Nasal-like extranodal NK/T-cell lymphoma (ENKL) primarily involves the nasal cavity. Although patients may consult an otolaryngologist with nasal symptoms, such as nasal obstruction and epistaxis, it would be difficult to make a correct diagnosis. We present a case of ENKL in which the patient was in remission after initial treatment and relapsed 14 years after treatment. The patient had worsening nasal symptoms before the recurrence, but on this occasion treatment such as sinusitis was successful in relieving the symptoms. Although recurrence of lymphoma 10 years after treatment is rare, the possibility of recurrence should always be considered in cases of post-malignant lymphoma as with any malignancy.
In the classification of the World Health Organization (WHO) (2017), nasal-type extranodal NK/T-cell lymphoma (ENKL) is classified as a natural killer (NK) cell tumor with NK-cell leukemia aggressive and chronic NK cell lymphoproliferative disorder . Although the majority of ENKL cases arise from NK cells, it is often difficult to differentiate NK cells from T cells with current techniques. Therefore, both are collectively described as NK/T cell lymphoma . Due to the poor efficacy of CHOP therapy (cyclophosphamide, doxorubicin hydrochloride, oncovine, prednisolone) and the rarity of the disease in ENKL, there is no standard treatment established by randomized controlled trials, and the Recommended treatment differs by country.
We report the case of an elderly man who relapsed 14 years after initial treatment with RT-DeVIC (dexamethasone, carboplatin, etoposide, ifosfamide).
Presentation of the case
At 67, the patient consulted our otolaryngology department for a tumor of the nasal cavities. The biopsy revealed a diagnosis of extranodal NK/T-cell lymphoma, nasal type (ENKL), and he was referred to the hematology department. After three courses of the DeVIC diet (carboplatin, 300 mg/m2 day 1; etoposide, 100 mg/m2 days 1 to 3; ifosfamide, 1500 mg/m2 days 1 to 3; dexamethasone, 40 mg/body on days 1-3) and radiotherapy (total 45 Gy) as ENKL with clinical stage IB and international prognostic index (IPI) 2 (LDH, age), patient was followed for 10 years, remained in remission and made regular visits to the hospital.
At the age of 79, he had nasal symptoms, such as increased purulent nasal discharge, and was referred to our otolaryngology department by his doctor’s otolaryngology department. generalist. Although ENKL recurrence was suspected, her symptoms improved with antibiotic treatment and nasal rinse.
He was again treated in a general practitioner’s ear, nose and throat clinic after more than a year; however, at age 81, he was again referred to the otolaryngology clinic due to a feeling of nasal obstruction and increased purulent nasal discharge from the right naris. He was treated with antibiotics but without any improvement (Figure 1). He had symptoms of oculomotor nerve palsy, such as diplopia and ptosis; thus, he underwent emergency endoscopic sinus surgery to decompress the orbit (Video 1). When the maxillary and ethmoid sinuses were opened, the pus was drained and the nasal mucosa was edematous and friable. The pathologic diagnosis of the tissue obtained at this time suggested ENKL recurrence (Table 1), and the patient was referred to the hematology department for a second visit.
Pretreatment with prednisolone (0.5 mg/kg/day) was initiated the day after the second visit. The patient was discharged from the hospital and a treatment plan was discussed; however, 15 days after the return visit, the patient was rushed to the emergency room with seizures and impaired consciousness. Computed tomography (computed tomography) and MRI (magnetic resonance imaging) of the head showed no obvious intracranial lesions, and CSF (cerebrospinal fluid) examination showed significant lymphocyte hyperplasia, which made suspect CNS (central nervous system) infiltration. The patient was admitted to the hematology department. On day 4 of hospitalization (18 days after the second visit), MTX (methotrexate; 15 mg), Ara-C (cytarabine; 40 mg) and DEX (dexamethasone, 4 mg) by intrathecal infusion ( IT) were administered, and symptoms of consciousness tended to improve. Due to his advanced age, SMILE therapy (dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide) was avoided, and a reduction in DeVIC dose (50% dose, from typical 2/3 dose to 3/4), IT, and re-irradiation were planned.
After being discharged from the hospital, he was again admitted to the scheduled hospital 46 days after the second visit, but his condition had deteriorated and his disease had progressed, with the appearance of elevated liver enzymes, d an increase in lactate dehydrogenase (LDH) based on IPI, and new lesions in the adrenal glands on a full body CT scan. The DeVIC regimen was started the next day and the IT was performed again two days later; however, irradiation was discontinued because local irradiation was considered insignificant at an already advanced stage of the disease. Although LDH decreased with treatment, the patient required blood transfusions due to myelosuppression, his performance index also decreased and the future course of action was reconsidered. Then, 57 days after the second visit, the patient’s oxygenation began to deteriorate, and in the early morning of 59 days after the second visit, the patient died. A pathological autopsy was proposed to look for the cause; however, the bereaved family did not wish to have him.
Nasal type extranodal natural killer T-cell lymphoma (ENKL) is a type of malignant lymphoma . Epidemiologically, there are large racial differences in its incidence, and it is rare among Caucasians in Europe and the United States; however, it is not uncommon in Asians and Latinos . Reports from South Korea and Hong Kong found 7-8% incidence of all malignant lymphomas . Initial symptoms are often localized, such as nasal obstruction, rhinorrhea, and epistaxis, and as the disease progresses tumor growth increases with bone destruction in the eye socket, skull base, and palate. . Advanced-stage tumor cells express multidrug-resistant P-glycoprotein that can expel drugs, and prognosis is poor regardless of primary site [6-7].
In the case of a lesion of the nasal cavity that develops destroying the surrounding area, ENKL is the differential, with granulomatous polyangiitis (conventional Wegener’s granulomatosis) and other diseases. Multiple tissue biopsies may be required due to necrosis and hemorrhage, and immunohistochemistry may be helpful, as well as EBER-1 on the spot to confirm the presence of EBV (Epstein-Barr virus) .
Relapse of malignant lymphoma more than 10 years after remission is rare. Although scattered reports of relapses several years after remission in ENKL were found, no reports of relapse more than 10 years after remission were identified. In this case, the patient had been treated for sinusitis before the recurrence. Even with this history, the possibility of recurrence should be considered when there is a history of lymphoma. Wang et al. reported that positive plasma EBV-DNA may predict ENKL recurrence and poor prognosis after asparaginase-based chemotherapy . Although the initial treatment regimen should be considered, it may be useful to consider EBV-DNA testing and tissue biopsy when a recurrence of ENKL is suspected.
ENKL is a rare lymphoma and was once considered refractory. Although treatment varies from country to country due to epidemiological racial differences, in Japan RT-2/3DeVIC, a concurrent chemoradiotherapy, is recommended for the first localized treatment ENKL and SMILE (dexamethasone, methotrexate, ifosfamide , L-asparaginase, etoposide) , combination chemotherapy, is recommended for advanced first stage and first relapse/refractory ENKL . In this case, the initial onset was over ten years ago and the DeVIC regimen dosage was different from current recommendations. Also, at the time of the recurrence, the patient was 81, which was above the study age range (15-69). , and his general condition was not good; thus, the introduction of SMILE therapy was not recommended.
In this case, we report a relapse 14 years after initial treatment with ENKL, which was previously in remission. The patient developed worsening nasal symptoms before the recurrence, but at that time the patient was successfully treated as a case of sinusitis. Clinicians should maintain a high index of suspicion for recurrence even in the distant history of ENKL in post-lymphoma treatment cases.