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Human-immunodeficiency-virus-negative, Human-herpes-virus-8-negative Abdominal Cavity Primary Effusion Lymphoma
Clinical Oncology (2005) 17: 636–638 doi:10.1016/j.clon.2005.05.012
Case Report Human-immunodeficiency-virus-negative, Human-herpes-virus-8-negative Abdominal Cavity Primary Effusion Lymphoma C. Jenkins*, Y. Sorour*, E. Blake*, R. Elliot*, A. I. Al-Sabahy, J. Greenz *Department of Haematology, University Hospital Wales, Cardiff, Wales, UK; yDepartment of Haematology, Llandough Hospital, Cardiff, Wales, UK; zDepartment of Gastroenterology, Llandough Hospital, Cardiff, Wales, UK ABSTRACT: Primary effusion lymphoma (PEL) is an unusual class of non-Hodgkin’s lymphoma, which is characterised by lymphomatous effusions in body cavities, but no associated mass lesions. It is usually associated with an immunodeficient state most often with the human immunodeficiency virus (HIV). We describe a case of a man with HIV-negative, human-herpes-virus-8 (HHV8)-negative PEL, with a history of heavy alcohol intake. The abdominal cavity was the only area involved; no solid tumour masses were observed on scanning, and the bone-marrow investigations were normal. The ascites contained numerous pleomorphic lymphoid, lymphoplasmacytoid cells of Bcell origin. The immunophenotyping was moderately positive for CD 38 and 138, and strongly positive for Ki 67. It is postulated that the immunosuppressed state in this patient may have been caused by the long history of heavy alcohol intake. Jenkins, C. et al. (2005). Clinical Oncology 17, 636–638 Ó 2005 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. Received: 7 February 2005 Revised: 23 May 2005
Introduction
Primary effusion lymphoma (PEL) is an unusual and rare type of non-Hodgkin’s lymphoma. It develops in serous cavities without lymph-node mass lesions [1–3]. It is associated with an immunocompromised state, and is often associated with infection with human-herpes-virus-type 8 [HHV8] [2,3]. Few cases have been reported of patients that are negative for the HIV and HHV8 viruses [2]. Case Report
A 61-year-old man was admitted to hospital with a 3-week history of increasing abdominal swelling and 2 stone loss in weight. He had a history of heavy alcohol intake (60–80 units a week for over 5 years). Physical examination revealed large volume ascites with minimal hepato-splenomegally. The presence of various stigmata of chronic liver, such as spider naevi, was observed. Blood investigations showed the following: Hb 7.1, WBC 6.1, Plat 278. Na 133, K 5.5, U 14.4, Crt 159, Alb 38, Alk 208, GGT 430, Ca 2.25, T Prot 102, Bili 7, LDH 852. Author for correspondence: Dr Christopher Jenkins, Department of Haematology, University Hospital Wales, Cardiff, Wales, UK. Tel: C44292-074-7747 ext 2373; E-mail: [email protected] 0936-6555/05/000000C03 $35.00/0
Accepted: 27 May 2005
Further blood tests showed liver autoantibodies to be normal, AFP 2, IgG 26.8 (5.1–15.8), IgA 8.07 (0.8–4.0), IgM 0.76 (0.48–1.9). Serum electrophoresis was normal, and urine electrophoresis showed no Bence–Jones protein. The patient was HIV-negative, also Hepatitis B- and Cnegative. A computed tomography of his abdomen showed massive abdominal ascites, a finely irregular liver margin and normal size spleen. One or two small lymph nodes near the coeliac axis were observed, but no generalised lymphadenopathy was seen. Increased density of the omental and mesenteric fat was incidentally noted. An ascitic tap was carried out, which showed the following: glucose 1.1, protein 63, LDH 6416. Cytology revealed numerous lymphoid cells of varied morphology. Most were medium sized, some had plasmacytoid features (Fig. 1). Immunophenotyping of the ascitic fluid showed a lymphoid population. The cells were negative for most B-cell markers (CD 19, 20, 23, 79b, FMC 7). There was weak expression of CD 10 and surface Ig. Medium-strength positivity was seen for CD 38 and 138, strong positivity for Ki 67. A bone-marrow aspirate and trephine biopsy showed no evidence of lymphoid infiltration. Computed tomography of the chest showed no pathological lymphadenopathy.
Ó 2005 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
HIV-NEGATIVE HHV8-NEGATIVE PEL
637
is presumed to have contributed to an immunosuppressed state. The patient was started on chemotherapy in the form of vincristine and cyclophosphamide. An excellent symptomatic improvement was achieved with, complete resolution of the ascites after just two courses. Primary Effusion Lymphoma
Fig. 1
A laparoscopy was carried out to gain further tissue for diagnosis. An enlarged cirrhotic-looking liver was found. Widespread stringy peritoneal adhesions were found throughout the abdomen, together with thick green ascites. Thickened omentum was also observed. Omental biopsies confirmed the appearance of a pleomorphic lymphoid infiltrate, as seen on the ascitic sample. Molecular polymerase chain reaction techniques showed that the sample was negative for HHV8. The diagnosis of PEL in an HIV- and HHV8-negative patient was made. The long history of heavy alcohol intake
Ascites are rarely caused by lymphoma, but this should be considered as part of the differential diagnosis. Different types of lymphoma can be implicated (e.g. low grade, such as follicular lymphoma or high grade, such as diffuse large B-cell, or Burkitt’s lymphoma). PEL is a rare clonal B-cell disorder (0.5–2% of all non-Hodgkin’s lymphomas) [2,4]. It tends to present as serous effusions, usually only affecting one area, with no contiguous solid tumour mass [1–3]. The most common site of involvement is the pleural space, with the abdomen and pericardium affected less often. Rarely, the local lymph nodes or bone marrow are affected. PEL is usually associated with HIV, with 4% of all AIDS-related lymphomas being of this type. It is also associated with HHV8 (a gamma herpes virus also implicated in Kaposi’s sarcoma) in most patients [2]. Rare HIV-negative, HHV8-positive cases have been reported, usually in areas of high HHV8 prevalence, such as the Mediterranean region [3] These tend to have a higher female to male sex ratio, older age of presentation, and more frequent association with other malignancies than the HIV-related cases [1]. Few HIV and HHV8-negative cases have previously been reported. These have had a variety of presentations, with pleural, pericardial or peritoneal involvement. Incidental associations with hepatitis C, cirrhosis and chronic hepatitis have been made [2]. The pathogenesis is unknown in HIV- and HHV8negative cases. The possibility of an unidentified viral agent must be considered. Other postulated causes include persistent antigenic stimulation, defective immunosurveillance against virally infected B-cells, or dysregulation of cytokine pathways. Immunosuppressive states caused by other malignancies or old age in some cases may contribute [2,3]. The clinical features of PEL are usually those of lymphoproliferative disorders: weight loss, night sweats and general malaise. The symptoms of the effusion also occur, such as abdominal distension and shortness of breath. The morphology of the affected fluid shows a variety of lymphoid cells. They tend to be large, with medium nuclear to cytoplasmic ratio, and basophilic cytoplasm. The nuclei are round to oval, and may have a perinuclear halo. Some larger cells may be seen and can resemble Reed–Sternberg cells. The immunophenotyping is usually negative for B-cell and T-cell markers, but positive for CD 30, 38 and 138 [1,2]. No characteristic cytogenetic markers have been identified, although there has been an association with the c-myc [2,5] oncogene rearrangement in some cases.
638
CLINICAL ONCOLOGY
The outcome is poor, with survival often less than 1 year. Various treatment regimens have been attempted, but no consensus about the optimum therapy has been reached.
References 1 Boulanger E, Hermine O, Fermand J, et al. Human herpes virus 8 (HHV-8) d associated peritoneal primary effusion lymphoma (PEL) in two HIV-negative elderly patients. Am J Hematol 2004;76:88–91.
2 Shimazaki M, Fujita M, Tsukamoto K, et al. An unusual case of primary effusion lymphoma in a HIV-negative patient not pathogenetically associated with HHV8. Eur J Haematol 2003;71:62–67. 3 Ascoli V, Scalzo C, Danese C, Vacca K, Pistilli A, Coco L. Human herpes virus-8 associated primary effusion lymphoma of the pleural cavity in HIV-negative elderly men. Eur Respir J 1999;14:1231–1234. 4 Kapelushnik J, Ariad S, Benharroch D, et al. Post renal transplant human herpesvirus 8-associated lymphoproliferative disorder and Kaposi’s sarcoma. Br J Haematol 2001;113:425–428. 5 Nador RG, Cesarman E, Chadburn A, et al. Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi’s sarcomaassociated herpes virus. Blood 1996;88:645–656.
Case Report Human-immunodeficiency-virus-negative, Human-herpes-virus-8-negative Abdominal Cavity Primary Effusion Lymphoma C. Jenkins*, Y. Sorour*, E. Blake*, R. Elliot*, A. I. Al-Sabahy, J. Greenz *Department of Haematology, University Hospital Wales, Cardiff, Wales, UK; yDepartment of Haematology, Llandough Hospital, Cardiff, Wales, UK; zDepartment of Gastroenterology, Llandough Hospital, Cardiff, Wales, UK ABSTRACT: Primary effusion lymphoma (PEL) is an unusual class of non-Hodgkin’s lymphoma, which is characterised by lymphomatous effusions in body cavities, but no associated mass lesions. It is usually associated with an immunodeficient state most often with the human immunodeficiency virus (HIV). We describe a case of a man with HIV-negative, human-herpes-virus-8 (HHV8)-negative PEL, with a history of heavy alcohol intake. The abdominal cavity was the only area involved; no solid tumour masses were observed on scanning, and the bone-marrow investigations were normal. The ascites contained numerous pleomorphic lymphoid, lymphoplasmacytoid cells of Bcell origin. The immunophenotyping was moderately positive for CD 38 and 138, and strongly positive for Ki 67. It is postulated that the immunosuppressed state in this patient may have been caused by the long history of heavy alcohol intake. Jenkins, C. et al. (2005). Clinical Oncology 17, 636–638 Ó 2005 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. Received: 7 February 2005 Revised: 23 May 2005
Introduction
Primary effusion lymphoma (PEL) is an unusual and rare type of non-Hodgkin’s lymphoma. It develops in serous cavities without lymph-node mass lesions [1–3]. It is associated with an immunocompromised state, and is often associated with infection with human-herpes-virus-type 8 [HHV8] [2,3]. Few cases have been reported of patients that are negative for the HIV and HHV8 viruses [2]. Case Report
A 61-year-old man was admitted to hospital with a 3-week history of increasing abdominal swelling and 2 stone loss in weight. He had a history of heavy alcohol intake (60–80 units a week for over 5 years). Physical examination revealed large volume ascites with minimal hepato-splenomegally. The presence of various stigmata of chronic liver, such as spider naevi, was observed. Blood investigations showed the following: Hb 7.1, WBC 6.1, Plat 278. Na 133, K 5.5, U 14.4, Crt 159, Alb 38, Alk 208, GGT 430, Ca 2.25, T Prot 102, Bili 7, LDH 852. Author for correspondence: Dr Christopher Jenkins, Department of Haematology, University Hospital Wales, Cardiff, Wales, UK. Tel: C44292-074-7747 ext 2373; E-mail: [email protected] 0936-6555/05/000000C03 $35.00/0
Accepted: 27 May 2005
Further blood tests showed liver autoantibodies to be normal, AFP 2, IgG 26.8 (5.1–15.8), IgA 8.07 (0.8–4.0), IgM 0.76 (0.48–1.9). Serum electrophoresis was normal, and urine electrophoresis showed no Bence–Jones protein. The patient was HIV-negative, also Hepatitis B- and Cnegative. A computed tomography of his abdomen showed massive abdominal ascites, a finely irregular liver margin and normal size spleen. One or two small lymph nodes near the coeliac axis were observed, but no generalised lymphadenopathy was seen. Increased density of the omental and mesenteric fat was incidentally noted. An ascitic tap was carried out, which showed the following: glucose 1.1, protein 63, LDH 6416. Cytology revealed numerous lymphoid cells of varied morphology. Most were medium sized, some had plasmacytoid features (Fig. 1). Immunophenotyping of the ascitic fluid showed a lymphoid population. The cells were negative for most B-cell markers (CD 19, 20, 23, 79b, FMC 7). There was weak expression of CD 10 and surface Ig. Medium-strength positivity was seen for CD 38 and 138, strong positivity for Ki 67. A bone-marrow aspirate and trephine biopsy showed no evidence of lymphoid infiltration. Computed tomography of the chest showed no pathological lymphadenopathy.
Ó 2005 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
HIV-NEGATIVE HHV8-NEGATIVE PEL
637
is presumed to have contributed to an immunosuppressed state. The patient was started on chemotherapy in the form of vincristine and cyclophosphamide. An excellent symptomatic improvement was achieved with, complete resolution of the ascites after just two courses. Primary Effusion Lymphoma
Fig. 1
A laparoscopy was carried out to gain further tissue for diagnosis. An enlarged cirrhotic-looking liver was found. Widespread stringy peritoneal adhesions were found throughout the abdomen, together with thick green ascites. Thickened omentum was also observed. Omental biopsies confirmed the appearance of a pleomorphic lymphoid infiltrate, as seen on the ascitic sample. Molecular polymerase chain reaction techniques showed that the sample was negative for HHV8. The diagnosis of PEL in an HIV- and HHV8-negative patient was made. The long history of heavy alcohol intake
Ascites are rarely caused by lymphoma, but this should be considered as part of the differential diagnosis. Different types of lymphoma can be implicated (e.g. low grade, such as follicular lymphoma or high grade, such as diffuse large B-cell, or Burkitt’s lymphoma). PEL is a rare clonal B-cell disorder (0.5–2% of all non-Hodgkin’s lymphomas) [2,4]. It tends to present as serous effusions, usually only affecting one area, with no contiguous solid tumour mass [1–3]. The most common site of involvement is the pleural space, with the abdomen and pericardium affected less often. Rarely, the local lymph nodes or bone marrow are affected. PEL is usually associated with HIV, with 4% of all AIDS-related lymphomas being of this type. It is also associated with HHV8 (a gamma herpes virus also implicated in Kaposi’s sarcoma) in most patients [2]. Rare HIV-negative, HHV8-positive cases have been reported, usually in areas of high HHV8 prevalence, such as the Mediterranean region [3] These tend to have a higher female to male sex ratio, older age of presentation, and more frequent association with other malignancies than the HIV-related cases [1]. Few HIV and HHV8-negative cases have previously been reported. These have had a variety of presentations, with pleural, pericardial or peritoneal involvement. Incidental associations with hepatitis C, cirrhosis and chronic hepatitis have been made [2]. The pathogenesis is unknown in HIV- and HHV8negative cases. The possibility of an unidentified viral agent must be considered. Other postulated causes include persistent antigenic stimulation, defective immunosurveillance against virally infected B-cells, or dysregulation of cytokine pathways. Immunosuppressive states caused by other malignancies or old age in some cases may contribute [2,3]. The clinical features of PEL are usually those of lymphoproliferative disorders: weight loss, night sweats and general malaise. The symptoms of the effusion also occur, such as abdominal distension and shortness of breath. The morphology of the affected fluid shows a variety of lymphoid cells. They tend to be large, with medium nuclear to cytoplasmic ratio, and basophilic cytoplasm. The nuclei are round to oval, and may have a perinuclear halo. Some larger cells may be seen and can resemble Reed–Sternberg cells. The immunophenotyping is usually negative for B-cell and T-cell markers, but positive for CD 30, 38 and 138 [1,2]. No characteristic cytogenetic markers have been identified, although there has been an association with the c-myc [2,5] oncogene rearrangement in some cases.
638
CLINICAL ONCOLOGY
The outcome is poor, with survival often less than 1 year. Various treatment regimens have been attempted, but no consensus about the optimum therapy has been reached.
References 1 Boulanger E, Hermine O, Fermand J, et al. Human herpes virus 8 (HHV-8) d associated peritoneal primary effusion lymphoma (PEL) in two HIV-negative elderly patients. Am J Hematol 2004;76:88–91.
2 Shimazaki M, Fujita M, Tsukamoto K, et al. An unusual case of primary effusion lymphoma in a HIV-negative patient not pathogenetically associated with HHV8. Eur J Haematol 2003;71:62–67. 3 Ascoli V, Scalzo C, Danese C, Vacca K, Pistilli A, Coco L. Human herpes virus-8 associated primary effusion lymphoma of the pleural cavity in HIV-negative elderly men. Eur Respir J 1999;14:1231–1234. 4 Kapelushnik J, Ariad S, Benharroch D, et al. Post renal transplant human herpesvirus 8-associated lymphoproliferative disorder and Kaposi’s sarcoma. Br J Haematol 2001;113:425–428. 5 Nador RG, Cesarman E, Chadburn A, et al. Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi’s sarcomaassociated herpes virus. Blood 1996;88:645–656.