OVERVIEW
Nasal-type extranodal NK/T-cell lymphoma is a malignant tumor that develops in the nasal cavity and its adjacent tissues, with most of its malignant cells originating from NK cells and a few from NK-like T cells, and it is a rare type of non-Hodgkin’s lymphoma. The World Health Organization (WHO) named this disease as extranodal NK/T-cell lymphoma, nasal type in 2008. The disease is characterized by significant geographic and racial variations, occurring mostly in Asia and South America, with a prevalence in the yellow race and in adult males. The lesions mostly originate in the upper respiratory tract, with the nasal cavity being the most common; a few may occur in extranasal sites, such as the skin, the gastrointestinal tract, the lungs, the testes, etc., the bone marrow and the central nervous system are rare, and lymph nodes are seldom involved. Typical lesions are necrotizing granulomatous lesions occurring in the middle of the face (especially the nose).
Etiology
The cause of the disease is unknown and may be related to viral infection or autoimmune factors. Recent studies have found that more than 95% of the cases are related to EBV infection.
Symptoms
Typical lesions are necrotic granulomatous lesions that occur in the middle of the face (especially in the nose). Cases with lesions outside the nose are less common, and the clinical manifestations are determined by the location of the lesion, with the digestive tract and skin being relatively more common. Typical manifestations of the lesions are as follows.
1. The most common symptom in the early stage is nasal congestion, and there may be symptoms such as pus flow and blood in the snot, followed by necrotic ulceration of the nasal mucosa, and there may be foul smell in the nasal cavity, which is similar to that of rhinitis or sinusitis, and when the tumor in the nasal cavity is large, there may be bulging outside of the nose, and perforation of the nasal septum.
2. When the lesion gradually extends to the neighboring tissues, there may be erosion, ulceration, hemorrhage and necrosis of the mucous membrane in the middle of the face such as the pharynx and lips, which may lead to the formation of extensive ulcers and granulomas.
3. In the late stage, perforation of the hard palate, protrusion of the eyeballs, facial swelling, cranial nerve palsy and other damages may occur.
4. In the terminal stage, the mucous membrane, cartilage, and bone in the middle of the face may be widely and severely damaged, resulting in disfigurement, and there may be serious consequences such as high fever, cachexia (extreme emaciation, anemia, systemic failure, etc.).
Examination
1. Nasal endoscopy
Nasal endoscopy can find out whether there are ulcers and necrosis in nasal mucosa, which can help to locate the tumor and take biopsy under direct vision, and provide the basis for the diagnosis of nasal extranodal NK/T-cell lymphoma.
2. Nasal cavity and sinus CT, magnetic resonance imaging
Nasal cavity and sinus CT and magnetic resonance examination are commonly used to determine the malignant tumor of nasal cavity and sinus, which can help to define the scope of lesions. However, it should be noted that the sensitivity of imaging examination for early lesions may be poor, and cannot be used as the basis for the definitive diagnosis of the disease.
3.Laboratory examination
Laboratory tests include routine blood test, blood sedimentation, liver and kidney function, electrolytes, serum immunology, serum complement test, lactate dehydrogenase (LDH), EBV serology, bacterial, fungal and viral cultures, etc. They are helpful in assessing the systemic condition. It helps to assess the general condition, evaluate whether there is EBV infection and EBV titer, and identify whether there is a combination of bacterial and fungal infections.
4. Histopathologic examination
The diagnosis of nasal-type extranodal NK/T-cell lymphoma relies on histopathologic examination. The histopathological features of this disease are: on the background of coagulative necrosis and multiple inflammatory cell infiltration, the tumor lymphocytes are scattered or diffusely distributed, with vascular destructive growth, heterogeneous reticulocytes, or nuclear schizophrenia; immunohistochemical staining can detect CD56(+) and CD2(+) lymphocytes; EBER nucleic acid in situ hybridization can assist in the determination of EBV infection. In addition, bone marrow aspiration + biopsy should be performed to clarify the presence of bone marrow invasion.
5. Other tests
Imaging of other parts of the body, including cranial enhancement MR, cervical/thoracic/abdominal/pelvic enhancement CT or positron emission-CT, is often required for disease staging. Upper respiratory or gastrointestinal endoscopy should also be performed if necessary to further define the extent of the disease.
Diagnosis
The diagnosis of nasal-type extranodal NK/T-cell lymphoma must be based on pathologic diagnosis.
Differential diagnosis
Early symptoms of nasal extranodal NK/T-cell lymphoma, such as nasal congestion and pus, need to be differentiated from rhinitis, sinusitis, nasal polyps, and nasopharyngeal carcinoma. It also needs to be differentiated from diseases such as inflammatory pseudotumor, olfactory mother neuroma, Wegener’s granulomatosis, and nonspecific peripheral T-cell lymphoma.
Treatment.
Due to the low incidence of nasal-type extranodal NK/T-cell lymphoma, there are no standard treatment options. Currently, comprehensive treatment is the mainstay, including local radiation therapy, systemic chemotherapy, and hematopoietic stem cell transplantation. It is necessary to choose the treatment method according to the stage of the tumor, the patient’s age, physical condition, symptoms, and the results of various examinations, and develop an individualized treatment plan.
1. Radiation therapy
Nosocomial extranodal NK/T-cell lymphoma is sensitive to radiation therapy, especially for early stage patients whose lesions are confined to the upper respiratory tract and the digestive tract. Radiation therapy is the key to the success or failure of the treatment, and it is closely related to the rate of localized regional control of the tumor and the prognosis.
2. Chemotherapy
Except for some patients with stage I and no risk factors, there is still a high risk of recurrence after chemotherapy alone, so most patients need systemic chemotherapy to reduce the recurrence rate.
L-ASP-containing chemotherapy is an effective treatment for nosocomial extranodal NK/T-cell lymphoma, and its efficacy is better than that of conventional anthracycline-containing chemotherapy. However, conventional L-ASP regimens are prone to allergic reactions and other adverse effects. The efficacy of polyethylene glycol asparaginase (PEG-ASP) is similar to that of conventional L-ASP, while the adverse effects are reduced, especially allergic reactions and other significant reductions. Currently, PEG-ASP + anthracycline-containing or gemcitabine-containing chemotherapeutic regimens are mostly used in clinical practice.
Note that during the period of receiving chemotherapy containing menthyl amidase, light and easy-to-digest food should be forbidden, avoid eating greasy food and overeating, and be alert to the occurrence of acute pancreatitis.
3. Hematopoietic stem cell transplantation
At present, it is still controversial whether autologous stem cell transplantation is needed in the first line for nasal-type extranodal NK/T-cell lymphoma. For some patients in early stage, radiotherapy can achieve good therapeutic effect and transplantation is no longer needed. For some patients with unsatisfactory therapeutic effect, accompanied by poor prognostic factors, and some advanced patients, autologous hematopoietic stem cell transplantation can be considered to consolidate the therapeutic effect in order to reduce the recurrence rate of the disease. For relapsed and refractory patients, high-dose chemotherapy + hematopoietic stem cell transplantation is still the first choice. If autologous HSCT is not suitable, allogeneic HSCT can be performed, but the supply of allogeneic HSCT is difficult to find and the risk is higher.
4. Other treatments
In addition, systemic supportive therapy (e.g. nutritional supportive therapy, blood transfusion, rehydration) and symptomatic therapy (appropriate application of antibiotics to control secondary infections, cleaning of nasal passages) should be given as appropriate to alleviate local and systemic symptoms.
Harms
1. Affecting life
Nasal congestion, ulceration in the middle of the face, fever and other systemic symptoms will seriously affect the quality of life.
2. Impact on appearance
The appearance of ulcers and granulomas in the middle of the face, perforation of the hard palate, protrusion of the eyeballs, facial swelling and other symptoms will affect the appearance of the face, and even disfigure the face in serious cases.
3.Causing psychological burden
Because of the damage to the appearance, it often causes others to look at it differently, which can easily cause the patient’s bad mood and low self-esteem.
4. Causing serious complications
Although the incidence of this disease is low, but the degree of malignancy is high, invasiveness is strong, the disease progresses quickly, and can be complicated by hemophagocytic syndrome, and in the terminal stage, there can be systemic failure, disseminated intravascular coagulation (DIC), etc., which is life-threatening.
Prognosis
The prognosis of nosocomial extranodal NK/T-cell lymphoma has been significantly improved with the continuous improvement of treatment options. For early-stage patients without adverse prognostic factors, the treatment outcome is ideal, and more than 90% of patients can be cured; even for stage II patients, 70% to 80% can still be cured. However, patients with advanced stage have a high degree of malignancy, rapid progression, and are prone to multiple complications, and the prognosis is still poor.