|Year : 2016 | Volume
| Issue : 4 | Page : 529-533
Plasmablastic lymphoma of the gastrointestinal tract: A rare entity with a dismal prognosis
AS Komaranchath1, RA Haleshappa1, LC Kuntegowdenahalli1, RV Kumar2, L Dasappa1, G Babu1
1 Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
2 Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
|Date of Web Publication||21-Apr-2017|
Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka
Source of Support: None, Conflict of Interest: None
INTRODUCTION: Plasmablastic lymphoma (PBL) is a rare and aggressive type of mature B-cell lymphoma, which is usually associated with HIV infection. The most common site of PBL is the oral cavity. Involvement of the gastrointestinal (GI) tract is rare, and literature is limited to few case reports and case series. AIMS: To retrospectively analyze the presentation, clinical findings, and outcome of patients presenting to our institute with a diagnosis of PBL involving the GI tract. MATERIALS AND METHODS: A retrospective observational study was conducted at our institute from February 2008 to January 2015 on consecutive patients presenting with PBL involving the GI tract. The data were compared to various case reports and series published in peer-reviewed journals. RESULTS: There were four patients diagnosed with PBL of the GI tract; three male and one female. The location of involvement was in the stomach, ileocecal junction, ascending colon, and rectum. Only one patient was HIV-positive and was on combination antiretroviral therapy since 2 years. Among the three immunocompetent patients, only one survived with therapy; however, the patient relapsed within 6 months of completion of treatment. CONCLUSION: PBL was seen to have a uniformly aggressive clinical course with poor outcomes even with optimal treatment. The prognosis of immunocompetent patients appears to be worse than that of HIV-AIDS patients. Although the most common histologies seen with GI lymphomas are mucosa-associated lymphoid tissue type lymphomas or diffuse large B-cell lymphoma, rarer and more aggressive histologies like PBL need to be kept in mind.
Keywords: Aggressive lymphomas, gastrointestinal lymphomas, HIV-related lymphomas, plasmablastic lymphoma
|How to cite this article:|
Komaranchath A, Haleshappa R, Kuntegowdenahalli L, Kumar R, Dasappa L, Babu G. Plasmablastic lymphoma of the gastrointestinal tract: A rare entity with a dismal prognosis. Indian J Cancer 2016;53:529-33
|How to cite this URL:|
Komaranchath A, Haleshappa R, Kuntegowdenahalli L, Kumar R, Dasappa L, Babu G. Plasmablastic lymphoma of the gastrointestinal tract: A rare entity with a dismal prognosis. Indian J Cancer [serial online] 2016 [cited 2020 Oct 19];53:529-33. Available from: https://www.indianjcancer.com/text.asp?2016/53/4/529/204756
| » Introduction|| |
Plasmablastic lymphoma (PBL) is a clinicopathological entity that was initially described in 1997 and is now considered a distinct subtype of diffuse large B-cell lymphoma seen more commonly in patients with HIV infection. Fifteen out of the sixteen patients in the original report by Delecluse et al. were HIV-positive and all had involvement of the oral cavity. In the last 10 years, several case reports and case series have been published on PBL among both HIV-positive and HIV-negative individuals.,,,,,,,,,,,, Involvement of the gastrointestinal (GI) tract is rare, and there have been only one case series of four cases  and several case reports ,,,,,, published in recent times.
The diagnosis of PBL is challenging because it has features that overlap with those of myeloma and with lymphomas that have plasmablastic morphology. This is compounded by its aggressive clinical course with frequent relapses, high rates of disease progression, and mortality despite the use of optimal treatment modalities.
We hereby present our experience with PBL involving the GI tract with the clinical presentation, investigations, and treatment outcomes.
| » Materials and Methods|| |
A retrospective, observational study was carried out at a referral cancer center in South India. After obtaining the clearance from the Institutional Ethics and Review Board, we included patients diagnosed with PBL of the GI tract from February 2008 to January 2015. Patient's medical records were reviewed for information regarding age, sex, presenting complaints, HIV status, Ann Arbor (Cotswold modification) stage, International Prognostic Index (IPI) score, treatment given, response to therapy, and treatment outcome. The diagnosis of PBL was confirmed by histopathology and immunohistochemistry (IHC) studies. Complete workup of patients including hemogram; biochemistry including lactate dehydrogenase, bone marrow biopsy, and cerebrospinal fluid examination; computed tomography (CT) scans of neck, chest, abdomen, and pelvis was done. The stage was assigned according to the Cotswold modification of the Ann Arbor staging system. The IPI score was assigned whenever possible if all five components constituting the score could be identified in the medical records. The Eastern Cooperative Oncology Group scale was used to determine the performance status. Response to the treatment was determined as per the International Working Group Criteria. The overall survival (OS) was defined as the time (in months) from disease diagnosis to death due to any cause. Progression-free survival was defined as the time (in months) from the date of diagnosis to the date of documented disease progression or death of disease or due to treatment toxic effects.
| » Results|| |
There were four patients diagnosed with GI PBL in the time period mentioned. There were three males and one female (median age 29.5 years; range: 13–45 years) [Table 1].
Our first patient was a 20-year-old immunocompetent male who presented with complaints of epigastric abdominal pain and several episodes of vomiting. Esophagogastroscopy showed an irregular, raised lesion in the antrum, and pylorus of the stomach. Whole body CT scan showed diffuse wall thickening with few perigastric lymph nodes, but no evidence of disease elsewhere. The stage of the disease was determined to be I AE according to the Ann Arbor staging system. Histopathology showed features suggestive of PBL [Figure 1] and IHC was positive for plasma cell markers, CD138 [Figure 2], and MUM1 [Figure 3]; but negative for cytokeratin, CD3, CD20, and CD117 [Figure 4], as well as for PAX5 and leukocyte common antigen (LCA). Latent membrane protein 1 (LMP1), which is a surrogate marker for Epstein–Barr virus (EBV) infection, was negative. Ki-67 index was 85% [Figure 5]. He was given six cycles of CHOP chemotherapy. There was a partial response seen in the interim assessment done after three cycles, but positron emission tomography-CT done after six cycles showed progressive disease (PD) in the form of interval increase in wall thickness of pylorus and antrum with persistence of perigastric lymph nodes. He has been started on salvage chemotherapy with CODOX-M/IVAC protocol at the time of preparation of this manuscript.
|Figure 1: Dense aggregates of plasmablasts and immunoblasts; high power field in the inset|
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|Figure 4: Negative markers: (a) Cytokeratin (−) (b) CD3(−) (c) CD20(−) (d) CD117(−)|
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The second case was a 13-year-old immunocompetent boy who came with low-grade, intermittent fever, right iliac fossa pain with tenderness, and recent onset of abdominal distension. On evaluation, he was found to have a mass lesion in the cecum extending to the ileocecal junction. Biopsy of the same showed PBL. IHC revealed LCA, CD138, and MUM1 positive; negative for CD20, CD30, CD79a, and LMP1. Ki-67 was 95%. On further evaluation, he had mediastinal lymphadenopathy, multiple lesions in the liver and spleen, and bone marrow was found to be involved. His stage was IVBES. He developed sepsis before chemotherapy could be initiated and died within 2 weeks of presentation.
A 45-year-old immunocompetent female came with primary complaints of abdominal pain. On evaluation, she was found to have a large polypoidal mass in the ascending colon. Histopathology of the biopsy specimen was suggestive of PBL and IHC was positive for CD138 and MUM1. CD20 was also positive and Ki-67 was 90%. LCA, LMP1, CD79a, and CD30 were negative. CT scan of the thorax, abdomen, and pelvis showed no other evidence of disease and she was staged I AE. She was started on R-CHOP chemotherapy; rituximab was added in view of CD20 positivity. After two cycles chemotherapy, she was found to have PD and died within 6 months of initial diagnosis.
The only HIV-infected patient in this series, a 39-year-old male, was already receiving antiretroviral drugs for the previous 3 years. He presented with altered bowel habits and bleeding per rectum. On evaluation, he was icteric, with biochemical parameters suggestive of obstructive jaundice. CT scans of thorax, abdomen, and pelvis showed both supra- and infra-diaphragmatic disease with multiple hypodensities in the liver. Colonoscopy showed a polypoidal growth in the lower one-third of the rectum, which was biopsied and proven to be PBL of the rectum. The positive IHC markers were CD138 and LCA. CD20, CD30, CD3, and CD79a negative. LMP1 was focally positive which suggested co-infection with EBV. The patient was not willing for EBV-encoded RNA 1 (EBER1) testing by in situ hybridization. The proliferation index (Ki-67) was 85%. Bone marrow was not involved. He was staged as IV BE. His CD4 counts at the time were 371/mm 3. Chemotherapy was deferred in view of poor performance status and after discussion with the patient and his relatives; he was given best supportive care. He died due to disease-related complications within 3 months of diagnosis.
| » Discussion|| |
PBL is a neoplasm of the mature B-cells which shows diffuse proliferation of the large neoplastic cells, most of which resemble B-immunoblasts and have the immunophenotype of plasma cells. Although PBL was originally described in the oral cavity of HIV-positive patients, this disease can be associated with other types of immunodeficiency (autoimmune or therapy-induced). HIV-positive patients with PBL are almost always found to have a concurrent EBV infection. PBL has been less frequently described in immunocompetent patients and in extraoral locations.
Based on IHC, molecular, and genetic studies, the cell of origin is thought to be a blastic proliferative B-cell that has switched its phenotype to a plasma cell stage of differentiation or is probably in the transition from immunoblast to plasma cell. There are certain chromosomal abnormalities thought to occur during this process of maturation that is associated with the development of malignancy. Valera et al. opined that IG/MYC rearrangement may be the major cytogenetic alteration in PBLs. There is a strong association seen with EBV, especially in the setting of HIV infection. In a series of 112 cases of HIV-associated PBL, 74% of patients were found to have co-infection with EBV. EBV co-infection occurs in a lesser number of patients in a posttransplant setting (67%) and least often in immunocompetent patients (50%). EBV infection could play a role in preventing apoptosis via several mechanisms such as induction of NF-kB, through syk/src mediation, and induction of BAX/BAK.
An association between PBL and HHV-8 is not so well defined. While several reports have demonstrated the expression of HHV8-associated proteins in PBL , some others have not.
PBL has a characteristic immunophenotype, wherein they are positive for the plasma cell markers such as CD38, CD138, and MUM1; and negative for the typical B-cell antigens such as CD20 and CD79a. There is usually a high level of proliferation as detected by high Ki-67 levels. Ki-67 values more than 80% have been seen to be an independent poor prognostic factor in various studies.,, All the four patients in our series had a Ki-67 over 80%, and only one patient was alive 6 months after the primary diagnosis. EBV estimation by in situ hybridization for EBER is not done routinely for immunocompetent patients in our institute. However, LMP1 is done in all cases of HIV-associated lymphomas. In the sole HIV-positive patient in our series (Case 4), LMP1 was found to be focally positive. LMP1 is an IHC marker for EBV infection, which has also been used in the setting of infectious mononucleosis and EBV-associated Hodgkin's lymphoma.
The GI tract appears to be the most common site of involvement (20%) in HIV-negative PBL, followed by soft tissue (17%), bone marrow (15%), and skin (12%). In a previously published series of GI PBL, the most common location appeared to be the distal gut with two out of the four cases arising from the small intestine, one from the colon and one from the anorectum. However, two of these patients had a history of long-standing Crohn's disease. There was only one patient in that series who was HIV-positive, and he was diagnosed with disease involving the anorectum. In our series as well, the only HIV-positive patient had involvement of the anorectum. A head to head comparison of the two series is given in [Table 2]. Another series on PBL published earlier from our institute had a total of eight patients with PBL: Four cases were of the oral cavity and four were extraoral. Two patients in each group were HIV-positive.
At the presentation, two of our patients were in Stage I and the other two were in Stage IV according to the Cotswolds modification of the Ann Arbor staging system. Both patients in Stage IV had B symptoms. Spleen, as well as bone marrow, was involved only in one patient in whom the disease had a rapid course and the patient succumbed to the illness before chemotherapy could be instituted. However, the Ann Arbor staging does not appear prognostic, and Stage I disease should be treated the same as those with advanced disease. Chemotherapy, radiotherapy, or a combination of both have been tried in PBL. The most common chemotherapy protocols used in PBL is CHOP or CHOP-like regimen. Other regimens that have been used are hyper-CVAD, dose-adjusted EPOCH, and CODOX-M/IVAC regimen. However, more aggressive regimens have not shown to produce a statistically significant improvement in outcome. Because of this, the NCCN guidelines also recommend CHOP in favor of more intensive regimens. In our series, both patients with Stage I disease were started with CHOP chemotherapy. Rituximab was added in Case 3 as her IHC showed CD20 positivity. However, both patients progressed on treatment. Case 1 has been started on a salvage regimen of CODOX-M/IVAC. The two cases with Stage IV disease had a very aggressive course, and chemotherapy could not be started. In view of the small numbers in this study, it is not possible to extrapolate differences in survival between HIV-positive and HIV-negative patients. Comparative studies have shown that HIV status does not appear to affect the outcomes in PBL., However, there was a suggestion that immunosuppression among HIV-negative patients was associated with worse outcomes. In the series published by our institute, HIV-positive patients with PBL seemed to do better with the addition of highly active antiretroviral therapy to chemotherapy.
| » Conclusion|| |
PBL is a rare entity seen most commonly in the setting of immunocompromise. The most common site involved in these patients is the oral cavity. However, this disease may present in extraoral sites in which the GI tract appears to be the most common. GI involvement also appears to be more common in immunocompetent patients. The prognosis is uniformly poor even with optimal management with cytotoxic agents.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]
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