PRIMARY NON-HODGKING LYMPHOMA OF COLEDOCO, WHICH SIMULATES CHOLANGIOCARCINOMA DIAGNOSED BY ENDOSCOPIC ULTRASONOGRAPHY: CASE REPORT AND LITERATURE REVIEW

¹Gastroenterology, Digestive Endoscopy and Hepatology Section, Hospital Universitario Fundación Santafe de Bogota, Colombia
²Pathology Department, Hospital Universitario Fundacion Santafa de Bogota, Colombia
³General Surgeon, Universidad Metropolitana, Fellow in Gastroenterology, Universidad de Cartagena, Colombia
⁴General Physician, Fundacion Santafe de Bogota, Colombia
⁵Resident Surgeon, Fundacion Santafe de Bogota, Colombia

^*Correspondence: Faruk Hernandez Sampayo, General Surgeon, Universidad Metropolitana, Fellow in Gastroenterology, Universidad de Cartagena, Colombia, Email:

Received: 01-Jun-2023, Manuscript No. Iphsj-23-13853; Editor assigned: 03-May-2023, Pre QC No. Iphsj-23-13853; Reviewed: 17-Jun-2023, QC No. Iphsj-23-13853; Revised: 22-Jun-2023, Manuscript No. Iphsj-23-13853(R); Published: 29-Jun-2023, DOI: 10.36648/1791- 809X.17.6.1026

Background

Non-Hodgkin lymphoma (NHL) is the term used to describe a group of diverse types of cancer that share one characteristic: they arise from a DNA injury in a progenitor lymphocyte, triggering their excessive growth in the lymphoid organs (nodes). Gastrointestinal involvement as a primary form is not common and represents about 10% of cases. However, as an extranodal secondary form, manifestations are reported in the stomach (50- 70%), small intestine (20-30%), and colon (5-15%) [1].

The liver is involved in 40% of secondary cases; however, primary non-Hodgkin lymphoma of the liver is extremely rare, representing less than 1% of all non-Hodgkin lymphoma cases worldwide [2] Primary lymphomas usually have a better prognosis at 5 years, with survival rates between 62-90% when diagnosed early, considering advances in chemotherapy (a pillar of treatment). In the case of secondary lymphomas, which indicate systemic spread, the prognosis is worse [1].

Involvement of the bile duct is extremely rare, especially as a cause of jaundice in a patient. Bulent Odemis et al [37]. Conducted retrospective searches for patients with biliary obstruction due to lymphoma between 1999 and 2005. Out of 1123 patients, they reported that the incidence of primary non-Hodgkin lymphoma in the biliary tract in patients with malignant cholangiocarcinoma was 0.6%, and primary biliary tract lymphoma represented 0.4% of extra nodal non-Hodgkin lymphomas and only 0.016% of all non-Hodgkin lymphoma cases. Its presentation with obstructive jaundice is mainly due to tumor-related compression in the bile duct, compression of the extra hepatic ducts by per portal, per hepatic, or per pancreatic lymph nodes [3, 4].

Some viruses are involved in the pathogenesis of NHL, probably due to their ability to induce chronic antigenic stimulation and cytokine dysregulation, leading to uncontrolled stimulation of B and T cells, proliferation, and lymphoma genesis. Hepatitis B virus, hepatitis C virus, HIV, Epstein-Barr virus, elevated lactate dehydrogenase levels, or a compromised immune system have been associated with the development of primary biliary non- Hodgkin lymphoma [5, 6].

According to a literature review, since Nguyen [7] reported the first case in 1982, a total of 43 cases have been reported, with the latest case reported in July 2022 [36]. Therefore, we aimed to compile all the reported cases worldwide to serve as a supportive study for future reports of similar cases, including our case number 44 Table 1. It is noteworthy that this is the second report in Latin America and the first case reported in our country, Colombia.

S.NO	Author	Age (years)	Gender	lymphoma subtype	Treatment	Follow-up (months)	Outcome
1	Nguyen7	59	M	Diffuse Large B-Cell Lymphoma	Surgery and Chemotherapy	8	Deceased
2	Takehara et al.8	60	M	Diffuse, Intermediate Size B-Cell	Surgery and Chemotherapy	Unknown	Unknown
3	Kaplan et al.9	42	M	Small Unsplit Lymphoma	Surgery and Chemotherapy	10	Deceased
4	Tartar y Balfe10	48	M	Unknown	Surgery and Chemotherapy	14	Alive
5	Tzanakakis et al.11	70	M	Mixed Small and Large B-Cell Diffuse	Surgery and Chemotherapy	4	Deceased
6	Kosuge et al.12	68	F	Small Unsplit Diffuse Large B-Cell	Surgery, Chemotherapy and Radiotherapy	16	Deceased
7	Brouland et al.13	34	F	T-Cell and Large B-Cell	Surgery and Chemotherapy	48	Alive
8	Machado et al.14	43	F	Mixed Small and Large Nodular B-Cell	Surgery and Chemotherapy	6	Alive
9	Chiu et al.15	25	F	Mixed Small and Large T-Cell Origin	Surgery	12	Deceased
10	André et al.16	44	F	Centrocytic-Centroblastic Follicular	Surgery and Chemotherapy	48	Alive
11	Maymind et al.17	39	F	Diffuse Large B-Cell Lymphoma	Surgery, Chemotherapy and Radiotherapy	13	Alive
12	Podbielski et al.18	66	M	Large B-Cell Lymphoma	Surgery	Unknown	Unknown
13	Oda et al.19	58	M	Mixed Small and Large B-Cell Diffuse	Surgery	32 days	Deceased
14	Corbinais et al.20	29	M	High-Grade T-Cell	Chemotherapy	12	Alive
15	Eliason y Grosso21	41	M	Diffuse Large B-Cell Lymphoma	Surgery	Unknown	Unkown
16	Gravel et al.22	4	M	Pre-B-cell Lymphoblastic Lymphomaw	Surgery and Chemotherapy	18	Alive
17	Kang et al.23	73	F	Low-grade B-cell MALT	Surgery	23	Alive
18	Young-Eun Joo et al 24	21	F	Diffuse Large B-Cell Lymphoma	Surgery and Chemotherapy	17	Alive
19	Yong Keun Park et al 25	81	F	MALT	Surgery	12	Alive
20	Carolina De La Rosa et al 26	50	M	Large B-cells	Surgery and Chemotherapy	Unknown	Unkown
21	Min A Yoon et al 27	62	M	MALT	Surgery	Unknown	Unknown
22	Jiamei Wu et al 28	59	F	Diffuse Large B-Cell Lymphoma	Surgery	2	Deceased
23	KV Ravindra et al 29	11	M	Low-grade B-cell Lymphoma	Surgery and Chemotherapy	62	Alive
24	KV Ravindra et al 29	30	F	Diffuse B-Cells	Surgery	3 days	Deceased
25	KV Ravindra et al 29	3	F	Diffuse B-Cells	Surgery and Chemotherapy	48	Alive
26	KV Ravindra et al 29	80	M	High-grade B-cell Lymphoma	Chemotherapy and bone marrow transplant	72	Alive
27	KV Ravindra et al 29	60	M	Low-grade B-cell Lymphoma	Chemotherapy	18	Alive
28	KV Ravindra et al 29	55	F	Diffuse Large B-Cell Lymphoma	Surgery and Chemotherapy	38	Alive
29	KV Ravindra et al 29	41	M	Large B-Cells	Surgery and Chemotherapy	Unknown	Deceased
30	KV Ravindra et al 29	10	F	Large B-Cells	Surgery and Chemotherapy	4	Alive
31	KV Ravindra et al 29	32	M	Large B-Cells	Surgery and Chemotherapy	Unknown	Unknown
32	Kasturi Das et al 30	36	M	Diffuse Large B-Cell Lymphoma	Surgery and Chemotherapy	68	Alive
33	Kasturi Das et al 30	51	M	Diffuse Large B-Cell Lymphoma	Surgery and Chemotherapy	18	Alive
34	F Yoneyama et al 31	55	F	Diffuse Large B-Cell Lymphoma	Surgery and Chemotherapy	53	Alive
35	Baron et al 32	41	M	Diffuse B-Cells	Surgery and immunosuppressants	12	Alive
36	Baron et al 32	59	F	Diffuse B-Cells	Surgery and immunosuppressants	24	Alive
37	Luigiano et al 33	30	M	Large B-Cells	Surgery and Chemotherapy	6	Alive
38	Gen Sugawara et al 34	33	M	Follicular Lymphoma	Surgery	12	Alive
39	Hideaki Dote et al 35	66	M	Diffuse Large B-Cell Lymphoma	Surgery and Chemotherapy	8	Alive
40	Nicolás Pararás et al 36	61	F	Diffuse Large B-Cell Lymphoma	Surgery and Chemotherapy	8	Alive
41	Bulent ¨ Odemis et al 37	57	F	Large B Cells	Surgery, Chemotherapy and Radiotherapy	10	Alive
42	Bulent ¨ Odemis et al 37	18	M	Large B Cells	Surgery	Unknown	Deceased
43	Bulent ¨ Odemis et al 37	64	F	Large B Cells	Surgery and Chemotherapy	Unknown	Unknown
44	Nuestro Estudio	65	F	Diffuse Large B-Cell Lymphoma	Chemotherapy	In follow-up	Alive

Table 1. Review of cases of biliary tract lymphoma worldwide.

Case Report

A 65-year-old female presented with a clinical picture of 24 hours of jaundice associated with generalized pruritus, with emphasis on the hands and feet. She had been experiencing alcoholic stools for the past 5 days, along with a feeling of fullness and a 4/10 intensity oppressive pain in the epigastria region that did not improve despite the use of antacids, leading her to seek medical attention. She had a history of depression, anxiety, hepatitis C, Clostridium difficile colitis, and past human papillomavirus infection. On physical examination, the only positive finding was jaundice. Laboratory tests showed leukocytes 5900, neutrophils 3200 (54.23%), hemoglobin 13.4, haematocrit 38.5, platelets 150,000, creatinine 0.82, sodium 136, potassium 4.32, chloride 104, partial thromboplastic time (PTT) 24.1/26.9, prothrombin time (PT) 10.2, international normalized ratio (INR) 0.93. [8-13] Aspartate aminotransferase (AST) 196, alanine aminotransferase (ALT) 456, alkaline phosphatase 486, total bilirubin 10.51, direct bilirubin 6.93, indirect bilirubin 3.58, gamma-glutamyl transferees (GGT) 353, CA 19-9 antigen: 2256 U/ml, serum alpha-fetoprotein 4.69, carcinoembryonic antigen 0.85.

Regarding radiological studies, an ultrasound was performed, which showed dilatation of the intrahepatic and extra hepatic bile ducts without being able to establish an obstructive etiology, hepatomegaly, and post-cholecystectomy state. Based on the findings, a magnetic resonance cholangiopancreatography (MRCP) was performed, which revealed focal irregular thickening of the walls of the distal common bile duct, with a solid lesion measuring 18 millimeters in diameter, with a neoplastic appearance, associated with peripancreatic and left retroperitoneal lymphadenopathy, resulting in biliary obstruction with significant dilatation of the biliary tract in a retrograde manner (Figure 1).

Figure 1: MRCP (Magnetic Resonance Cholangiopancreatography) showing obstruction at the level of the middle and distal common bile duct due to a solid tumor of the biliary tract..

The patient presented with obstructive biliary syndrome, where a solid lesion associated with lymphadenopathy in the distal common bile duct and pancreas was documented. The primary diagnostic possibility established was cholangiocarcinoma. Endoscopic ultrasound was recommended to better characterize the lesion and perform a biopsy guided by this method. Additionally, during the same surgical procedure, endoscopic retrograde cholangiopancreatography (ERCP) was indicated for biliary diversion. Further imaging studies including abdominal/ thoracic magnetic resonance imaging (MRI) and positron emission tomography (PET scan) were also recommended [13-16].

High-resolution chest MRI

No signs of metastatic disease involvement in the chest were observed. There is mild centrilobular emphysema and inflammatory involvement of the medium and small caliber airways, with sub segmental distribution in the lung bases.

Abdominal MRI

Per pancreatic lymphadenopathy and dilation of the biliary tract, with collapsed distal bile duct and concentric thickening of the mid-common bile duct showing high cellularity, consistent with the lymphadenopathy. The pancreas does not show any lesions, and the pancreatic duct is not dilated. There are no liver lesions suggestive of secondary involvement [17-23].

Considering the previous findings, a consultation was made to the hepatobiliary surgery department, which concluded that there is likely an end luminal lesion in the mid-common bile duct, with no evidence of distant metastatic lesions but with local lymphadenopathy. The patient is deemed a surgical candidate, and the possibility of performing a pancreatoduodenectomy is considered.

Endoscopic ultrasound was performed, revealing the following findings: thickening of the walls of the mid-common bile duct due to a hypo echoic, heterogeneous lesion with irregular borders, measuring 13 mm in diameter, showing exophytic growth; per biliary lymphadenopathy, round [24, 25] well-defined, hypo echoic, homogeneous, with characteristics suggestive of secondary neoplastic infiltration; and dilation of the bile duct, with a maximum diameter of 12 mm. A biopsy was performed using a 22 G acquire needle (fine needle biopsy - FNB) with two passes using a fanning technique, obtaining adequate material for histology without complications (Figure 2 & 3).

Figure 2: EUS (Endoscopic Ultrasound) image showing the needle biopsy (FNB) of the solid lesion within the common bile duct..

Figure 3: EUS (Endoscopic Ultrasound) image showing a solid lesion in the middle common bile duct with secondary obstruction and per biliary lymphadenopathy..

ERCP findings

The ampulla of Vater appears normal in the second portion of the duodenum. There is dilation of the intrahepatic and extra hepatic bile ducts, with the common bile duct measuring 16 mm in diameter and obstruction and stenosis at the level of the midcommon bile duct. A fully covered self-expandable metal biliary stent is implanted [26].

PET scan

Hyper metabolic nodular thickening of the extra hepatic bile duct in the peri-pancreatic region, suggestive of a tumor. Hyper metabolic lymph node adjacent to the peri-pancreatic region (precaval), suggestive of a tumor. The study does not show evidence of other hyper metabolic lesions suspicious for tumor involvement (Figure 4).

Figure 4: PET-SCAN: Significant hyper metabolic focus is observed in the biliary and per biliary region..

The histopathological findings are consistent with a neoplasm composed of uniform and large lymphoid cells. Immunohistochemical studies reveal that these tumor cells express CD20, CD10, BCL6, and BCL2, while they are negative for C-MYC and MUM1. The cellular proliferation index measured by KI67 is 90% Figure 5.

Figure 5: A) Hematoxylin-Eosin 40X. Large lymphoid tumor cells B). CD20 positive in the cytoplasmic membrane of the tumor cells C). BCL2 positive in the membrane of the tumor cells D). CD10 positive in the membrane of the tumor cells E). BCL6 positive in the nuclei of the tumor cells F) KI67 proliferation index of 90%..

The immunophenotypic analysis by flow cytometry using the Euro Flow platform shows a polyclonal B-cell lymphocyte immunophenotypic, with a cellularity of 1%. T lymphocytes are 7.1% (CD5+), CD4+ cells are 20%, CD8+ cells are 37.1%, and mature B lymphocytes represent 42.9% of which 29.2% are kappa-positive and 13.7% are lambda-positive (Figure 5).

In situ hybridization studies are performed, which show no translocation for BCL2 (18q21), BCL6 (3q27), and C-MYC (8q24). The immunophenotypic findings are consistent with a diffuse large B-cell lymphoma, suggestive of a germinal centre origin [27-33].

Considering the pathological findings, the possibility of surgery is discarded, and the patient is evaluated by the hematologyoncology department. They initiate immunochemotherapy with doxorubicin, rituximab, cyclophosphamide, vincristine, and prednisone (R-CHOP).

Discussion

The worldwide review of case reports Table 1 allows us to conclude that the average age of presentation is higher in younger patients, with an average of 46.22 years (4-81 years) [34-37] including the presence of 3 pediatric patients under 18 years old (4, 10, and 11 years old). These contrasts significantly with the previously reported average age of 70 years by the European-American Lymphoma Association [38], indicating a warning signal to consider it at younger ages. The gender distribution is comparable, with 54.4% [24] male and 45.4% [20] female cases. The average follow-up period was 22.6 months, with 59.09% alive, 22.7% deceased, and 18.1% without reported outcomes. Regarding histological findings, considering that we have collected cases from 1982 [7] until the present, there are variations in the nomenclature. However, we can group them as follows: 45.4% [20] diffuse large B-cell lymphoma, 34% [15] large B-cell lymphoma, 6.8% MALT lymphoma, 4.5% T-cell lymphoma, 2.2% [1] follicular lymphoma, and in 6.8% [3] the histological type was not reported.

Regarding the therapy used, 86.3% underwent hepatopancreatoduodenectomy and hepaticojejunostomy with Roux-en-Y reconstruction, some accompanied by chemotherapy (69%), and only 9% received chemotherapy as exclusive treatment [39-41].

It is necessary to highlight that among the 86.3% of patients who underwent surgery, the diagnosis of primary biliary tract tumor was made on the pathology specimen, which could have been avoided if, as in our case, endoscopic ultrasound with biopsy and needle aspiration (FNB) had been used.

The International Prognostic Index (IPI) groups a series of prognostic factors that allow predicting the probable clinical course of NHL. In our case, the IPI was developed and validated before adding rituximab to curative anthracycline-based chemotherapy [40]. Our patient has an IPI score of 1, indicating a 77% progression-free survival and 90% overall survival. Clinical trials [41-44] have confirmed that rituximab can improve the survival of patients with diffuse large B-cell lymphoma, and therefore, the appropriate management for it is immunochemotherapy with doxorubicin, rituximab, cyclophosphamide, vincristine, and prednisone (R-CHOP), as in our case (Table 1).

Conclusion

The manifestations of primary biliary tract lymphoma include jaundice, fever, abdominal pain, weight loss, and the presence of an abdominal mass. In our case, only pain and jaundice were present. Primarily, the diagnosis of primary biliary tract lymphoma is virtually anecdotal, accounting for 0.4% and 0.016% of all non-Hodgkin lymphoma cases [3, 4]. The diagnosis of primary extra hepatic bile duct lymphoma is challenging through computed tomography, magnetic resonance imaging, or magnetic resonance cholangiopancreatography because in most cases, the associated clinical and radiological features closely resemble those of cholangiocarcinoma, and there is no objective way to differentiate them. Therefore, tissue biopsy is required to obtain a histological diagnosis, which should become the gold standard when considering biliary tract surgery. Various methods are available for biopsy, such as ultrasound-guided biopsy of the tumor mass or CT-guided biopsy, endoscopic brushings during endoscopic retrograde cholangiopancreatography (ERCP), percutaneous trans luminal cholangiography, or cholangioscopy [37]. The success rates of these methods can vary from 20% to 80% depending on the expertise available at the institution [39]. Considering the approach, we believe that endoscopic ultrasound-guided fine-needle aspiration biopsy (FNB) should be the method of choice for the preoperative evaluation of biliary tract tumors, as in our case, to avoid unnecessary surgeries and the associated high morbidity and mortality rates reported, such as hepatopancreatoduodenectomy and hepaticojejunostomy with Roux-en-Y reconstruction.

The gold standard treatment for this disease is immunochemotherapy with doxorubicin, rituximab, cyclophosphamide, vincristine, and prednisone (R-CHOP) [25,33].

References

Kimura Y, Sato K, Imamura Y (2011) Small cell variant of MCL is an indolent lymphoma characterized for BM involvement, splenomegaly and low Ki 67. Cancer Sci 102: 1734-41.