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Challenges Related to the Oral Cavity, Head and Neck: From Diagnosis to Therapy

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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 (31 July 2025) | Viewed by 22404

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Dr. Saverio Capodiferro

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Department of Interdisciplinary Medicine, University of Bari Aldo Moro, 70124 Bari, Italy
Interests: dental prosthesis; oral pathology; implant dentistry; dental materials; dentures
Special Issues, Collections and Topics in MDPI journals

Dr. Antonio D’Amati

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1. Anatomic Pathology Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70121 Bari, Italy
2. Department of Medicine and Surgery, LUM University "Giuseppe DeGennaro", 70010 Casamassima, Italy
Interests: pathology; molecular pathology; molecular oncology; neuropathology; CNS tumors; gynecological pathology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The intricacies of disorders of the oral cavity, head, and neck present clinicians with significant challenges, necessitating a multidisciplinary approach to achieve accurate diagnosis and effective therapeutic strategies. This Special Issue aims to explore the spectrum of complex cases encountered in these anatomical regions, encompassing diverse etiologies, diagnostic dilemmas, and therapeutic interventions. By delving into nuanced clinical scenarios, this collection seeks to foster a deeper understanding of the complexities that are inherent to managing conditions ranging from oral cancers and maxillofacial trauma to rare pathologies and treatment-resistant diseases. Through case presentations, innovative diagnostic techniques, therapeutic modalities, and outcome assessments, this Special Issue endeavors to advance our knowledge and enhance clinical practice regarding disorders of the oral cavity, head, neck. Contributions from clinicians, researchers, and allied healthcare professionals are invited, in order to enrich this exploration and contribute to our collective effort to address the formidable challenges posed by these interlinked clinical scenarios. For this Special Issue, we would particularly like to publish research articles and comprehensive reviews.

Dr. Saverio Capodiferro
Dr. Antonio d'Amati
Guest Editors

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Keywords

oral oncology
oral diseases
head and neck
diagnosis
therapeutic approach

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Published Papers (11 papers)

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Research

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12 pages, 1321 KB

Open AccessArticle

Evaluation of CK8/18 and CK19 Expression as Adjunct Immunohistochemical Markers in Non-Keratinizing Nasopharyngeal Carcinoma

by Ummul Afila Omar, Suria Hayati Binti Md Pauzi, Mohd Razif Bin Mohamad Yunus, Rosnah Sutan, Nur Maya Sabrina binti Tizen Laim, Muaatamarulain bin Mustangin and Reena Rahayu Md Zin

Diagnostics 2025, 15(18), 2292; https://doi.org/10.3390/diagnostics15182292 - 10 Sep 2025

Viewed by 806

Abstract

Background: Nasopharyngeal carcinoma (NPC), particularly the non-keratinizing subtype (NK-NPC), is prevalent in Southeast Asia and often presents diagnostic challenges due to overlapping histological features with benign nasopharyngeal lesions. While Epstein–Barr virus (EBV) serology supports diagnosis in many cases, its limitations in sensitivity and specificity necessitate additional tissue-based markers. Objective: To assess the immunohistochemical expression of cytokeratins CK8/18 and CK19 in NPC compared to benign nasal tissue and evaluate their potential as adjunct immunohistochemical markers. Methods: This retrospective study evaluated the immunohistochemical expression of cytokeratins CK8/18 and CK19 in 24 NK-NPC and 22 benign nasopharyngeal tissue samples collected between April 2021 and April 2024 at Hospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia. Staining intensity and distribution were scored semi-quantitatively, and statistical analysis was performed using SPSS v29.0 (p < 0.05). Results: CK19 was expressed in all NK-NPC cases, with strong positivity in 79.2%, while CK8/18 was positive in 92%, primarily with weak to moderate staining. Only one benign case (inverted papilloma) showed focal positivity. The differences in expression between malignant and benign tissues were statistically significant (p < 0.001). Sub-analysis of EBER-positive cases (n = 15) confirmed consistently strong CK19 expression. Conclusions: Based on this small retrospective cohort, CK8/18 and particularly CK19 demonstrate expression patterns that may support their use as adjunct immunohistochemical markers in the histopathological assessment of NK-NPC, especially in morphologically ambiguous cases. Further validation in larger studies is needed before these markers can be considered for routine diagnostic application. Full article

(This article belongs to the Special Issue Challenges Related to the Oral Cavity, Head and Neck: From Diagnosis to Therapy)

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10 pages, 3271 KB

Open AccessArticle

The Condition of the Masseter Muscles After Orthodontic Treatment with Fixed Appliances

by Sebastian Szajkowski, Jarosław Pasek and Grzegorz Cieślar

Diagnostics 2024, 14(23), 2755; https://doi.org/10.3390/diagnostics14232755 - 6 Dec 2024

Viewed by 1509

Abstract

Background: One of the methods used in malocclusion treatment is the use of fixed appliances. Research conducted so far has revealed that changes in bite force occurring over the course of orthodontic treatment are directly related to the functional status of the masticatory muscles. It is therefore advisable to find out how the biomechanical parameters of the masseter muscles change after treatment with the application of fixed appliances. Methods: The study material comprised 74 individuals, divided into the study group (n = 37) treated by means of fixed orthodontic appliances over the average time of 12.27 months and the control group (n = 37) consisting of individuals did not undergo orthodontic treatment. The biomechanical properties of the masseter muscles were examined by means of myotonometry. Results: Upon completion of orthodontic treatment, the values of the parameters of tension, stiffness, and elasticity of masseter muscles located on both sides did not statistically significantly differ between patients from the study group who were treated by means of fixed orthodontic appliances and patients from control group who did not undergo orthodontic treatment. Conclusions: Treatment of malocclusions with the use of fixed appliances does not affect the biomechanical and visco-elastic properties of the masseter muscles (stiffness, tension, and elasticity) assessed by means of myotonometry and it appears safe for masticatory muscles. Full article

(This article belongs to the Special Issue Challenges Related to the Oral Cavity, Head and Neck: From Diagnosis to Therapy)

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9 pages, 217 KB

Open AccessArticle

Gingivitis and Its Causes in Children Aged 3–7 Years

by Dorota Olczak-Kowalczyk, Anna Turska-Szybka, Marcin Studnicki and Paula Piekoszewska-Ziętek

Diagnostics 2024, 14(23), 2690; https://doi.org/10.3390/diagnostics14232690 - 29 Nov 2024

Cited by 6 | Viewed by 3347

Abstract

Objectives: Gingivitis manifests as redness, swelling, and bleeding of the gingiva but no loss of connective tissue attachment. It is usually painless and rarely leads to spontaneous bleeding, and most patients are unaware of the disease or are unable to recognize it. In children and adolescents, it is most often caused by plaque accumulation. The purpose of the following study was to determine the prevalence of gingivitis and its causes in children aged 3 to 7 years. Methods: Patients were classed in the following three age groups: 3-year-olds, 5-year-olds, and 7-year-olds, who were generally healthy, not taking permanent medication, and without developmental defects of dentition were eligible for the study. A questionnaire survey assessed socioeconomic factors, frequency of dental visits, and hygiene and dietary habits. The clinical examination assessed the condition of the teeth based on dmft/DMFT, and the presence of gingivitis was based on the bleeding on probing. The obtained results were subjected to statistical analysis. Results: A total of 3558 patients were examined. Gingivitis was present in 436 (12.25%) of the patients. In the group of 3-year-olds, gingivitis was significantly more common in boys (p = 0.0024). There were significant positive correlations between gingivitis and the average number of teeth affected by caries for the male gender in the group of 5- and 7-year-olds and in all age groups with dmft/DMFT > 0 values and the occurrence of symptomatic visits. Conclusions: The prevalence of gingivitis in children aged 3–7 years is influenced by socioeconomic, oral hygiene, and diet-related factors. Poor dental health predisposes to the occurrence of gingivitis. Full article

(This article belongs to the Special Issue Challenges Related to the Oral Cavity, Head and Neck: From Diagnosis to Therapy)

17 pages, 327 KB

Open AccessArticle

The Relationship Between Dental Anxiety and Oral Health-Related Quality of Life in Patients with Periodontitis

by Nicole Padilla-Fonseca, Agatha Araya-Castillo, María Paula Arias-Campos, Ana Paula Solís-Rivera, Jeniffer Jiménez-Matarrita and Karol Ramírez

Diagnostics 2024, 14(23), 2624; https://doi.org/10.3390/diagnostics14232624 - 22 Nov 2024

Cited by 1 | Viewed by 2406

Abstract

Objectives: This study aimed to (1) investigate whether dental anxiety (DA) and oral health-related quality of life (OHRQoL) differed between patients diagnosed with periodontitis and individuals with periodontal health, (2) examine associations and correlations between these patient-reported measures, and (3) analyze demographic and clinical parameters. Methods: Ninety-six patients diagnosed with periodontitis and age- and sex-matched periodontally healthy controls were included. Participants’ demographic characteristics, smoking status, current dental pain, dental pain during the last month, the Modified Corah’s Scale (MDAS), and the Oral Health Impact Profile (OHIP-14) were determined. Results: The mean age of participants was 48.51 years ± 11.41. Patients with periodontitis experienced higher pain in the last month compared to controls (p = 0.003). Patients with periodontitis exhibited significantly higher MDAS total and sub-scores (p < 0.001). Compared to controls, the periodontitis group indicated extreme DA (1.04% vs. 7.79%, p = 0.034). Patients with periodontitis feared having a foreign object in the mouth compared to controls (p = 0.004). The periodontitis group exhibited worse OHIP-14 global and sub-scores (all Ps < 0.001). Positive associations and correlations of MDAS total and sub-scores with OHIP-14 global and domain scores were found for the periodontitis group, but not for controls. Patients with periodontitis who reported “moderate and extreme anxiety” had poorer OHRQoL compared to controls (p = 0.001). The minimal importance difference for this finding indicates a large effect size and a moderate standardized response mean between groups. Conclusions: Patients with periodontitis had higher levels of DA and worse OHRQoL compared to controls. Our study highlights the importance of providing a comprehensive approach, including psychosocial well-being, when diagnosing and treating periodontal disease. Full article

(This article belongs to the Special Issue Challenges Related to the Oral Cavity, Head and Neck: From Diagnosis to Therapy)

18 pages, 4347 KB

Open AccessArticle

Epidemiological, Clinical, and Histopathological Features of the Head and Neck Region Schwannomas—Our Experience in the Western Part of Romania with Surgical Insights

by Adrian Nicoara, Marina Rakitovan, Raluca Maria Closca, Marius Militaru, Alexandru-Cristian Cindrea and Flavia Zara

Diagnostics 2024, 14(20), 2334; https://doi.org/10.3390/diagnostics14202334 - 20 Oct 2024

Cited by 4 | Viewed by 2375

Abstract

Introduction: Schwannomas are benign solitary, slow-growing, encapsulated, asymptomatic tumors arising from Schwann’s sheath of nervous fibers. Objectives: The current paper presents all the cases diagnosed with different types of schwannomas in the head and neck region between January 2009 and December 2023 in the Western part of Romania. In this period, ten cases of schwannoma were identified. Materials and Methods: The pathological exams were performed at the Department of Pathology using morphological Hematoxylin–Eosin staining. In addition, immunohistochemical reactions were used in order to confirm the diagnosis. Results: Demographic and clinical data, imaging features, surgical approach, and morphological and immunohistochemical aspects are presented. The results also display an impressive clinical picture of a gigantic ancient schwannoma. Conclusions: This retrospective study describes our experience with head and neck schwannomas, the diagnostic methods available, the surgical decisions, and the histopathological aspects while analyzing the data and reviewing the published specialized literature in the English language. Full article

(This article belongs to the Special Issue Challenges Related to the Oral Cavity, Head and Neck: From Diagnosis to Therapy)

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Review

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14 pages, 428 KB

Open AccessReview

Primary Sinonasal Mucosal Melanoma: A Narrative Review

by Nikola Todorovic, Petar Djurkovic, Aleksandar Krstic, Nada Tomanovic, Pavle Milanovic, Djurdjina Kablar, Zlata Rajkovic Pavlovic, Momir Stevanovic, Jovana Milanovic, Aleksandra Arnaut, Ivan Ljubisavljevic, Dragica Selakovic, Gvozden Rosic and Milica Vasiljevic

Diagnostics 2025, 15(4), 496; https://doi.org/10.3390/diagnostics15040496 - 18 Feb 2025

Cited by 9 | Viewed by 3328

Abstract

Mucosal melanomas (MMs) are under-researched tumors with a poor prognosis that arise from melanocytes found in the mucous membranes at different anatomical locations throughout the body. MMs are an uncommon yet highly aggressive tumor that typically develops on mucosal surfaces, predominantly in the head and neck region. MM of the head and neck occurs in 8–10% of all head and neck melanomas. It most commonly affects the mucosa of the nasal cavity and paranasal sinuses (75%), followed by the oral cavity mucosa (25%). A family history and the presence of mucosal nevi are associated with the occurrence of MM. Inhaled and dietary carcinogens are also linked to the development of sinonasal melanoma, much like other malignancies of the nasal cavity. Overexpression of the C-KIT gene is found in more than 80% of all primary mucosal melanomas, with somatic mutations in 10–30% of cases. The presence of these genetic alterations is also reflected in recent clinical studies of specific gene inhibitors that have proven efficiency in the systemic therapy of melanoma. There are various treatment modalities for MM. Surgical therapy involves en bloc surgical resection with a macroscopically visible and palpable mucosal margin of 1.5–2 cm. Partial resection of the maxilla may be considered if it ensures adequate tumor-free margine. Because of its rarity, outcome data for locally advanced head and neck MM is limited and primarily derived from retrospective studies with small case numbers. This review aims to update and summarize findings from clinical trials, prospective observational studies, and retrospective studies, while also exploring future directions for multimodal treatment approaches in this area. Full article

(This article belongs to the Special Issue Challenges Related to the Oral Cavity, Head and Neck: From Diagnosis to Therapy)

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10 pages, 9879 KB

Open AccessReview

Diagnostic Challenges of Traumatic Ulcerative Granuloma with Stromal Eosinophilia in the Hard Palate

by Giacomo Setti, Stefania Caramaschi, Giuseppe Barile, Antonio d’Amati, Marta Forte, Giuseppe D’Albis, Pierantonio Bellini, Giovanna Garuti, Luisa Limongelli and Saverio Capodiferro

Diagnostics 2025, 15(2), 199; https://doi.org/10.3390/diagnostics15020199 - 16 Jan 2025

Cited by 1 | Viewed by 2590

Abstract

Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a benign lesion that may arise from the oral mucosa consisting in an ulcerative lesion usually localized in the tongue or cheek. Palate localization is very rare. Background/Objectives: The aim of this study is to describe a case of TUGSE occurring in the hard palate of an 83 y.o. female patient, manifesting as a non-painful growing palatal lesion approximately of 3.5 × 2 cm with firm consistency and a central area of erosion and erythema, the difficulties in clinical diagnosis, and the criteria for the differential diagnosis. Also, considering the rare occurrence of TUGSE in the palate, we performed a review of the literature too. Methods: A comprehensive review of the literature was conducted following the 2020 PRISMA guidelines and a total of seven records were identified as matching the inclusion criteria of this study. Results Conclusions: Although TUGSE is a benign lesion, the clinical presentation as a proliferative and ulcerative lesion may be challenging for clinicians mainly when arising in rare sites of occurrence (e.g., the hard palate). Full article

(This article belongs to the Special Issue Challenges Related to the Oral Cavity, Head and Neck: From Diagnosis to Therapy)

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Other

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20 pages, 2667 KB

Open AccessSystematic Review

Peripheral Odontogenic Keratocyst of the Gingiva: A Systematic Review of the Literature and Case Report

by Marta Forte, Alfonso Manfuso, Giuseppe D’Albis, Giulia Cianciotta, Eliano Cascardi, Grazia Pinto, Giuseppe Ingravallo, Gianfranco Favia, Antonio d’Amati, Luisa Limongelli and Saverio Capodiferro

Diagnostics 2025, 15(20), 2616; https://doi.org/10.3390/diagnostics15202616 - 16 Oct 2025

Viewed by 890

Abstract

Background/Objectives: Odontogenic keratocysts are benign cysts originating from remnants of the dental lamina, rarely showing peripheral (gingival) localization. In this study, we compiled data on the peripheral variant by reviewing the literature and presenting a new case to establish criteria for accurate differential diagnosis and treatment. Methods: A systematic literature review was conducted following the PRISMA flowchart, leading to the collection of existing data on peripheral odontogenic keratocyst. In addition, we present a new case of a 68-year-old female patient referred to our attention for an asymptomatic swelling of the mandible in the premolar area. Radiographic examination revealed a round radiolucency with well-defined borders located between teeth #4.3 and #4.4, surgically removed and diagnosed as a peripheral (gingival) keratocyst. Results: Including the herein described new case, 37 cases were reviewed from data literature showing occurrence in the mandible (43.2%) and maxilla (46%)—with 10.8% of cases not stated-, with an age range of 14–83 year old, recurrence rate of 12.5–13.6% (total recurrences/total cases) and median follow-up time of 19 months. Conclusions: Data from literature highlights the rarity of odontogenic keratocyst with peripheral (gingival) localization, which can be misleading for differential diagnosis, emphasizing the necessity of histopathological examination as the definitive diagnostic tool for all the cystic lesions of the jaws. The absence of pathognomonic clinical and radiological features, combined with the potential for extraosseous manifestation of odontogenic lesions with high recurrence rates, underscores the importance of complete excision to ensure proper healing and prevent recurrence of odontogenic keratocyst. Full article

(This article belongs to the Special Issue Challenges Related to the Oral Cavity, Head and Neck: From Diagnosis to Therapy)

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12 pages, 2212 KB

Open AccessCase Report

Cocaine-Triggered PR3-ANCA Vasculitis Localized to a Post-Surgical Neck Field: A Case of Locus Minoris Resistentiae in Drug-Induced Autoimmunity

by Marko Tarle, Koraljka Hat, Lea Šalamon, Joško Mitrović, Marina Raguž, Danko Müller and Ivica Lukšić

Diagnostics 2025, 15(16), 1999; https://doi.org/10.3390/diagnostics15161999 - 10 Aug 2025

Viewed by 1110

Abstract

Background and Clinical Significance: Cocaine-induced vasculitis (CIV), especially when associated with PR3-ANCA positivity, can be very similar both clinically and serologically to idiopathic granulomatosis with polyangiitis (GPA). The distinction between these entities is crucial due to the different etiologies, treatment strategies, and prognoses. We present a unique case of CIV that manifested exclusively in a previously dissected neck area—an example of the locus minoris resistance phenomenon—and was initially misinterpreted as skin melanoma recurrence. Case presentation: A 59-year-old man with a history of skin melanoma (pT4b, left pectoral region) and a previous modified radical neck dissection presented in 2024 with new onset of painful subcutaneous nodules and ulcerative lesions at the surgical site. The imaging procedures (CT and PET-CT) raised the suspicion of locoregional malignant recurrence. However, histology revealed necrotizing granulomatous inflammation without tumor cells. Extensive infectious and autoimmune investigations ruled out alternative causes. Subsequently, the patient developed a perforation of the nasal septum and ulcers on the oral mucosa. PR3-ANCA was strongly positive (up to 49 U/mL). Urine toxicology revealed intranasal cocaine use. A diagnosis of cocaine-induced PR3-ANCA vasculitis was made. After immunosuppressive therapy (high-dose glucocorticoids and methotrexate) and substance withdrawal counseling, the patient showed significant clinical improvement. Conclusions: This case highlights the importance of including CIV in the differential diagnosis of granulomatous or ulcerative lesions, especially when they are localized to previous surgical sites. The presentation illustrates the concept of locus minoris resistentiae and highlights the role of toxicological testing in atypical ANCA-positive disease. Full article

(This article belongs to the Special Issue Challenges Related to the Oral Cavity, Head and Neck: From Diagnosis to Therapy)

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13 pages, 17789 KB

Open AccessCase Report

A Simultaneous Presentation of Nasopharyngeal Carcinoma and Latent Cervical Tuberculosis: Insights into a Complex Case

by Ingrid-Denisa Barcan, Raluca Maria Closca, Marina Rakitovan, Andreea-Mihaela Banta, Flavia Zara, Sorin Adalbert Dema, Claudia Raluca Balasa Virzob and Ioana Delia Horhat

Diagnostics 2025, 15(3), 357; https://doi.org/10.3390/diagnostics15030357 - 4 Feb 2025

Viewed by 1647

Abstract

Background and Clinical Significance: Tuberculosis infection triggers a chronic inflammatory response that can create a favorable environment for the development of cancer cells. Chronic inflammation can lead to DNA damage, increased cell proliferation, and impaired immune surveillance. Nasopharyngeal carcinoma is an aggressive malignant tumor with a very poor prognosis, despite the current oncology therapy. Case Presentation: The case presents following clinical, imaging, and histopathological aspects, as well as the oncological follow-up of the patient over a period of 8 years. This paper presents the case of a 49-year-old patient diagnosed with cervical lymph node tuberculosis while biopsied for the diagnosis of nasopharyngeal carcinoma with cervical lymph node metastases. Conclusions: The overlap of this malignancy with an infection of mycobacterial etiology complicates the outcome of the disease even more, making treatment and prognosis difficult. Full article

(This article belongs to the Special Issue Challenges Related to the Oral Cavity, Head and Neck: From Diagnosis to Therapy)

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6 pages, 2040 KB

Open AccessInteresting Images

Hydrolethalus Syndrome: A Case of a Rare Congenital Disorder

by Valerica Belengeanu, Diana Marian, Horia Ademir Stana, Carolina Cojocariu, Cristina Popescu and Ioana Elena Lile

Diagnostics 2025, 15(2), 202; https://doi.org/10.3390/diagnostics15020202 - 17 Jan 2025

Viewed by 1295

Abstract

This is a fatal case of multiple complicated congenital anomalies displaying several symptoms consistent with hydrolethalus syndrome. The newborn’s phenotype is characterized by a combination of serious anatomical abnormalities such as open-book cerebral hemispheres, defective lobulation of the lungs (one lobe on the left, two on the right), a smaller right kidney, a smooth cerebral surface, and a specific keyhole-shaped defect in the skull base, primarily associated with hydrocephalus. Full article

(This article belongs to the Special Issue Challenges Related to the Oral Cavity, Head and Neck: From Diagnosis to Therapy)

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