements in the palatine tonsils (PT) patients’ management is to distinguish chronic tonsillitis and malignant tumor. The single-time-point (STP) 2-deoxy-2-[¹⁸ F]fluoro-D-glucose positron emission tomography/computed tomography (¹⁸ F-FDG PET/CT) examination offers the most significant sensitivity and specificity in the head and neck (H&N) region evaluation among commonly used methods of imaging. However, introducing dual-time-point (DTP) scanning might improve the specificity and sensitivity of the technique, limited by the ¹⁸ F-FDG non-tumor-specific patterns, especially when comparing different metabolic parameters. The study aims to compare several surrogates of the maximal standardized uptake value (SUVmax), obtained in 36 subjects, divided into confirmed by pathologic study PT cancer and tonsillitis in patients who underwent DTP ¹⁸ F-FDG PET/CT scanning. In this study, we observed the increased sensitivity and the specificity of the DTP ¹⁸ F-FDG PET/CT when compared with the standard PET/CT protocol. It could be concluded that DTP ¹⁸ F-FDG PET/CT improves the PT cancer and chronic tonsillitis differential diagnosis. Full article

(This article belongs to the Special Issue Biomarkers of Oral Cancer)

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20 pages, 2839 KiB

Open AccessArticle

Diagnostic and Prognostic Value of Salivary Biochemical Markers in Oral Squamous Cell Carcinoma

by Lyudmila V. Bel’skaya, Elena A. Sarf, Denis V. Solomatin and Victor K. Kosenok

Diagnostics 2020, 10(10), 818; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10100818 - 14 Oct 2020

Cited by 8 | Viewed by 2106

Abstract

The purpose of the work is a comprehensive assessment of biochemical saliva markers for the diagnosis and prognosis of oral cancer. The group of patients included 68 patients with oral squamous cell carcinoma, 50 with non-cancerous diseases of the oral cavity, and 114 healthy volunteers. Before the start of treatment, 23 biochemical parameters of saliva were determined. Participants were monitored for six years to assess survival rates. The statistical analysis was performed by means of Statistica 10.0 and R package. A complex of metabolic changes occurring in saliva in oral cancer is described. It was shown that none of the studied parameters could be used to diagnose oral cancer in an independent variant; the use of combinations of parameters is more informative. The high prognostic value of the content of malondialdehyde (MDA) and the Na/K-ratio in saliva before treatment was established. Thus, the content of MDA ˂ 7.34 nmol/mL and the Na/K-ratio > 1.09 c.u. is a prognostically unfavorable factor (HR = 7.88, 95% CI 1.10–54.62, p = 0.01876), which may be useful for optimizing the treatment of patients with oral cancer. It has been shown that saliva has great potential for the development of diagnostic and prognostic tests for oral cancer. Full article

(This article belongs to the Special Issue Biomarkers of Oral Cancer)

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10 pages, 3887 KiB

Open AccessArticle

The Prognostic Significance of Immune-Related Metabolic Enzyme MTHFD2 in Head and Neck Squamous Cell Carcinoma

by Li Cui, Huan Chen and Xinyuan Zhao

Diagnostics 2020, 10(9), 689; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10090689 - 11 Sep 2020

Cited by 10 | Viewed by 2236

Abstract

Metabolic dysregulation has emerged as a crucial determinant of the clinical responses to immunotherapy. The aim of this study was to determine the clinical significance of the candidate immune-related metabolic enzymes (IRMEs) methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2 (MTHFD2) in head and neck squamous cell carcinoma (HNSCC). The gene expression profile of HNSCC cohort and the corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA). The differentially expressed IRMEs were identified, and then, the prognosis-associated IRMEs were revealed by univariate cox regression analysis. The prognostic significance of MTHFD2 in HNSCC as well as the association between MTHFD2 and immune cell infiltration were further analyzed. A total of 121 significantly altered IRMEs were identified between HNSCC and normal tissues, and 21 IRMEs were found to be strongly associated with overall survival of HNSCC. Upregulation of MTHFD2 was positively correlated with adverse clinicopathological factors in TCGA HNSCC cohort, which was further validated with our own cohort using immunohistochemical analysis. Interestingly, bioinformatic analysis further revealed that increased MTHFD2 expression was negatively associated with NK cells activation, while positively correlated with mast cells activation. In conclusion, MTHFD2 overexpression is closely correlated with unfavorable prognosis of HNSCC, and it might play an important role in modulating the tumor immune microenvironment. Full article

(This article belongs to the Special Issue Biomarkers of Oral Cancer)

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16 pages, 1514 KiB

Open AccessArticle

UBE2C is a Potential Biomarker for Tumorigenesis and Prognosis in Tongue Squamous Cell Carcinoma

by Pei-Feng Liu, Chun-Feng Chen, Chih-Wen Shu, Hui-Min Chang, Cheng-Hsin Lee, Huei-Han Liou, Luo-Ping Ger, Chun-Lin Chen and Bor-Hwang Kang

Diagnostics 2020, 10(9), 674; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10090674 - 04 Sep 2020

Cited by 17 | Viewed by 2714

Abstract

Ubiquitin-conjugating enzyme 2C (UBE2C) involves in numerous cellular processes and the tumor progression in many cancers. However, its role in oral squamous cell carcinoma (OSCC) is unclear. We aimed to investigate the role and clinical significance of UBE2C in OSCC. The expression levels of UBE2C were examined by immunohistochemistry in 185 buccal mucosa squamous cell carcinomas, 247 tongue squamous cell carcinomas (TSCCs) and 75 lip squamous cell carcinomas. The roles of UBE2C in cell growth, invasion/migration and cancer stemness were also examined in OSCC cells. The expression levels of UBE2C protein were higher in tumor tissues than they were in the corresponding tumor adjacent normal tissues from OSCC patients. Higher UBE2C expression was associated with poor cell differentiation and lymph node invasion in OSCC patients. High UBE2C expression was also correlated with shorter disease-specific survival in TSCC patients having poor cell differentiation, advanced pathological stages, lymph node metastasis as well as receiving radiation therapy. Compared to control cells, OSCC cells in which UBE2C was silenced showed decreased cell proliferation, migration/invasion and colony formation and they exhibited lower expression levels of the following cancer stemness markers—ALDH1/A2, CD44, CD166 and EpCAM. High co-expression levels of UBE2C/CD44, UBE2C/CD166 and UBE2C/EpCAM were associated with poor prognosis in oral cancer patients from The Cancer Genome Atlas database. Our findings indicated that UBE2C might be a potential biomarker for tumorigenesis and prognosis in TSCC. Full article

(This article belongs to the Special Issue Biomarkers of Oral Cancer)

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19 pages, 5715 KiB

Open AccessArticle

The Oncogenic Roles of PTTG1 and PTTG2 Genes and Pseudogene PTTG3P in Head and Neck Squamous Cell Carcinomas

by Inga Grzechowiak, Justyna Graś, Dominika Szymańska, Martyna Biernacka, Kacper Guglas, Paulina Poter, Andrzej Mackiewicz and Tomasz Kolenda

Diagnostics 2020, 10(8), 606; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080606 - 18 Aug 2020

Cited by 9 | Viewed by 2962

Abstract

Background: Head and neck squamous cell carcinomas are a group of heterogeneous diseases that occur in the mouth, pharynx and larynx and are characterized by poor prognosis. A low overall survival rate leads to a need to develop biomarkers for early head and neck squamous cell carcinomas detection, accurate prognosis and appropriate selection of therapy. Therefore, in this paper, we investigate the biological role of the PTTG3P pseudogene and associated genes PTTG1 and PTTG2 and their potential use as biomarkers. Methods: Based on TCGA data and the UALCAN database, PTTG3P, PTTG1 and PTTG2 expression profiles and clinicopathological features with TP53 gene status as well as expression levels of correlated genes were analyzed in patients’ tissue samples. The selected genes were classified according to their biological function using the PANTHER tool. Gene Set Enrichment Analysis software was used for functional enrichment analysis. All statistical analyses were performed using GraphPad Prism 5. Results: In head and neck squamous cell carcinomas, significant up-regulation of the PTTG3P pseudogene, PTTG1 and PTTG2 genes’ expression between normal and cancer samples were observed. Moreover, the expression of PTTG3P, PTTG1 and PTTG2 depends on the type of mutation in TP53 gene, and they correlate with genes from p53 pathway. PTTG3P expression was significantly correlated with PTTG1 as well as PTTG2, as was PTTG1 expression with PTTG2. Significant differences between expression levels of PTTG3P, PTTG1 and PTTG2 in head and neck squamous cell carcinomas patients were also observed in clinicopathological contexts. The contexts taken into consideration included: T-stage for PTTG3P; grade for PTTG3, PTTG1 and PTTG2; perineural invasion and lymph node neck dissection for PTTG1 and HPV p16 status for PTTG3P, PTTG1 and PTTG2. A significantly longer disease-free survival for patients with low expressions of PTTG3P and PTTG2, as compared to high expression groups, was also observed. Gene Set Enrichment Analysis indicated that the PTTG3 high-expressing group of patients have the most deregulated genes connected with DNA repair, oxidative phosphorylation and peroxisome pathways. For PTTG1, altered genes are from DNA repair groups, Myc targets, E2F targets and oxidative phosphorylation pathways, while for PTTG2, changes in E2F targets, G2M checkpoints and oxidative phosphorylation pathways are indicated. Conclusions: PTTG3P and PTTG2 can be used as a prognostic biomarker in head and neck squamous cell carcinomas diagnostics. Moreover, patients with high expressions of PTTG3P, PTTG1 or PTTG2 have worse outcomes due to upregulation of oncogenic pathways and more aggressive phenotypes. Full article

(This article belongs to the Special Issue Biomarkers of Oral Cancer)

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8 pages, 2257 KiB

Open AccessCommunication

Impact of Chromosome 9 Numerical Imbalances in Oral Squamous Cell Carcinoma: A Pilot Grid-Based Centromere Analysis

by Efthymios Kyrodimos, Aristeidis Chrysovergis, Nicholas Mastronikolis, Evangelos Tsiambas, Christos Riziotis, Dimitrios Roukas, Panagiotis Fotiades, Chara Stavraka, Vasileios Ragos, Minas Paschopoulos and Vasileios Papanikolaou

Diagnostics 2020, 10(7), 501; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10070501 - 21 Jul 2020

Cited by 2 | Viewed by 2242

Abstract

Oral squamous cell carcinoma (OSCC) is considered an aggressive malignancy, mainly due to its increased propensity to provide local and distant lymph node metastases. Gross chromosome instability (CI; polysomy/aneuploidy/monosomy), combined or not with specific gene alterations, is implicated in the development and progression of solid malignancies, including OSCC. In order to further study the relationship between these genetic alterations and the aggressive biological behavior of OSCCs, we investigated the frequency and impact of chromosome 9 numerical imbalances in these tumors. Fifty (n = 50) formalin-fixed, paraffin-embedded primary OSCC tissue sections were used. Chromogenic in situ hybridization (CISH) was implemented for detecting chromosome 9 (CEN—centromere enumeration) numerical alterations. Concerning the screening process in CISH slides, a novel, real-time reference and calibration grid platform was implemented. Chromosome 9 polysomy was observed in 8/50 (16%) tissue sections, whereas the rest of them demonstrated a normal, diploid pattern (42/50; 84%). Chromosome 9 polysomy was associated with the grade of differentiation of the examined tumors (p = 0.036). Chromosome 9 numerical imbalances (polysomy) were observed in sub-groups of OSCCs correlating with a progressive dedifferentiation of the malignant tissues. Concerning the implementation of the proposed grid-based platform as described above on CISH slides, it provides a novel, fast, and accurate screening mapping mechanism for detecting chromosome numerical imbalances. Full article

(This article belongs to the Special Issue Biomarkers of Oral Cancer)

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9 pages, 2319 KiB

Open AccessArticle

Overexpression of EIF5A2 Predicts Poor Prognosis in Patients with Oral Squamous Cell Carcinoma

by Yueh-Min Lin, Mei-Ling Chen, Chia-Lo Chen, Chung-Min Yeh and Wen-Wei Sung

Diagnostics 2020, 10(7), 436; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10070436 - 27 Jun 2020

Cited by 9 | Viewed by 2002

Abstract

Oral squamous cell carcinoma (OSCC) is the most common epithelial malignancy affecting the oral cavity, and it is especially significant in Asian countries. Patients diagnosed with OSCC have an unfavorable prognosis and additional prognostic markers would help improve therapeutic strategies. We sought to investigate the association between eukaryotic translation initiation factor 5A2 (EIF5A2) and epithelial–mesenchymal transition (EMT) markers as well as the prognostic significance of EIF5A2 in OSCC. The expression of EIF5A2 and EMT markers was measured through the immunohistochemical staining of specimens from 272 patients with OSCC. In addition, the correlation between different clinicopathological factors and EIF5A2 expression was analyzed. The prognostic role of EIF5A2 was then analyzed via Kaplan–Meier analysis and Cox proportional hazard models. Among the 272 patients, high EIF5A2 expression was significantly associated with an advanced N value (p = 0.008). High tumor expression of EIF5A2 was prone to the expression of low E-cadherin and high beta-catenin (p = 0.046 and p = 0.020, respectively). Patients with high EIF5A2 expression had unfavorable five-year survival rates as compared with those with low expression (49.7% and 67.3%, respectively). The prognostic role of EIF5A2 was further confirmed through multivariate analysis (hazard ratio = 1.714, 95% confidence interval: 1.134–2.590, p = 0.011). High EIF5A2 expression is associated with an advanced N value and EMT markers and may serve as a marker for an unfavorable prognosis in patients with OSCC. Full article

(This article belongs to the Special Issue Biomarkers of Oral Cancer)

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16 pages, 1069 KiB

Open AccessReview

Head and Neck Squamous Cell Carcinoma: Epigenetic Landscape

by Kamila Romanowska, Agnieszka Sobecka, Agnieszka A. Rawłuszko-Wieczorek, Wiktoria M. Suchorska and Wojciech Golusiński

Diagnostics 2021, 11(1), 34; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics11010034 - 27 Dec 2020

Cited by 26 | Viewed by 3304

Abstract

Head and neck squamous carcinoma (HNSCC) constitutes the sixth most prevalent cancer worldwide. The molecular pathogenesis of HNSCC includes disorders in cell cycle, intercellular signaling, proliferation, squamous cell differentiation and apoptosis. In addition to the genetic mutations, changes in HNSCC are also characterized by the accumulation of epigenetic alterations such as DNA methylation, histone modifications, non-coding RNA activity and RNA methylation. In fact, some of them may promote cancer formation and progression by controlling the gene expression machinery, hence, they could be used as biomarkers in the clinical surveillance of HNSCC or as targets for therapeutic strategies. In this review, we focus on the current knowledge regarding epigenetic modifications observed in HNSCC and its predictive value for cancer development. Full article

(This article belongs to the Special Issue Biomarkers of Oral Cancer)

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7 pages, 4504 KiB

Open AccessCase Report

Use of Liquid-based Cytology and Cell Block Combined Technique for an Accurate Diagnosis of Oral Diffuse Large B Cell Lymphoma: A Case Report

by Aya Yoshino, Shintaro Ishida, Shinsuke Nakamura, Ryosuke Kita, Mika Seto, Shinji Matsumoto, Morishige Takeshita and Seiji Kondo

Diagnostics 2020, 10(10), 823; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10100823 - 14 Oct 2020

Viewed by 2464

Abstract

Primary oral diffuse large B cell lymphoma (DLBCL) is rare and the differential diagnosis is difficult due to its low incidence and nonspecific symptoms, which resemble those of common oral diseases in the initial clinical setting. We aimed to discuss the value of making an accurate diagnosis using liquid-based cytology (LBC) and cell block (CB) for not only the morphological interpretation but also cytohistological assessment of oral DLBCL. LBC and CBs made from oral brushing materials were prepared on the first medical examination and a morphological analysis and immunohistochemical analysis of specific biomarkers were performed. The analysis of LBC preparations showed the presence of large-size lymphocytes with large irregular nuclei and prominent nucleoli, suggesting the existence of large B-cell lymphoma. A more detailed histological subclassification of the CB specimen was performed, which was classified as the activated B-cell (ABC) phenotype of DLBCL, by confirming the immunohistochemical expression of CD10−/ B-cell lymphoma 6 (BCL6)+/ multiple myeloma oncogene 1(MUM1)+, which is a significant risk factor in DLBCL. Our findings suggest that the combination of LBC and CB is a useful and informative tool for making an accurate molecular diagnosis of oral DLBCL in cases in which lymphomas are clinically suspected. Full article

(This article belongs to the Special Issue Biomarkers of Oral Cancer)

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8 pages, 5889 KiB

Open AccessCase Report

Intraepithelial Macrophage Expressing CD163 Is a Histopathological Clue to Evaluate the Malignant Potency of Oral Lichenoid Condition: A Case Report and Immunohistochemical Investigation

by Manabu Shigeoka, Yu-ichiro Koma, Maki Kanzawa, Masaya Akashi and Hiroshi Yokozaki

Diagnostics 2020, 10(9), 624; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10090624 - 23 Aug 2020

Cited by 4 | Viewed by 2831

Abstract

Oral lichenoid conditions (OLC), including oral lichen planus (OLP), oral lichenoid lesions and oral lichenoid dysplasia, differ in pathogenesis and biological malignancy. However, distinguishing them based on clinical or histological features is difficult. It is well known that CD163⁺ macrophages are associated with oral cancer aggressiveness. We recently demonstrated that CD163⁺ macrophages of noncancerous lesions infiltrate the stroma, not the intraepithelial area. In this report, we describe a case of OLC that was not detected as malignant by the first local biopsy. Furthermore, we evaluated the malignant potency of OLC by retrospectively comparing the histological findings between local biopsy and resected specimens focusing on CD163⁺ macrophages. A 72-year-old man with a white lesion in the unilateral buccal mucosa was diagnosed with OLP through the biopsy although invasive cancer was detected two years later. Intraepithelial CD163⁺ macrophages were found not only on the resected specimen but also biopsy. This is the first report to demonstrate that intraepithelial CD163⁺ macrophages may be noteworthy indicators to identify the malignant potency of OLC. Full article

(This article belongs to the Special Issue Biomarkers of Oral Cancer)

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9 pages, 5436 KiB

Open AccessCase Report

Biphasic Thyroid-Like Low-Grade Nasopharyngeal Papillary Adenocarcinoma with a Prominent Spindle Cell Component: A Case Report

by Sang Hwa Lee, Hyunjin Kim, Min Ju Kim, Byungwha Kim and Hyun-Soo Kim

Diagnostics 2020, 10(5), 323; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10050323 - 19 May 2020

Cited by 5 | Viewed by 3270

Abstract

Thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TLLG-NPPA) is a distinctly rare malignancy of the nasopharynx. Morphologically and immunophenotypically, TLLG-NPPA resembles papillary thyroid carcinoma (PTC) and is characterized by a papillary architecture with PTC-like nuclear features and thyroid transcription factor-1 expression. Recently, some cases of TLLG-NPPA with a spindle cell component have been reported. In this study, we report a very interesting case of biphasic TLLG-NPPA that was predominantly composed of spindle cells, with comprehensive analyses of its clinical, pathological, and immunophenotypical features. A 50-year-old woman presented with a sensation of a foreign body in the nasopharynx. Nasopharyngoscopy and computed tomography demonstrated a pedunculated mass arising from the nasopharyngeal roof. Based on the clinical impression of a nasopharyngeal tumor, an excisional biopsy was performed. At low-power magnification, the nasopharyngeal mass consisted of papillary tumor tissue, the growth pattern and architecture of which resembled those of PTC. The papillae were complex and packed tightly with fibrovascular cores. At high-power magnification, each papillary structure was lined with a pseudostratified cuboidal-to-columnar epithelium. The tumor cell nuclei frequently showed a ground-glass appearance, intranuclear grooves, pseudoinclusions, and membrane thickening and irregularity, resembling the characteristic nuclear morphology of PTC. These histological features were compatible with TLLG-NPPA. Intriguingly, in between the papillary components were spindle cells that appeared very similar to the glandular epithelial cells that imperceptibly merged with the papillary component. This spindle cell component comprised two-thirds of the entire tumor volume. The nuclear morphology of the spindle cell component was similar to that of the papillary component. On immunostaining, both the papillary and spindle cell components were diffusely and strongly positive for thyroid transcription factor-1, cytokeratin 7, cytokeratin 19, vimentin, and Hector Battifora mesothelial-1. In contrast, the tumor cells tested negative for p63, p40, smooth muscle actin, S-100, cytokeratin 5/6, thyroglobulin, BRAF V600E, and Epstein–Barr virus-encoded small RNAs. Only two cases of biphasic TLLG-NPPA exhibiting a prominent spindle cell component had been reported previously in the English literature. When the pathologist receives a primary nasopharyngeal mass with the aforementioned histological features, particularly biopsy specimens with predominant spindle cells, biphasic TLLG-NPPA should be considered in the differential diagnosis. By describing its detailed clinicopathological characteristics, we anticipate that this report will expand the existing knowledge on the spindle cell component associated with TLLG-NPPA. Full article

(This article belongs to the Special Issue Biomarkers of Oral Cancer)

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