Kaposi’s sarcoma in renal transplantation:Report of three cases

E. Razeghi1, A. Hadadi2, P. Khashayar3 and G. Pourmand4

1Nephrology, 2Infectious Diseases, 3Research and Development Center and4Urology, Urology Research Center, Sina Hospital, Medical Sciences,

University of Tehran, Iran

Kaposi’s sarcoma in renal transplantation

Abstract. Kaposi’s sarcoma (KS) is oneof the most common post transplant malig-nancies. A variety of factors appears to con-tribute to the development of KS includinggenetic factors, sex hormones, immunosup-pression and oncogene viruses. We present 3cases with concurrent KS and cytomegalo-virus (CMV) infection in the first year afterkidney transplantation. The suspicion on KSdue to the skin lesions was confirmed by bi-opsy. The diagnosis of CMV infection wasmade by detecting pp65 antigen in blood. TheKS lesions were limited to the skin in 2 pa-tients, while skin and gastrointestinal tractwere involved in 1 patient. Many factors arereported to be involved in KS development,but the simultaneous occurrence of KS andCMV infection in our three cases suggestedCMV as an inducing factor for KS.

Introduction

It is well established that organ transplant

recipients receiving immunosuppressants

have an increased risk for malignancy devel-

opment [Boubenider et al. 1997].

Indeed, more than one in five patients ex-

periences malignancy within 15 years after

kidney transplantation, this rate rises to more

than two in five patients within 20 years [Lon-

don et al. 1995]. Malignancies related to vi-

ruses occur more often in patients who have

undergone kidney transplantation compared

with the general population [Brunner et al.

1995, Kasiske et al. 2000, London et al.

1995].

Kaposi sarcoma (KS) is one of the most

common post transplant malignancies. An

epidemiological study has shown a 400 -500

fold increase in the incidence of Kaposi sar-

coma in this group of patients compared with

the control subjects of the same ethnic origin

[Bedan et al. 1999].

Several studies have shown that in com-

parison to colorectal and breast cancer, KS is

more prevalent in transplant recipients. It

should be noted that this tumor may be cured

if the immunosuppressants are discontinued

or reduced in this group of patients [Penn

2001].

KS has a multi-centric origin and is char-

acterized by vascular and fibroblastic prolif-

eration [Bedan et al. 1999]. Skin, conjunctiva

or oropharyngolaryngeal mucosa are in-

volved in 58% of transplant patients with KS;

as for visceral disease mainly involving the

gastrointestinal tract, lung and lymph nodes,

they are reported to be present in about 42%

of the patients [Bedan et al. 1999, Penn 2001].

The cause of post transplant KS remains

unknown. Oncogenic viruses of the herpes

type are believed to play an important etiolog-

ical role [Brunner et al. 1995]. In kidney re-

cipients, the definite associating role of other

viruses such as cytomegalovirus, the most

common source of opportunistic infection, is

not yet clear [Moosa 2005].

We present 3 cases of kidney transplant

recipients who developed KS concurrently or

shortly after cytomegalovirus infection in the

first year after transplantation.

Case 1

A 50-year-old man with end stage renal

disease secondary to autosomal dominant

polycystic kidney disease received a living

unrelated renal allograft. The CMV antibody

state prior to transplantation was positive in

both recipient (R+) and donor (D+).

Key words

transplant – Kaposi’s

sarcoma – CMV infec-

tion

Received

June 2, 2008;

accepted in revised form

June 24, 2008

Correspondence to

E. Razeghi, MD

Associate Professor of

Nephrology, Urology

Research Center, Sina

Hospital, Imam

Khomeini St. 11367-

46911, Tehran, Iran

Effatl62@yahoo.com

CaseReport

©2009 Dustri-Verlag Dr. K. FeistleISSN 0301-0430

Clinical Nephrology, Vol. 71 – No. 2/2008 (214-216)

He was prescribed a triple immunosup-

pressive regimen including cyclosporine

(Neoral), mycophenolate mofetil (MMF) and

prednisolone.

Three months after transplantation, the

patient presented with fever, fatigue, weak-

ness and diarrhea. The diagnosis of CMV was

made by detecting PP65 antigen and gan-

ciclovir was prescribed. In the following

month, he developed diffuse reddish blue

plaques and papules on the skin, with no

lymphadenopathy. Biopsy of the skin lesions

confirmed the diagnosis of KS. Thoracic Gal-

lium Scan was negative. Gastrointestinal en-

doscopy and colonoscopy showed Kaposi-

like mucosal lesions which were confirmed

by biopsy.

Cyclosporine and mycophenolate mofetil

were stopped but KS did not regress and so

chemotherapy was started.

Case 2

A 53-year-old man with endstage renal

disease secondary to diabetes mellitus re-

ceived a living unrelated renal allograft. The

CMV state before transplantation was docu-

mented to be R+, D+.

He received an immunosuppressive regi-

men consisting of cyclosporine (Neoral),

MMF and prednisolone. He returned to hos-

pital with diffuse purple skin lesions and con-

stitutional complaints after 5 months. Biopsy

of the lesions confirmed KS and immuno-

histological assay for PP65 confirmed CMV

infection. Thoracic computerized tomogra-

phy and gastrointestinal endoscopy were both

negative. Antiviral therapy was started and

immunosuppressive drugs were reduced.

Recovery to some extent was first re-

ported however the skin lesions reappeared

after a few months. So chemotherapy was

recommended.

Case 3

A43-year-old woman with endstage renal

disease of unknown etiology received a renal

allograft. She received the immunosuppres-

sive drugs including cyclosporine, azathio-

prine and prednisolone. The CMV state was

reported to be R+, D+ before transplantation.

At the 8th month after transplantation, she

presented with weakness, fatigue, thrombo-

cytopenia, anemia and purpuric lesions.

During the necessary work-up, the labora-

tory data supported possible CMV infection

and as a result ganciclovir was prescribed.

One month later, she presented with purple

lesions on the anterior side of both legs. Bi-

opsy of the lesions confirmed KS. Cyclo-

sporine maintenance therapy was reduced to

2 mg/kg/day and radiotherapy was indicated.

After a few months the lesions regressed.

Discussion

Kaposi’s sarcoma secondary to an immuno-

suppressed state was first identified in 1969 in

kidney recipients. Since then, several cases of

KS were reported in patients receiving im-

munosuppressives. This disease was also re-

ported as the most frequent cancer following

kidney transplant in developing countries

[Moosa 2005].

Two histologically characteristic features

of KS are known to be proliferation of

angiomatous lesions and of spindle shaped

cells [Itkura et al. 1990]. The cause of post

transplant KS remains unknown. Some fac-

tors such as genetic predisposition and onco-

genic viruses particularly herpes viruses are

reported to be involved in addition to the im-

munosuppression therapy [Regumey et al.

1998].

Genetic differences are based on ethnical

differences; for instance, compared with the

normal population, HLA-A2 is more frequent

in KS patients of Saudi Arabia because of the

higher prevalence of HHV-8 in this group

[Moosa 2005].

According to epidemiologic, serologic

and geographic studies and the histological

findings, CMV is identified as a risk factor for

Kaposi sarcoma [Itkura et al. 1990]. In an-

other study carried out to reveal the relation

between CMV infection and Kaposi’s sar-

coma in 64 patients with classic, endemic and

epidemiologic KS, CMV -DNA was only

identified in 10 of the patients who had AIDS

and in neither of classic or endemic cases.

This study did not confirm the distribution

and location of infected CMV cells as a major

pathologic stimulant factor for KS. In other

words, similar to other immuno-suppressed

Kaposi’s sarcoma in renal transplantation 215

patients, CMV was identified as an opportu-

nistic infection in these patients [Chakala-

rouski et al. 1992].

In our patients, KS developed concur-

rently or shortly after CMV infection which

was similar to other studies [Seigal et al.

1990].

In a study reactivation of cytomegalovirus

was reported in the serologic tests when KS

was diagnosed [Vlasic-Matas et al. 1994]. It

is possible that CMV infection secondary to

the considerable pharmacological immuno-

suppression was the cause making our pa-

tients more susceptible to develop KS.

In neither of the patients presented in this

article, there was no sign of regression fol-

lowing the immunosuppressive medication.

It is possible that the unresponsiveness of our

patients was due to the severity of disease or

other factors. In addition, the presence of

other factors (particularly HHV8) could

neither be excluded nor discussed in order to

define their hypothetical pathogenic role.

The association of CMV and KS suggests

CMV as an inducing factor in KS. However it

is not possible to completely rule out other

factors especially herpes Type 8 and their

pathologic role. Association of KS and CMV

infection in these three patients suggests the

role of CMV in developing Kaposi sarcoma.

Finally, simultaneous CMV infection as the

most important opportunistic infection indi-

cates the severe immunosuppressive condi-

tion in patients. As a result it is recommended

to check the CMV state in patients with KS

lesions, because the infection is treatable.

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Razeghi, Hadadi, Khashayar and Pourmand 216