Non-Healing Tongue Ulcer in a Patient Taking Methotrexate
A 61-year-old woman is referred with a 6-week history of a painful ulcer on the left lateral border of the tongue. It measures 1.5 cm, has rolled margins, and is indurated; a 1.5-cm fixed submandibular lymph node is palpable. She has rheumatoid arthritis treated with methotrexate 15 mg once weekly and folic acid, plus prednisolone 5 mg daily. She has never smoked and drinks about two units of alcohol per week. A two-week trial of chlorhexidine mouthwash and topical triamcinolone has not helped. Full blood count shows hemoglobin 10.8 g/dL, MCV 102 fL, white cells 3.2 × 10^9/L, neutrophils 1.4 × 10^9/L, and platelets 180 × 10^9/L. Liver enzymes are mildly raised. She asks whether the ulcer is a side effect of methotrexate and whether she can simply stop the drug.
1. What is your differential diagnosis, and why must malignancy remain at the top despite her immunosuppression?
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The differential includes squamous cell carcinoma, a methotrexate-related ulcer, major aphthous ulceration, lymphoma, infection (including tuberculosis and deep fungal infection), and a traumatic or lichenoid ulcer. Malignancy must remain at the top because the ulcer is 6 weeks old, indurated, has rolled margins, and is associated with a fixed submandibular node. Those features are not typical of a simple drug-induced aphthous ulcer, which is usually painful but not indurated and does not cause a fixed node. Immunosuppression is a risk factor for both infection and malignancy, and methotrexate can cause oral ulceration through folate antagonism and marrow suppression. The low white cell count and raised MCV are consistent with methotrexate toxicity, but they do not exclude cancer. The absence of smoking does not rule out oral squamous cell carcinoma. A biopsy is required.
2. Describe the investigations you would arrange and the sequence, including the role of incisional biopsy and direct immunofluorescence.
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I would arrange urgent referral to oral and maxillofacial surgery or oral medicine for incisional biopsy. The biopsy should include the edge of the ulcer and adjacent clinically normal tissue, avoiding the necrotic center, and should be deep enough to include epithelium and connective tissue. Direct immunofluorescence should be requested if a vesiculobullous disorder is suspected, but the clinical picture is more concerning for malignancy. I would also request a full blood count, liver function tests, renal function, and a chest radiograph, and arrange ultrasound of the neck with fine-needle aspiration of the node if malignancy is suspected. Contrast-enhanced CT or MRI may be needed for staging if biopsy confirms carcinoma. I would not wait for methotrexate to be stopped before biopsy, because delay could allow tumour progression. The biopsy result guides whether the node needs further sampling or neck dissection.
3. How would you manage the methotrexate and the patient's anxiety before histology is available?
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I would not stop methotrexate myself. The patient should be advised that the ulcer may be related to methotrexate toxicity, especially with leukopenia and macrocytosis, but that cancer must be excluded. I would contact her rheumatologist the same day to discuss withholding the next dose and checking blood counts, and to decide whether folinic acid rescue or admission is needed if she has severe mucositis or pancytopenia. I would explain that stopping the drug without a plan could worsen her rheumatoid arthritis and does not treat a possible cancer. I would provide a clear safety net: if she develops fever, difficulty swallowing, breathing difficulty, or rapid swelling, she should go to the emergency department. I would document the discussion and ensure urgent biopsy follow-up.