Primary cutaneous posttransplant lymphoproliferative disorders (PTLD) are rare. This retrospective, multicenter study of 35 cases aimed to better describe this entity. Cases were (re)-classified according to the WHO-EORTC or the WHO 2008 classifications of lymphomas. Median interval between first transplantation and diagnosis was 85 months. Fifty-seven percent of patients had a kidney transplant. Twenty-four cases (68.6%) were classified as primary cutaneous T cell lymphoma (CTCL) and 11 (31.4%) as primary cutaneous B cell PTLD. Mycosis fungoides (MF) was the most common (50%) CTCL subtype. Ten (90.9%) cutaneous B cell PTLD cases were classified as EBV-associated B cell lymphoproliferations (including one plasmablastic lymphoma and one lymphomatoid granulomatosis) and one as diffuse large B cell lymphoma, other, that was EBV-negative. Sixteen (45.7%) patients died after a median follow-up of 19.5 months (11 [68.8%] with CTCL [6 of whom had CD30+ lymphoproliferative disorders (LPD)] and 5 [31.2%] with cutaneous B cell PTLD. Median survival times for all patients, CTCL and cutaneous B cell PTLD subgroups were 93, 93, and 112 months, respectively. Survival rates for MF were higher than those for CD30+ LPD. The spectrum of primary CTCL in organ transplant recipients (OTR) is similar to that in the general population. The prognosis of posttransplant primary cutaneous CD30+ LPD is worse than posttransplant MF and than its counterpart in the immunocompetent population. EBV-associated cutaneous B cell LPD predominates in OTR.
B cell lymphoma
cutaneous B cell lymphomas
cyclophosphamide, doxorubicin, vincristine and prednisolone
cutaneous T cell lymphomas
epithelial membrane antigen
Groupe Français d'Etude des Lymphomes Cutanés
latent nuclear antigen
large T cell lymphoma
not otherwise specified
organ transplant recipients
primary cutaneous lymphoma
prednisolone, mitoxantrone, cyclophosphamide, etoposide, bleomycin and vincristine
posttransplant lymphoproliferative disorders
squamous cell carcinoma
Skin Care in Organ Transplant Patients, Europe
Société Française de Dermatologie
Statistical Package for Social Sciences
T cell lymphoma.
Posttransplant lymphoproliferative disorders (PTLD) constitute the second most common form of neoplasia in adult solid organ transplant recipients (OTR) [1-3]. Most PTLD are reported to be of B cell origin and are positive for EBV [1, 3, 4]; they usually present in extranodal sites [3, 4], and represent the leading cause of cancer-related death and graft loss .
The term ‘primary cutaneous lymphoma’ (PCL) encompasses cutaneous T cell lymphomas (CTCL) and cutaneous B cell lymphomas (CBCL) presenting in the skin without extracutaneous disease at the time of diagnosis . In contrast to PTLD presenting in noncutaneous extranodal sites, PTLD with cutaneous presentation are rare [6, 7]. Furthermore, they seem to present with a different subtype distribution (mostly of B cell origin) and natural course (better and worse outcomes for B cell PTLD and T cell PTLD, respectively) compared to primary CBCL and CTCL in immunocompetent populations [8-10]. Because fewer than 100 cases are reported in the literature, the clinical and histological features and prognosis of primary cutaneous PTLD are not well characterized. The present study was undertaken in order to characterize the clinical and histological features and natural course of primary cutaneous PTLD using the latest WHO-EORTC  and WHO 2008  lymphoma classifications.
This was a retrospective, international, multicenter study involving 18 specialist transplant dermatology clinics across Europe within the ‘Skin Care in Organ Transplant Patients, Europe’ (SCOPE) Network and the French Group of Skin and Organ Graft (Groupe Peau et Greffe d'Organes) and the Cutaneous Lymphoma Study Group (Groupe Français d'Etude des Lymphomes Cutanés-GFELC) of the French Society of Dermatology (Société Française de Dermatologie-SFD). Data were acquired with a questionnaire (provided as Supplementary Material) between September 2008 and July 2011 and by collecting the total number of OTR transplanted at each center in order to calculate the incidence of primary cutaneous PTLD.
Paraffin blocks or unstained sections of diagnostic biopsies together with clinical photographs were submitted. Each case was reexamined histopathologically (W. K.) and (re)-classified according to the WHO-EORTC classification for PCL  or the WHO 2008 classification of lymphomas . Immunostaining for CD30, MUM-1, CD138, bcl-2, bcl-6 and HHV-8-related latent nuclear antigen (LANA), in situ hybridization for immunoglobulin kappa and lambda light chains as well as for EBV-encoded RNA (EBER) in cutaneous B cell PTLD was performed where required.
Statistical analyses were performed with the Statistical Package for Social Sciences 17.0 (SPSS, Inc, Chicago, IL). Quantitative variables (means ± SD) were compared between groups using the nonparametric Mann–Whitney U-test. Overall survival (OS) was calculated from the date of histologically confirmed diagnosis until the patients' death or the latest follow-up without event. Survival curves were calculated according to Kaplan and Meier. The curves were compared by log-rank testing. p-Value <0.05 was considered significant.
Data from 35 OTR with primary cutaneous PTLD were collected from 13 centers (20 cases from France [Paris (2 centers), Lyon, Clermont-Ferrand, and Amiens], 5 cases from United Kingdom [London and Oxford], 3 cases each from Austria [Vienna] and Switzerland [Zurich and Lausanne], 2 cases from Belgium [Brussels], 1 case each from Italy [Padua] and Turkey [Ankara]). Five additional centers (Netherlands [Leiden], Ireland [Dublin], Spain, [Barcelona], Norway [Oslo], and The Czech Republic [Pilsen]) declared no OTR with primary cutaneous PTLD in their records.
The demographic characteristics, allograft type and immunosuppressive drug regimens of the patients, the median interval between the first transplantation and diagnosis of primary cutaneous PTLD and the median follow-up period after the diagnosis are shown in Table 1 and Supplementary Table S1.
|All PTLD||T cell PTLD (n = 24)||B cell PTLD (n = 11)||p-Value|
|Male sex, n (%)||27 (77.1)||19 (79.2)||8 (72.7)||>0.05|
|Mean age at diagnosis of PTLD, years||57.5||57.5||57.4||>0.05|
|Median interval between first transplant and diagnosis of PTLD (months)||85||114.2||85.9||>0.05|
|Median follow–up period (months)||27||28.5||10|
|Allograft type, n (%)|
|Kidney||20(57.1)||17 (70.8)||3 (27.3)|
|Heart||8 (22.9)||4 (16.7)||4 (36.4)|
|Lung||3 (8.6)||2 (8.3)||1 (9.1)|
|Kidney and pancreas||2 (5.7)||–||2 (18.2)|
|Kidney and lung||1 (2.9)||1 (4.2)||–|
|Heart and lung||1 (2.9)||–||1 (9.1)|
|EBV DNA/RNA (tumor)3||70.6||16.6||90.9|
|AK/Bowen's disease||5 (14.3)||2 (8.3)||3 (27.3)|
|Cutaneous SCC||10 (28.6)||4 (16.7)||6 (54.5)|
|BCC||8 (22.9)||5 (20.8)||3 (27.3)|
|Adnexal carcinoma||1 (9.1)||–||1 (9.1)|
|Hidrocystoma||1 (9.1)||1 (4.2)||–|
|B cell PTLD following T cell PTLD||1 (9.1)||1 (4.2)||–|
|ATLL (nodal)||1 (2.9)||1 (4.2)||–|
|Lung adenocarcinoma||1 (2.9)||1 (4.2)||–|
|Cerebral EBV–negative B cell PTLD||1 (2.9)||1 (4.2)||–|
|EBV-associated B cell PTLD (renal allograft)||1 (2.9)||1 (4.2)||–|
|B cell PTLD (nodal)||1 (2.9)||1 (4.2)||–|
|Bladder carcinoma||1 (2.9)||1 (4.2)||–|
|B cell PTLD (lungs)||1 (2.9)||–||1 (9.1)|
|Colonic adenoma||1 (2.9)||–||1 (9.1)|
|Alive||19 (54.3)||13 (54.2)||6 (54.5)|
|Without disease||13 (37.1)||8 (33.3)||5 (45.5)|
|With disease||6 (17.1)||5 (20.8)||1 (9.1)|
|Kidney||10 (62.5)||8 (72.7)||2 (40)|
|Lung||3 (18.8)||2 (18.2)||1 (20)|
|Heart||2 (12.5)||1 (9.1)||1 (20)|
|Heart and lung||1 (6.3)||–||1 (20)|
|Of PTLD||10 (28.6)||7 (29.2)||3 (27.3)|
|Of unknown or other cause||6 (17.1)||4 (16.7)||2 (18.2)|
Based on clinical, histologic, immunophenotypical and genotypic features, 24 patients (68.6%) were classified as primary CTCL and 11 (31.4%) as primary cutaneous B cell PTLD. In all patients, any organomegaly or staging procedures including blood tests, radiologic imaging tests and lymph node biopsy (if required) were negative when they had been first diagnosed with cutaneous PTLD (TNM classification of the patients are shown in Supplementary Table S1). In the CTCL group, mycosis fungoides (MF) along with its variants (eight classic, and three folliculotropic and one folliculotropic and syringotropic MF) was the most common entity, accounting for 50% of all CTCL and 34.3% of all primary cutaneous PTLD. Primary cutaneous CD30+ lymphoproliferative disorders (LPD; eight cases of CD30+ anaplastic large T cell lymphoma [LTCL] and one case of lymphomatoid papulosis [LyP]) were the second most prevalent group, accounting for 37.5% of all CTCL and 25.7% of all primary cutaneous PTLD. Primary cutaneous peripheral T cell lymphoma (TCL), not otherwise specified (NOS), Sézary syndrome (SS) and HTLV-1-associated adult T cell leukemia/lymphoma (ATLL) (one case of each) were also observed.
Regarding primary cutaneous B cell PTLD (11 cases; 31.4% of all PTLD), 10 cases (90.9% of all B cell PTLD) were classified as EBV-associated B cell lymphoproliferations (including plasmablastic lymphoma [PL] and lymphomatoid granulomatosis [LG] [one case of each]) and one as diffuse large B cell lymphoma, other, that was EBV-negative.
Primary cutaneous T cell posttransplant lymphoproliferative disorders
Seven patients (87.5%) with classic MF presented with infiltrated plaques, and one with papules. The trunk and upper and lower extremities were commonly involved, followed by the buttocks and the face (Supplementary Figure S1).
Plaques (two cases), comedo-like lesions (two cases), localized alopecia (two cases) and follicular keratotic papules (two cases) were observed in patients with folliculotropic MF. They were located on the trunk, upper or lower extremities, or the buttocks (Supplementary Figure S1).
CD30+ lymphoproliferative disorders
All eight patients with CD30+ anaplastic LTCL presented with typical nodular and/or tumoral or plaque lesions, ulcerated in three patients. The lesions were located on the lower extremities (four cases), the upper extremities, the face, the buttocks (one case of each) and the trunk (two cases). Nodules on the neck and upper extremities were observed in one patient with LyP (Supplementary Figure S1).
One patient with ATLL presented with eczematous dermatitis and papules. The patient with SS had erythroderma, plaques and tumors. One patient with primary cutaneous peripheral TCL, NOS had a solitary plaque (Supplementary Figure S1).
Primary cutaneous B cell posttransplant lymphoproliferative disorders
Five of ten patients with EBV-associated B cell lymphoproliferation had one or multiple nodules, while one had a solitary tumor, one had an area of ulceration and one had a single plaque. The lesions were located on the legs, the face, the oral mucosa and the scalp (three, two, two and one patient(s), respectively). The patient with LG had erythroderma, plaques, nodules and ulcerations on her trunk and lower limbs. The patient with PL had nodules and plaques on his legs, and the one with diffuse large BCL, other, presented with a nodule on his arm (Supplementary Figure S2).
Viral status and clonality
Of 24 patients in whom EBV serology was investigated, 21 (87.5%) were EBV-seropositive. Data regarding EBV seroconversion were unavailable. EBV was sought in the tumor by in situ hybridization or PCR in 17 cases; EBV RNA or DNA was found in 10 EBV-associated B cell lymphoproliferations including one LG and one PL (90.9% of all B cell PTLD cases), and one CD30+ anaplastic LTCL (viral RNA or DNA was sought in five CD30+ LPD cases) (Table 1 and Supplementary Table S1). CMV serology was positive in 19 of 25 (76%) patients (12 CTCL and 7 B cell PTLD cases). The identical nucleotide sequence of the most variable viral region of HHV-8 was found in the skin lesions of both case 19 and another patient with secondary cutaneous non-Hodgkin's lymphoma and Kaposi's sarcoma who had also received an allograft from the same donor as case 19 (data not shown). Other than the ATLL case, HTLV-1 was also detected immunohistochemically in the tumor of a patient with diffuse large BCL, other.
Most (88.9%) of the tumors had a clonal T and/or B cell population while the remaining tumors were polyclonal (Table 1 and Supplementary S1).
Thirty-three biopsy specimens were available for study. Classic and folliculotropic MF cases (cases 1–8 and 9–12, respectively) showed the characteristic features as in immunocompetent individuals (follicular mucinosis was also observed in cases 10 and 12 and additional syringotropism in case 10). The intraepidermal lymphocytes expressed CD3 and CD4, and partially co-expressed CD4 and CD8 in cases 6 and 10.
In the primary cutaneous CD30+ LPD group, primary cutaneous anaplastic LTCLs (cases 13–17, 19 and 20) showed dense cohesive infiltrates of pleomorphic and anaplastic large lymphoid cells. Neither numerous neutrophils/eosinophils nor angiocentric growth were observed. CD30 was expressed by more than 75% of tumor cells. All anaplastic LTCL cases were negative for ALK-1/p80 and epithelial membrane antigen (EMA), except for case 15, that was EMA+ and harbored EBER. The LyP case (case 21) showed clusters of large anaplastic CD30+ tumor cells admixed with few neutrophils and eosinophils.
ATLL (case 24) displayed prominent epidermotropism of medium to large lymphocytes with nuclear atypia. Tumor cells were CD4/CD25+. Cutaneous peripheral TCL, NOS (case 23) contained small- to medium-sized lymphocytes with atypical nuclear contours expressing CD4, CD8, TIA-1, granzyme B and perforin.
B cell PTLD contained dense diffuse or nodular monomorphous infiltrates of centroblastic, immunoblastic or plasmablastic cells and often contained numerous apoptotic tumor cells. In EBV-associated B cell lymphoproliferations (cases 25–30, 32, 33), plasmablastic cells predominated and showed a high proliferation rate (at least 25%; cases 25, 30 and 35). Case 33 showed features consistent with LG, but immunohistochemistry and artifactual changes of the tissue did not allow precise categorization. In most cases, tumor cells almost consistently expressed CD20 and/or CD79a as well as MUM-1.
At the latest follow-up, 19 of 35 (54.3%) patients were alive with a median follow-up time of 42 months (range, 2–178); 6 of 19 (31.6%) patients still had cutaneous PTLD while 13 (68.4%) were in complete remission.
Primary cutaneous T cell posttransplant lymphoproliferative disorders
Reduction and/or discontinuation of one or several immunosuppressive agent(s) was the initial treatment approach in 23 (65.7%) patients, along with switching to (11.4%), or addition of (5.7%) rapamycin or everolimus. Fourteen of 23 patients had cutaneous T cell PTLD (5 with classic MF and 6 with CD30+ anaplastic LTCL, and one each with folliculotropic MF, SS and peripheral TCL, NOS). Reduction, discontinuation and/or changes of immunosuppression was the sole treatment initially in three patients with classic MF (relapse was observed in two patients and partial remission in one patient), three patients with CD30+ anaplastic LTCL (lymph node involvement developed in two, and relapse in the other), and in one patient with peripheral TCL, NOS (relapse developed).
In addition to changes in immunosuppressive therapy, classic MF (except one patient) patients and one folliculotropic MF patient were also treated with single or multiple skin-directed therapies (topical corticosteroids, mechlorethamine and/or PUVA). Three of the eight classic MF patients died of bacterial pneumonia, severe pulmonary fibrosis or unknown reasons. No obvious difference in treatment modalities was noted between the patients who died and those who were alive at the latest follow-up. The SS patient initially received chlorambucil and etretinate, and cyclophosphamide, doxorubicin, vindesine and bleomycin when B cell PTLD occurred in the lymph nodes; he eventually died of lymphoma.
The case with LyP (case 21) remained in complete remission with topical corticosteroids. Surgical excision was initially performed in four of eight patients with CD30+ anaplastic LTCL, radiotherapy in six of eight, and mono (methotrexate)- or multiagent chemotherapy (CHOP or cyclophosphamide, epirubicin, vindesine and prednisolone) in seven of eight after disease progression or systemic involvement. Two patients were alive without lymphoma at the latest follow-up (20 and 27 months) while six had died from lymphoma (four patients), lymphoma and systemic aspergillosis (one patient) or heart failure (one patient).
Switching to (or addition of) mTOR inhibitors was preferred in four patients with classic MF and one patient with folliculotropic MF; one with classic MF (case 1) died of bacterial pneumonia; three with classic MF were alive with PCL and the one with folliculotropic MF was in complete remission at the latest follow-up.
Primary cutaneous B cell posttransplant lymphoproliferative disorders
In 8 of 11 patients, the immunosuppressive therapy was modified at the time of diagnosis. In six patients, multiagent chemotherapy was given initially, and in two patients after relapse (CHOP in five and PMitCEBO in three, and additional methotrexate in two patients). Along with multiagent chemotherapy, five patients were treated with rituximab initially or after relapse. Surgical excision was initially performed in five patients and in one patient also after relapse. Radiotherapy as initial treatment was given to two patients. Five B cell PTLD patients died, three of progression or systemic involvement of PTLD and two of sepsis or an unrelated (unknown) cause. At the latest follow-up, five patients were in complete and one in partial remission. The immunosuppressive regimens were similar in patients who died or were alive at the latest follow-up, except for case 25 who had been switched to sirolimus and was in complete remission at the latest follow-up.
Sixteen (45.7%) patients (11 and 5 of whom had CTCL and cutaneous B cell PTLD, respectively) died after a median follow-up of 19.5 months (range, 3–131). Of those, 62.5% had a kidney transplant (Table 1). The overall mortality rates for CTCL and cutaneous B cell PTLD were similar (45.8% and 45.4%, respectively). Median survival times for all cutaneous PTLD patients, CTCL and B cell PTLD subgroups were 93, 93 and 112 months, respectively.
The OS rates of all patients at 1 and 5 years after diagnosis were 72% and 59%, respectively (Figure 1A). The OS rates of the CTCL subgroup at 1 and 5 years after diagnosis were 77% and 60%, respectively, while those of the B cell PTLD subgroup were 60% at both 1 and 5 years after diagnosis. Combined OS rates of the classic and follicular MF were higher than those of the CD30+ LPD (log rank; p = 0.037, Figure 1B).
PTLD comprise a spectrum ranging from usually EBV-driven, mostly B cell polyclonal proliferations to B- and T cell lymphomas indistinguishable from their counterparts occurring in immunocompetent individuals . All primary cutaneous T cell PTLD in our series showed the clinical and histological features of classic CTCL in the general population, whereas the primary cutaneous B cell PTLD comprised 10 cases of EBV-associated B cell lymphoproliferations including PL and LG (one case of each), and one case of diffuse large B cell lymphoma, other, that was EBV-negative. Seven patients (cases 12, 13, 17–19, 22 and 33) had been reported previously [12-18]. The relative proportions of T cell (68.6%) and B cell (31.4%) PTLD in this series are similar to those of the Dutch and Austrian registries for PCL in the general population . According to the Cincinnati Transplant Tumor Registry, most PTLD are of B cell origin or, more rarely, T cell proliferations . The distribution of cutaneous T cell and B cell PTLD in this study contrasts with previous reports of PTLD with isolated skin involvement [6, 7]. The relatively few primary EBV-associated B cell PTLD might result from underreporting of cases because of preemptive EBV monitoring entailing rituximab therapy.
In the general population, MF is the most common type of CTCL accounting for almost 50% of all PCL . Along with its variant, folliculotropic MF, it was also the most frequent CTCL subtype observed in our series accounting for 50% of all CTCL and 34.3% of all cutaneous PTLD. This contrasts with a recent review article where CD30+ primary anaplastic LTCL was noted as the most common subtype . Our patients with classic MF had a 5-year OS rate of 66% whereas the OS rate of limited patch/plaque-stage MF in the general population is not impaired . In the general population, folliculotropic MF is uncommon and has a worse prognosis than classic plaque-stage MF [19, 20]. In our series, four patients had folliculotropic MF, suggesting a relatively high frequency (11.4%) of this entity among OTR. All were alive with a median follow-up of 87 months with three being in complete remission, suggesting a rather indolent clinical course of folliculotropic MF in OTR. Unlike most reported patients with follicular MF , our patients did not have head and neck involvement, which might explain their favorable outcome.
CD30+ LPD was the second most common CTCL subtype (37.5% versus 30% of all CTCL in the general population ). In contrast to the usually favorable prognosis with a disease-specific 10-year survival exceeding 90% in the general population , the prognosis seemed poor in OTR; indeed, six of nine (67%) OTR with CD30+ LPD died during follow-up, five of whom of lymphoma progression. Recently, a worse outcome was reported for a subset of primary cutaneous anaplastic LTCL with extensive limb involvement [13, 21]. Of our five patients with CD30+ LPD who died of lymphoma, three had extensive limb disease. We believe that OTR with CD30+ LPD should be treated more aggressively than immunocompetent patients .
Contrary to previous reports [6, 7], the proportion of primary cutaneous B cell PTLD (31.4%) was lower than that of primary cutaneous T cell PTLD. The prognosis of cutaneous B cell PTLD limited to the skin is likely to be better than that of the systemic forms [6, 10, 23]; however, five of our 11 cases with primary cutaneous B cell PTLD had a fatal outcome. We also encountered some rare lymphoma variants, namely ATLL, PL, LG, and peripheral TCL, NOS (one case of each).
OTR receiving calcineurin inhibitors are at high risk of developing PTLD [3, 24]. The mTOR inhibitors, namely sirolimus and everolimus inhibit angiogenesis and tumor growth . The conversion from calcineurin to mTOR inhibitors (or the addition of mTOR inhibitors) is beneficial in SCC of the skin . Five of six OTR in whom this conversion was performed were alive at the latest follow-up.
PTLD are more common after heart and lung transplantation than after kidney or liver transplantation . Consistent with previous reports of primary cutaneous PTLD [8, 17, 23]; however, 57.1% of our cases developed the disease after kidney transplantation. On the other hand, cardiothoracic transplantation seems to be overrepresented in our cohort, which supports the previously published data . The period of highest risk for systemic PTLD is early posttransplant (typically the first year) [1, 3], whereas the median interval between first transplant and diagnosis of cutaneous PTLD was 7 years in our cohort.
Retrospective and multicenter study designs were the limitations of this study. Conclusions regarding the outcome of different primary cutaneous PTLD subtypes cannot be drawn with certainty as our patients were followed in different transplant centers and had received different immunosuppressive regimens and lymphoma treatment. Also, disease-specific survival could not be calculated because of the unknown definitive cause of death in two patients. We could not calculate the overall incidence rate of primary cutaneous PTLD, as the data regarding the total number of OTR could not be obtained from all centers. However, we calculated the incidence rates of primary cutaneous PTLD from two main contributing centers, Paris and Lyon, France: 7.5 primary cutaneous PTLD/1000 total PCL/year for the years 2001–2010 (date of diagnosis; GFELC data, unpublished), and 0.7/1000 solid OTR (excluding intestinal-transplant patients)/year for the years 2007–2010 (date of organ transplantation) (Rapport Annuel de l'Agence de la Biomédecine 2010, http://www.agence-biomedecine.fr).
This case series suggests that primary cutaneous T cell PTLD are more common than primary cutaneous B cell PTLD. MF still seems to be the most common form of posttransplant primary CTCL, followed by CD30+ LPD, indicating that the spectrum of primary CTCL in OTR is similar to that in the general population. However, the excellent prognosis associated with exclusively cutaneous form of the CD30+ anaplastic LTCL in the general population apparently does not apply to its posttransplant counterpart. The spectrum of primary cutaneous B cell PTLD differs significantly from CBCL in the general population, with a predominance of EBV-associated lymphoproliferations.
We are indebted to members of GFELC study group, including Martine Bagot, Michel D'Incan, Catherine Lok, Olivier Dereure, Saskia Oro and Groupe Peau et Greffes d'Organes on behalf of the Société Française de Dermatologie (SFD). We also thank Dr. Murat Durdu and Gökhan Ekinci for helping to prepare the tables and figures.
D.S. developed the retrospective study protocol, collected and analyzed the data of the study cases and primarily wrote the paper; all authors except E.D. participated in subject enrollment and/or critiquing the paper; E.D. performed the statistical analyses and W.K. re-classified the study cases histopathologically. G.F.L.H. served as senior author, participated in subject enrollment and revised the paper.
The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.