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Year : 2015  |  Volume : 58  |  Issue : 4  |  Page : 496-499
Extracavitary primary effusion lymphoma: A case report from India

1 Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of Surgery, Christian Medical College, Vellore, Tamil Nadu, India

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Date of Web Publication4-Nov-2015


We present a case of extracavitary primary effusion lymphoma presenting, as jejunal polyps in a 38-year-old man. This is the first report of this entity from India. Although rare in our country, the diagnosis should be suspected in cases of CD20 negative large cell lymphoma with plasmablastic or immunoblastic differentiation in seropositive patients. Immunostaining for latency-associated nuclear antigen-1 and in situ hybridization for Epstein-Barr virus-associated RNA will confirm the diagnosis.

Keywords: Extracavitary primary effusion lymphoma, Human herpes virus-8, small intestine

How to cite this article:
Sampath R, Manipadam MT, Nair S, Samarasam I. Extracavitary primary effusion lymphoma: A case report from India. Indian J Pathol Microbiol 2015;58:496-9

How to cite this URL:
Sampath R, Manipadam MT, Nair S, Samarasam I. Extracavitary primary effusion lymphoma: A case report from India. Indian J Pathol Microbiol [serial online] 2015 [cited 2020 Dec 3];58:496-9. Available from: https://www.ijpmonline.org/text.asp?2015/58/4/496/168851

   Introduction Top

Kaposi sarcoma associated herpes virus/Human herpes virus-8 (KSHV/HHV8) was first discovered in 1994 by isolating its DNA sequences in a Kaposi sarcoma tumor in an AIDS patient.[1] In 1995, it was isolated from a distinct subset of AIDS related non-Hodgkin lymphoma localized in the body cavities.[2] The spectrum of KSHV/HHV8 associated diseases include primary effusion lymphoma, multicentric Castleman disease, extracavitary KSHV associated large B-cell lymphoma, and lymphomas with unconfirmed/controversial association with KSHV/HHV8.[2],[3],[4] The spectrum of HHV8 associated lymphomas has expanded subsequently including the recent identification of extracavitary solid lymphomas without serous effusions.[2]

Extracavitary KSHV associated large B-cell lymphoma is a recent and rare entity without lymphomatous effusions.[5],[6] These are virtually indistinguishable from the primary effusion lymphomas on the basis of morphology, phenotype and are known to occur in HIV-infected males with an aggressive clinical course and extranodal presentation.[2],[7] Very few cases of HHV8 related tumors such as Kaposi's Sarcoma have been reported from India in HIV positive individuals. There have been no reports of primary effusion lymphomas from India.

We report a case of KSHV/HHV8 associated lymphoma in an HIV infected male, which based on morphology, immunophenotype, co-infection of KSHV/HHV8 and Epstein-Barr virus (EBV), and extranodal involvement with absence of serous effusions were categorized as extracavitary primary effusion lymphoma. This has recently been renamed as extracavitary KSHV associated large B-cell lymphoma.[3] This is an index case from India. We emphasize the importance of detecting HHV8 association in lymphomas in HIV-infected individuals, which is essential for diagnosing this rare entity.[8]

   Case Report Top

Of the 73 lymphomas diagnosed in HIV positive patients during the 5 years period from January 2007 to December 2011, there was only one case of extracavitary primary effusion lymphoma. The patient, a 66-year-old gentleman, presented with a mass in the left side of the abdomen for 6 months associated with recent onset pain, bilious type of vomiting, and loss of weight. There was no peripheral lymphadenopathy. He was a known diabetic under regular medications. Computerized tomography revealed thickening of the gastric wall in the antral and pyloric regions. Jejunal intussusception with wall thickening and a luminal mass was noted. Multiple mesenteric, paraaortic, and omental nodes were present. There was no pleural or peritoneal effusion.

His blood investigations revealed anemia (7.9%), neutrophilic leukocytosis (total white blood cell count – 18,300/cu mm; neutrophils – 88%) and thrombocytopenia (29,000/cu mm). He was seropositive for HIV ELISA and had a CD4 positive T-cell count of 219 cells/μL. Upper gastrointestinal endoscopy revealed a deep ulcer in the stomach of size 4 cm with a clean base and everted margins, of which a biopsy was taken.

He underwent laparotomy on the 10th admission day. The resected jejunal segment revealed an intussusception due to a 5.3 cm × 3.5 cm × 2.3 cm polypoidal mass with a grey white homogenous cut surface. Three other smaller polypoidal masses were also present in the jejunum [Figure 1]. There were two small mesenteric lymph nodes which showed reactive hyperplasia on microscopy. Bone marrow examination showed no evidence of lymphoma.
Figure 1: Segment of jejunum with multiple polypoid tumor masses

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Morphology and immunophenotype

Endoscopic mucosal biopsy from gastric ulcer showed diffuse infiltration by sheets of large cells with vesicular nuclei, 2-3 prominent nucleoli and moderate amounts of cytoplasm. Admixed with these were a few small lymphocytes. Mitotic activity was brisk. Sections from the jejunal polyps showed infiltration by sheets of large cells with similar morphology. In many of these cells, nuclei were eccentrically located giving it a plasmacytoid appearance. Brisk mitotic and apoptotic activity were present with foci of necrosis [Figure 2]. The overlying mucosa was ulcerated and covered by acute inflammatory exudate and microbial colonies.
Figure 2: Plasmablast like cells infiltrating the lamina propria of the small intestine H and E ×200

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Immunohistochemistry was performed using envision technique on Ventana Benchmark XT and Automated Immunostainer. HHV8 latency-associated nuclear antigen 1 (LANA1) and EBV latent membrane protein 1 (LMP1) immunohistochemistry was performed manually under standard protocol. In situ hybridization (ISH) technique was used to detect EBV encoded RNA (EBER) with Benchmark XT Autostainer, Ventana Medical Systems using INFORM EBER Probe 800-2842 from Ventana Medical Systems and detected using Ventana ISH iVIEW Blue Detection Kit, which showed a nuclear staining (blue precipitate) on light microscopy.

The tumor cells in both the sites were positive for MUM1, CD138, and CD30. CD20 was focally positive. CD56 was negative. CD3 stained reactive T-lymphocytes. MIB-1 labeling index was about 80%. The tumor cells from both the sites showed characteristic punctuate nuclear staining for HHV8 latent nuclear antigen (LNA) [Figure 3] and strong nuclear positivity for EBER by ISH technique [Figure 4]. Immunohistochemistry for EBV LMP1 was negative.
Figure 3: Lymphoid cells showing granular nuclear positivity for Human herpes virus-8-latency-associated nuclear antigen ×400

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Figure 4: Lymphoid cells positive for Epstein-Barr virus encoded RNA-in situ hybridization ×400

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Our case was lost to follow-up.

   Discussion Top

The term primary effusion lymphoma was first defined in WHO 2001 classification for the primary lymphomatous effusions associated with KSHV/HHV8 infection, that predominantly occurs in immunosuppressed individuals infected with HIV.[2] Subsequently, rare cases of extracavitary lymphoma without serous effusions associated with KSHV/HHV8 have been reported [5],[6] and had been termed as extracavitary primary effusion lymphoma.[7] This has been recently renamed, as extracavitary KSHV associated large B-cell lymphoma [3] and is included within the spectrum of primary effusion lymphoma.[9] So far, 53 cases of extracavitary KSHV associated large B-cell lymphoma have been reported in the literature.[3],[10] We report a case, which is the single index case from India.

KSHV associated large B-cell lymphomas are known to occur in immunocompromised HIV-infected individuals. Severe depletion of CD4 positive T-lymphocytes is common, which along with the presence of B symptoms, synergistically results in the aggressive clinical course. The primary site of involvement is either nodal or extranodal, the former being more common.[7] Among the extranodal sites, the gastrointestinal tract is the most common, followed by spleen, liver, skin and rarely heart, bladder, and soft tissue.[3],[6],[8],[11],[12],[13],[14] A recent case report documented an unusual intravascular location.[10] Most of these patients present at Stage III/IV.[6] In one case report, leukemic presentation was noted.[5]

The cell of origin is defined by immunophenotyping and gene expression studies. The origin is similar to that of primary effusion lymphoma.[2] It represents the postgerminal center/preterminal stage of B-cell maturation, as suggested by the presence of immunoglobulin gene rearrangement, somatic hypermutation, down regulation of B-cell antigens (CD19, CD20, and CD79a) and features of plasma cell differentiation (CD138).[2],[7],[15] Gene expression profiling studies and proteomic analysis of the secretomes present in the neoplastic cells reveal that the secreted proteins present in primary effusion lymphoma and the extracavitary variant are identical and hence, the later can be considered to be within the spectrum of primary effusion lymphoma.[9]

Co-infection of these cells by HHV8 and EBV leads to lymphomagenesis. The main gene responsible for this is HHV8 LANA and EBV acts, as a cofactor. Both of these viruses exhibit the latency pattern of infection, LNA1 latency gene in the case of HHV8 and type I pattern of latency (EBNA1 and EBER latency genes) in case of EBV.[2]

The morphology is similar to that of primary effusion lymphoma. The neoplastic cells are usually large cells with wide range of morphology, predominantly immunoblastic followed by plasmacytoid, centroblastic and rarely Reed-Sternberg such as cells, anaplastic or pleomorphic.[2],[3],[7] Our case had centroblastic and plasmacytoid morphology.

Immunophenotype is also almost similar to that of primary effusion lymphoma,[3] except for the frequency of expression of certain antigens. CD45 expression determines the lymphoid origin.[2] Down regulation of B-cell antigens such as CD19 and CD20 is more commonly seen in primary effusion lymphoma when compared to the extracavitary variant.[3],[7] Our case showed focal positivity for CD20. Aberrant expression of T-cell antigens (CD3) is seen in 29% of the cases.[3] Our case did not express CD3. CD138, VS38 and MUM1/IRF4, the markers of plasma cell differentiation are more commonly seen in the extracavitary variant when compared to the primary effusion lymphoma.[2],[3],[7] Our case showed strong positivity for CD138 and MUM1. Expression of CD30, a feature of immunoblastic differentiation was also present in our case as described in the literature.[2],[3]

EBV association, as detected by EBER-ISH was present in our case, as described in the literature.[3],[7] Evidence of HHV8 infection in the neoplastic cells, as detected by immunohistochemistry, molecular studies or polymerase chain reaction is essential for the diagnosis of this entity. In our case, HHV8 positivity was documented by immunohistochemistry for LNA1, the latent gene expressed by HHV8.[2],[7] Serology may also show positivity for HHV8.[2]

The overall survival is generally poor with a median survival period of 6 months.[2],[3] Highly active antiretroviral therapy (HAART) for AIDS has many beneficial effects in treating these patients and the absence of HAART therapy along with poor performance status predicts the poorer clinical outcome.[2] In addition to chemotherapy, HHV8 as the therapeutic target in KSHV associated lymphomas can represent a novel treatment strategy.[16] Other strategies proposed include targeting of the latency phase genes such as LNA1.[2]

   Conclusion Top

HHV8 and EBV association should be suspected in any anaplastic solid tumor arising in an HIV-infected individual.[13] Hence, the demonstration of both EBV, particularly by EBER-ISH and HHV8 by HHV8-LNA1 in tumor tissues is very important in detecting the rarer entities of AIDS related non-Hodgkin lymphomas. An extensive search of the literature so far has not reported any extracavitary primary effusion lymphoma from India. KS is also rare in HIV positive patients in India indicating the low incidence of HHV8 related tumors in our country.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 1994;266:1865-9.  Back to cited text no. 1
Carbone A, Gloghini A. KSHV/HHV8-associated lymphomas. Br J Haematol 2008;140:13-24.  Back to cited text no. 2
Pan ZG, Zhang QY, Lu ZB, Quinto T, Rozenvald IB, Liu LT, et al. Extracavitary KSHV-associated large B-Cell lymphoma: A distinct entity or a subtype of primary effusion lymphoma? Study of 9 cases and review of an additional 43 cases. Am J Surg Pathol 2012;36: 1129-40.  Back to cited text no. 3
Deloose ST, Smit LA, Pals FT, Kersten MJ, van Noesel CJ, Pals ST. High incidence of Kaposi sarcoma-associated herpesvirus infection in HIV-related solid immunoblastic/plasmablastic diffuse large B-cell lymphoma. Leukemia 2005;19:851-5.  Back to cited text no. 4
Navarro JT, Ribera JM, Juncà J, Millá F. Anorectal lymphoma without effusion associated with Human herpes virus-8 and type 1 Epstein-Barr virus in an HIV-infected patient. Hum Pathol 2003;34:630.  Back to cited text no. 5
Carbone A, Gloghini A, Vaccher E, Cerri M, Gaidano G, Dalla-Favera R, et al. Kaposi's sarcoma-associated herpesvirus/Human herpesvirus type 8-positive solid lymphomas: A tissue-based variant of primary effusion lymphoma. J Mol Diagn 2005;7:17-27.  Back to cited text no. 6
Chadburn A, Hyjek E, Mathew S, Cesarman E, Said J, Knowles DM. KSHV-positive solid lymphomas represent an extra-cavitary variant of primary effusion lymphoma. Am J Surg Pathol 2004;28:1401-16.  Back to cited text no. 7
Zhang H, Yang XY, Hong T, Feldman T, Bhattacharyya PK. Kaposi sarcoma-associated herpesvirus (Human herpes virus type 8)-associated extracavitary lymphoma: Report of a case in an HIV-positive patient with simultaneous Kaposi sarcoma and a review of the literature. Acta Haematol 2010;123:237-41.  Back to cited text no. 8
Carbone A, Volpi CC, Caccia D, Gualeni AV, Cilia AM, Bongarzone I, et al. Extracavitary KSHV-positive solid lymphoma: A large B-cell lymphoma within the spectrum of primary effusion lymphoma. Am J Surg Pathol 2013;37:1460-1.  Back to cited text no. 9
Crane GM, Ambinder RF, Shirley CM, Fishman EK, Kasamon YL, Taube JM, et al. HHV-8-positive and EBV-positive intravascular lymphoma: An unusual presentation of extracavitary primary effusion lymphoma. Am J Surg Pathol 2014;38:426-32.  Back to cited text no. 10
Arora M, Cossor FI. Diagnosis of extracavitary primary effusion lymphoma by urine cytology. Blood 2012;119:2707.  Back to cited text no. 11
Costes V, Faumont N, Cesarman E, Rousset T, Meggetto F, Delsol G, et al. Human herpes virus-8-associated lymphoma of the bowel in human immunodeficiency virus-positive patients without history of primary effusion lymphoma. Hum Pathol 2002;33:846-9.  Back to cited text no. 12
Kim Y, Leventaki V, Bhaijee F, Jackson CC, Medeiros LJ, Vega F. Extracavitary/solid variant of primary effusion lymphoma. Ann Diagn Pathol 2012;16:441-6.  Back to cited text no. 13
Pantanowitz L, Wu Z, Dezube BJ, Pihan G. Extracavitary primary effusion lymphoma of the anorectum. Clin Lymphoma Myeloma 2005;6:149-52.  Back to cited text no. 14
Klein U, Gloghini A, Gaidano G, Chadburn A, Cesarman E, Dalla-Favera R, et al. Gene expression profile analysis of AIDS-related primary effusion lymphoma (PEL) suggests a plasmablastic derivation and identifies PEL-specific transcripts. Blood 2003;101:4115-21.  Back to cited text no. 15
Klass CM, Offermann MK. Targeting human herpes virus-8 for treatment of Kaposi's sarcoma and primary effusion lymphoma. Curr Opin Oncol 2005;17:447-55.  Back to cited text no. 16

Correspondence Address:
Dr. Marie Therese Manipadam
Department of Pathology, Fourth Floor, ASHA Building, Christian Medical College, Vellore - 632 004, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.168851

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

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