Primary lymphoma of the gallbladder is quite rare and is defined as a disease confined to the gallbladder, with or without involvement of adjacent lymph nodes[3], and there are few reports in the literature. According to the new classification of World Health Organization (WHO) in 2016, B-cell lymphoma is the most common of primary gallbladder lymphoma, such as diffuse large B-cell lymphoma and mucosal-associated lymphoid tissue lymphoma. ENKTL is rarely reported [4]. The current case is only the third case that has occurred in the gallbladder and bile duct [5 6]. Which one case that occurred in the bile duct was found at autopsy. The other case was diagnosed as non-Hodgkin lymph oma after cholecystectomy, bone marrow biopsy results suggest a diagnosis of bone marrow non-Hodgkin’s lymphoma, NK/T cell tumor.
ENKTL is a kind of non-Hodgkin lymphoma that originates from mature NK cells and NK-like T cells[7]. It usually occurs in the nasal cavity, nasopharynx, sinuses and palate, but it is also rare in lungs, testes, adrenal glands, etc [8 9]. Those who occur in the nasal cavity have nasal congestion, necrosis of the diseased mucosa and ulcers, and the accessory sinuses are involved. Skin lesions are manifested as nodules and often accompanied by ulcers. Perforations are common in those who occur in the intestines. Some cases may be associated with hematopoietic syndrome. This patient presented with pain in the upper abdomen, nausea, and vomiting. No masses in the nasal cavity and other parts.
The pathogenesis of ENKTL is not fully understood. At present, it is found to be closely related to Epstein-Barr virus (EBV) infection, especially in nasal cases, EBV infection is present at 80–100% [10], while the detection rate of EBV in other non-nasal parts is relatively low (15–50%). Some previous studies have shown that, compared with CD56 + EBV+ lymphoma, CD56 + EBV− lymphoma at external nasal sites is a less aggressive malignant tumor and shows less necrosis [11]. Moreover, they propose that ENKTL at extra nasal sites should be diagnosed based on EBV infection status, cytotoxic T or NK phenotype, and not related to genotype. In our case, the patient’s EBER is negative, which may indicate a better prognosis.
Morphologically, 1) necrosis is common in the mucosa, with diffuse infiltration of tumor cells; 2) destruction of blood vessel walls and fibrinoid necrosis are common; 3) accompanied by infiltration of various inflammatory cells, such as lymphocytes, eosinophils, tissue cells, and plasma cells Iso-reactive inflammatory cells infiltrate; 4) tumor cells have various morphologies, irregular or long nuclei, granular chromatin, inconspicuous nucleoli or small nucleoli, light to translucent cytoplasm, and mitotic figures are easy to see. Immunohistochemistry shows the tumor cells positively expressed CD3, CD56, CD43, CD2, TIA-1, Granzyme B, Perforin, negative in CD20, CD79a and other about B-cell-related antigens [6]. In the current case, our findings were consistent with the histological form of this disease.
Primary ENKTL of the gallbladder is rare, so it needs to be distinguished from inflammatory lesions or other lymphomas. Inflammatory lesions usually lack of a clonal marker for NK-cells (CD56). Other lymphomas can usually be distinguished based on immune markers. T-cell lymphomas are usually positive for T cell markers and TCR rearrangement; B-cell lymphomas are usually B-cell markers positive and IgH gene rearrangement.
Nasal NK/T cell lymphoma is sensitive to radiotherapy, but often insensitive to chemotherapy, or relapse quickly after a short remission. It is currently believed that combined radiotherapy and chemotherapy is the best choice for the treatment of this type of lymphoma [12]. Our patient received 4 cycles of CHOP since he was diagnosed with ENKTL. Now with no recurrence, and we will continue to follow up.
In conclusion, we present a case with primary ENKTL with gallbladder. The incidence of such condition is extremely low but has significant clinical value. This case broadens the scope of differential diagnosis of gallbladder lymphoma. After all, most of the lymphomas currently reported in the gallbladder are B-cell lymphomas. After the diagnosis of ENKTL, it is necessary to fully understand the patient's medical history to rule out nasal metastasis. At the same time, the negative EBV in this case may also be related to a good prognosis.