Abstract
Primary hepatopancreatobiliary lymphoma (PHPBL) is extremely rare, which is defined as a lympho-proliferative disease confined to the hepatobiliary system and pancreas without any involvement of lymph nodes, bone marrow, or other organs. The clinical and imaging manifestations of PHPBL are variable and non-special, which are akin to those of tumors of the hepatobiliary and pancreatic systems. The overall prognosis and management of PHPBL differ from those of other tumors in the hepatobiliary system and pancreas. Proper diagnosis and prompt treatment are essential for improving clinical outcomes. Due to its rarity, the optimal treatment has not been issued. However, combination chemotherapy is considered as a standard treatment for them. This review provides an overview of the pathogenesis, diagnosis, pathology, and management of PHPBL and offers clinicians the diagnosis and management schedule for PHPBL.
Introduction
Lymphoma accounts for about 4.8% of newly diagnosed cases of cancer in the United States, 90% of which is non-Hodgkin lymphoma (NHL), and about 3.6% of all cancer deaths (1). Lymphoma is traditionally classified as Hodgkin lymphoma (HL) and NHL. They can both locate in sites except for the lymphatic system, which is commonly found in NHL (2). The most common site of extranodal involvement is the gastrointestinal tract, particularly stomach and small bowel (3). Involvement of hepatobiliary and pancreatic system is rare and is divided into primary and secondary lymphoma (4). Primary hepatopancreatobiliary lymphoma (PHPBL) is a rare entity, which has a lower incidence than secondary hepatopancreatobiliary lymphoma (SHPBL), commonly presented in widespread lymphoma.
The commonly accepted diagnosis criteria for PHPBL, as defined by previous studies, include a mass in the hepatobiliary and pancreatic systems, no enlargement of superficial and mediastinal lymph nodes, no involvement of other organs, and normal leukocyte count in the peripheral blood smear (5, 6).
Primary hepatic lymphoma (PHL), primary biliary lymphoma (PBL), and primary pancreatic lymphoma (PPL) are rare and account for 0.4%, 0.4%, and 1% of extranodal non-Hodgkin’s lymphomas, respectively (7–9). PHL and PPL both affect middle-aged people, with a marked male preponderance, whereas PBL often affect elderly individuals, with a sight female preponderance (10–12). Due to their non-specific clinical manifestations and radiological features, PHPBL is always confused with other diseases of the hepatobiliary system and pancreas. The discrepancy in their treatment and prognosis makes it important to achieve a proper diagnosis.
In this article, we will discuss the pathogenesis, epidemiology, clinical presentation, imaging feature, pathological finding, and treatment of PHPBL (Tables 1–3). We aim to raise clinicians’ awareness of the possibility of PHPBL, when they meet a patient with a mass in the hepatobiliary system and pancreas, and offer them the diagnosis and management schedule for PHPBL.
Table 1
| Histotype | Clinical manifestations | Imaging findings | Pathology | Immunophenotype | Behavior | Treatment |
|---|---|---|---|---|---|---|
| DLBCL | Abdominal pain; B symptom; nausea, vomiting; jaundice | A solid mass/multiple masses | Diffuse infiltration of large lymphocytes with prominent nucleoli and increased or atypical mitotic figures | CD20+, CD79a+, CD19+, CD3- GC group: CD10+ or/and BCL-6+, MUM-1- Non-GC group: MUM-1+, BCL-6-, CD10- | Aggressive | Surgery+ chemotherapy (CHOP/R-CHOP) +/- radiation; chemotherapy; surgery |
| BL | Diffuse infiltration of medium-sized lymphocytes, with distinct nucleoli, scant cytoplasm, and increased mitotic figures; starry-sky appearance | Monotypic sIgM+, CD20+, CD10+, CD43+, BCL-6+; CD3-, CD5-, CD23-, BCL-2- | ||||
| MALT | A solid mass/multiple masses in portal fields of the liver | Diffuse infiltration of small-sized lymphocytes, with mildly irregular nucleoli, dense chromatin and scant cytoplasm, without germinal center differentiation; lymphoepithelial lesions in bile duct | CD20+, CD79α+, Bcl-2+, CD21+ CD3-, CD10-, CD5-, CD23-, CD43-, and cyclinD1- | Mostly indolent | ||
| FL | A solid mass/multiple masses | Distinct follicles, formed by small-to-medium-sized centrocytes; follicular meshworks | CD20+, CD10+, BCL-2+, BCL-6+, CD23+, CD21+ |
Summary of the main features of primary hepatic lymphoma.
*DLBCL, diffuse large B-cell lymphoma; BL, Burkitt lymphoma; MALT, mucosa-associated lymphoid tissue lymphoma; FL, follicular lymphoma.
Table 2
| Histotype | Clinical manifestations | Imaging findings | Pathology | Immunophenotype | Behavior | Treatment |
|---|---|---|---|---|---|---|
| DLBCL | Obstructive jaundice; abdominal pain; B symptom; nausea, vomiting | A solid mass/multiple masses | Diffuse infiltration of large cell with prominent nucleoli, numerous mitoses | CD20+, CD79a+, CD19+, CD3-, CD45- GC group: CD10+ or/and BCL-6+, MUM-1- Non-GC group: MUM-1+, BCL-6-, CD10- | Aggressive | Surgery+ chemotherapy (CHOP/R-CHOP) +/- radiation; chemotherapy; surgery |
| MALT | An irregular thickening in the gallbladder or bile duct wall | Diffuse infiltration of small cell with intact mucosal layer and occasional lymphoid follicles; lymphoepithelial lesions | CD20+, CD79a+, CD19+, BCL-6-, CD10-, cyclin D1- | Mostly indolent | ||
| FL | Infiltration of small or medium cleaved lymphocytes, forming follicles; follicular meshworks | CD20+, CD10+, BCL-2+, CD23+, CD3-, CD5- |
Summary of the main features of primary biliary lymphoma.
*DLBCL, diffuse large B-cell lymphoma; MALT, mucosa-associated lymphoid tissue lymphoma; FL, follicular lymphoma.
Table 3
| Histotype | Clinical manifestations | Imaging findings | Pathology | Immunophenotype | Behavior | Treatment |
|---|---|---|---|---|---|---|
| DLBCL | Abdominal pain; jaundice; B symptoms; acute pancreatitis; duodenal obstruction; nausea, vomiting; | A solid mass/multiple masses/diffuse enlarged pancreas without marked dilation of pancreatic duct and vascular infiltration | Diffuse infiltration of large atypical B cells with round nuclei, dispersed chromatin, some marked nucleoli, and scant cytoplasm | CD20+, CD79a+, CD19+, CD5-, cyclin D1-, CD30-, CD56- GC group: CD10+ or/and BCL-6+, MUM-1- Activated GC group: CD10+ or/and BCL-6+, MUM-1+ Activated non-GC group: CD10-, BCL-6-, MUM-1+ | Aggressive | Surgery+ chemotherapy (CHOP/R-CHOP) +/- radiation; chemotherapy; surgery |
| FL | Infiltration of the small or medium-sized cleaved cells forming uniform and dense follicles | CD20+, CD10+, CD19+, BCL-2+, BCL-6+; CD3-, CD5- | Mostly indolent | |||
| MALT | Infiltration of morphologically heterogeneous small B cells | CD20+, CD79α+, Bcl-2+, CD21+ BCL-6-, CD3-, CD10-, CD5-, and cyclinD1- | ||||
| BL | Diffuse infiltration of medium-sized lymphocytes, with round-to-irregular nucleoli, scant cytoplasm; starry-sky appearance | Monotypic sIgM+, CD20+, CD10+, and Bcl-6+; CD3-, CD5-, TdT-, Bcl-2- | Aggressive |
Summary of the main features of primary pancreatic lymphoma.
*DLBCL, diffuse large B-cell lymphoma; BL, Burkitt lymphoma; MALT, mucosa-associated lymphoid tissue lymphoma; FL, follicular lymphoma.
Primary hepatic lymphoma
Risk factors and pathogenesis
The exact risk factors are not clear and several studies have suggested that chronic liver diseases play an etiological role in the development of PHL, including Epstein–Barr virus (EBV), hepatitis B or C virus infection, liver cirrhosis, and primary biliary cirrhosis (13–17). Like gastric mucosa-associated lymphoid tissue (MALT) lymphoma, primary MALT lymphoma of liver may also be associated with H. pylori infection (18). In addition, PHL could present in patients with autoimmune diseases (19, 20), those with acquired immune deficiency syndrome (AIDS), and immunosuppressive drug-treated transplant recipients (21–23).
In all conditions, chronic inflammation of the liver represents the common steps in the pathogenesis of PHL, which induce lymphocyte migration to liver, mediated by some adhesion molecules, and cause B lymphocyte chronic proliferation, eventually leading to hepatic lymphoma (24, 25). Lack of T-cell surveillance is also cited as an inciting factor.
Among all these conditions, hepatitis C virus (HCV) infection is strongly associated with PHL (26), which causes malignant transformation by indirect methods. HCV, a lymphotropic virus, brings about chronic stimulation of B-cell and polyclonal proliferation, eventually leading to hepatic lymphoma. It may also induce a t (14, 18) translocation resulting in overexpression of BCL-2, an anti-apoptotic factor, and rearrangement of monoclonal IgH. Furthermore, through the viral core proteins, it can downregulate the transcription of tumor suppressor genes like p21, p53, and Ras (24).
In primary hepatic MALT lymphoma, the most frequent translocation is t (14, 18) (q32; q21), which brings the mucosa-associated lymphoid tissue 1 (MALT1) gene to the downstream of the IgG enhancer and makes MALT1 overexpressed, thus resulting in activation of the NF-κB pathway. Meanwhile, activated MALT1 has protease activities, causing hydrolyzation of tumor necrosis factor alpha inducible protein 3 (TNFAIP3), which act as a NF-κB negative regulator, further promoting NF-κB activation. Overexpression of MALT1 and BCL-10 can upregulate the BAFF expression, thus enhancing the activation of the non-canonical NF-κB pathway (Figure 1) (27).
Figure 1
TNFAIP3 plays a key role in the regulation of several inflammation signaling pathways, which can negatively regulate the NF-κB pathway by inhibiting signals from various surface receptors to activate the signaling pathway. Therefore, the inactivating mutation or deletion of TNFAIP3 gene can downregulate its expression and reduce the repression of NF-kB activation (Figure 1) (18, 27). Such genetic abnormalities play an essential role in lymphomagenesis.
Cyclic adenosine monophosphate response element binding protein (CREBBP) is a transcriptional coactivator, which is involved in several signaling pathways. Due to the lack of acetylation, the mutant CREBBP protein can activate BCL-6 and decrease the tumor suppressor activity of p53, thus protecting atypical lymphocytes from apoptosis. Deletion of CREBBP gene can downregulate the expression of MHC-II gene, leading to immune escape of malignant cells for proliferation and invasion (Figure 1) (18, 28).
Epidemiology and clinical features
PHL is extremely rare, which makes up only 0.4% of extranodal NHL, and 0.016% of all NHL (7). PHL affects individuals of varying age, but it is essentially a disease of middle-aged people (median age: 50 years old). Men are affected approximately twice as women (10).
Although the clinical features of PHL are wide-ranging, patients with PHL usually present with a complaint of upper right abdominal pain (29). The typical B symptoms of fever and weight loss can be found in one-third of all cases (24). Other symptoms include fatigue, anorexia, nausea, jaundice, and vomiting (30–33). On the physical examination of abdomen, tenderness in the upper right quadrant and hepatomegaly are the common presenting features. Splenomegaly occasionally can be observed in a few cases, as a consequence of hepatic dysfunction and portal hypertension (24, 31, 34).
Typical serum findings include variably elevated lactic dehydrogenase (LDH), bilirubin levels, as well as elevated liver enzyme levels (35, 36). The level of LDH, as a prognostic marker, increases in 30%–80% of all cases (24). The significantly increased LDH and normal tumor markers are useful clues in the diagnosis of PHL (37). Full blood counts are usually within the normal range unless the bone marrow or spleen is involved (38). Other occasional laboratory findings include monoclonal paraproteinemia and hypercalcemia, which is possibly the result of the secretion of calcitriol by lymphoma cells (39, 40).
Imaging
The imaging features of PHL are wide-ranging, and are commonly evaluated by abdominal ultrasound (US), CT, and MRI. At imaging, PHL can appear as a solitary mass, multiple lesions, or diffuse infiltration (41), mimicking other liver diseases, such as hepatocellular carcinoma, cholangiocarcinoma, metastatic disease of liver, and hepatitis.
On US, PHL mostly appears as homogeneous hypoechoic lesions confined in the liver (30, 42). Anechoic lesion can occasionally be seen, which may be confused with cyst (43). If there is a mass in the porta hepatis, dilation of the intra- and extra-hepatic bile ducts can also be found (44). The manifestations of contrast-enhanced US show mild heterogeneous enhancement in the arterial phase and washout in the portal and late phases (45).
On CT, PHL always presents as hypoattenuating lesions, with or without distinct margins (Figures 2A, 3A) (46, 47), the center of which may have a lower intensity, suggesting necrosis (2). However, it also presents as homogeneous or heterogeneous hepatomegaly without definite hepatic masses (48). Unlike hepatic carcinoma, PHL shows that hepatic vessels passed through the lesions without evidence of compression, or infiltration (48). On contrast-enhanced CT (CECT), the hepatic lesions show mild enhancement in the arterial phase (Figures 2B, 3B) and progressive enhancement in the venous phase, which is vital to differentiate from hepatocellular carcinoma. Rim enhancement can also be noted (46, 47, 49).
Figure 2
Figure 3
On MRI, the lesions of PHL tends to show hypointense signal on the T1-weighted images (T1WI) and hyperintense signal on the T2-weighted images (T2WI) (Figures 2C, D, 3C,D) (50, 51). Some PHLs show a heterogeneous signal because of necrosis or fibrosis within the mass (52). Nearly half of PHLs show enhancement after the intravenous administration of the contrast agent, which is lower than that of normal liver parenchyma (Figures 2E, 3E), whereas 40% of PHLs are hypointense. PHL patients mainly present as a significant signal restriction in diffusion-weighted imaging (DWI), with a lower ADC value (median ADC value: 0.83 × 10-3 mm2/s) than other malignant hepatic diseases (Figures 2F, 3F) (53). Like CT features of PHL, we can also observe no distortion of the blood vessels and bile ducts passing through hepatic lesions on MRI, which is called “insinuative growth” (54).
PET/CT has been an excellent modality for the diagnosis, staging, and follow-up of tumor, which can evaluate the involvement of other sites in patients with lymphoma and differentiate primary liver lesions from metastatic diseases (55, 56). The hypermetabolic lesions with a maximum Standardized Uptake Value (SUVmax, mainly ranging from 4.5 to 33.5) might be observed, with tumor confined in the liver without abnormal uptake in any other tissues or organs (57).
Pathology and immunohistochemistry
The clinical and radiological findings of PHL are non-special, and a definite diagnosis can only be made after pathological analysis. Liver tissue can be obtained by fine needle biopsy (FNB), image-guided percutaneous biopsy, laparoscopic biopsy, or open biopsy (2, 58).
As the most common subtype of PHL, diffuse large B-cell lymphoma (DLBCL) accounts for up to 80% of all PHL cases (10), followed by MALT lymphoma, follicular lymphoma, Burkitt lymphoma, and T-cell lymphoma (24, 59–62).
Microscopically, on low-power magnification, the lymphoid cells infiltrate the hepatic parenchyma and form solitary, multiple nodules or diffuse infiltration (63). On high-power magnification, the histological features vary, depending on the subtypes of PHL. In primary hepatic DLBCL, the lesions are formed by diffuse large-sized lymphoid cells with prominent nucleoli and increased or atypical mitotic figures (Figure 2G) (64–66). In primary hepatic MALT lymphoma, the atypical lymphoid cells are small in size, with mildly irregular nucleoli, dense chromatin, and scant cytoplasm, without germinal center differentiation (Figure 3G) (64, 67). Because MALT lymphomas commonly involve the portal fields of the liver, lymphoepithelial lesions are always presented in the bile ducts, which is a typical accompanying feature of hepatic MALT lymphoma (68). In primary hepatic follicular lymphoma, it mainly presents as distinct follicles, formed by small- to intermediate-sized centrocytes, with germinal center differentiation (69). The presence of follicular meshworks is a vital feature in the diagnosis of follicular lymphoma (64). In primary hepatic Burkitt lymphoma, diffuse medium-sized lymphocytes, with distinct nucleoli, scant cytoplasm, and increased mitotic figures, form the lesions (64). A typical starry-sky appearance has been reported, which is formed by the dispersal of numerous tangible-body macrophages among malignant cells (62, 70).
Immunohistochemistry is always required for classification of lymphoma, which is important to obtain the correct diagnosis. Most PHLs are of B-cell origin, which are always positive for part of or all the B-cell markers, usually including CD19, CD20, and CD79a, and negative for CD3 (Figures 2H, 3H, I) (71–74). However, different immunophenotypes have their own characteristics, which are essential for the classification of PHL. In DLCBL, they are often positive for CD45, PAX5, and BCL-2 with a high Ki-67 index (Figure 2I) (30, 75, 76). Patients with DLBCL are always subclassified into the germinal center B-cell (GCB) group, expressing CD10 and/or BCL-6 without MUM-1, and the non-GCB group, expressing MUM-1 without CD10 and BCL-6 (Figures 2J–L) (37, 64). In MALT lymphoma, they are also positive for IgM and CD21 and negative for CD5, CD10, and cyclin D1, with a low Ki-67 index (Figures 3J–L) (68, 77–79). In Burkitt lymphoma, they are also positive for monotypic surface IgM, CD10, BCL-6, and MYC and negative for BCL-2, with a high Ki-67 proliferative index, which is nearly 100% (64, 80). In follicular lymphoma, they are also positive for CD10, BCL-2, and BCL-6, with a low Ki-67 proliferative index. Immunostaining with CD21 and CD23 can highlight the follicular meshworks (64, 81, 82). The characteristics of pathology and immunophenotype of PHL are summarized in Table 1.
Differential diagnosis
Due to non-special symptoms and imaging features, a number of liver diseases should be considered during differential diagnosis of PHL including hepatocellular carcinoma, metastatic disease of liver, cholangiocarcinoma, hepatitis, or systemic NHL with secondary hepatic involvement. Some clinical and imaging features are helpful in differentiating between these entities.
Hepatocellular carcinoma appears as marked enhancement in late arterial phase, which becomes both progressive washout of contrast compared to healthy liver tissue in portal venous or delayed phases (83). The “bulls-eye” sign is a characteristic feature of metastatic carcinoma of liver. It always appears as a thick rim-like enhancement in the arterial phase and a hypo-enhancement in portal venous and delayed phases (84). Patients with acute hepatitis appear to have a thickening of the gallbladder wall and hepatic periportal lucency, which can favor a diagnosis of acute hepatitis (85). SHL typically presents as multifocal or diffuse lesions along with extrahepatic involvements, which can be detected by CT, MRI, or PET/CT (86).
Although some features are useful clues in diagnosis, it is difficult to make a definite diagnosis without histological analysis, which is the gold standard of diagnosis.
Prognosis and treatment
PHL with different infiltration types has a different prognosis. The 1-year and 3-year survival of patients with nodular infiltration are 70% and 57%, respectively, whereas those of patients with diffuse infiltration are 38% and 18%, indicating a poorer prognosis (87). In addition, the prognosis of indolent lymphoma, like follicular lymphoma and MALT lymphoma, is better than that of aggressive diseases like DLBCL, Burkitt lymphoma, and T-cell lymphoma (88). Major prognostic factors associated with survival are the large size of the tumor, high proliferation of cells, old age, systemic symptoms, unfavorable histologic subtype, disease stage, and complications (44, 68). An elevated level of LDH, β2 microglobulin, or serum calcium, as prognostic markers, suggests a worse prognosis (41).
Because of the rarity of PHL, no consensual recommendation for treatment has been issued. The choices of management for PHL contains surgery, chemotherapy, radiotherapy, or combinations of the above modalities (49). Liver transplantation has also been used in PHLs (68). The isolated case report and case series studies of PHL in the recent 10 years are summarized in Supplementary Table 1. As shown in Table S1, systemic combination chemotherapy is commonly used as the main therapeutic approach, which could usually achieve disease remission (89–91). Moreover, chemotherapy with CHOP-based regimens (cyclophosphamide, doxorubicin, vincristine, and prednisone) is the first-line treatment (92, 93). The combination of rituximab with conventional chemotherapy can prolong survival of PHL patients who are positive for CD20 (69, 94–96). The role of surgery is not clear, but some studies have found that surgical resection can offer a good outcome (97–102). Solitary lesions could be considered as the best candidates for hepatectomy and another indication for surgery is related to an uncertain diagnosis (30). In a review of 72 patients with PHL, Avlonitis et al. confirmed that surgical resection followed by adjuvant chemotherapy and radiotherapy is the optimal treatment for PHL. Patients treated with surgery and chemotherapy might have better prognosis than those treated with chemotherapy alone (38). However, due to the rarity of PHL, the definite role of surgery still needs to be further confirmed. Lymphomas also respond to radiotherapy, while radiotherapy is not as effective as chemotherapy, which is always used as an adjunct to chemotherapy (93, 103–106). Radiofrequency ablation (RFA), a new option for the treatment of PHL, has good efficacy in the short term. When the preoperative diagnosis is clear and the mass measures less than 2 cm, RFA can be selected. However, the effect of RFA in the long term needs more relevant cases (77).
Primary biliary lymphoma
Risk factors and pathogenesis
Due to the rarity of PBL, the exact etiological factor is obscure. Several studies found that half of all reported cases had gallstone, and this implies that PBL may be related to inflammation such as chronic cholecystitis or cholangitis associated with cholelithiasis or infected bile (107). Furthermore, mechanical irritation of gallstones is more responsible for the pathogenesis of PBL (108). PBL can also be found in patients with hepatitis virus infections and immunosuppression, such as HIV infection and organ transplantation (109, 110).
Whatever the specific cause of inflammation, cholecystitis or cholangitis induces lymphocyte migration to the mucosa of the biliary tract and prolonged lymphoid reactive proliferation, which is antigen-dependent, and accumulation in the site of inflammation, thus leading to irreversible chromosomal translocations, which can inhibit apoptosis and cause antigen-independent proliferation (111–113). Bisig et al. (108) detected a specific chromosomal translocation t (11, 18) (q21; q21) in primary biliary MALT lymphoma, leading to the expression of a transcript fusing the apoptosis inhibitor 2 (API2) gene to MALT1 gene. API2/MALT1 fusion can reduce the inhibition of API2 on apoptosis response to antigen stimulation, thus leading to MALT lymphoma of the biliary tract (108). Its production can also induce expression of BCL-10 and activation of the NF-κB pathway, leading to cell proliferation (Figure 1) (27). Another possible mechanism is that prolonged chronic inflammation causes irreversible genetic rearrangements, thus disabling the response of cells to IL-2 regulation, eventually helping in the development of MALT lymphoma (114).
In addition, another possible pathogenesis was reported by Angelopoulou and his colleagues. In PBL, the malignant transformation of the original clone could have occurred outside the biliary system with subsequent homing by an adhesion molecule mechanism (115).
Epidemiology and clinical features
PBL is an extremely rare entity, which could be divided into intrahepatic bile duct and the extrahepatic biliary system. The clinical and radiological findings of lymphoma of the intrahepatic duct resemble those of hepatic lymphoma. Hence, we only discuss primary lymphoma of the extrahepatic biliary system here. Extrahepatic biliary non-Hodgkin’s lymphoma (EBNHL) constitutes 0.6% of malignant biliary tumors, including lymphoma of gallbladder and extrahepatic bile duct (8). Primary lymphoma of gallbladder has a higher prevalence than extrahepatic bile duct lymphoma. PBL can occur in various age groups and commonly affect elderly individuals with a mean age of 75.8 years old, with a slight female preponderance (11).
Patients with primary gallbladder lymphoma commonly present with symptoms of acute or chronic cholecystitis, and the most common symptom is upper right abdominal pain (11, 116). The common clinical manifestation of primary bile duct lymphoma is obstructive jaundice (8). Fever, night sweats, weight loss, nausea, and vomiting can also be present in these patients (117). The physical examination of these patients is often normal, while yellowing of skin and sclera with itching marks on the skin can be found in PBL patients with biliary obstruction (118). Slight tenderness in the upper right quadrant is also be observed in some cases.
The common abnormalities revealed by laboratory test results associated with PBLs include variably elevated bilirubin and liver enzyme levels, which suggest cholestasis (119). Interleukin (IL)-2 receptor, a serum marker of lymphoma, increases in patients with PBL (107, 120). Tumor markers are often within normal range, which can differentiate PBL from carcinoma of the biliary system, while mildly elevated CA19-9 can be observed in some cases (117). Full blood counts are usually normal at the early stage; however, the number of erythrocytes, leukocytes, and platelets might decrease when bone marrow or spleen is involved (8). In addition, other rare laboratory abnormalities include elevated serum and urine amylase level (121).
Imaging
Radiological characteristics of PBL depend on their pathological classifications. Their imaging appearances can be divided into two morphological groups (1): a solid mass, seen in high-grade lymphomas, such as DLBCL; and (2) an irregular thickening in the gallbladder or bile duct wall, seen in low-grade lymphomas, such as MALT and follicular lymphoma (107, 111).
US is the modality of choice in the initial evaluation of gallbladder and biliary diseases (122). The common US features of primary gallbladder lymphoma present as thickening of the gallbladder wall or a soft tissue mass located in gallbladder with or without gallstone (107, 109), which has lower echo compared to gallbladder carcinoma (123). In addition, patients with primary bile duct lymphoma usually present with thickening of the bile duct or a hypoechoic mass with dilation of the proximal bile duct (124). The imaging features of endoscopic ultrasound (EUS) are similar to those of typical US.
The common CT feature of primary gallbladder lymphoma is a thickened gallbladder wall with intact mucosa and layered enhancement after administration of the contrast agent (Figure 4A) (107, 125). The other common CT feature presents as a focal mass confined in the gallbladder with slight enhancement (120, 126). Patients with primary bile duct lymphoma present with segmental circumferential wall thickening of the bile duct or a bile duct mass, with proximal bile duct dilatation and smooth mucosal layer (127).
Figure 4
On MRI, the gallbladder or bile ductal lesion shows lower and slightly higher signal intensity on the T1WI and T2WI, compared to the surrounding normal liver parenchyma (111, 127). Homogeneous enhancement of biliary lesion can be observed on contrast-enhanced images. The dilation of upstream bile duct can also be seen in most lymphomas of bile duct on MRI (128). MR cholangiopancreatography (MRCP) has rarely been applied to gallbladder lymphoma, and thus, the MRCP findings of gallbladder lymphoma are rarely reported. Moreover, MRCP features of primary bile duct lymphoma are similar to those of cholangiocarcinoma, commonly presenting as a segmental luminal narrowing of bile duct without mucosal irregularity and with dilation of the proximal bile duct (128). Endoscopic retrograde cholangiopancreatography (ERCP) can observe similar features (Figure 4B).
On PET/CT, the location and size of PBL are similar to other imaging modalities. The common imaging feature with PET/CT demonstrates hypermetabolic activity in gallbladder or bile duct without other metastatic areas (129, 130). PET/CT is a preferred choice for staging lymphoma and helpful for differentiating PBL from secondary lymphoma and other diseases, particularly cholecystitis.
Pathology and immunohistochemistry
Like other lymphoma, adequate biopsy is needed for definitive diagnosis. Most PBL patients obtain pathologic specimens by surgery, while it can also be obtained under CT, EUS, or ERCP guidance (131).
Grossly, low-grade PBL presents as thickening of the bile duct and gallbladder with intact mucosal layer; however, in high-grade PBL, it shows a mass defined in the biliary system. Histologically, a dense and diffuse infiltration of atypical lymphoid cells in the gallbladder or bile duct wall, with intact mucosal layer and occasional lymphoid follicles, could be observed in patients with low-grade lymphoma [127, 132], whereas in patients with high-grade lymphoma, it demonstrated diffuse infiltration of large-sized lymphocytes with prominent nucleoli and abundant mitoses [36].
As summarized in Table 3, the most common subtypes of primary lymphoma of gallbladder or bile duct are DLBCL and MALT, followed by follicular lymphoma and B-lymphoblastic lymphoma (11). The immunohistochemical features and molecular findings of different subtypes of PBL are summarized in Table 3, which are similar to those of PHL (83, 112, 123–128, 132, 133).
Differential diagnosis
PBL is a rare disorder that can be present as a focal mass or a thickening in the gallbladder or bile duct wall and imitate the characteristics of biliary tumors such as adenocarcinoma or inflammatory process such as sclerosing cholangitis and cholecystitis (119).
Patients with cholangiocarcinoma presented as concentric or eccentric wall thickening without intact mucosa, resulting in varying degrees of luminal stenosis (134). Gallbladder carcinoma always appears as a mass or thickening of the gallbladder wall, with disruption of the mucosal layer (135). Primary sclerosing cholangitis (PSC), associated with inflammatory bowel disease (IBD), presents as multifocal biliary strictures (136). Radiographical findings of cholecystitis show a thickened gallbladder wall (>4 mm), often accompanied by gallstones and pericholecystic fluid (137). Besides imaging features, patient’s disease history, physical examination, and laboratory studies are essential for differentiation diagnosis (122).
The prognosis and treatment of PBL are different from other biliary diseases, and the proper diagnosis of the disease is important. The histological analysis is indispensable for a correct diagnosis.
Prognosis and treatment
PBL has a better prognosis than cholangiocarcinoma and gallbladder carcinoma (118). Like other NHLs, the prognosis of PBL may be associated with age, tumor stage, subtype, and treatment. Due to lack of sufficient case series, this association has not been confirmed; more studies are needed to prove this.
Due to the low incidence of PBL, there is no consensus on the optimal treatment. As shown in Table S2, the management consists of surgery, chemotherapy, radiotherapy, or a combination of all. Because of the difficulty of acquiring pathological diagnosis, surgical resection is commonly performed in most PBL patients (Table S2) (120). Surgery can also be a therapeutic option for patients with complicating biliary obstruction, or who fail to respond to chemotherapy (119). Surgical intervention is proven curative in many cases (121, 138). Chemotherapy is considered as the predominant management modality and an integral part of the postoperative treatment (124). Radiotherapy is often considered an adjunct to chemotherapy, which might increase the survival of patients with residue after chemotherapy (128). From reviewing previous PBL case studies, surgical resection, combined with chemotherapy with or without radiotherapy may be a treatment regimen for improved survival rate, which need further studies to confirm.
Primary pancreatic lymphoma
Risk factors and pathogenesis
Due to the rarity of PPL, the consensus of pathogenesis is still not issued. It is commonly associated with immunosuppression, related to HIV infection or solid organ transplantation (139). A few studies have implied that HCV or HBV infection is associated with PPL (140, 141).
However, to our knowledge, HBV and HCV are hepatotropic and are main etiologies of liver cancer. The possible reasons that hepatitis virus can cause pancreatic damage are the proximity of the liver to the pancreas and shared blood vessels and ducts. The possibility is further supported by findings of hepatitis B surface antigen (HBsAg) in pancreatic juice and hepatitis virus replication in pancreatic cells among patients with HBV infection (142, 143).
Like PHL, HBV or HCV infection may indirectly give rise to inflammation-associated lymphomagenesis in the pancreas. It may induce cytokine and cytokine growth, perhaps affecting various genes and causing proliferation of lymphoid cells (140). Moreover, it may also reduce the threshold of antigen response or result in DNA mutations by binding to surface receptors of B lymphocytes, thus leading to lymphoproliferation (141).
Epidemiology and clinical features
PPL is a rare disease and accounts for approximately 1% of extranodal lymphoma and 0.5% of pancreatic cancers (9). PPL commonly affects middle-age individuals with a median age of 53 years old and has a male predilection (male:female ratio of 1.5:1) (12).
Clinical features of PPL are non-specific and include epigastric pain, abdominal mass, weight loss, obstructive jaundice (144–146), intestinal obstruction, and rarely acute pancreatitis (147), which are similar to those of pancreatic adenocarcinoma (148, 149). However, the typical symptoms of NHL, such as fever, chills, and night sweats, are rare in PPL (150). A physical examination was significant for epigastric tenderness, abdominal mass, and jaundice, but not for organomegaly or lymphadenopathy.
The tumor marker levels in PPL patients, such as CA19-9 and CEA, are commonly normal or slightly elevated in the case of biliary obstruction, which are apparently increased in most pancreatic adenocarcinoma patients (151). An elevated LDH level and serum beta-2-microglobulin are often presented in patients with pancreatic lymphoma. Although their elevations are not necessarily required for the diagnosis of PPL, they are useful markers, high levels of which are indicators of a poor prognosis for patients with PPL (152). Elevated liver enzymes and bilirubin levels are found in PPL patients with biliary obstruction.
Imaging
Radiologically, the lesions of PPL appear as focal and well-defined lesions or diffuse infiltration of pancreas (153), as summarized in Table 2. The tumor is most commonly located in the head of the pancreas, though it can be found in other portions of the pancreas, such as the body and tail (149, 154). PPL almost presents as bulky masses with a median size of 7.9 cm (155).
The most common US finding is a bulky homogeneous hypoechoic mass confined to the pancreas, with or without dilatation of bile ducts. Peripancreatic vessels are encompassed by mass, but are always not infiltrated, which can be distinguished from pancreatic adenocarcinoma (12, 156). The appearances of EUS are consistent with those of typical US; however, it has a higher sensitivity (157).
Boninsegna et al. found that PPLs have the following common CT features: a large and hypo-attenuation mass with mild enhancement (Figures 6A–C), peri-pancreatic fat stranding, vessel encasement without infiltration, rare pancreatic duct dilatation, and absence of necrosis (158, 159). These findings are in agreement with some studies reported by other teams (12, 160, 161). The “sandwich sign”, in which a mesenteric mass surrounds the mesenteric vessels, without vascular infiltration, is frequently observed in patients with PPL (161, 162).
The MRI characteristics of PPL appear as a bulk lesion with mild enhancement, without significant pancreatic duct dilatation, which has a lower signal intensity on T1WI and a higher signal on T2WI (Figures 5A, B) (12, 163, 164). Unlike CT, MRI shows a slightly heterogeneous character of the lesion, especially on T2WI (165). In some cases, PPL may present with diffuse enlargement of pancreas, mimicking pancreatitis (166, 167). Occasionally, PPL may initially present only as acute pancreatitis and can be diagnosed only on follow-up imaging (167). MPD dilatation can rarely be found in PPL patients. However, mildly upstream MPD dilatation is another feature of PPL with diffuse pancreatic enlargement (165).
Figure 5
The most common PET/CT feature is a solitary hypermetabolic lesion in the pancreas, with SUVmax ranging from 7.4 to 26.5 (the mean SUVmax is 13.2) (168–171).
Pathology and immunohistochemistry
Pancreatic tissue can be obtained by percutaneous/endoscopic FNA or biopsy (172), exploratory laparotomy, or resection surgery. EUS-guided FNA or biopsy is an optimal method to obtain preoperative diagnosis (132, 157, 173–175).
As confirmed in Table S3, the most predominant PPL subtype is DLBCL (occupying nearly 77%), followed by follicular lymphoma (occupying 14%) (155). Furthermore, Burkitt lymphoma, small lymphocytic and T-cell lymphoma, or Hodgkin’s lymphoma can also be present in PPL (176–180).
The specific pathologic and immunohistochemical findings of PPL are demonstrated in Table 2 and in Figures 6D–I (181–194).
Figure 6
Differential diagnosis
The clinical manifestations of PPL may mimic those of other neoplastic or inflammatory pancreatic diseases, such as pancreatic adenocarcinoma, pancreatic neuroendocrine tumor, acute pancreatitis, and autoimmune pancreatitis (AIP) (195). Although PPL has overlapped symptoms and imaging findings with other pancreatic diseases, some characteristic findings can help in the diagnosis of PPL.
In contrast to PPL, pancreatic ductal dilatation, and ductal and peripancreatic vascular invasion were frequently shown in pancreatic adenocarcinoma (196, 197).
Both PPL and AIP might appear as diffuse enlargement, a focal lesion, or multifocal lesions, making differential diagnosis difficult. Ishigami et al. (166) observed 8 patients with pancreatic lymphoma and 21 patients with AIP to identify the point of imaging discrimination for the two diseases. They concluded that patients with AIP present with delayed enhancement with a capsule-like rim on CT and MRI, which was absent in the PPL imaging feature (166, 198). In addition, elevated serum c-globulin levels, particularly immunoglobulin G, can be observed in almost all of the patients with AIP, but not in PPL patients (199).
Even if some findings can help with the diagnosis, histological analysis is still required for a definitive diagnosis.
Prognosis and treatment
The prognosis for PPL is much better than that of other pancreatic malignant tumors. A cohort study showed a median overall survival of 53 months (200). Patients with advanced age have a worse overall survival. Similarly, patients with stage IV or aggressive subtype have a worse prognosis, with a median survival of only 13 months, whereas those with an earlier stage have a longer survival of 80 months. Undergoing chemotherapy is also significantly associated with better overall survival, while location of tumor, race, and sex are not associated with overall survival (200).
The rarity of PPL patients makes it difficult to draw a definite conclusion about the optimal treatment, which is mainly determined by the histological subtype. As summarized in Table S3, the strategy for PPL includes surgery, chemotherapy, radiotherapy, or a combination of all (9). Considering that the pathology of most PPL patients is DLBCL, chemotherapy is the standard treatment (12, 155, 201). The most commonly used regimen is CHOP or R-CHOP (176). The majority of patients with PPL receiving only chemotherapy can achieve long-term disease remission (12, 148, 149, 163, 202). Vijungco et al. (203) found that early-stage NHL patients treated with radiotherapy alone have a high overall cure rate. However, in the last decade, radiotherapy has often been used as an adjunct to chemotherapy, rather than used alone (144, 151, 175, 188, 204). Some studies demonstrated that patients treated with chemotherapy with radiotherapy had a high overall response rate (144, 188). However, the role of radiotherapy has also not yet been well defined (204). Surgical intervention is not adopted as the primary treatment for PPL, which is considered when the diagnosis of a mass in pancreas remains uncertain or patients present symptoms caused by obstruction of the biliary tract (155). Behrns et al. (205) reported that the combination of surgery and chemotherapy has a better survival benefit than chemotherapy alone. Interestingly, a study by Facchinelli et al. (188) showed different results. Thus, surgical intervention remains controversial and needs to clarify its benefits through numerous PPL study series (188).
Conclusion
PHPBL often overlaps with other diseases of hepatobiliary and pancreas in clinical and radiological features, resulting in misdiagnosis and delayed treatment. Since early diagnosis depends on the alertness of clinicians, mainly radiologists, gastroenterologists, and hepatopancreatobiliary surgeons, it is important for them to know more clinical and imaging features of PHPBL, in order to obtain a proper diagnosis and management. Clinical manifestation, imaging findings, and laboratory studies could provide helpful clues for diagnosis, whereas histological analysis is the gold standard for accurate diagnosis and subtype analysis. Due to the rarity of the disease, there is no consensus on treatment options. The optimal therapeutic choice, including surgery, chemotherapy, radiotherapy, immunotherapy, or other treatments, either alone or in combination, needs further investigation. The management of PHPBL needs an experienced multidisciplinary team, involving radiologists, gastroenterologists, hepatopancreatobiliary surgeons, pathologists, hematologists, and radiation oncologists, to provide individualized therapy and better prognosis (Figure 7).
Figure 7
Funding
This review was funded by grants from the National Natural Science Foundation of China (No. 81570698).
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Statements
Author contributions
Conceptualization, BZ. Literature search, QW, YL, and ZS. Investigation, KW and XZ. Project administration, BZ and SW. Writing—original draft, QW. Data curation, KW, XZ, and SW. Formal analysis, YL and ZS. Writing—review and editing, BZ. All authors have read and agreed to the published version of the manuscript.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fonc.2022.951062/full#supplementary-material
References
1
SiegelRLMillerKDFuchsHEJemalA. Cancer statistics, 2021. CA Cancer J Clin (2021) 71(1):7–33. doi: 10.3322/caac.21654
2
IppolitoDPortaMMainoCPecorelliARagusiMGiandolaTet al. Diagnostic approach in hepatic lymphoma: Radiological imaging findings and literature review. J Cancer Res Clin Oncol (2020) 146(6):1545–58. doi: 10.1007/s00432-020-03205-x
3
ZuccaERoggeroEBertoniFCavalliF. Primary extranodal non-hodgkin's lymphomas .1. gastrointestinal, cutaneous and genitourinary lymphomas. Ann Oncol (1997) 8(8):727–37. doi: 10.1023/a:1008282818705
4
HedgireSSKudrimotiSOliveiraISNadkarniNMcDermottSHahnPFet al. Extranodal lymphomas of abdomen and pelvis: Imaging findings and differential diagnosis. Abdom Radiol (NY) (2017) 42(4):1096–112. doi: 10.1007/s00261-016-0964-8
5
LeiKI. Primary non-hodgkin's lymphoma of the liver. Leuk Lymphoma (1998) 29(3-4):293–9. doi: 10.3109/10428199809068566
6
BehrnsKESarrMGStricklerJG. Pancreatic lymphoma: Is it a surgical disease? Pancreas (1994) 9(5):662–7. doi: 10.1097/00006676-199409000-00019
7
FreemanCBergJWCutlerSJ. Occurrence and prognosis of extranodal lymphomas. Cancer (1972) 29(1):252–60. doi: 10.1002/1097-0142(197201)29:1<252:aid-cncr2820290138>3.0.co;2-#
8
GaoFZhaoHCChenXDDongXSLiuTFuXF. Gallbladder non-hodgkin's lymphoma: Case report. Int J Surg Case Rep (2019) 61:218–21. doi: 10.1016/j.ijscr.2019.07.064
9
DunphyLAbbasSHAl ShoekIAl-SaltiW. Primary pancreatic lymphoma: A rare clinical entity. BMJ Case Rep (2020) 13(1):e231292. doi: 10.1136/bcr-2019-231292
10
PengYQingACCaiJCYueCJFrenchSWQingX. Lymphoma of the liver: Clinicopathological features of 19 patients. Exp Mol Pathol (2016) 100(2):276–80. doi: 10.1016/j.yexmp.2016.02.001
11
ManiHClimentFColomoLPittalugaSRaffeldMJaffeES. Gall bladder and extrahepatic bile duct lymphomas: Clinicopathological observations and biological implications. Am J Surg Pathol (2010) 34(9):1277–86. doi: 10.1097/PAS.0b013e3181e9bb8b
12
FacchinelliDBoninsegnaEViscoCTecchioC. Primary pancreatic lymphoma: Recommendations for diagnosis and management. J Blood Med (2021) 12:257–67. doi: 10.2147/IJBM.S273095
13
BronowickiJPBineauCFeugierPHermineOBrousseNObertiFet al. Primary lymphoma of the liver: Clinical-pathological features and relationship with HCV infection in French patients. Hepatology (2003) 37(4):781–7. doi: 10.1053/jhep.2003.50121
14
MrabetSZaghouaniHMestiriSAkkariIBen JaziaE. Primary Hepatic Lymphoma in a patient with chronic hepatitis b. Case Rep Gastroenterol (2020) 14(3):632–6. doi: 10.1159/000511248
15
PanjalaCTalwalkarJALindorKD. Risk of lymphoma in primary biliary cirrhosis. Clin Gastroenterol Hepatol (2007) 5(6):761–4. doi: 10.1016/j.cgh.2007.02.020
16
TsujiHYoshifujiHShindoTHishizawaMIshidaAFujimotoMet al. Primary hepatic lymphoma as other iatrogenic immunodeficiency-related lymphoproliferative disorders: a case report and review of the literature. Mod Rheumatol Case Rep (2021) 5(1):172–7. doi: 10.1080/24725625.2020.1826627
17
ZaimiYAyariMCherifiWLetaief KsontiniFAyadiSBel Hadj MabroukEet al. Primary hepatic large b-cell lymphoma following direct-acting antiviral treatment for hepatitis c. BMJ Open Gastroenterol (2021) 8(1):e000721. doi: 10.1136/bmjgast-2021-000721
18
HaefligerSMilowichDSciarraATrimecheMBouillyJKaiserJet al. Primary hepatic marginal b cell lymphoma of mucosa-associated lymphoid tissue (MALT) and non-alcoholic steatohepatitis (NASH): More than a coincidence? Ann Hematol (2019) 98(6):1513–6. doi: 10.1007/s00277-018-3565-5
19
ScucchiLNeriBArgiròRNassoDProvenzanoIPotenzaSet al. Hepatic follicular lymphoma in an old patient with crohn's disease: A rare case and review of the literature. Eur Rev Med Pharmacol Sci (2020) 24(19):10045–50. doi: 10.26355/eurrev_202010_23219
20
ParkJELeeKMChoiHYAhnSEYouMW. Methotrexate associated primary hepatic lymphoma and cranial neuropathy in a patient with rheumatoid arthritis: A case report with clinical follow-up over a 7-year period. Med (Baltimore) (2019) 98(17):e14997. doi: 10.1097/MD.0000000000014997
21
García-BermúdezVMorales-OrtegaAJaquero-ValeroMIKhedaouiRTardíoJCBernal-BelloD. Primary liver lymphoma and systemic sclerosis. Rheumatol (Oxford) (2022) 61(8):e247–248. doi: 10.1093/rheumatology/keac026
22
JacobsSLRozenblitA. HIV-Associated hypervascular primary Burkitt's lymphoma of the liver. Clin Radiol (2006) 61(5):453–5. doi: 10.1016/j.crad.2005.12.007
23
MuttilloEMDégotTCanuetMRiouMRenaud-PicardBHirschiSet al. Primary Hepatic Lymphoma After lung transplantation: A report of 2 cases. Transplant Proc (2021) 53(2):692–5. doi: 10.1016/j.transproceed.2021.01.030
24
NoronhaVShafiNQObandoJAKummarS. Primary non-hodgkin's lymphoma of the liver. Crit Rev Oncol Hematol (2005) 53(3):199–207. doi: 10.1016/j.critrevonc.2004.10.010
25
ShettySBrunsTWestonCJStamatakiZOoYHLongHMet al. Recruitment mechanisms of primary and malignant b cells to the human liver. Hepatology (2012) 56(4):1521–31. doi: 10.1002/hep.25790
26
KikumaKWatanabeJOshiroYShimogamaTHondaYOkamuraSet al. Etiological factors in primary hepatic b-cell lymphoma. Virchows Arch (2012) 460(4):379–87. doi: 10.1007/s00428-012-1199-x
27
Rodríguez-SevillaJJSalarA. Recent advances in the genetic of MALT lymphomas. Cancers (2022) 14(1):176. doi: 10.3390/cancers14010176
28
JungHYooHYLeeSHShinSKimSCLeeSet al. The mutational landscape of ocular marginal zone lymphoma identifies frequent alterations in TNFAIP3 followed by mutations in TBL1XR1 and CREBBP. Oncotarget (2017) 8(10):17038–49. doi: 10.18632/oncotarget.14928
29
MastorakiAStefanouMIChatzoglouEDaniasNKyriaziMArkadopoulosNet al. Primary hepatic lymphoma: Dilemmas in diagnostic approach and therapeutic management. Indian J Hematol Blood Transfus (2014) 30(3):150–4. doi: 10.1007/s12288-013-0263-2
30
CesarettiMLoustauMRobbaCSenescendeLLe BianAZ. Reappraisal of primary hepatic lymphoma: Is surgical resection underestimated? Crit Rev Oncol Hematol (2018) 123:1–6. doi: 10.1016/j.critrevonc.2018.01.004
31
HaiTZouLQ. Clinical management and susceptibility of primary hepatic lymphoma: A cases-based retrospective study. World J Clin cases (2021) 9(31):9417–30. doi: 10.12998/wjcc.v9.i31.9417
32
El NouwarREl MurrT. Primary hepatic diffuse Large b-cell lymphoma mimicking acute fulminant hepatitis: A case report and review of the literature. Eur J Case Rep Intern Med (2018) 5(6):878. doi: 10.12890/2018_000878
33
KanekoRMitomiHNakazakiNYanoYOgawaMSatoY. Primary hepatic lymphoma complicated by a hepatic inflammatory pseudotumor and tumor-forming pancreatitis. J Gastrointestin Liver Dis (2017) 26(3):299–304. doi: 10.15403/jgld.2014.1121.263.eko
34
FaragFMorcusRRamachandranPPasrijaURWangJC. Fever of unknown origin due to primary hepatic diffuse Large b-cell lymphoma: A case report. Cureus (2019) 11(3):e4220. doi: 10.7759/cureus.4220
35
NagataSHarimotoNKajiyamaK. Primary hepatic mucosa-associated lymphoid tissue lymphoma: a case report and literature review. Surg Case Rep (2015) 1:87. doi: 10.1186/s40792-015-0091-8
36
PatelTSMalvaniaRShahMCShahMJGamiAG. Primary hepatic lymphoma: A case report. J Cytol (2015) 32(1):36–8. doi: 10.4103/0970-9371.155232
37
MyoteriDDellaportasDArkoumaniEMarinisAZizi-SermpetzoglouA. Primary hepatic lymphoma: A challenging diagnosis. Case Rep oncological Med (2014) 2014:212598. doi: 10.1155/2014/212598
38
AvlonitisVSLinosD. Primary hepatic lymphoma: A review. Eur J Surg (1999) 165(8):725–9. doi: 10.1080/11024159950189474
39
AliAMOmoreIRiazMFPaliouMSimonK. Primary Hepatic Lymphoma Masquerading as symptomatic hypercalcemia. Cureus (2020) 12(9):e10633. doi: 10.7759/cureus.10633
40
HsuAGagnierMRyerESalhabMRosmarinAG. Hypercalcemia due to primary hepatic lymphoma. Case Rep Hematol (2016) 2016:1876901. doi: 10.1155/2016/1876901
41
AbdelrahimWEMohamedKEMekkiSOSaadEA. Primary Hepatic Lymphoma Presenting as an acute abdomen in a young female patient: A case report and literature review. Case Rep Surg (2019) 2019:6784325. doi: 10.1155/2019/6784325
42
PandaSSBaisakhMPandaADasH. Primary hepatic marginal zone lymphoma: A rare coincidence. Curr Probl Cancer (2018) 42(3):322–8. doi: 10.1016/j.currproblcancer.2018.01.002
43
TomasianASandrasegaranKElsayesKMShanbhogueAShaabanAMeniasCO. Hematologic malignancies of the liver: Spectrum of disease. Radiographics (2015) 35(1):71–86. doi: 10.1148/rg.351130008
44
ForghaniFMasoodiMKadivarM. Primary hepatic lymphoma mimicking cholangiocarcinoma. Oman Med J (2017) 32(4):335–8. doi: 10.5001/omj.2017.63
45
FoschiFGDall’AglioACMaranoGLanziASaviniPPiscagliaFet al. Role of contrast-enhanced ultrasonography in primary hepatic lymphoma. J Ultrasound Med (2010) 29(9):1353–6. doi: 10.7863/jum.2010.29.9.1353
46
BetianuCIDimaAPavaloiuG. Primary hepatic mucosa-associated lymphoid tissue lymphoma in a patient with no chronic liver disease: Case report. Radiol Case Rep (2017) 12(4):715–9. doi: 10.1016/j.radcr.2017.08.004
47
WuGBHuangCYHuangSRuHMXiangBDYuanWPet al. Primary hepatic non-hodgkin's lymphoma with rectal cancer: A case report. Oncol Lett (2015) 9(1):324–6. doi: 10.3892/ol.2014.2673
48
LuQZhangHWangWPJinYJJiZB. Primary non-hodgkin's lymphoma of the liver: sonographic and CT findings. Hepatobiliary Pancreat Dis Int (2015) 14(1):75–81. doi: 10.1016/S1499-3872(14)60285-X
49
MehtaNJayapalLGoneppanavarMRamakrishnaiahVPN. Primary hepatic lymphoma: A rare case report. JGH Open (2019) 3(3):261–3. doi: 10.1002/jgh3.12131
50
CoenegrachtsKVanbeckevoortDDeraedtKVan SteenbergenW. Mri findings in primary non-hodgkin's lymphoma of the liver. JBR-BTR (2005) 88(1):17–9.
51
DoTDNeurohrCMichlMReiserMFZechCJ. An unusual case of primary hepatic lymphoma mimicking sarcoidosis in MRI. Acta Radiol Short Rep (2014) 3(4):2047981613493625. doi: 10.1177/2047981613493625
52
RajeshSBansalKSurekaBPatidarYBihariCAroraA. The imaging conundrum of hepatic lymphoma revisited. Insights Imaging (2015) 6(6):679–92. doi: 10.1007/s13244-015-0437-6
53
ColagrandeSCalistriLGrazziniGNardiCBusoniSMoranaGet al. MRI Features of primary hepatic lymphoma. Abdom Radiol (NY) (2018) 43(9):2277–87. doi: 10.1007/s00261-018-1476-5
54
AroraARajeshSBihariC. Additional radiologic clue to diagnosing hepatic lymphoma. Radiographics (2015) 35(7):2149–50. doi: 10.1148/rg.2015150040
55
SchaeferNGHanyTFTavernaCSeifertBStumpeKDMvon SchulthessGKet al. Non-Hodgkin lymphoma and Hodgkin disease: Coregistered EDG PET and CT at staging and restaging - do we need contrast-enhanced CT? Radiology (2004) 232(3):823–9. doi: 10.1148/radiol.2323030985
56
PanBWangCSHanJKZhanLFNiMXuSC. F-18-fluorodeoxyglucose PET/CT findings of a solitary primary hepatic lymphoma: A case report. World J Gastroenterol (2012) 18(48):7409–12. doi: 10.3748/wjg.v18.i48.7409
57
WangLDongPHuWMTianBL. F-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography in the diagnosis and follow-up of primary hepatic diffuse large b-cell lymphoma: A clinical case report. Med (Baltimore) (2020) 99(5):e18980. doi: 10.1097/MD.0000000000018980
58
NishikawaKKatsutaKTanakaSFujibeKHattoriAShionoYet al. Primary hepatic lymphoma diagnosed using endoscopic ultrasound-guided liver biopsy: a case report. J Med Case Rep (2021) 15(1):199. doi: 10.1186/s13256-021=02791-9
59
ChoiSKimJHKimKKimMChoiHJKimYMet al. Primary hepatic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. J Pathol Transl Med (2020) 54(4):340–5. doi: 10.4132/jptm.2020.03.18
60
MuthukrishnanSAmudhanARajendranS. Primary hodgkin's lymphoma of liver in HIV-a case report and review of literature. AME Case Rep (2018) 2:21. doi: 10.21037/acr.2018.04.08
61
HuHJLiaoMYQuYJ. Primary hepatic peripheral T-cell lymphoma: A case report. Oncol Lett (2014) 8(1):258–62. doi: 10.3892/ol.2014.2119
62
ModiGMadabhaviIPatelARevannasiddaiahSAnandAPanchalHet al. Primary hepatic burkitt lymphoma: A bizarre site and triumph tale. J Clin Exp Hepatol ([amp]](2015)) 5(2):159–62. doi: 10.1016/j.jceh.2015.05.002
63
RazikAMallaSGoyalAGamanagattiSKandasamyDDasCJet al. Unusual primary neoplasms of the adult liver: Review of imaging appearances and differential diagnosis. Curr Probl Diagn Radiol (2022) 51(1):73–85. doi: 10.1067/j.cpradiol.2020.10.001
64
ChoiWTGillRM. Hepatic lymphoma diagnosis. Surg Pathol Clin (2018) 11(2):389–402. doi: 10.1016/j.path.2018.02.003
65
XingAYDongXZZhuLQLiuLSunDGuoS. Clinicopathological characteristics and molecular phenotypes of primary hepatic lymphoma. Front Oncol (2022) 12:906245. doi: 10.3389/fonc.2022.906245
66
Ul HaqFAminSYunusHUllahBAliW. Diagnosis of primary hepatic lymphoma in a 55-Year-Old Male patient presented with pain in the right hypochondrium: A very rare case. Cureus (2022) 14(5):e25547. doi: 10.7759/cureus.25547
67
GreweSShahidMZhangLJiangK. Clinically unsuspected primary hepatic mucosa-associated lymphoid tissue lymphoma collision with an intrahepatic cholangiocarcinoma: A case report and literature review. SAGE Open Med Case Rep (2021) 9:2050313X211041838. doi: 10.1177/2050313X211041838
68
LiuJGuoRRFangJCZhongL. Primary hepatic mucosa-associated lymphoid tissue lymphoma with hepatocellular carcinoma: A case report and literature review. J Dig Dis (2020) 21(9):526–8. doi: 10.1111/1751-2980.12917
69
GomyoHKagamiYKatoHKawaseTOhshiroAOyamaTet al. Primary hepatic follicular lymphoma: A case report and discussion of chemotherapy and favorable outcomes. J Clin Exp Hematop (2007) 47(2):73–7. doi: 10.3960/jslrt.47.73
70
CitakECSariIDemirciMKarakusCSahinY. Primary hepatic burkitt lymphoma in a child and review of literature. J Pediatr Hematol Oncol (2011) 33(8):e368–71. doi: 10.1097/MPH.0b013e31822ea131
71
ZentarATarchouliMElkaouiHBelhamidiMSRatbiMBBouchentoufSMet al. Primary hepatic lymphoma. J Gastrointest Cancer (2014) 45(3):380–2. doi: 10.1007/s12029-013-9505-7
72
ImraniKZnatiKAmouriWNassarIBillahNM. Primary hepatic lymphoma in liver cirrhosis: A rare case report. .Radiol Case Rep (2021) 16(8):2179–83. doi: 10.1016/j.radcr.2021.05.028
73
YuYDKimDSByunGYLeeJHKimISKimCYet al. Primary hepatic marginal zone b cell lymphoma: a case report and review of the literature. Indian J Surg (2013) 75(Suppl 1):331–6. doi: 10.1007/s12262-012-0695-1
74
YakaMChehabFAllaouiMAit AliAZentarA. Postsurgical diagnosis of an unusual case of primary hepatic lymphoma presenting as liver abscess with an uncommon complication: A hepatogastric fistula. Case Rep Hematol (2021) 2021:6647558. doi: 10.1155/2021/6647558
75
TakeiDAbeTAmanoHHiranoNKobayashiTOhdanHet al. Methotrexate-associated primary hepatic malignant lymphoma following hepatectomy: A case report. Int J Surg Case Rep (2017) 31:5–9. doi: 10.1016/j.ijscr.2016.12.012
76
ValladolidGAdamsLLWeisenbergEMakerVKMakerAV. Primary hepatic lymphoma presenting as an isolated solitary hepatic cyst. J Clin Oncol (2013) 31(2):e21–3. doi: 10.1200/JCO.2012.44.9728
77
XuZPangCSuiJGaoZ. A case of primary hepatic extranodal marginal zone b-cell mucosa-associated lymphoid tissue (MALT) lymphoma treated by radiofrequency ablation (RFA), and a literature review. J Int Med Res (2021) 49(3):300060521999539. doi: 10.1177/0300060521999539
78
MurakamiJFukushimaNUenoHSaitoTWatanabeTTanosakiRet al. Primary hepatic low-grade b-cell lymphoma of the mucosa-associated lymphoid tissue type: a case report and review of the literature. Int J Hematol (2002) 75(1):85–90. doi: 10.1007/BF02981985
79
BohlokADe GrezTBouazzaFDe WindREl-KhouryMRepulloDet al. Primary hepatic lymphoma mimicking a hepatocellular carcinoma in a cirrhotic patient: Case report and systematic review of the literature. Case Rep Surg (2018) 2018:9183717. doi: 10.1155/2018/9183717
80
MartínezDTESánchez-ChicaPADel Valle LoartePGanozaGECPérez-GonzálezMVVázquez-EcharriJet al. Primary hepatic lymphoma: The importance of liver biopsy. J Gastrointest Cancer (2017) 48(4):373–5. doi: 10.1007/s12029-016-9836-2
81
XuJHuSLiSGaoYWangWZhouXet al. Primaryhepatic follicular lymphoma: A case report and literature review. J Med Case Rep (2020) 14(1):168. doi: 10.1186/s13256-020-02471-0
82
WilliamsMOAkhondiHKhanO. PrimaryHepatic follicular lymphoma presenting as Sub-acute liver failure: A case report and review of the literature. Clin Pathol (2019) 12:2632010X19829261. doi: 10.1177/2632010X19829261
83
ClarkTMaximinSMeierJPokharelSBhargavaP. Hepatocellular carcinoma: Review of epidemiology, screening, imaging diagnosis, response assessment, and treatment. Curr Probl Diagn Radiol (2015) 44(6):479–86. doi: 10.1067/j.cpradiol.2015.04.004
84
HoriMMurakamiTKimTTomodaKNakamuraH. CT scan and MRI in the differentiation of liver tumors. Dig Dis (2004) 22(1):39–55. doi: 10.1159/000078734
85
LeeJAJeongWKMinJHKimJ. Primary hepatic lymphoma mimicking acute hepatitis. Clin Mol Hepatol (2013) 19(3):320–3. doi: 10.3350/cmh.2013.19.3.320
86
AlvesAMATorresUSVelloniFGRibeiroBJTiferesDAD'IppolitoG. The many faces of primary and secondary hepatic lymphoma: imaging manifestations and diagnostic approach. Radiol Bras (2019) 52(5):325–30. doi: 10.1590/0100-3984.2018.0013
87
EmileJFAzoulayDGornetJMLopesGDelvartVSamuelDet al. Primary non-hodgkin's lymphomas of the liver with nodular and diffuse infiltration patterns have different prognoses. Ann Oncol (2001) 12(7):1005–10. doi: 10.1023/a:1011131930409
88
QiuMJFangXFHuangZZLiQTWangMMJiangXet al. Prognosis of primary hepatic lymphoma: A US population-based analysis. Transl Oncol (2021) 14(1):100931. doi: 10.1016/j.tranon.2020.100931
89
PageRDRomagueraJEOsborneBMedeirosLJRodriguezJNorthLet al. Primary hepatic lymphoma - favorable outcome after combination chemotherapy. Cancer (2001) 92(8):2023–9. doi: 10.1002/1097-0142(20011015)92:8<2023::AID-CNCR1540>3.0.CO;2-B
90
WidjajaDAlShellehMDanielMSkaradinskiyY. Complete remission of primary hepatic lymphoma in a patient with human immunodeficiency virus. World J Clin cases (2015) 3(2):186–90. doi: 10.12998/wjcc.v3.i2.186
91
ZafarMSAggarwalSBhallaS. Complete response to chemotherapy in primary hepatic lymphoma. J Cancer Res Ther (2012) 8(1):114–6. doi: 10.4103/0973-1482.95187
92
LiuYJiangJWuQZhangQXuYQuZet al. A case of primary hepatic lymphoma and related literature review. Case Rep Hepatol (2016) 2016:6764121. doi: 10.1155/2016/6764121
93
OzakiKIkenoHKoneriKHiguchiSHosonoNKosakaNet al. Primaryhepatic diffuse large b-cell lymphoma presenting unusual imaging features. Clin J Gastroenterol (2020) 13(6):1265–72. doi: 10.1007/s12328-020-01203-7
94
KawakamiHKubotaYBanT. Primary hepatic diffuse Large b-cell lymphoma mimicking intrahepatic cholangiocarcinoma. Intern Med (2019) 58(1):143–4. doi: 10.2169/internalmedicine.1436-18
95
DantasESantosJCoelhoMSequeiraCSantosICardosoCet al. Primary hepatic lymphoma in a patient with cirrhosis: A case report. J Med Case Rep (2020) 14(1):168. doi: 10.1186/s13256-020-02471-0
96
LaroiaSTRastogiAPandaDSarinSK. Primary hepatic non-hodgkin's lymphoma: An enigma beyond the liver, a case report. World J Oncol (2015) 6(2):338–44. doi: 10.14740/wjon900w
97
YasudaTNakagawaSImaiKOkabeHHayashiHYamashitaYet al. A case of primary hepatic mucosa-associated lymphoid tissue lymphoma incidentally found in the sustained virological response state of chronic hepatitis c: Review of the literature of this rare disease. Int Cancer Conf J (2020) 9(2):59–65. doi: 10.1007/s13691-019-00397-z
98
XieHLvJJiYDuXYangX. Primary hepatic mucosa-associated lymphoid tissue lymphoma: A case report and literature review. Medicine(Baltimore) (2019) 98(13):e15034. doi: 10.1097/MD.0000000000015034
99
YuJJYanWTLiCYangT. An unusual primaryhepaticlymphoma. Dig Liver Dis (2018) 50(8):855. doi: 10.1016/j.dld.2018.02.016
100
ParkJIJungBH. Primary hepatic lymphoma treated with liver resection followed by chemotherapy: a case report. Ann Hepatobiliary Pancreat Surg (2017) 21(3):163–7. doi: 10.14701/ahbps.2017.21.3.163
101
BouliarisKChristodoulidisGKoukoulisGMamaloudisIIoannouMBouronikouEet al. A primary hepatic lymphoma treated with liver resection and chemotherapy. Case Rep Surg (2014) 2014:749509. doi: 10.1155/2014/749509
102
StellerEJvan LeeuwenMSvan HillegersbergRSchipperMERinkesIHMolenaarIQ. Primary lymphoma of the liver - a complex diagnosis. World J Radiol (2012) 4(2):53–7. doi: 10.4329/wjr.v4.i2.53
103
ResendeVOliveiraTSGomesRTLaboissièreRSTavares-JuniorWCde Melo CoutoOF. Primary hepatic lymphoma: A case report. Int J Surg Case Rep (2013) 4(12):1165–8. doi: 10.1016/j.ijscr.2013.10.003
104
TammanaVSBegumROnealPKarpurapuHMuleyAYeruvaSLet al. A novel use of early radiation therapy in the treatment of hyperbilirubinemia in a patient with primary hepatic lymphoma and chronic hepatitis c. Case Rep Gastrointest Med (2014) 2014:724256. doi: 10.1155/2014/724256
105
AlbanoDGiubbiniRBertagnaF. 18F-FDG PET/CT and primary hepatic MALT: a case series. Abdom Radiol (NY) (2016) 41(10):1956–9. doi: 10.1007/s00261-016-0800-1
106
ZhangKJChenSChenJLDongLH. Complete response to comprehensive treatment of a primary hepatic diffuse large b cell lymphoma: A case report. Oncol Lett (2015) 9(4):1557–60. doi: 10.3892/ol.2015.2920
107
OnoATanoueSYamadaYTakajiYOkadaFMatsumotoSet al. Primary malignant lymphoma of the gallbladder: A case report and literature review. Br J Radiol (2009) 82(973):e15–19. doi: 10.1259/bjr/30768802
108
BisigBCopie-BergmanCBaiaMGaulardPDelbecqueKFassotteMFet al. Primary mucosa-associated lymphoid tissue lymphoma of the gallbladder: Report of a case harboring API2/MALT1 gene fusion. Hum Pathol (2009) 40(10):1504–9. doi: 10.1016/j.humpath.2009.02.018
109
BaturAOdevK. Primary lymphoma of the gallbladder accompanied by cirrhosis: CT and MRI findings. BMJ Case Rep (2014) 2014:bcr2013203101. doi: 10.1136/bcr-2013-203101
110
DasKFisherAWilsonDJdela TorreANSeguelJKoneruB. Primary non-hodgkin’s lymphoma of the bile ducts mimicking cholangiocarcinoma. Surgery (2003) 134(3):496–500. doi: 10.1067/s0039-6060(03)00149-1
111
PsarrasKSymeonidisNVlachakiEBaltatzisMPapatoliosGPavlidisEet al. Primary gallbladder small lymphocytic lymphoma as a rare postcholecystectomy finding. ase Rep Hematol (2014) 2014:716071. doi: 10.1155/2014/716071
112
ParkYKChoiJEJungWYSongSKLeeJIChungCW. Mucosa-associated lymphoid tissue (MALT) lymphoma as an unusual cause of malignant hilar biliary stricture: A case report with literature review. World J Surg Oncol (2016) 14(1):167. doi: 10.1186/s12957-016-0928-z
113
DierlammJBaensMWlodarskaIStefanova-OuzounovaMHernandezJMHossfeldDKet al. The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the tq21; q21) associated with mucosa-associated lymphoid tissue lymphomas. Blood (1999) 93(11):3601–9. doi: 10.1182/blood.V93.11.3601.411a47_3601_3609
114
ChoYHByunJHKimJHLeeSSKimHJLeeMG. Primary malt lymphoma of the common bile duct. Korean J Radiol (2013) 14(5):764–8. doi: 10.3348/kjr.2013.14.5.764
115
AngelopoulouMKKontopidouFNPangalisGA. Adhesion molecules in b-chronic lymphoproliferative disorders. Semin Hematol (1999) 36(2):178–97.
116
PezzutoRDi MauroDBonomoLPatelARicciardiEAttanasioAet al. An unusual case of primary extranodal lymphoma of the gallbladder. Hematol Rep (2017) 9(1):6972. doi: 10.4081/hr.2017.6972
117
MikailCSefaTTamerKAnilSOGulcinY. Primary extrahepatic bile duct lymphoma mimicking klatskin's tumor, dramatic response to chemotherapy. Int J Surg Case Rep (2015) 8C:147–9. doi: 10.1016/j.ijscr.2015.01.034
118
ZakariaAAl-ObeidiSDaradkehS. Primary non-hodgkin’s lymphoma of the common bile duct: A case report and literature review. Asian J Surg (2017) 40(1):81–7. doi: 10.1016/j.asjsur.2013.09.009
119
ElbannaKYAl-ShiebanSAzzumeeaF. Primary follicular lymphoma of the common bile duct mimicking cholangiocarcinoma. J Clin Imaging Sci (2014) 4:72. doi: 10.4103/2156-7514.148267
120
KatoHNaganumaTIizawaYKitagawaMTanakaMIsajiS. Primary non-hodgkin's lymphoma of the gallbladder diagnosed by laparoscopic cholecystectomy. J Hepatobiliary Pancreat Surg (2008) 15(6):659–63. doi: 10.1007/s00534-007-1283-9
121
ShahKSVShelatVGJogaiSTrompetasV. Primary gallbladder lymphoma presenting with perforated cholecystitis and hyperamylasaemia. Ann R Coll Surg Engl (2016) 98(2):e13–5. doi: 10.1308/rcsann.2016.0001
122
WillsMHarveyCJKuzmichSAfaqACosgroveD. Ultrasound of the gall bladder and biliary tree: part 1. Br J Hosp Med (Lond) (2014) 75(6):312–7. doi: 10.12968/hmed.2014.75.6.312
123
ZhangMZ. Primary malignant lymphoma of the gallbladder–a case report. Zhonghua Zhong Liu Za Zhi (1985) 7(1):70–1.
124
WongDLDeschnerBWKingLCGlazerES. Primary diffuse Large b cell lymphoma of the common bile duct. J Gastrointest Surg (2020) 24(10):2376–8. doi: 10.1007/s11605-020-04569-8
125
KariaMMitsopoulosGPatelKRafiqueAShethH. Primary gallbladder lymphoma in a Male patient with no risk factors detected incidentally by CT colonography. Case Rep Surg (2015) 2015:813708. doi: 10.1155/2015/813708
126
AcharyaVNgaiJWhitelawDMotallebzadehR. Primary gallbladder lymphoma presenting as a polyp. BMJ Case Rep (2014) 2014:bcr2013202715. doi: 10.1136/bcr-2013-202715
127
YoonMALeeJMKimSHLeeJYHanJKChoiBIet al. Primary biliary lymphoma mimicking cholangiocarcinoma: A characteristic feature of discrepant CT and direct cholangiography findings. J Korean Med Sci (2009) 24(5):956–9. doi: 10.3346/jkms.2009.24.5.956
128
JooYEParkCHLeeWSKimHSChoiSKChoCKet al. Primary non-hodgkin's lymphoma of the common bile duct presenting as obstructive jaundice. J Gastroenterol (2004) 39(7):692–6. doi: 10.1007/s00535-004-1367-0
129
SoASheldonJKuaH. Gallbladder lymphoma detected by 18F-fluorodeoxyglucose positron emission tomography. World J Nucl Med (2020) 19(4):428–31. doi: 10.4103/wjnm.WJNM_19_20
130
DurhamCJaiswalDWongL. Bile duct lymphoma disguised as cholangiocarcinoma. Proc (Bayl Univ Med Cent) (2017) 30(2):190–1. doi: 10.1080/08998280.2017.11929580
131
ItoYMiyauchiMNakamuraTTakaharaNNakaiYTaokaKet al. Significance of biopsy with ERCP for diagnosis of bile duct invasion of DLBCL. Int J Hematol (2019) 110(3):381–4. doi: 10.1007/s12185-019-02661-7
132
ShitoMKakefudaTOmoriTIshiiSSugiuraH. Primary non-hodgkin's lymphoma of the main hepatic duct junction. J Hepatobiliary Pancreat Surg (2008) 15(4):440–3. doi: 10.1007/s00534-007-1229-2
133
DoteHOhtaKNishimuraRTeramotoNAsagiANadanoSet al. Primary extranodal non-hodgkin’s lymphoma of the common bile duct manifesting as obstructive jaundice: Report of a case. Surg Today (2009) 39(5):448–51. doi: 10.1007/s00595-008-3894-4
134
OliveiraISKilcoyneAEverettJMMino-KenudsonMHarisinghaniMGGanesanK. Cholangiocarcinoma: classification, diagnosis, staging, imaging features, and management. Abdom Radiol (NY) (2017) 42(6):1637–49. doi: 10.1007/s00261-017-1094-7
135
GaneshanDKambadakoneANikolaidisPSubbiahVSubbiahIMDevineC. Current update on gallbladder carcinoma. Abdominal Radiol (2021) 46(6):2474–89. doi: 10.1007/s00261-020-02871-2
136
KarlsenTHFolseraasTThorburnDVesterhusM. Primary sclerosing cholangitis – a comprehensive review. J Hepatol (2017) 67(6):1298–323. doi: 10.1016/j.jhep.2017.07.022
137
KnabLMBollerAMMahviDM. Cholecystitis. Surg Clin North Am (2014) 94(2):455–70. doi: 10.1016/j.suc.2014.01.005
138
YuSC. Education and imaging: Hepatobiliary and pancreatic: Primary bile duct lymphoma. J Gastroenterol Hepatol (2012) 27(11):1761. doi: 10.1111/j.1440-1746.2012.07225.x
139
JonesWFSheikhMYMcClaveSA. AIDS-related non-hodgkin’s lymphoma of the pancreas. Am J Gastroenterol (1997) 92(2):335–8.
140
BhagatVHSepeT. Pancreatic lymphoma complicating early stage chronic hepatitis c. BMJ Case Rep (2017) 2017:bcr2016216698. doi: 10.1136/bcr-2016-216698
141
GhobakhlouMAlizadehAHMNaderiNHaghighiSMolaeiMRafiezadehMet al. A patient with chronic hepatitis c and a pancreatic mass in endoscopic ultrasound. Case Rep Gastroenterol (2012) 6(2):387–93. doi: 10.1159/000339693
142
HoefsJCRennerIGAskhcavaiMRedekerAG. Hepatitis b surface antigen in pancreatic and biliary secretions. Gastroenterology (1980) 79(2):191–4. doi: 10.1016/0016-5085(80)90129-8
143
HassanMMLiDHEl-DeebASWolffRABondyMLDavilaMet al. Association between hepatitis b virus and pancreatic cancer. J Clin Oncol (2008) 26(28):4557–62. doi: 10.1200/JCO.2008.17.3526
144
Rodríguez-InfanteAFernández-MartínezDIglesias-GarcíaEGarcía-FlórezLJ. Primary pancreatic lymphoma as a cause of obstructive jaundice. Rev Gastroenterol Mex (Engl Ed) (2019) 84(1):114–5. doi: 10.1016/j.rgmx.2018.01.003
145
PragalathanBIndranathKJenilAGobishangarS. Pancreatic non-Hodgkin lymphoma, a rare cause for obstructive jaundice. a case reports. Int J Surg Case Rep (2021) 78:369–71. doi: 10.1016/j.ijscr.2020.12.071
146
BaysalBKayarYInceATAriciSTürkmenIŞentürkH. Primary pancreatic lymphoma: A rare cause of pancreatic mass. Oncol Lett (2015) 10(3):1701–3. doi: 10.3892/ol.2015.3412
147
FangYHPengKRChenFBTangLJChenJ. Pancreatitis as the initial manifestation and abdominal lymph node enlargement in a boy. Zhongguo Dang Dai Er Ke Za Zhi (2018) 20(10):844–7. doi: 10.7499/j.issn.1008-8830.2018.10.012
148
TikueABedanieGBrandiLIslamSNugentK. Primary pancreatic Large b-cell lymphoma presenting as acute pancreatitis. Cureus (2020) 12(8):e9583. doi: 10.7759/cureus.9583
149
AlzerwiNAN. Primary pancreatic lymphoma masquerading as carcinoma. Case Rep Oncol Med (2020) 2020:5160545. doi: 10.1155/2020/5160545
150
SaifMW. Primary pancreatic lymphomas. JOP: J pancreas (2006) 7(3):262–73.
151
LinHLiSDHuXGLiZS. Primary pancreatic lymphoma: Report of six cases. World J Gastroenterol (2006) 12(31):5064–7. doi: 10.3748/wjg.v12.i31.5064
152
ChenWLuoRCFanWWMaSD. Clinical value of combined detection of LDH, TPS, CEA and beta2-MG in patients with non- hodgkin's lymphoma. Nan fang yi ke da xue bao = J South Med Univ (2006) 26(2):227–30.
153
LiakakosTMisiakosEPTsapralisDNikolaouIKaratzasGMacherasA. A role for surgery in primary pancreatic b-cell lymphoma: a case report. J Med Case Rep (2008) 2:167. doi: 10.1186/1752-1947-2-167
154
ZafarYKaurABannoFAnujS. Primary pancreatic lymphoma: An uncommon presentation in the pancreatic tail. Cureus (2019) 11(8):e5479. doi: 10.7759/cureus.5479
155
SadotEYahalomJDoRKGTeruya-FeldsteinJAllenPJGonenMet al. Clinical features and outcome of primary pancreatic lymphoma. Ann Surg Oncol (2015) 22(4):1176–84. doi: 10.1245/s10434-014-4176-6
156
AnandDLallCBhosalePGaneshanDQayyumA. Current update on primary pancreatic lymphoma. Abdom Radiol (NY) (2016) 41(2):347–55. doi: 10.1007/s00261-015-0620-8
157
JohnsonEABensonMEGudaNPfauPRFrickTJGopalDV. Differentiating primary pancreatic lymphoma from adenocarcinoma using endoscopic ultrasound characteristics and flow cytometry: A case-control study. Endosc Ultrasound (2014) 3(4):221–5. doi: 10.4103/2303-9027.144530
158
RadNKhafafAAlizadehAHM. Primary pancreatic lymphoma: what we need to know. J Gastrointest Oncol (2017) 8(4):749–57. doi: 10.21037/jgo.2017.06.03
159
BoninsegnaEZamboniGAFacchinelliDTriantopoulouCGourtsoyianniSAmbrosettiMCet al. CT imaging of primary pancreatic lymphoma: experience from three referral centres for pancreatic diseases. Insights Imaging (2018) 9(1):17–24. doi: 10.1007/s13244-017-0585-y
160
SegaranNSandrasegaranKDevineCWangMXShahCGaneshanD. Features of primary pancreatic lymphoma: A bi-institutional review with an emphasis on typical and atypical imaging features. World J Clin Oncol (2021) 12(9):823–32. doi: 10.5306/wjco.v12.i9.823
161
YadavRAgarwalGRGuptaYSharmaVGuptaA. Primary pancreatic lymphoma-diagnosed on computed tomography: A rare case report. Radiol Case Rep (2022) 17(6):1831–5. doi: 10.1016/j.radcr.2022.02.058
162
HughesBHabibNChuangKY. The computed tomography "Sandwich sign" for primary pancreatic lymphoma. ACG Case Rep J (2019) 6(10):e00230. doi: 10.14309/crj.0000000000000230
163
Iglesias-GarciaJde la Iglesia-GarciaDOlmos-MartinezJMLarino-NoiaJDominguez-MunozJE. Differential diagnosis of solid pancreatic masses. Minerva Gastroenterol Dietol (2020) 66(1):70–81. doi: 10.23736/S1121-421X.20.02646-X
164
MutluogluMCruytLGryspeerdtS. Imaging features of primary pancreatic lymphoma. Rev Gastroenterol Mex (Engl Ed) (2022) 87(2):253–5. doi: 10.1016/j.rgmxen.2022.05.005
165
FujinagaYLallCPatelAMatsushitaTSanyalRKadoyaM. MR features of primary and secondary malignant lymphoma of the pancreas: a pictorial review. Insights Imaging (2013) 4(3):321–9. doi: 10.1007/s13244-013-0242-z
166
IshigamiKTajimaTNishieAUshijimaYFujitaNAsayamaYet al. MRI Findings of pancreatic lymphoma and autoimmune pancreatitis: A comparative study. Eur J Radiol (2010) 74(3):e22–8. doi: 10.1016/j.ejrad.2009.03.022
167
ShiraiYOkamotoTKanehiraMOndaSSuzukiFItoRet al. Pancreatic follicular lymphoma presenting as acute pancreatitis: Report of a case. Int Surg (2015) 100(6):1078–83. doi: 10.9738/INTSURG-D-14-00132.1
168
DongASCuiYGaoLWangYZuoCJYangJJ. Patterns of FDG uptake in pancreatic non-hodgkin's lymphoma lesions. Abdom Imaging (2014) 39(1):175–86. doi: 10.1007/s00261-013-0041-5
169
WangPPChengXHuoLLiF. Primary pancreatic lymphoma on FDG PET/CT. Clin Nucl Med (2020) 45(10):830–2. doi: 10.1097/RLU.0000000000003205
170
León-Asuero-MorenoIMartín-MarcuartuJJde-Bonilla-DamiáÁJiménez-Hoyuela-GarcíaJM. Primary pancreatic lymphoma in a 18F-FDG PET/CT study. Evol Esp Med Nucl Imagen Mol (Engl Ed) (2021) 40(4):249–50. doi: 10.1016/j.remnie.2020.09.005
171
AbeYTamuraKSakataIIshidaJMukaiMOhtakiMet al. Unique intense uptake demonstrated by (18)F-FDG positron emission tomography/computed tomography in primary pancreatic lymphoma: A case report. Oncol Lett (2010) 1(4):605–7. doi: 10.3892/ol_00000107
172
GanQCarawayNPDingCStewartJM. Primary pancreatic lymphoma evaluated by fine-needle aspiration. Am J Clin Pathol (2022) 158(2):242–8. doi: 10.1093/ajcp/aqac030
173
YamaiTIkezawaKDaikuKMaedaSAbeYKaiYet al. Primary pancreatic mantle cell lymphoma diagnosed via endoscopic ultrasound-guided fine-needle aspiration. Case Rep Gastroenterol (2021) 15(2):482–7. doi: 10.1159/000515570
174
SadafSLoyaAAkhtarNYusufMA. Role of endoscopic ultrasound-guided-fine needle aspiration biopsy in the diagnosis of lymphoma of the pancreas: A clinicopathological study of nine cases. Cytopathology (2017) 28(6):536–41. doi: 10.1111/cyt.12442
175
ZhuNXWangXYTongTXuJHYangYYTianL. Primary pancreatic lymphoma diagnosed by endoscopic ultrasound-guided fine needle biopsy. Hepatobiliary Pancreat Dis Int (2022) 21(1):99–102. doi: 10.1016/j.hbpd.2021.05.001
176
YuLLChenYJXingLG. Primary pancreatic lymphoma: two case reports and a literature review. Onco Targets Ther (2017) 10:1687–94. doi: 10.2147/OTT.S121521
177
MohamadnejadMKhosraviPKhaniMNikmaneshAEloubeidiMA. Primary pancreatic hodgkin’s lymphoma diagnosed on EUS-guided FNA. Gastrointest Endosc (2016) 83(4):844–5. doi: 10.1016/j.gie.2015.09.028
178
MatsubayashiHTakagakiSOtsuboTIiriTKobayashiYYokotaTet al. Pancreatic T-cell lymphoma with high level of soluble interleukin-2 receptor. J Gastroenterol (2002) 37(10):863–7. doi: 10.1007/s005350200143
179
CagleBAHolbertBLWolaninSTappouniRLalwaniN. Knife wielding radiologist: A case report of primary pancreatic lymphoma. Eur J Radiol Open (2018) 5:141–6. doi: 10.1016/j.ejro.2018.08.007
180
LiuWHuaRZhangJFHuoYMLiuDJSunYW. First report of primary pancreatic natural killer/T-cell nasal type lymphoma. Eur Rev Med Pharmacol Sci ([amp]](2013)) 17(3):318–22.
181
ZhengSMZhouDJChenYHJiangRWangYXZhangYet al. Pancreatic t/histiocyte-rich large b-cell lymphoma: A case report and review of literature. World J Gastroenterol (2017) 23(24):4467–72. doi: 10.3748/wjg.v23.i24.4467
182
SoodVAgrawalNAlamSRawatDKhannaRBansalKet al. Primary pancreatic lymphoma simulating acute cholestatic hepatitis in a 7-Year-Old child. ACG Case Rep J (2015) 2(3):190–2. doi: 10.14309/crj.2015.51
183
SavariOAl-DuwalZWangZJGanesanSDanan-RayesRAyubS. Pancreatic lymphoma: A cytologic diagnosis challenge. Diagn Cytopathol (2020) 48(4):350–5. doi: 10.1002/dc.24349
184
NayerHWeirEGShethSAliSZ. Primary pancreatic lymphomas: A cytopathologic analysis of a rare malignancy. Cancer (2004) 102(5):315–21. doi: 10.1002/cncr.20488
185
OkamotoTSasakiTNishimuraNTakamatsuMMoriCMieTet al. Pancreatic follicular lymphoma: A report of two cases and literature review. Clin J Gastroenterol (2021) 14(6):1756–65. doi: 10.1007/s12328-021-01507-2
186
KonjetiVRHeffermanGMPaluriSGanjooP. Primary pancreatic burkitt's lymphoma: A case report and review of the literature. Case Rep Gastrointest Med (2018) 2018:5952315. doi: 10.1155/2018/5952315
187
ShnitserAHalegoua-DeMarzioDLorenDE. Primary pancreatic lymphoma presenting as acute pancreatitis. Gastroenterol Hepatol (NY) (2016) 12(7):456–8.
188
FacchinelliDSinaSBoninsegnaEBorinATisiMCPiazzaFet al. Primary pancreatic lymphoma: Clinical presentation, diagnosis, treatment, and outcome. Eur J Haematol (2020) 105(4):468–75. doi: 10.1111/ejh.13468
189
JonesHQiaoJPadillaOOraziA. Primary pancreatic diffuse large b-cell lymphoma, activated b-cell subtype, diagnosed by endoscopic ultrasound-guided fine needle aspiration-a case report and review of the literature. Clin Case Rep (2020) 9(2):669–72. doi: 10.1002/ccr3.3605
190
QiuTLiWGengHShiS. Clinicopathological characteristics of primary pancreatic lymphoma: report of two cases. Int J Clin Exp Pathol (2017) 10(11):10941–6.
191
RaviSStephenSNGochhaitDPotakkatBNiranjaniRSiddarajuN. Primary pancreatic diffuse large b-cell lymphoma diagnosed by endoscopic ultrasound guided FNAC: A rare entity. Diagn Cytopathol (2020) 48(1):57–60. doi: 10.1002/dc.24307
192
SallapanSAbu BakarNZJarminRMasirNMohammedF. Primary follicular lymphoma of the pancreas: A rare tumour mimicking pancreatic carcinoma. Malays J Pathol (2018) 40(3):359–71.
193
WuXZhaoGLiuHYaoYGaoZGuoQ. Primary pancreatic mucosa-associated lymphoid tissue lymphoma transformed into diffuse large b-cell lymphoma: A case report and literature review. Ann Palliat Med (2021) 10(10):11226–31. doi: 10.21037/apm-21-2418
194
McCullaghDMcNeiceARicePMainieI. PRIMARY PANCREATIC LYMPHOMA. Ulster Med J (2020) 89(1):41–2.
195
MimeryADe ClercqS. Primary pancreatic lymphoma presenting as recurrent idiopathic pancreatitis: a diagnostic dilemma. ANZ J Surg (2020) 90(4):E81–2. doi: 10.1111/ans.15309
196
VareedayahAAAlkaadeSTaylorJR. Pancreatic adenocarcinoma. Mo Med (2018) 115(3):230–5.
197
PrayerLSchurawitzkiHMallekRMostbeckG. CT in pancreatic involvement of non-Hodgkin lymphoma. Acta Radiol (1992) 33(2):123–7. doi: 10.1080/02841859209173144
198
IrieHHondaHBabaSKuroiwaTYoshimitsuKTajimaTet al. Autoimmune pancreatitis: CT and MR characteristics. Am J Roentgenol (1998) 170(5):1323–7. doi: 10.2214/ajr.170.5.9574610
199
WuWCYaoXZJinDYWangDSLouWHQinXY. Clinical strategies for differentiating autoimmune pancreatitis from pancreaticobiliary malignancy to avoid unnecessary surgical resection. J Dig Dis (2013) 14(9):500–8. doi: 10.1111/1751-2980.12075
200
MukhijaDNagpalSJSSohalDPS. Epidemiology, tumor characteristics, and survival in patients with primary pancreatic lymphoma: A Large population-based study using the SEER database. Am J Clin Oncol (2019) 42(5):454–8. doi: 10.1097/COC.0000000000000544
201
WallaceDDangNDhawanMKulkarniA. Diagnosis of a patient with primary pancreatic lymphoma. Gastroenterol Hepatol (N Y) (2012) 8(12):850–2.
202
BadrinathMTambeAMandruRSaleemSHeisigD. Large Pancreatic mass with chylous ascites. Proc (Bayl Univ Med Cent) (2019) 33(1):53–4. doi: 10.1080/08998280.2019.1668661
203
VijungcoJPhillipsRHendricksonFRMillburnLF. Stage I and II non-hodgkin’s lymphoma: results of regional radiation therapy. Am J Roentgenol Radium Ther Nucl Med (1973) 117(1):45–9. doi: 10.2214/ajr.117.1.45
204
ShaharKHCarpenterLSJorgensenJTruongLBakerKTheBS. Role of radiation therapy in a patient with primary pancreatic lymphoma. Clin Lymphoma Myeloma (2005) 6(2):143–5. doi: 10.3816/CLM.2005.n.042
205
BattulaNSrinivasanPPrachaliasARelaMHeatonN. Primary pancreatic lymphoma: Diagnostic and therapeutic dilemma. Pancreas (2006) 33(2):192–4. doi: 10.1097/01.mpa.0000227910.63579.15
Summary
Keywords
primary hepatic lymphoma, primary biliary lymphoma, primary pancreatic lymphoma, diagnosis, treatment
Citation
Wang Q, Wu K, Zhang X, Liu Y, Sun Z, Wei S and Zhang B (2022) Primary hepatopancreatobiliary lymphoma: Pathogenesis, diagnosis, and management. Front. Oncol. 12:951062. doi: 10.3389/fonc.2022.951062
Received
23 May 2022
Accepted
08 August 2022
Published
30 August 2022
Volume
12 - 2022
Edited by
Kanjoormana Aryan Manu, Amala Cancer Research Centre, India
Reviewed by
Giovanni Morana, ULSS2 Marca Trevigiana, Italy; Linda Calistri, University of Florence, Italy
Updates
Copyright
© 2022 Wang, Wu, Zhang, Liu, Sun, Wei and Zhang.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Bo Zhang, jjs10@zju.edu.cn; Shumei Wei, 2307001@zju.edu.cn
This article was submitted to Gastrointestinal Cancers: Hepato Pancreatic Biliary Cancers, a section of the journal Frontiers in Oncology
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.