Page 1 of 3

Case report

Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)

For citation purposes: Tsavari A, Koulia K, Skafida E, Myoteri D, Zisi A, Grammatoglou X, et al. Primary anaplastic large-cell lymphoma, ALK1 negative, of the liver: A case report. OA Case Reports 2013 Feb 28;2(2):20.

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Primary anaplastic large-cell lymphoma, ALK1 negative,

of the liver: A case reportA Tsavari1, K Koulia1, E Skafida1*, D Myoteri1, A Zisi2, X Grammatoglou1, T Vasilakaki1

AbstractIntroductionPrimary extranodal lymphomas of the liver are notably rare. A propor-tion of cases are associated with infection with hepatitis C or B, HIV, EBV or primary biliary cirrhosis. We report the case of a 45-year-old man who presented with abdominal pain and weight loss.Case reportPhysical examination revealed an enlarged liver, but ascites, jaundice, splenomegaly and peripheral lym-phadenopathy were absent. Labora-tory studies showed elevated hepatic enzymes. Tumour markers CEA and AFP were normal. Abdominal com-puted tomography revealed multiple hypodense lesions in both lobes of the liver. Liver biopsy examination con-firmed a diagnosis of non-Hodgkin’s anaplastic large-cell lymphoma of T phenotype. Immunohistochemically, the neoplastic cells were positive for CD43, CD4, CD2, CD3, CD30, CD5 and granzyme B and negative for CD20, CD79a, CD10, EBV, CD15, CEA, EMA, CD56, CD57 and ALK1. Bone marrow biopsy did not reveal lymphomatous involvement. The patient received combination chemotherapy, and he was alive 2 years after diagnosis.ConclusionAlthough primary lymphoma of liver is rare compared with secondary hepatic involvement by lymphoma, primary epithelial neoplasms and metastatic carcinoma, the diagnosis

should be considered in certain clinical circumstances. The prognosis relates to the specific disease entity.

IntroductionPrimary hepatic lymphoma (PHL) is defined as an extranodal lymphoma arising in the liver. Primary lym-phoma of the liver is very rare and mainly a disease of middle-aged men. It represents 0.4% of all extran-odal lymphomas1–5. Most are diffuse large B-cell lymphoma; mucosa- associated lymphoid tissue lympho-mas are the second most common. The exact cause of PHL is still unclear. A proportion of cases are associated with infection with hepatitis C virus, hepatitis B virus, HIV, EBV or prima-ry biliary cirrhosis6,7. We present a very rare case of primary anaplastic large-cell lymphoma, ALK1 negative, of the liver.

Case reportWe report the case of a 45-year-old man who presented with abdomi-nal pain and weight loss for the last 3 months. Physical examination revealed an enlarged liver, but as-cites, jaundice, splenomegaly and peripheral lymphadenopathy were absent. Laboratory studies showed elevated hepatic enzymes such as al-kaline phosphatase, LDH and SGOT. Tumour markers CEA and AFP were normal, but the tumour marker Ca 19.9 was increased (143.25 U/ml). Serology was negative for HIV and for hepatitis C and B viruses. Abdominal computed tomography (CT) revealed multiple hypodense lesions in both lobes of the liver but no signs of lymphadenopathy or as-citic fluid. The pancreas, spleen and biliary tract were normal. CT of the

chest did not reveal any mediasti-nal lymphadenopathy. Past history did not appear to be contributory regarding the aetiology. Liver bi-opsy examination confirmed a diag-nosis of non-Hodgkin’s anaplastic large-cell lymphoma of T phenotype. The tumour consisted of a popu-lation of medium- to large-sized cells with irregular, sometimes cer-ebriform nuclei (Figures 1 and 2). Immunohistochemically, the neo-plastic cells were positive for CD43, CD4, CD2, CD3, UCHL1, CD30, CD5 and granzyme B and negative for CD20, CD79a, CD10, EBV, CD15, CEA, EMA, CD56, CD57, TIA-1 and ALK1 (Figure 3). Among the tumour cells, there were non-neoplastic cells con-sisting of small lymphocytes and histiocytes. Bone marrow biopsy did not reveal lymphomatous involve-ment. The patient received combina-tion chemotherapy, and he was alive 2 years after diagnosis.

DiscussionAlthough primary lymphoma of liver is rare compared with secondary hepatic involvement by lymphoma, primary epithelial neoplasms and metastatic carcinoma, the diagno-sis should be considered in certain clinical circumstances. In a middle-aged patient presenting with an enlarged liver, upper abdominal pain, weight loss, nausea and fever and having laboratory studies that demonstrate elevated liver function tests but normal alpha–fetoprotein and CEA levels, lymphomatous in-volvement of the liver is more likely than metastatic or primary carci-noma1–5. The exact cause of PHL is unknown6,7. The cell of origin of primary liver lymphoma has been

* Corresponding author Email: evelinaskafida@yahoo.gr

¹ Department of Pathology, Tzaneion, General Hospital Piraeus, Greece

² Department of Chemistry, University of Athens ‘Kapodistriako’ Athens, Greece

Page 2 of 3

Case report

Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)

For citation purposes: Tsavari A, Koulia K, Skafida E, Myoteri D, Zisi A, Grammatoglou X, et al. Primary anaplastic large-cell lymphoma, ALK1 negative, of the liver: A case report. OA Case Reports 2013 Feb 28;2(2):20.

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are diffuse large B-cell lymphomas. Low-grade B-cell lymphomas of mucosa-associated lymphoid tissue type are characterized by a dense

disputed, and some have postulated the Kupffer cell, but today all point to a transformed lymphocyte as the cell of origin1. The majority of PHLs

lymphoid infiltrate within the por-tal tracks6–8. Primary non-Hodgkin’s lymphomas of T or null pheno-type are very rare in the liver. Ana-plastic large-cell lymphoma were first described by Stein et al. in 1985, and the most common involvement site is the lymph nodes followed by skin, bone, soft tissue and lung9. Treatment includes surgery, chem-otherapy and radiotherapy, all of which give good results. Surgical resection when feasible is benefi-cial. Most patients are treated with chemotherapy. The standard treat-ment for patients with diffuse large B-cell lymphoma is CHOP2,3,5,10–12. The prognosis for patients with PHL relates to the specific disease entity.

ConclusionAlthough primary lymphoma of liv-er is rare compared with secondary hepatic involvement by lymphoma, primary epithelial neoplasms and metastatic carcinoma, the diagno-sis should be considered in certain clinical circumstances. The prog-nosis relates to the specific disease entity.

ConsentWritten informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Abbreviations listCT, computed tomography; PHL, pri-mary hepatic lymphoma.

Figure 2: Anaplastic lymphoma, H&E, ×400.

Figure 1: Anaplastic lymphoma, H&E, ×100.

References1. Osborne BM, Butler J, Guarde L. Prima-ry lymphoma of the liver. Ten cases and a review of the literature. Cancer. 1985 Dec;56:2902–10.2. Noronha V, Shafi NQ, Obando JA, Kum-mar S. Primary non-Hodgkin’s lymphoma of the liver. Crit Rev Oncol Hematol. 2005 Mar;53(3):199–207.

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Case report

Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)

For citation purposes: Tsavari A, Koulia K, Skafida E, Myoteri D, Zisi A, Grammatoglou X, et al. Primary anaplastic large-cell lymphoma, ALK1 negative, of the liver: A case report. OA Case Reports 2013 Feb 28;2(2):20.

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7. Page RD, Romagnera JE, Osborn B, Medeiros LJ, Rodriguez J, North L, et al. Primary hepatic lymphoma favorable outcome after combination chemothera-py. Cancer 2001 Oct; 92(8):2023–9.8. Bauduer F, Marty F, Gemain MC, Dulu-bac E, Bordahandy R. Primary non-Hodg-kin’s lymphoma of the liver in a patient with hepatitis B, C, HIV infections. Am J Hematol. 1997 Mar;54(3):265.9. Costes-Martineau V, Delfour C, Obled S, Lamart L, Pageaux G-P, Baldet P, et al. Anaplastic lymphoma kinase (ALK) protein expressing lymphoma after liver transplantation: case report and literature review. J Clin Pathol. 2002 Nov;55(11):868–71.10. Winter MC, Hancock BW. Ten years of rituximab in NHL. Expert Opin Drug Saf. 2009 Mar;8(2):223–35.11. Coiffier B, Lepaye E, Briere J, Her-brecht R, Tilly H, Bouabdallah R, et al. Chop chemotherapy plus rituximab compared with chop alone in elderly patients with diffuse large B-cell lym-phoma. N Engl J Med. 2002 Jan;346(4): 235–42.12. Avlonitis V, Linos D. Primary hepatic lymphoma: a review. Eur J Surg. 1999 Aug;165(8):725–9.

Figure 3: Anaplastic lymphoma, CD34, ×400.

3. Massod A, Kairouz S, Hudhud KH, He-gazi AZ, Banu A, Gupta NG. Primary non-Hodgkin lymphoma of the liver. Curr Oncol. 2009 Aug; 16(4): 74–9.4. Agmon-Levin N, Berger I, Shtalrid M, Schlanger H, Sthoeger ZM. Primary hepatic lymphoma: a case report and re-view of the literature. Age Ageing. 2004 Nov;33(6):637–40.