Primary hepatic lymphoma: about two cases

H.Romdhane | S.Ben Slama | Z.Mzoughi | R.Ennaifer | A.Lahmar |

La tunisie chirurgicale - 2018 ; Vol 2017

Resumé

Extra nodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is a low-grade malignant lymphoma that appears frequently in the stomach, but other sites can also be involved: the intestinal tract, lungs, head, neck, skin, thyroid, breasts and liver. Primary non-Hodgkin lymphomas confined only to the liver are very rare (only 0.016% of all cases of all non-Hodgkin's lymphomas) and MALT is not the most frequent type. Hepatic lymphoma is defined as primary when there is liver damage without involvement of the spleen, bone marrow or other lymphatic organs. We present the case of two patients with primary liver lymphoma without any other localisation.

Mots Clés

medullar biopsy, bone marrow , lymphoma, morphological assessment, other lymphoid organs

Introduction :

Primary liver lymphoma is defined as a liver damage without involvement of the spleen, bone marrow or other lymphoid organs (1). Extra-nodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is a low-grade malignant lymphoma that appears frequently in the stomach, but other sites can also be involved: the intestinal tract, lungs, head, neck, skin, thyroid, breasts and liver. Hepatic localisations of lymphoma are usually a result of a general and disseminated disease. Primary localisation in the liver is a rather rare condition occurring in 1% of extra-lymphatic lymphomas and in only 0.016% of all cases of all non-Hodgkin's lymphomas (2). Yet, the natural history, treatment and prognosis of this disorder are not well standardized. Usually, it occurs in adult male patients, commonly immunocompromised (3). Clinical history is not specific made of jaundice, fever and general alteration (4). Biology shows hepatic chemical disorders. CT-scan is mandatory for the assessment of disease spread, though, nowadays PET scan is an excellent tool for detection of lymphoid localisations that shows, in this specific case, the absence of fixation of FDG in extra-hepatic tissues (5). We present the study of two cases of primary hepatic lymphoma.

Article

Patient(s) and observation(s)

Case 1:

A fifty-two year-old male, without any past medical history, was admitted to investigate a hepatomegaly associated to fatigue and weight loss over a month. Clinical examination found hepatomegaly of 15 cm without other anomalies. Biological tests showed cholestasis and elevated liver enzymes, HIV and hepatic viral serology were negative. Alpha-foeto-protein rate was normal. CT-scan concluded at a poly-lobed liver mass of 16 cm without presence of lymph nodes. This images evocated lymphoma. The patient underwent a biopsy of the tumor was and histological examination concluded at a B cell lymphoma of the liver. Immunohistochemistry confirmed the B nature of lymphoma as cells were positive for CD 20 and negative for CD 30, EMA and D1 cyclin. There was no primary lesion identified after morphological assessment and medullar biopsy.

The patient was referred to oncologists for chemotherapy. There was no relapse after 6 months of treatment.

Case 2:

A 94-year-old woman was admitted for right upper-quadrant pain and fever since 10 days. His past medical included hypertension and diabetes well controlled with medications, but no autoimmune disease. On physical examination, the patient was jaundiced with fever (39°). Laboratory tests showed cholestasis and cytolysis. Computed tomography (CT) showed dilated intrahepatic bile duct and gallstones in the common bile duct (Figure 1). A cholecystectomy was performed as well as a hepatic surgical biopsy, motivated by a biological findings. The patient was discharged 10 days later. Histological examination revealed chronic cholecystitis without acute lesions that can explain the symptoms of cholangitis. Histopathological examination of liver biopsy revealed presence of lymphoid infiltrate with predominant nodular growth pattern comprising essentially centrocytes and some centroblasts (Figures 2 and 3).  Immunohistochemistry showed positive expression of anti-CD19, anti-CD20, anti-Bcl2 and anti- CD10 (Figure 4). Tumor cells were negative for CD5. We concluded on B-cell non-Hodgkin’s follicular lymphoma Grade 1 confined to the liver. There was no evidence of involvement of the lymph nodes or any other organ on magnetic resonance imaging of the abdomen and chest. The bone marrow biopsy was negative. These findings established the diagnosis of primary hepatic lymphoma. No additional treatment was given. The patient remained symptom free until 15 months later and she was lost to follow-up.

Discussion 

Primary liver lymphoma is defined as a hepatic lymphoma without evidence of splenic, medullar or any other lymphoid structure involvement (1).

Non-Hodgkin liver lymphoma is a very rare condition as it represents less than 1% of extra nodal lymphomas and about 0.016% of all non-Hodgkin’s lymphoma (NHL) (2). Yet, it has been reported an increase in the incidence of non-Hodgkin lymphomas. There are approximately 12.2 cases per 100,000 persons per year in the United Kingdom and almost 55,000 new cases annually in the United States making NHL the fifth leading cause of death per cancer (6). Thirty per cent of NHL are the result of extra-nodal disease with only 0.4% localised in the liver (7).

Diagnostic criteria are no splenomegaly or lymph nodes on clinical examination, a normal CT-scan unless the liver involvement and a normal medullar biopsy (8).

The pathogenesis of this lymphoma remains unclear. Some reports have suggested the involvement of viral hepatitis B and especially C, cirrhosis, HIV infection, systemic lupus erythematosus and transplanted patients under immunosuppressive therapy (9). Almost 4% of transplant recipients develop post-transplantation lymphoproliferative disorders. This phenomena has been related to Epstein Barr Virus reactivation as it is thought that this virus may trigger B-cell proliferation in immunocompromised patients in whom the regulatory function of T-cells is deficient (10). HCV is a lymphotropic virus and causes chronic B-cell stimulation leading to B-cell expansion. Otherwise, HVC may induce a translocation t(14 ; 18) that stimulates monoclonal rearrangement and B-cell proliferation (10). Furthermore, 5 case reports have described the development of primary hepatic lymphoma in patients with primary biliary cirrhosis (11).

Clinical presentation of primary lymphoma is non-specific and very heterogeneous. The disease presents at an average age of 55 years (5 to 87 years). The sex ratio is 2/1. The abdominal symptoms are the most frequent with abdominal discomfort or right upper quadrant pain. Otherwise, constitutional symptoms including fever, anorexia and weight loss are common. Meanwhile, about 10% of patients remain asymptomatic and rare cases may present like surgical emergency such as acute cholangitis. This was the case of one of our patients. Physical examination shows hepatomegaly in 60 to 80% (12). Jaundice is less frequent noticed in progressed disease, in cirrhotic patients and in case of compressive lymph nodes. Rapidly progressive liver failure characterised by jaundice, encephalopathy, coagulopathy and lactic acidosis is noticed in widespread disease with poor prognosis (13).

The main biological features are perturbed liver function tests including cholestasis and cytolysis in almost 70% of patients. Increased lactate dehydrogenase is noticed in 30- 80% of cases (12). Otherwise, inflammatory markers are seen in 30% of patients and Bêta-2-microglobuline is increased in almost all the cases (14). however, blood count cells is usually normal as there is no bone marrow neither splenic involvement (15). Alpha-feoto-protein is normal. Hypercalcemia may be noticed. Tests for HIV, EBV, HBV, HCV and systemic lupus erythematosus should be ruled out to seek for an etiological pattern.

Imaging study of primary hepatic lymphoma is mandatory to establish the diagnosis and the extent of the disease. Primary hepatic lymphoma may present as solitary lesion in about 55 to 60% of cases, multiple lesions in 35 to 40%, rarely as diffuse hepatic infiltration or only as a homogeneous hepatomegaly (16). Ultrasound imaging is the first radiological test but CT-scan and/or MRI are the most essential for diagnosis and performing biopsies.

Histopathology with immunohistochemistry is the main test for diagnosis and prognosis needing a good liver biopsy. Percutaneous liver biopsy or laparoscopic examination are highly necessary as fine needle aspiration may provide false negative results because of tissue necrosis frequently seen in this condition. Diffuse large B-cell lymphoma is the most frequent type followed by marginal-zone MALT type (17). Burkitt’s lymphoma and lymphoblastic or diffuse immunoblastic are very rare. T-cell lymphoma is less frequent including peripheral T-cell lymphoma, anaplastic and hepatosplenic T-cell lymphoma (12). Rarely, immunohistochemistry is not enough to confirm diagnosis leading to complementary tests such as cellular immunology gene rearrangement and molecular biology to assist diagnosis (4).

Generally, primary liver lymphoma has a poor prognosis with a median survival of 15 months ranging from 3 to 123 months (14). The factors determining the prognosis are the pathological subtype and the pattern of liver involvement (16).

Surgery, chemotherapy and radiotherapy or combined therapy are the main modalities of treatment. Surgical resection is proposed in low-volume localized disease with good performance status and good liver function. Otherwise, chemotherapy followed or not with surgery or radiation is considered whenever the tumor is large or the subtype is chemo-sensible. New modalities of therapy tend to combine many treatment options in the same patient to optimize results and to extant survival (11,14).

Conclusion:

Primary hepatic lymphoma is a rare condition in daily practice. This lymphoma has many similarities on morphology, pathology and immunohistochemistry with nodal forms. The main types are diffuse large B-cell lymphoma and marginal zone MALT lymphoma. Viral origin such as HCV, HIV and EBV is the most reported ethiopathological theory without proved link. Treatment is based on chemotherapy, radiation and surgery and survival tend to be increased through combining therapy. However, prospective randomized controlled clinical trials are still lacking to codify management of this disease.

 

Figure 1A : Tomodensitométrie : masse hypodense polylobée de 16 cm de diamètre

du foie droit (dôme hépatique et le segment VII), inhomogène ne se rehaussant pas

après l’injection de produit de contraste et sans adénopathies profondes.

 

Figure 1B : Aspect histologique : Elargissement des espaces-porte par un infiltrat

lymphoïde d’organisation nodulaire. Infiltrat lymphoïde fait de petites cellules à

noyaux clivés type centrocyte-like (cartouche).

 

 

 

 

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