Not every periapical lesion is an infection. What if it is actually something far worse? Imagine performing a routine root canal treatment, only to later discover that the ‘infection’ was actually leukemia or lymphoma.
A new systematic review highlights how frequently these malignancies are misdiagnosed as endodontic lesions, leading to unnecessary endodontic procedures and missed opportunities for early intervention.
How Often Are Leukemia and Lymphoma Misdiagnosed as Endodontic Lesions?
To better understand this issue, two researchers systematically searched PubMed, EMBASE, Scopus, Web of Science, and LILACS for studies published up to March 2023. Their search identified 3,617 articles, which were then screened for relevance. After applying strict inclusion criteria, they selected 32 studies, comprising 26 case reports and 6 case series, covering a total of 37 patients with leukemia or lymphoma mimicking periapical conditions.
The review analysed clinicopathologic, radiographic, and management aspects of these cases, with diagnoses confirmed through biopsies and immunohistochemistry. The findings reveal a concerning pattern of misdiagnosis and inappropriate treatment.
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What the Review Found
- 91.9% of cases (34 out of 37) were non-Hodgkin lymphoma, 5.4% (2 cases) were leukemia, and 2.7% (1 case) was Hodgkin lymphoma.
- The anterior maxilla and posterior mandible were the most commonly affected sites, each accounting for 29.7% of cases.
- 97.3% of the lesions appeared as radiolucent areas in the periapical region, mimicking endodontic infections.
- 94.6% of cases underwent endodontic treatment before a diagnosis of leukemia or lymphoma was made. In 5.4% of cases, retreatment was performed.
- The mean time to final diagnosis was 4.9 months, ranging from 0.5 to 36 months.
The Challenge of Diagnosis
The study found that leukemia and lymphoma can present as radiolucent lesions in the periapical region, often resembling endodontic infections. This makes diagnosis particularly difficult, as these malignancies share overlapping symptoms with common dental conditions.
Key signs that could indicate a malignancy rather than a typical periapical infection include:
- Persistent pain and swelling
- Tooth mobility that is not responding to endodontic treatment
- Paresthesia or numbness in the affected area
- Poor response to conventional therapy
- Multiple teeth being involved rather than a single localised lesion
What Dentists Should Look Out For
To prevent misdiagnosis, the review suggests that dentists should be particularly cautious if they notice:
- Atypical radiographic features – Lesions with poorly defined or diffuse borders may indicate malignancy rather than infection.
- Lesions that persist despite conventional treatment – If a radiolucent lesion does not improve after endodontic therapy, further investigation is needed.
- Systemic symptoms – Fatigue, weight loss, night sweats, and unusual gingival presentations, such as bleeding or enlargement, may suggest an underlying malignancy.
Failing to recognise these signs can lead to delayed diagnosis, unnecessary dental procedures, and missed opportunities for early intervention in serious conditions.
Study Limitations
The review relied on case reports and case series, as cohort studies are rare due to the low incidence of leukemia and lymphoma in the periapical region. While this provides valuable insights, further research is needed to establish clearer diagnostic guidelines.
Final Thoughts
Leukemia and lymphoma are rare but important considerations in the differential diagnosis of periapical conditions. While periapical lesions are most commonly associated with endodontic infections, this review highlights that malignancies can present in a nearly identical way.
For dentists, the key takeaway is to remain vigilant. If a lesion behaves atypically, does not respond to expected treatment, or presents with systemic symptoms, a biopsy or further medical evaluation should be considered.
Misdiagnosis can lead to unnecessary root canals, delays in cancer treatment, and poorer patient outcomes. But by staying informed and adopting a cautious approach, dentists can help identify these cases sooner—potentially making a life-saving difference.
About Dr. Jamal
Dr. Jamal Giri is an orthodontist and associate professor at B.P. Koirala Institute of Health Sciences in Nepal. He obtained his orthodontic training from the Institute of Medicine, Tribhuvan University, Nepal, in 2014.
Currently pursuing a PhD at the University of Adelaide, Dr. Jamal’s research focuses on the genetic and environmental factors influencing malocclusion development. He also holds a postgraduate certificate in clinical education from the University of Edinburgh and a master’s in medical education from the University of Nottingham.Dr. Jamal teaches on the Diploma in Orthodontics and Dentofacial Orthopaedics at the London Dental Institute.
Reference
de Melo Queiroga IS, Drumond VZ, Abreu LG, Schuch LF, Mesquita RA, Souza EM, de Andrade BA, de Arruda JA, Sampaio GC. Leukemia and lymphoma mimicking periapical conditions resulting in endodontic treatment: a systematic review. Journal of Endodontics. 2025;51:106-117.
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