Surreal illustration of a healthy mouth surrounded by constellations of oral pathologies, symbolizing diagnostic journeys.

Oral Mysteries Unveiled: Rare Cases and What They Teach Us

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Mira Elwood in Health & Wellness October 2026 • 5 min read.

"Exploring unusual oral conditions, from EBV-related lymphomas to unique tumor types, and why accurate diagnosis is crucial."


The landscape of oral and maxillofacial pathology is vast and varied, encompassing a wide array of conditions that can affect the mouth and surrounding structures. While common dental issues like cavities and gingivitis are familiar to most, there exists a spectrum of less common and often perplexing disorders that require specialized knowledge to diagnose and manage effectively. These rare cases not only present diagnostic challenges but also offer valuable insights into the complex interplay of factors that influence oral health.

This article delves into a selection of intriguing case studies drawn from the field of oral and maxillofacial pathology, shedding light on the unique presentations, diagnostic pathways, and treatment strategies associated with these conditions. From aggressive tumors to unusual inflammatory processes, we will explore the nuances of each case, emphasizing the importance of accurate diagnosis and appropriate management in achieving favorable outcomes. By examining these rare scenarios, we aim to enhance awareness and understanding of the diverse range of pathologies that can manifest in the oral cavity.

Whether you're a healthcare professional seeking to expand your knowledge base or an individual curious about the intricacies of oral health, this exploration of rare case studies promises to be both informative and engaging. Join us as we unravel the mysteries behind these unusual conditions and uncover the lessons they hold for the field of oral and maxillofacial pathology.

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Oral Lymphomas and EBV

Research has examined the histologic class and immunologic phenotype of lymphomas that initially present in the oral cavity, including whether they show a high incidence of Epstein-Barr virus (EBV) infection. One reported study found EBV infection in 14% of B-cell lymphomas, a rate higher than that reported for B-cell lymphomas outside the oral cavity but lower than the rate described in some other settings. EBV is also widespread, with Pathology Outlines reporting that 95% of the worldwide population has an asymptomatic lifelong carrier state.

Diagnosis and Its Limits

A 2023 study aimed to describe the clinical manifestations of oral cavity lymphomas and assess whether clinical features could be associated with specific lymphoma subtypes. Another source reports that EBV may play a limited role in lymphoma initiation in immunocompetent patients but may become important in disease progression in more aggressive tumors as immunosuppression occurs. Saliva analysis has also been investigated as a screening approach for early diagnosis of oral and oropharyngeal cancer because it may identify potential biomarkers, although the source describes this as a developing diagnostic possibility.

Recognizing EBV-Positive Ulcers

Pathology Outlines describes an EBV-positive mucocutaneous ulcer in a patient with a history of Hodgkin lymphoma treated with chemotherapy and radiation therapy two years earlier. Biopsy showed diffuse infiltration by large atypical lymphoid cells. The cells were positive for CD20, CD30, PAX5, and EBV, and negative for CD15 and CD56.

Decoding EBV-Positive Diffuse Large B-Cell Lymphoma in the Elderly

Surreal illustration of a healthy mouth surrounded by constellations of oral pathologies, symbolizing diagnostic journeys.

Diffuse large B-cell lymphoma (DLBCL) is a prevalent type of lymphoma affecting the oral cavity. A subset of DLBCL is associated with the Epstein-Barr virus (EBV), typically impacting older adults and showing aggressive clinical behavior. A noteworthy case involved a 54-year-old woman presenting with significant mandibular swelling. Diagnostic workup revealed the presence of EBV-positive DLBCL, highlighting the importance of considering this aggressive lymphoma in elderly patients presenting with unusual oral symptoms.

The diagnosis of EBV-positive DLBCL requires a combination of clinical evaluation, histopathological analysis, and specialized testing to confirm the presence of the virus within the lymphoma cells. Immunohistochemistry and in situ hybridization play crucial roles in identifying EBV-associated markers and differentiating this subtype of DLBCL from other lymphomas affecting the oral cavity.

  • Clinical Presentation: Extensive, asymptomatic mandibular swelling.
  • Microscopic Analysis: Large lymphoid cells with prominent nucleoli and a “starry sky” pattern due to macrophages.
  • Immunohistochemistry: Positive for LCA, CD20, CD10, and MUM1; negative for CD3, cyclin D1, CD138, and CD5.
  • Proliferative Index: Ki-67 achieved 85%.
  • EBV Confirmation: Positive in situ hybridization.
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Evidence Gaps and Recurrence

A systematic-review overview of odontogenic keratocyst management found that the overall methodological quality of the reviews was critically low. Its authors said this demonstrates the need for more studies to support treatment choices. In a separate report on glomus tumors of the floor of the mouth, follow-up was available for only 11 cases, ranging from two months to seven years, and local recurrence was noted in two cases.

Small Samples, Different Outcomes

A systematic review of oral leiomyomatous hamartoma identified 5,562 articles, but only 55 met the inclusion criteria, covering 66 subjects. A separate review of keratocystic odontogenic tumour reported recurrence rates that varied substantially by treatment modality. The reported rates were 0% for resection, 0% for enucleation with peripheral ostectomy and Carnoy's solution, 18.18% for enucleation with peripheral ostectomy, 26.09% for enucleation alone, 40% for marsupialisation, and 50% for enucleation with Carnoy's solution.

This case emphasizes the need for heightened vigilance when encountering unusual oral manifestations in elderly patients. Prompt and accurate diagnosis is critical, though the aggressive nature of EBV-positive DLBCL often presents significant treatment challenges, as highlighted by the patient's rapid decline.

The Importance of Vigilance and Expert Evaluation

The cases highlighted in this article serve as a reminder of the diverse and sometimes unexpected ways in which oral diseases can manifest. By staying informed and collaborating with specialists when faced with diagnostic dilemmas, healthcare professionals can optimize patient care and improve outcomes in even the most challenging cases.

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PBL, Immunity, and EBV

The sources characterize oral plasmablastic lymphoma (PBL) as a rare, aggressive subtype of non-Hodgkin lymphoma. It is predominantly reported in immunocompromised patients, particularly those with chronic HIV infection, and commonly affects the oral cavity. Both sources associate PBL closely with EBV, describing the virus as present in the majority of cases and emphasizing its role in the disease's pathogenesis.

Toward Better EBV-Lymphoma Care

A 2025 Frontiers review aims to provide an in-depth overview of EBV-associated lymphomas, covering their biology, diagnostic methods, current treatment modalities, and prospective therapeutic strategies. It highlights continuing challenges and future directions in the field. Another 2025 Frontiers source concerns a rare case of chronic genian fistula with oral mucosal hair follicle inclusion and places it within broader work on oro-facial pain, molecular mechanisms, diagnostic innovation, and multidisciplinary management.

Immunodeficiency and Oral Disease

A reported case of oral EBV mucocutaneous ulceration involved a person with complex primary immunodeficiency disorders. The disorders included common variable immunodeficiency disease associated with T-cell dysfunction. The case illustrates why oral EBV-related lesions must be considered in the context of the patient's underlying immune status.

What the oral ulcer evidence suggests

Oral EBV-positive ulcers can resemble other serious or inflammatory conditions at first, so the clinical appearance alone did not settle the diagnosis in the reported cases; the conclusion came from considering medical history alongside tissue examination.[1]

Some oral cases interfere with eating despite no reported systemic symptoms, showing that a lesion can have a meaningful local effect without the accompanying whole-body signs listed in the source.[2]

How the rare oral tumors compare

For oral glomus tumors, temperature or touch-triggered pain is described as common, with a proposed explanation involving nerve fibers and pressure within the lesion. This offers a possible account of symptoms, not proof that every lesion behaves this way.[3]

Glomus tumors are characterized by smooth-muscle-like markers, and the cited features are consistent with an origin from modified smooth muscle cells of the glomus body. This is a tissue interpretation rather than a clinical outcome measure.[3]

Terms used in oral pathology

Glomus tumor of uncertain malignant potential
A glomus tumor that does not meet the stated malignancy criteria but has at least one atypical feature.[4]

Sources

  1. Epstein-Barr virus-positive mucocutaneous ulcer arising in the oral cavity of MTX-treated patients: Report of three cases and review of 25 cases reported in Japan (www.jstage.jst.go.jp)
  2. A review of EBV-positive mucocutaneous ulcers focusing on clinical and pathological aspects (pmc.ncbi.nlm.nih.gov)
  3. Glomus tumor in the buccal mucosa: A case report and review of the literature (pmc.ncbi.nlm.nih.gov)
  4. Glomus tumor of the hyoid bone: a case report and literature review (pmc.ncbi.nlm.nih.gov)

About this Article -

Written with AI assistance from published research, and reviewed by the Mystum team. See our About page for more information.

Everything You Need To Know

1

What is EBV-positive diffuse large B-cell lymphoma (DLBCL), and why is it important to recognize?

EBV-positive diffuse large B-cell lymphoma (DLBCL) is a specific and aggressive form of lymphoma linked to the Epstein-Barr virus (EBV). It's a type of cancer that affects B-cells, which are a crucial part of the immune system. This particular lymphoma tends to occur more frequently in older adults and can present with unusual symptoms. Its significance lies in its aggressive nature and the diagnostic challenges it poses. The implications include the need for rapid and accurate identification through clinical evaluation, histopathological analysis, and specialized testing like immunohistochemistry and in situ hybridization to differentiate it from other lymphomas.

2

Why is getting an accurate diagnosis so important when dealing with oral and maxillofacial pathologies?

Accurate diagnosis in cases of oral and maxillofacial pathology, such as with EBV-positive DLBCL, is crucial for several reasons. First, it ensures that patients receive the correct treatment promptly. In the case of EBV-positive DLBCL, which is an aggressive lymphoma, a delay in diagnosis can lead to rapid disease progression and poorer outcomes. Second, accurate diagnosis helps to differentiate between various conditions that may present with similar symptoms, guiding appropriate management strategies. The implications of a misdiagnosis can be severe, leading to ineffective treatment, unnecessary procedures, and potentially life-threatening consequences.

3

What specific tests are done to diagnose EBV-positive diffuse large B-cell lymphoma (DLBCL), and why are they essential?

In diagnosing EBV-positive diffuse large B-cell lymphoma (DLBCL), several key tests are performed. These include clinical evaluation to assess symptoms, histopathological analysis to examine tissue samples under a microscope, immunohistochemistry to identify specific markers on cells, and in situ hybridization to detect the presence of the Epstein-Barr virus (EBV) within the lymphoma cells. Immunohistochemistry looks for markers such as LCA, CD20, CD10, and MUM1, while excluding others like CD3, cyclin D1, CD138, and CD5. These tests are essential because they confirm the presence of EBV, distinguish EBV-positive DLBCL from other lymphomas, and guide treatment decisions. Without these tests, accurate diagnosis and appropriate management would be impossible.

4

What does the term "starry sky" pattern mean in the context of lymphomas, and why is it significant?

The term "starry sky" pattern refers to a microscopic appearance observed in certain lymphomas, including EBV-positive diffuse large B-cell lymphoma (DLBCL). It describes the presence of numerous macrophages interspersed among the lymphoma cells, creating a visual effect resembling stars in the night sky. These macrophages are actively engulfing cellular debris from the rapidly proliferating lymphoma cells. Its significance lies in aiding pathologists in recognizing specific types of aggressive lymphomas. The implications of identifying a "starry sky" pattern include prompting further investigation to confirm the diagnosis of an aggressive lymphoma and initiating appropriate treatment strategies promptly.

5

What does the proliferative index (Ki-67) tell us about tumors like EBV-positive diffuse large B-cell lymphoma (DLBCL)?

The proliferative index, often measured by Ki-67 staining, is a marker used in pathology to assess the growth rate of cells in a tumor. In the context of EBV-positive diffuse large B-cell lymphoma (DLBCL), a high Ki-67 index, such as 85%, indicates that a large proportion of the lymphoma cells are actively dividing and multiplying rapidly. Its significance lies in providing prognostic information about the aggressiveness of the tumor. The implications of a high proliferative index include predicting a more aggressive clinical course and guiding treatment decisions. Tumors with high Ki-67 indices may require more intensive therapies to achieve remission.

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