|Year : 2017 | Volume
| Issue : 2 | Page : 67-69
Eighteen years on postrenal transplantation, lymphoproliferative disorder, and its implication
Arun Kumar Narayanan1, Rahul Ramachandran2, Sreejith G Nair3, Rekha A Nair4, Sandeep Patil1, Jayshree Ramdas Pisharody4, Satish Balan1, Keshavan Nair2, Ramdas Pisharody1
1 Department of Nephrology, KIMS, Trivandrum, Kerala, India
2 Department of Respiratory Medicine, KIMS, Trivandrum, India
3 Department of Medical Oncology, Regional Cancer Centre, Trivandrum, Kerala, India
4 Department of Pathology, Regional Cancer Centre, Trivandrum, Kerala, India
|Date of Submission||03-Jan-2017|
|Date of Acceptance||04-Jul-2017|
|Date of Web Publication||21-Sep-2017|
Arun Kumar Narayanan
# A-3,2nd floor, Manushka Garden, Venpalavattom, Anayara Trivandrum- 695029, Kerala
Source of Support: None, Conflict of Interest: None
Post-transplant lymphoproliferative disorder (PTLD) represents a life-threatening disorder occurring after transplantation, ranging from a polyclonal mononucleosis-like illness to a monomorphic high-grade neoplasm with cytologic and histopathologic evidence indicative of transformation to lymphoma. PTLD of diffuse large B-cell lymphoma subtype isolated to the lungs is a rare diagnosis. We describe here a case of an immunocompromised adult diagnosed with diffuse large B-cell lymphoma PTLD limited to his lung with an associated mass and locoregional lymphadenopathy on imaging. Even more unique to our case was the absence of underlying cytomegalovirus and Epstein–Barr virus infection. In the post-transplant setting, immunocompromised state or Epstein–Barr virus-positive state has risk for PTLD. A live-related donor kidney transplant recipient, donor being the father, presented with cough, expectoration, and fever, which were not responding to sequential antibiotics. Evaluation showed large B-cell lymphoma of the lung after 18 years of transplant, which has not been reported before for its occurrence so late after renal transplantation.
Keywords: kidney transplant, large B-cell lymphoma, post-transplant lymphoproliferative disorder
|How to cite this article:|
Narayanan AK, Ramachandran R, Nair SG, Nair RA, Patil S, Pisharody JR, Balan S, Nair K, Pisharody R. Eighteen years on postrenal transplantation, lymphoproliferative disorder, and its implication. J Egypt Soc Nephrol Transplant 2017;17:67-9
|How to cite this URL:|
Narayanan AK, Ramachandran R, Nair SG, Nair RA, Patil S, Pisharody JR, Balan S, Nair K, Pisharody R. Eighteen years on postrenal transplantation, lymphoproliferative disorder, and its implication. J Egypt Soc Nephrol Transplant [serial online] 2017 [cited 2018 Jun 19];17:67-9. Available from: http://www.jesnt.eg.net/text.asp?2017/17/2/67/215223
| Introduction|| |
Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized complication of both solid organ transplantation and allogeneic hematopoietic stem cell transplantation. PTLD may range from a monomorphic high-grade neoplastic disease to a polyclonal mononucleosis-like illness ,,,.
| Presentation of the case|| |
Mr S is a live-related donor kidney transplant recipient, donor being his Father. Surgery was performed in Chennai, India, on 29 January 1997. He received antithymocyte globulin (rabbit) for premptive acute rejection. After transplant, the patient had marginal increase in serum creatinine (1.4 mg/dl). He was on oral prednisolone 75 mg bis in die (BD) until August 1997. He also received second and third antithymocyte globulin (rabbit) with methyl prednisolone during October 1997. Maximum creatinine during this period was 2.1 mg/dl and nadir serum creatinine was 1.6 mg/dl. By 4 months the patient had stage II avascular necrosis of right hip, which was managed conservatively. Patient was on cyclosporine; the dose was minimized in 2010 and was gradually withdrawn in 2012 when serum creatinine was 1.2–1.5 mg/dl. There was a slight increase in serum creatinine in March 2014, after which mycophenolate was resumed. One year after mycophenolate, in March 2015, the patient presented with cough, expectoration, and fever to us, which was not responding to sequential antibiotics. Radiography of the chest showed reticulonodular shadows in the upper and middle zones. Computed tomography of the thorax showed multiple nodules in both lungs more towards the upper zone with collapse of the left lower lobe. Bronchoscopy performed in May 2015 showed chronic inflammatory changes on both sides with a nodule at the end of the left main bronchus almost completely occluding the left lower lobe bronchus. Biopsy and brushings taken from the nodule left behind an ulcer crater. Biopsy report showed large B-cell lymphoma with a MIB-1 index of 80%. Epstein–Barr virus (EBV) and cytomegalovirus serology was negative. The patient was initiated on CHOP-R regimen. After treatment with Cyclophosphamide Doxorubicin Vincristine Prednisolone - Rituximab regimen he developed left hemiplegia; brain metastasis was suspected and computed tomography of the brain was performed, which was normal. The patient was given cytosine arabinoside. His limb power has improved over 4 weeks. Now he is ambulant and on last cycle of Cyclophosphamide Doxorubicin Vincristine Prednisolone - Rituximab regimen ([Figure 1] and [Figure 2]).
|Figure 1 CD20 Large cells, large atypical lymphoid cells admixed with inflammatory cells. H &E X 400.|
Click here to view
|Figure 2 CD20 Large atypical lymphoid cells CD20 positivity. H &E X 400.|
Click here to view
| Discussion|| |
Primary EBV infection in EBV-seronegative recipients usually occurs in the first 3–6 months . In the paediatric population, the highest incidence of lymphoma occurs in the first year after transplantation, with 47% of cases occurring within 6 months, 62% within 1 year, and 90% within 5 years of transplant . In adults slightly more than 50% of patients are diagnosed beyond 12 months with a predilection for EBV-associated tumours to occur sooner than EBV-negative tumour types . Approximately 85% of PTLDs are B-cell in origin and most commonly of the monomorphic diffuse large B-cell lymphoma (DLBCL) type (50%) typically occurring after solid organ transplant. The major risk factor in developing PTLD is the type, degree and cumulative length of immunosuppression as well as EBV status .
A greater percentage of lymphomas occur extranodally in transplant recipients compared with the general population, and prognosis is poor for extranodal versus nodal disease .
A study by Gibson and colleagues on 95 615 solid organ transplant performed from 2000 to 2008 showed that DLBCL risk was highest in the first year following transplantation, and standardized incidence ratio for early onset DLBCL risk was elevated in association with EBV-negative serostatus and use of polyclonal antibody induction therapy .
Kirby et al.  performed a laboratory database search, which revealed that 28 of 2140 renal allograft recipients (18 male and 10 female, 25–77 years old, mean age 53 years) required a biopsy for respiratory symptoms. The incidence of neoplasia on lung biopsy was 0.4% (nine cases), of which two were post-transplant B-cell lymphoproliferative disorders .
Kirby et al.  also observed that the time from kidney transplantation to lung biopsy ranged from 4 to 345 months (mean: 81 months). The majority of patients (18/28 or 64%) received a deceased donor kidney. Eight (29%) patients received kidneys from living related donors; two (7%) patients received kidneys from living unrelated donors.Our patient was identified to have an isolated PTLD of the DLBCL type in the lung. Primary lung B-cell lymphoma outside of the post-transplant setting has been reported, but is also very rare ,. The incidence of PTLD in paediatric patients was higher than that in the adult transplant population, presumably secondary to the population being more frequently EBV naive.
Our patient was treated with CHOP-R (cyclophosphamide, doxorubicin, vincristine, and prednisolone and rituximab) chemotherapy. He has responded well to treatment thus far. In general, the treatment for EBV-driven PTLD remains a controversial subject, with no evidence-based treatment or multicentred trials to support any particular treatment modality. However, a downregulation of immunosuppression is the most common management but this is not effective enough to control disease, therefore typically necessitating immunochemotherapy with rituximab.
In our case it is important to comment on the delayed duration and also the seronegativity to cytomegalovirus and EBV. This is a rare presentation of PTLD after 18 years of transplant not reported in the literature.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Knight JS, Tsodikov A, Cibrik DM, Ross CW, Kaminski MS, Blayney DW. Lymphoma after solid organ transplantation: risk, response to therapy, and survival at a transplantation center. J Clin Oncol 2009; 27:3354–3362.
Sakhuja V, Ramachandran R, Kohli HS, Jha V, Gupta KL, Rathi M et al.
Spectrum of lymphoproliferative disorders following renal transplantation in North India. Indian J Nephrol 2013; 23:287–291.
Allen U, Preiksaitis J. Epstein-barr virus and posttransplant lymphoproliferative disorder in solid organ transplant recipients. Am J Transplant 2009; 9(Suppl 4):S87–S96.
Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. MKDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009; 9(Suppl 3):S1–S157.
Shroff R, Rees L. The post-transplant lymphoproliferative disorder − a literature review. Pediatr Nephrol 2004; 19:369–377.
Kinch A, Baecklund E, Backlin C, Ekman T, Molin D, Tufveson G et al.
A population-based study of 135 lymphomas after solid organ transplantation: the role of Epstein-Barr virus, hepatitis C and diffuse large B-cell lymphoma subtype in clinical presentation and survival. Acta Oncol 2014; 53(September 2013):669–679.
Kirby S, Satoskar A, Brodsky S, Pope-Harman A, Nunley D, Hitchcock C et al.
Histological spectrum of pulmonary manifestations in kidney transplant recipients on sirolimus inclusive immunosuppressive regimens. Diagn Pathol BioMed Central Ltd 2012; 7:25.
Cader RA, Mohd R, Gafor HA, Kong NCT. Post transplant lymphoproliferative disorder: a case series and review of literature. EXCLI J 2013; 12:144–149.
Kinch A, Baecklund E, Backlin C, Ekman T, Molin D, Tufveson G et al.
A population-based study of 135 lymphomas after solid organ transplantation: the role of Epstein-Barr virus, hepatitis C and diffuse large B-cell lymphoma subtype in clinical presentation and survival. Acta Oncol 2014; 53:669–679.
Ghorbani RP, Shokouh-Amiri H, Gaber LW. Intragraft angiotropic large-cell lymphoma of T cell-type in a long-term renal allograft recipient. Mod Pathol; 1996; 9:671–676.
[Figure 1], [Figure 2]