Publications by authors named "Ibrahim O Bello"

27 Publications

  • Page 1 of 1

Sialolipoma of the Floor of the Mouth with Immunohistological Analysis.

Case Rep Dent 2021 5;2021:6623045. Epub 2021 Apr 5.

Department of Oral Medicine and Diagnostic Sciences, King Saud University and University Dental Hospital, Riyadh, Saudi Arabia.

Lipomas are relatively rare in the head and neck, and sialolipoma was described as an entity about 20 years ago as lipoma that entraps salivary gland tissue. Less than 10 cases have been described in the floor of the mouth not related to the major salivary glands. Here, we report a case of sialolipoma affecting the floor of the mouth in a 47-year-old patient and reviewed the clinical, histologic, and immunohistochemical characteristics of the lesion.
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http://dx.doi.org/10.1155/2021/6623045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049828PMC
April 2021

Authorization of the first COVID-19 emergency vaccines: The matters arising.

EXCLI J 2021 15;20:655-660. Epub 2021 Mar 15.

Department of Medical Laboratory Science, Nigerian Navy School of Health Sciences, Offa, Kwara State, Nigeria.

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http://dx.doi.org/10.17179/excli2021-3384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056048PMC
March 2021

Biopsy quality is essential for preoperative prognostication in oral tongue cancer.

APMIS 2021 Mar 28;129(3):118-127. Epub 2020 Dec 28.

Department of Pathology, University of Helsinki, Helsinki, Finland.

A role for incisional biopsy in preoperative prognostication is increasingly being advocated in oral tongue squamous cell carcinomas (OTSCC). Biopsies at two locations were compared, and prognostic factors in biopsies and their corresponding resections were evaluated. A total of 138 OTSCC biopsy slides from Finland and Saudi Arabia were compared for size (horizontal and vertical) and invasive front. The Finnish cases were assessed for tumor stroma ratio (TSR) and tumor-infiltrating lymphocytes (TILs) using light microscopy and digital image analysis assessment and compared. Furthermore, TSR, TILs, and previously analyzed budding and depth of invasion (BD) score in biopsies were compared with their evaluation in the corresponding resections. Fifty-nine percent of Finnish and 42% of Saudi Arabian biopsies were ≥ 5 mm deep, while 98% of Saudi Arabian and 76% of Finnish biopsies were ≥ 5 mm wide. Assessment of invasion front was possible in 72% of Finnish in comparison with 40% of Saudi Arabian biopsies. There was 86.8% agreement between TSR and 75% agreement between TIL evaluation using light microscopy and digital assessment. Significant agreement was obtained on comparing the TSR (p = 0.04) and BD (p < 0.001) values in biopsies and resections. Biopsies of ≥ 5 mm depth from representative OTSCC areas are essential for prognostic information. Clinical pathologists are advised to assess BD score and TSR for prognostic features in such biopsies.
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http://dx.doi.org/10.1111/apm.13104DOI Listing
March 2021

Stromal categorization in early oral tongue cancer.

Virchows Arch 2021 May 21;478(5):925-932. Epub 2020 Sep 21.

Institute of Biomedicine, Pathology, University of Turku and Turku University Hospital, Turku, Finland.

Stromal categorization has been used to classify many epithelial cancer types. We assessed the desmoplastic reaction and compared its significance with other stromal characteristics in early (cT1-2N0) oral tongue squamous cell carcinoma (OTSCC). In this multi-institutional study, we included 308 cases treated for early OTSCC at five Finnish university hospitals or at the A.C. Camargo Cancer Center in São Paulo, Brazil. The desmoplastic reaction was classified as immature, intermediate, or mature based on the amount of hyalinized keloid-like collagen and myxoid stroma. We compared the prognostic value of the desmoplastic reaction with a stromal grading system based on tumor-stroma ratio and stromal tumor-infiltrating lymphocytes. We found that a high amount of stroma with a weak infiltration of lymphocytes was associated statistically significantly with a worse disease-free survival with a hazard ratio (HR) of 2.68 (95% CI 1.26-5.69), worse overall survival (HR 2.95, 95% CI 1.69-5.15), and poor disease-specific survival (HR 2.66, 95% CI 1.11-6.33). Tumors having a high amount of stroma with a weak infiltration of lymphocytes were also significantly associated with a high rate of local recurrence (HR 4.13, 95% CI 1.67-10.24), but no significant association was found with lymph node metastasis (HR 1.27, 95% CI 0.37-4.35). Categorization of the stroma based on desmoplastic reaction (immature, intermediate, mature) showed a low prognostic value for early OTSCC in all survival analyses (P > 0.05). In conclusion, categorization of the stroma based on the amount of stroma and its infiltrating lymphocytes shows clinical relevance in early OTSCC superior to categorization based on the maturity of stroma.
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http://dx.doi.org/10.1007/s00428-020-02930-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099799PMC
May 2021

FAK, paxillin, and PI3K in ameloblastoma and adenomatoid odontogenic tumor.

Clin Oral Investig 2021 Mar 17;25(3):1559-1567. Epub 2020 Jul 17.

Medical Informatics and Statistics Research Group, University of Oulu, Oulu, Finland.

Objective: Integrins function to bind cells to extracellular matrix in tissues, which triggers downstream signaling cascades that are important in cell survival, proliferation, cytokine activation, and cytoskeleton reorganization. These processes also play significant roles in neoplasms. This work aimed to investigate the pattern of expression of FAK, paxillin, and PI3K in ameloblastoma and adenomatoid odontogenic tumor (AOT).

Materials And Methods: Immunohistochemistry was used to study FAK, paxillin, and PI3K in 45 ameloblastomas (32 conventional, 12 unicystic, and 1 peripheral types), 7 AOTs, and two developing human teeth.

Results: Weak expression of FAK was seen in all AOT cases, while ameloblastoma had varying expression patterns, mostly strong to weak. The pattern of expression of paxillin and PI3K was relatively similar in both tumor types. In the dental germ, FAK and paxillin stained all the enamel organ components, while PI3K stained strongly the inner enamel epithelium. Stromal expression of FAK was not found to be useful in differentiating between tumors or tumor classes.

Conclusion: The expression of the proteins in the enamel organ suggests that their signaling may be important in odontogenesis. While some ameloblastomas strongly expressed FAK, all cases of AOT had weak signals suggesting low presence and phosphorylating activity of FAK in the latter.

Clinical Relevance: A subset of FAK-positive ameloblastoma (as well as their malignant or metastasizing counterparts) which may have relatively aggressive behavior may be candidates for drug targeting of FAK as an additional management option.
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http://dx.doi.org/10.1007/s00784-020-03465-4DOI Listing
March 2021

Histological characteristics of early-stage oral tongue cancer in young versus older patients: A multicenter matched-pair analysis.

Oral Dis 2020 Jul 14;26(5):1081-1085. Epub 2020 Feb 14.

Department of Pathology, University of Helsinki, Helsinki, Finland.

Little is known about the histopathological characteristics that may differentiate early oral tongue cancer (OTSCC) between young and older patients. From a total of 311 cases diagnosed with clinically early-stage OTSCC at 6 institutions, only 42 patients were young patients were aged ≤45 years. For comparison, 42 patients >60 years old were matched for center of management, clinical stage and gender. We compared epithelial and stromal histopathologic parameters between the two groups. Most of the parameters were similar between the two groups, although the young patients appeared to have marginally higher intensity of tumor budding, histologic risk score, infiltrative pattern of invasion and tumor-stroma ratio. However, none of the factors showed significant difference when comparing the two groups. The histological parameters reflect mechanisms of invasive growth and tissue response to invasive growth, but not the etiological difference in OTSCC between young and older patients. Further investigations are necessary to compare the genetic background of early OTSCC in the two groups.
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http://dx.doi.org/10.1111/odi.13288DOI Listing
July 2020

Lateral Periodontal Cyst Treated with Enucleation and Guided Bone Regeneration: A Report of a Case and a Review of Pertinent Literature.

Case Rep Dent 2019 8;2019:4591019. Epub 2019 Jul 8.

Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia.

Lateral periodontal cyst (LPC) is an uncommon developmental odontogenic cyst arising on the lateral surface of tooth roots. Commonly reported in mandibular canine-premolar or maxillary anterior regions, it presents as a well-circumscribed or tear drop-shaped radiolucency with a sclerotic border. Associated teeth are asymptomatic and vital, and roots may be displaced without resorption. Histopathologically, cystic lining resembles reduced enamel epithelium along with glycogen-rich clear cells and epithelial plaques. Unilateral variant of LPC has low recurrence and is managed by enucleation. A 43-year-old male patient reported with asymptomatic swelling in the left mandibular canine and first premolar region. Both teeth were vital, and radiographs revealed well-circumscribed radiolucency between the roots. Following consent, surgical enucleation and guided bone regeneration (GBR) with xenograft and resorbable collagen membrane were done under local anesthesia. The immediate postoperative period was uneventful, and complete bone fill of cystic cavity and healing of periodontal tissues was observed after a one-year follow-up. Histopathologic examination confirmed the diagnosis. LPC should be a differential diagnosis in cystic lesions lateral to the surface of a tooth and without any associated inflammation. Based on this case report, unicystic LPC can be successfully managed through surgical enucleation with GBR for better periodontal healing.
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http://dx.doi.org/10.1155/2019/4591019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644300PMC
July 2019

Assessment of Tumor-infiltrating Lymphocytes Predicts the Behavior of Early-stage Oral Tongue Cancer.

Am J Surg Pathol 2019 10;43(10):1392-1396

Departments of Pathology.

Tumor-infiltrating lymphocytes (TILs) have shown a promising prognostic value in many epithelial cancers. We sought to assess the prognostic value of TILs in a multicenter cohort of early oral tongue squamous cell carcinoma (OTSCC). The percentage of TILs was assessed on the surgical resection slides stained with hematoxylin and eosin. The assessment of TILs was performed in the stromal compartment and in the intraepithelial compartment (at the invasive front and at the center of the tumor). We followed the method that was described recently by the International Immuno-Oncology Biomarker Working Group for the assessment of TILs. A total of 308 cases from the 5 Finnish university hospitals and from A.C. Camargo Cancer Center, São Paulo, Brazil, were included. We found a promising prognostic value for stromal TILs at the invasive front in the multivariable analysis with a hazard ratio of 2.61 (95% confidence interval [CI], 1.77-3.83; P<0.001) for overall survival, 1.99 (95% CI, 1.07-3.69; P=0.040) for disease-specific survival, and 1.94 (95% CI, 1.14-3.29; P=0.020) for disease-free survival. In conclusion, evaluation of TILs is simple and can aid in identifying the high-risk cases of early OTSCC. The method introduced by the International Immuno-Oncology Biomarker Working Group can be used for standardized determination of TILs in early OTSCC.
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http://dx.doi.org/10.1097/PAS.0000000000001323DOI Listing
October 2019

Comparison of histological grading methods in mucoepidermoid carcinoma of minor salivary glands.

Indian J Pathol Microbiol 2016 Oct-Dec;59(4):457-462

Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, King Saud University, Riyadh, Saudi Arabia.

Context: Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy and its grading is greatly consequential in the management and prognosis of patients with the disease.

Aims: To compare histologic grading systems in MEC of minor salivary glands.

Settings And Design: Two qualitative (modified Healy and Memorial Sloan-Kettering Cancer Center [MSKCC] methods) and two quantitative (Armed Forces Institute of Pathology [AFIP] and Brandwein methods) were evaluated.

Subjects And Methods: Diagnostics slides of 19 patients including one recurrent case were evaluated using the four grading systems.

Statistical Analysis Used: Percentages and proportions were used.

Results: Agreement across all grading system was found to be very low (32%) while there was a better agreement between AFIP and MSKCC methods (84%) between modified Healy and Brandwein (58%). The method that gave the poorest agreement with all the others was the Brandwein grading. In general, the AFIP and MSKCC methods tended to grade the tumors lower while the Brandwein and modified Healy methods seemed to grade them higher.

Conclusions: Most MEC of minor salivary glands appear to be low-grade tumors. It is conceivable that some grading methods (Brandwein and modified Healy) may lead to an unnecessary escalation of management methods in these tumors. The MSKCC method may have emphasized some parameters which may not have much importance in minor salivary gland MEC. The AFIP method appears to be the most appropriate to use for the grading of minor salivary gland MEC. Further studies are required to confirm or disprove this finding.
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http://dx.doi.org/10.4103/0377-4929.191765DOI Listing
March 2017

The range of diagnoses for oral soft-tissue biopsies of geriatric patients in a Saudi Arabian teaching hospital.

Saudi Dent J 2016 Apr 13;28(2):96-101. Epub 2016 Apr 13.

Department of Oral Medicine and Diagnostic Sciences, King Saud University College of Dentistry, Saudi Arabia.

Introduction: The increased life expectancy being observed worldwide necessitates careful planning for future geriatric oral health care needs, which should be based on epidemiologic surveys to identify these needs. We aimed to survey the range of lesions diagnosed in soft-tissue biopsies of patients over age 60 over a 30-year period in a Saudi Arabian teaching hospital.

Methods: The histopathology records of geriatric patients with complete demographic data who were diagnosed between 1984 and 2013 at the College of Dentistry, King Saud University, were reviewed. The lesions were then classified into eight broad categories. Associations between variables were evaluated using Pearson's Chi square test.

Results: There were 231 soft-tissue biopsies obtained from geriatric patients whose complete records were available. The male to female ratio was 1.1:1, and the mean age was 66.7 years. Most lesions (69%) occurred in patents aged 60-69 years. Although reactive lesions were generally the most common, the most common lesions were squamous cell carcinoma and fibroma. Lesions were most commonly located on the buccal mucosa and the alveolar ridge/gingivae.

Conclusions: The range of lesions seen in Saudi geriatric patients were similar to those reported for other parts of the world, although the lesions were more similar to those reported from developing countries. The very high rate of oral cancer, however, is expected to take the majority of the resources allocated to geriatric oral health care, except if a strong, population-based prevention program is initiated immediately.
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http://dx.doi.org/10.1016/j.sdentj.2016.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957536PMC
April 2016

Does securin expression have significance in prognostication of oral tongue cancer? A pilot study.

Eur Arch Otorhinolaryngol 2016 Nov 18;273(11):3905-3911. Epub 2016 Apr 18.

Department of Pathology, University of Helsinki, Helsinki, Finland.

The proliferation marker, securin, is involved in the progression of many carcinomas. However, its expression in oral tongue squamous cell carcinoma (OTSCC) has not been previously studied. We examined securin expression by immunohistochemistry in OTSCC. A total of 93 cases treated for OTSCC were included in this study. Expression of securin in OTSCC was studied by immunohistochemistry of tissue microarrays (52 cases) and routine tumor sections (41 cases). Securin overexpression is significantly associated with higher tumor grade (P = 0.03). Overexpression of securin was observed more frequently in advanced stages of OTSCC than in earlier stages but the difference was not statistically significant. These findings suggest that overexpression of securin in OTSCC may be important during progression of this cancer. No significant association was found between securin expression and the prognosis of OTSCC.
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http://dx.doi.org/10.1007/s00405-016-3964-yDOI Listing
November 2016

For early-stage oral tongue cancer, depth of invasion and worst pattern of invasion are the strongest pathological predictors for locoregional recurrence and mortality.

Virchows Arch 2015 Jul 3;467(1):39-46. Epub 2015 Apr 3.

Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.

Despite early diagnosis and treatment, almost 20% of patients with early-stage (cT1-cT2N0) oral tongue squamous cell carcinoma (OTSCC) still die of their disease. The prognosis of OTSCC patients is influenced by several demographic, clinical, and histopathologic factors. The aim of this multicenter international study was to find which of the factors age, gender, stage, grade, lymphocytic host response, perineural invasion, worst pattern of invasion, or depth of invasion has the strongest prognostic power in early-stage OTSCC. Patient data of 479 patients with early-stage (cT1-2N0) OTSCC in Finland, Brazil, and the USA were retrieved and analyzed using Cox proportional hazards regression models. Our results indicate that depth of invasion (DOI) and worst pattern of invasion (WPOI) are the strongest pathological predictors for locoregional recurrence, with a hazard ratio (HR) for 4 mm DOI of 1.67 (95% confidence interval (CI) 1.07-2.60) and HR for WPOI of 1.46 (95% CI 0.95-2.25). In addition, mortality from early OTSCC was also predicted by DOI (HR 2.44, 95% CI 1.34-4.47) and by WPOI (HR 2.34, 95% CI 1.26-4.32). We suggest that clinically early-stage oral tongue carcinomas 4 mm or deeper, or with a growth pattern of small cell islands or satellites, should be considered as high-risk tumors which require multimodality treatment.
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http://dx.doi.org/10.1007/s00428-015-1758-zDOI Listing
July 2015

Insights into the role of components of the tumor microenvironment in oral carcinoma call for new therapeutic approaches.

Exp Cell Res 2014 Jul 22;325(2):58-64. Epub 2014 Jan 22.

Department of Oral Pathology and Oral Medicine, School of Dentistry, Tel Aviv University, Tel Aviv 69978, Israel.

The research on oral cancer has focused mainly on the cancer cells, their genetic changes and consequent phenotypic modifications. However, it is increasingly clear that the tumor microenvironment (TME) has been shown to be in a dynamic state of inter-relations with the cancer cells. The TME contains a variety of components including the non-cancerous cells (i.e., immune cells, resident fibroblasts and angiogenic vascular cells) and the ECM milieu [including fibers (mainly collagen and fibronectin) and soluble factors (i.e., enzymes, growth factors, cytokines and chemokines)]. Thus, it is currently assumed that TME is considered a part of the cancerous tissue and the functionality of its key components constitutes the setting on which the hallmarks of the cancer cells can evolve. Therefore, in terms of controlling a malignancy, one should control the growth, invasion and spread of the cancer cells through modifications in the TME components. This mini review focuses on the TME as a diagnostic approach and reports the recent insights into the role of different TME key components [such as carcinoma-associated fibroblasts (CAFs) and inflammation (CAI) cells, angiogenesis, stromal matrix molecules and proteases] in the molecular biology of oral carcinoma. Furthermore, the impact of TME components on clinical outcomes and the concomitant need for development of new therapeutic approaches will be discussed.
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http://dx.doi.org/10.1016/j.yexcr.2013.12.029DOI Listing
July 2014

Key architectural changes in tumor-negative lymph nodes from metastatic-free oral cancer patients are valuable prognostic factors.

Clin Exp Metastasis 2014 Mar 7;31(3):327-38. Epub 2014 Jan 7.

Institute of Pathology, The Chaim Sheba Medical Center, Tel Hashomer, Israel,

Regional lymph node (LN) metastasis in oral cancer patients is the most significant grave prognostic factor. We evaluated the relationship between clinical outcomes and different histopathological changes in tumor-negative LNs (LN0) selected from neck dissections without metastatic disease (pN0). A total of 435 LN0 selected from pN0 neck dissections (up to three nodes in each level) were scored for histopathological parameters of LN areas, capsule thickness, subcapsular and medullary sinus ectasia, lobular architecture and percent of cortical reactive follicles. These were compared to 328 LN0 selected from neck dissections with metastases (pN+) after exclusion of metastatic LNs. Data were presented by maximum scores of each parameter in I-III (close) and in IV-V (distant) levels. Limited data from level V and regression analyses inferred that the values in level IV represented the worst changes for most patients. Cox proportional hazard regression on each parameter in close and distant levels demonstrated that capsule thickness, number of lobules and percent of reactive follicles were significantly associated with time to death from disease. The higher the change in distant levels, the shorter the time to death, while the higher the change in close levels (given a stable change in distant levels), the longer the time to death. After adjustment for gender, age and location, only the effect of the percent of reactive follicles retained their significant effect. Logistic regression of metastases demonstrated that all parameters except for percent of reactive follicles were significantly associated with risk of metastases, with differences between close and distant levels similar to those found for time to death. After adjustment for gender, age and location, only the area and number of lobes retained their significance. The findings of this study suggested that selective histopathological changes in tumor-negative LNs in metastatic-free patients provide new valuable prognostic parameters.
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http://dx.doi.org/10.1007/s10585-013-9631-4DOI Listing
March 2014

Human bone marrow mesenchymal stem cells induce collagen production and tongue cancer invasion.

PLoS One 2013 21;8(10):e77692. Epub 2013 Oct 21.

Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Oulu, Finland.

Tumor microenvironment (TME) is an active player in carcinogenesis and changes in its composition modify cancer growth. Carcinoma-associated fibroblasts, bone marrow-derived multipotent mesenchymal stem cells (BMMSCs), and inflammatory cells can all affect the composition of TME leading to changes in proliferation, invasion and metastasis formation of carcinoma cells. In this study, we confirmed an interaction between BMMSCs and oral tongue squamous cell carcinoma (OTSCC) cells by analyzing the invasion progression and gene expression pattern. In a 3-dimensional myoma organotypic invasion model the presence of BMMSCs inhibited the proliferation but increased the invasion of OTSCC cells. Furthermore, the signals originating from OTSCC cells up-regulated the expression of inflammatory chemokines by BMMSCs, whereas BMMSC products induced the expression of known invasion linked molecules by carcinoma cells. Particularly, after the cell-cell interactions, the chemokine CCL5 was abundantly secreted from BMMSCs and a function blocking antibody against CCL5 inhibited BMMSC enhanced cancer invasion area. However, CCL5 blocking antibody did not inhibit the depth of invasion. Additionally, after exposure to BMMSCs, the expression of type I collagen mRNA in OTSCC cells was markedly up-regulated. Interestingly, also high expression of type I collagen N-terminal propeptide (PINP) in vivo correlated with the cancer-specific mortality of OTSCC patients, whereas there was no association between cancer tissue CCL5 levels and the clinical parameters. In conclusion, our results suggest that the interaction between BMMSC and carcinoma cells induce cytokine and matrix molecule expression, of which high level of type I collagen production correlates with the prognosis of OTSCC patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0077692PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804615PMC
August 2014

Recurrent unilateral submandibular swelling.

Oral Surg Oral Med Oral Pathol Oral Radiol 2013 Jun 12;115(6):705-9. Epub 2012 May 12.

Department of Oral Medicine and Diagnostic Oral Sciences, King Saud University, College of Dentistry, Riyadh, Saudi Arabia.

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http://dx.doi.org/10.1016/j.oooo.2012.01.022DOI Listing
June 2013

Depth of invasion, tumor budding, and worst pattern of invasion: prognostic indicators in early-stage oral tongue cancer.

Head Neck 2014 Jun 2;36(6):811-8. Epub 2013 Sep 2.

Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.

Background: Oral (mobile) tongue squamous cell carcinoma (SCC) is characterized by a highly variable prognosis in early-stage disease (T1/T2 N0M0). The ability to classify early oral tongue SCCs into low-risk and high-risk categories would represent a major advancement in their management.

Methods: Depth of invasion, tumor budding, histologic risk-assessment score (HRS), and cancer-associated fibroblast (CAF) density were studied in 233 cases of T1/T2 N0M0 oral tongue SCC managed in 5 university hospitals in Finland.

Results: Tumor budding (≥5 clusters at the invasive front of the tumor) and depth of invasion (≥4 mm) were associated with poor prognosis in patients with early oral tongue SCC (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.17-3.55; HR, 2.55; 95% CI, 1.25-5.20, respectively) after multivariate analysis. The HRS and CAF density did not predict survival. However, high-risk worst pattern of invasion (WPOI), a component of HRS, was also an independent prognostic factor (HR, 4.47; 95% CI, 1.59-12.51).

Conclusion: Analyzing the depth of invasion, tumor budding, and/or WPOI in prognostication and treatment planning of T1/T2 N0M0 oral tongue SCC is recommended.
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http://dx.doi.org/10.1002/hed.23380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229066PMC
June 2014

Unicystic mucoepidermoid carcinoma presenting as a salivary duct cyst.

Int J Surg Pathol 2013 Apr 27;21(2):181-5. Epub 2012 Jul 27.

King Saud University, Riyadh, Saudi Arabia.

A cystic swelling in the parotid gland should lead to a differential diagnosis that includes benign cystic lesion of the gland, benign tumors that are frequently associated with cystic degeneration or entirely cystic de novo, or even a malignant neoplasm. The case presented is that of a cystic parotid swelling of 2 years' duration in a 52-year-old female patient. The clinical differentials in the present case were reviewed and were entirely different from the final histological diagnosis of low-grade mucoepidermoid carcinoma. The uniqueness of this case is the very rare unicystic presentation of the lesion. The authors also discuss why the clinical and radiological investigations were not suggestive of the final diagnosis.
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http://dx.doi.org/10.1177/1066896912454918DOI Listing
April 2013

Epithelial salivary gland tumors in two distant geographical locations, Finland (Helsinki and Oulu) and Israel (Tel Aviv): a 10-year retrospective comparative study of 2,218 cases.

Head Neck Pathol 2012 Jun 7;6(2):224-31. Epub 2012 Jan 7.

Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Oulu, Finland.

Salivary gland tumors (SGTs) of epithelial origin are relatively rare, and worldwide reports show considerable variations in their epidemiology. The aim of this study was to examine, for the first time, the records of SGTs from two very distant geographical locations, Finland (two medical centers) and Israel (one medical center) between 1999 and 2008, based exclusively on the 2005 WHO classification of head and neck tumors, and to compare those data to the other available (single-center) studies that used the same classification. A total of 2,218 benign and malignant tumors diagnosed in the three centers were analyzed. Differences in classification of the tumors were found between the two geographical locations as well as between the two centers from Finland. There was a higher ratio of benign-to-malignant SGTs in the Finnish centers (5.4:1 and 7:1) compared to the Israeli center (2:1), a higher frequency of tumors of minor salivary glands in the Israeli center (34%) than in the Finnish centers (4 and 11%), and a higher frequency of malignant SGTs in the minor salivary glands in Israel (64.5%) than in Finland (10.9 and 27%). The diversity of these multicenter data are compatible with reports from different parts of the world. We conclude that conducting epidemiologic surveys based on the latest WHO classification provides clinicopathologic correlations on SGTs that seem to be characteristic even in small geographical regions.
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http://dx.doi.org/10.1007/s12105-011-0316-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370031PMC
June 2012

Peripheral dentinogenic ghost cell tumor: report of a case and literature review.

Int J Surg Pathol 2012 Oct 30;20(5):494-9. Epub 2011 Nov 30.

King Saud University, Riyadh, Saudi Arabia.

Peripheral dentinogenic ghost cell tumor is a rare tumor with only 24 cases previously described in the English literature. The majority of cases have been reported to occur in the anterior part of the jaws. A case occurring in posterior (molar region) of the mandible in a 75-year-old edentulous woman is reported. The patient presented with a nodular swelling in the left mandible that showed erosion (saucerization) of the underlying bone radiographically. On microscopy, the tumor showed mainly solid epithelial islands resembling ameloblastoma in fibrous connective tissue. The islands were associated with ghost cells and dysplastic dentin. This report includes the clinical, radiographic, and microscopic features of the patient, in addition to the review of the English literature on the tumor.
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http://dx.doi.org/10.1177/1066896911429299DOI Listing
October 2012

Expression pattern of claudins 1 and 3-an auxiliary tool in predicting behavior of mucoepidermoid carcinoma of salivary gland origin.

Virchows Arch 2011 Mar 24;458(3):341-8. Epub 2010 Dec 24.

Department of Otolaryngology-Head and Neck Surgery, Helsinki University Central Hospital, Helsinki, Finland.

Claudins (CLDNs) are a family of membrane proteins important for permeability of tight junctions. They have also been implicated in carcinogenesis and tumor progression. We analyzed patterns of distribution and intensity of expression of CLDNs 1, 3, 4, and 7 in mucoepidermoid carcinoma (MEC) of salivary gland in 39 patients. Correlations between the expression of CLDNs, tumor grade, and survival were explored. In immunohistochemical analysis, high expression of CLDN 1 was seen in low-grade MEC, and it appeared to be a suitable auxiliary marker of good prognosis. It classified MEC similarly to histological grading in 89.7% of cases (p = 0.001). High CLDN 3 expression was seen in intermediate- and high-grade MEC, while it was low in low-grade MEC. CLDN 3 intensity correctly categorized tumors into grades in 71.8% of cases (p = 0.017). However, in multivariate analysis CLDN 1 and CLDN 3 did not achieve significance over tumor grade in predicting patient behavior. We conclude that analysis of staining intensities of CLDN 1 and 3 is useful as an auxiliary diagnostic and prognostic tool in patients with salivary gland MEC.
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http://dx.doi.org/10.1007/s00428-010-1026-1DOI Listing
March 2011

Cancer-associated fibroblasts, a parameter of the tumor microenvironment, overcomes carcinoma-associated parameters in the prognosis of patients with mobile tongue cancer.

Oral Oncol 2011 Jan 26;47(1):33-8. Epub 2010 Nov 26.

Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Oulu FI-90014, Finland.

Mobile tongue squamous cell carcinoma (MTSCC) is known for its strong propensity for regional metastasis and poor patient survival despite aggressive treatment, thus calling for new and reliable markers for predicting prognosis and guiding therapeutic management. Towards this end, three classes of markers were investigated: cancer-associated fibroblasts (CAFs; α-SMA positivity) as a representative of the tumor microenvironment, maspin (mammary serine protease inhibitor) as a tumor marker likely to be modulated by factors within the tumor microenvironment, and DNA content and Ki-67 labeling index as inbuilt tumor markers in 128 cases of MTSCC using immunohistochemistry and image cytometry. Of these markers, only CAF density was independently and relatively strongly associated with elevated mortality from MTSCC. The hazard ratio in the CAF-rich type of tumor microenvironment was 4.85 (95% CI 1.41-16.6, versus the CAF-poor) when adjusted by proportional hazards modeling for the center where the patient was managed, gender, tumor stage, presence of neck metastasis and age at diagnosis. CAF density was unrelated to non-MTSSC mortality. Given the strong association between increased CAF density and higher mortality in MTSCC, routine assessment of CAF density for disease course prognosis and inclusion as an integral part of treatment protocols are recommended.
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http://dx.doi.org/10.1016/j.oraloncology.2010.10.013DOI Listing
January 2011

Prognostic evaluation of oral tongue cancer: means, markers and perspectives (I).

Oral Oncol 2010 Sep 15;46(9):630-5. Epub 2010 Jul 15.

Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Oulu, Finland.

Oral (mobile) tongue squamous cell carcinoma (OTSCC) is the most common cancer diagnosed within the oral cavity. Due to the inherent disadvantages of the mobile tongue OTSCC behaves aggressively and is generally associated with higher rates of occult metastasis and neck nodal metastasis than any other cancer of the oral cavity. The prognosis remains relatively poor and is still heavily reliant on TNM (tumor, node, metastasis) staging of the tumor despite a vast array of literature on possible prognostic indicators. This is a two-part article which examines the methods by which the behavior and prognosis of OTSCC has been studied, the prognostics markers, and the relevance and future direction of prognostic studies. In this first part, we discuss the relative merits of the methods used in prognostic studies and the clinicopathologic prognostic factors.
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http://dx.doi.org/10.1016/j.oraloncology.2010.06.006DOI Listing
September 2010

Prognostic evaluation of oral tongue cancer: means, markers and perspectives (II).

Oral Oncol 2010 Sep 15;46(9):636-43. Epub 2010 Jul 15.

Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Oulu, Finland.

Squamous cell carcinoma of the oral (mobile) tongue (OTSCC) is increasingly regarded as a biologically different entity compared to cancer affecting other oral sites. It is more aggressive and generally associated with a higher rate of metastasis. This is the concluding part of our two-part article that examines the methods by which the behavior and prognosis of OTSCC has been studied, the prognostics markers, and the relevance and future direction of prognostic studies. In this part, we continue our discussion of the histopathologic and molecular prognostic factors, and serum and salivary biomarkers in of OTSCC, and emphasize the need to regard OTSCC as a high risk variant of oral cancer. We conclude with future direction of prognostic studies of OTSCC.
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http://dx.doi.org/10.1016/j.oraloncology.2010.06.008DOI Listing
September 2010

Cancer-associated fibroblasts and epithelial-mesenchymal transition in metastatic oral tongue squamous cell carcinoma.

Int J Cancer 2010 Sep;127(6):1356-62

Institute of Pathology; Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.

We examined cancer-associated fibroblasts (CAFs) and a panel of immunohistochemical markers of epithelial-mesenchymal transition (EMT) in 19 pair-matched oral tongue squamous cell carcinoma (SCC) and metastatic tumors to regional lymph nodes (RLNs). alpha-Smooth muscle actin (alpha-SMA) was studied to identify CAFs. EMT was studied with syndecan-1, Cadherin-11, fibroblast-specific protein (FSP)-1, secreted protein acidic and rich in cysteine (SPARC) and Twist. Triple immunostaining in RLNs was used to highlight the carcinoma cells (E-cadherin and Ki-67) and their relationship to the CAFs (alpha-SMA). We found that metastatic RLNs hosted CAFs similarly as in pair-matched primary tumors. Expression of EMT markers is common in both primary and metastatic tumors. We demonstrate that metastatic carcinoma cells (Ki-67 positive) downregulate E-cadherin expression at the periphery of cancer islands, where they are in direct contact with CAFs. The supporting connective tissue microenvironment also commonly expresses syndecan-1, Cadherin-11, FSP-1, and SPARC. In conclusion, CAFs are common to both primary and metastatic SCC. We hypothesize that CAFs not only promote tumor invasion but also facilitate metastases, either by cometastasizing and/or being recruited to lymph nodes. Evidence of EMT is common within primary tumors and metastatic SCC and may be further modulated by CAFs.
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http://dx.doi.org/10.1002/ijc.25358DOI Listing
September 2010

Expression of claudins 1, 4, 5, and 7 and occludin, and relationship with prognosis in squamous cell carcinoma of the tongue.

Hum Pathol 2008 Aug 10;39(8):1212-20. Epub 2008 Jun 10.

Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Oulu University Hospital, Oulu, Finland.

Claudins and occludin are tight junctional proteins known to play a role in normal tissues and epithelial tumors. We analyzed the distribution patterns of claudins 1, 4, 5, and 7 and occludin in the superficial and invasive front of squamous cell carcinoma of the tongue of 97 patients and their relationship to cause-specific (squamous cell carcinoma of the tongue) patient survival (median follow-up period of 33.5 months; range, 1-234 months). Claudins 1 and 7 were strongly expressed, claudin 4 had moderate expression, whereas claudin 5 was least expressed. Occludin staining was mostly negative or very weak. Western blot analysis of tongue carcinoma (HSC-3) cells showed that all these proteins are also expressed in vitro. In cause-specific survival analysis, strong and low immunoreactivity of claudin 7 tended to be associated with decreased survival compared with medium immunoreactivity. We suggest that analyzing the immunohistologic staining levels of claudin 7 could be used for the prognostic purposes in patients with tongue squamous cell carcinoma.
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http://dx.doi.org/10.1016/j.humpath.2007.12.015DOI Listing
August 2008

Claudins 1, 4, 5, 7 and occludin in ameloblastomas and developing human teeth.

J Oral Pathol Med 2007 Jan;36(1):48-54

Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, Oulu, Finland.

Background: To analyze the distribution pattern of claudins 1, 4, 5, 7 and occludin in benign and malignant ameloblastomas and developing human teeth.

Methods: Paraffin-embedded tissue specimens of 25 benign and four malignant ameloblastomas and two developing human teeth were examined immunohistochemically using antibodies against claudins 1, 4, 5, 7 and occludin.

Results: In ameloblastomas strongest expression was seen for claudins 1 and 7 while claudin 4 was expressed less frequently. Claudin 5 and occludin were seen only in a minority of cases. There were no evident differences in the expression of claudins or occludin neither between different histologic subtypes of ameloblastomas nor between benign or malignant cases. The strongest expression for claudins was present in the central stellatum reticulum-like cells surrounding the microcysts and in the areas with squamous differentiation of the ameloblastomas. In developing teeth both claudin 1 and 7 stained strongly in the enamel epithelium, ameloblasts, and enamel matrix, but staining for claudin 4 was relatively weak. Claudin 5 was preferentially expressed only in vessels, and occludin staining ranged from negative to weak in ameloblastomas and teeth germs.

Conclusion: There were no clear differences in the expression levels between benign and malignant ameloblastic tumors. The overexpression of claudins in the areas with microcyst formation may indicate their attempt to maintain the interepithelial cohesion of the cells. The strong immunoreactivity of ameloblasts and newly synthesized enamel matrix for claudins 1 and 7 indicates that they may be involved in cell signaling influencing enamel formation.
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http://dx.doi.org/10.1111/j.1600-0714.2006.00497.xDOI Listing
January 2007