ENKL is a rare but distinct entity of non-Hodgkin's lymphoma, mostly derived from natural killer cell lineage and occasionally cytotoxic T cell lines.14
It is characterised by ethnic preponderance (more common in East Asians and Latin Americans than Caucasians), consistent association with EBV infection, predilection for upper aerodigestive tracts, particularly nasal and paranasal areas (80% cases), mixed cellular infiltrate with angiocentricity, angioinvasion and necrosis on histological examination, and aggressive locally destructive nature.14–16
It affects males more commonly than females and has a median age of onset of 52 years.17
However, as highlighted by this case report, it can also occur in young adults. Initial symptoms are non-specific and include pain, obstruction, discharge, foul smelling and bleeding, which can masquerade sinusitis.18
These symptoms usually predate ulceration and local destruction by months to years.16 17
However, the disease can have a rapidly progressive course as in this patient, who presented with a relatively short history. Fever and weight loss are present only in advanced cases. Increased LDH levels and B symptoms are reported in less than half of all cases.16 17
Several infectious, inflammatory and neoplastic conditions can cause destruction of palate and adjacent areas. Diagnosing the underlying cause could be very challenging as illustrated by this case and requires consideration of several factors as well as gram stain, fungal stain, culture and histopathologic examination of biopsy specimen (). The diagnosis can be further complicated by isolation of normal oral flora. Therefore, it is important to continue the search for alternate diagnosis if a patient fails appropriate and adequate therapy for infectious aetiology. It is important to realise that the angiocentric cellular infiltrate of ENKL can be mistaken for the vasculitic picture of Wegener's granulomatosis. Absence of other features of Wegener's granulomatosis should alarm a physician about this possibility. In addition, immunophenotyping can make the definite diagnosis of ENKL. ENKL is typically CD2+, CD56+, surface CD3−, cytoplasmic CD3epsilon+ and cytotoxic granule-associated protein (TIA-1, granzyme B and perforin) positive.14 17
EBV positivity, detected by in situ hybridisation, can further help identify neoplastic from non-neoplastic lymphocytes.16
Differentiating common causes of palatal ulceration and/or naso-oral fistula
Treatment of ENKL consists of radiotherapy or chemotherapy, either alone or in combination, depending on the extent of disease, age and comorbidity. ENKL often remains localised in the nasal primary site; regional nodal spread (15–30%) or systemic dissemination (<20%) is uncommon at the time of presentation. Early-stage localised nasal disease is highly curable whereas disseminated disease has very poor prognosis.14
This underlines the importance of early diagnosis and therapy.
- Failure of standard therapy for bacterial osteomyelitis and invasive fungal infection in a patient with palatal ulceration and fever should trigger diagnostic work up for possible rheumatological and neoplastic conditions.
- The angiocentric cellular infiltrate seen in ENKL can be confused with the vasculitic picture of Wegener's granulomatosis. Therefore, the diagnosis of Wegener's granulomatosis should not be based solely on histopathological findings rather should also be supported by the ANCA positivity and other clinical features.
- Misdiagnosis of ENKL or delaying the treatment has serious consequences. Therefore, in the absence of conclusive diagnosis, we recommend immunophenotyping and EBER staining of the biopsy to rule out the possibility of ENKL.
- Fungal lesions, such as mucormycosis, are likely to produce an oronasal fistula, thus mimicking the destruction pattern of an ENKL. Therefore, in these cases, it is advisable to perform fungal staining and culture.