Nephrol Dial Transplant (1998) 13: 2373–2376
Nephrology
Dialysis
Transplantation
Case Report
The dialysed patient with both Castleman disease and Kaposi sarcoma
M. R. Narayanan Nampoory, Kaivilayil V. Johny, Chitra Sarkar, Ismail Al-Masry, Nabil Al-Hilali
and Jehoram T. Anim
Department of Medicine and Pathology, Mubarak Al-Kabeer Teaching Hospital and Faculty of Medicine,
Kuwait University, Safat, Kuwait
Key words: angiofollicular lesions; Castleman disease;
dialysis; end-stage renal disease; immunocompromised
state; Kaposi sarcoma; multicentric giant lymph-node
hyperplasia
Introduction
Castleman disease, also known as giant lymph-node
hyperplasia is an unusual form of lymphoproliferative
disorder [1]. Until 1991 there were only 231 cases
reported in the literature [2]. Since then there have
been other reports of Castleman disease occurring as
such or associated with other diseases [3–6 ]. However,
occurrence of Castleman disease in patients with endstage renal disease ( ESRD) has not been reported to
date in English medical literature. Similarly, there have
been no reports of Kaposi sarcoma in patients with
ESRD on regular dialysis treatment. We report the
case of an elderly patient with ESRD on regular
dialysis treatment who concomitantly developed these
two rare conditions: multicentric Castleman disease in
association with Kaposi sarcoma.
Case
MF, a 70-year-old male developed ESRD due to
chronic tubulointerstitial disease. He had been maintained on regular intermittent peritoneal dialysis for 1
year. He remained stable with controlled uraemia and
blood pressure and haemoglobin of 90 g/l (Hct 31%).
He became more anaemic 6 months ago and total
haematological evaluation revealed normal serum B ,
12
folate, iron and ferritin levels. He had no evidence of
bleeding, and stool for occult blood was negative.
Hence he was started on parenteral recombinant
human erythropoietin (rHuEpo) treatment. He did not
respond to rHuEpo in spite of receiving 18 000 units
Correspondence and offprint requests to: Professor K. V. Johny MD
FRCP(C ) FRCP, Chairman, Department of Medicine, Faculty of
Medicine, PO Box 24923, Safat, 13110 Kuwait.
per week for more than 16 weeks. His serum aluminium
and parathyroid hormone levels were normal. Six
weeks ago he had started getting intermittent fever.
All roentogenographic, serological, virological, and
microbiological measures to delineate the cause of
fever failed and he received several courses of empiric
antibiotic treatments.
He was transferred to our unit in view of continuing
fever and severe anaemia. He did not have any specific
symptoms other than fever and severe weakness. A
detailed clinical examination revealed fever (38°C ) and
normal blood pressure and pulse. He was anaemic and
had multiple, raised, purplish and non-tender skin
lesions in hands and legs. He had enlarged, non-tender,
firm and discrete lymph nodes in axillae, submandibular, and inguinal regions. Examination of the patient’s
throat, abdomen, respiratory, cardiovascular, and central nervous systems did not reveal any abnormal
findings. He did not have signs of meningeal irritation,
and optic fundi were normal.
The haematological investigations revealed haemoglobin 5 g%, haematocrit 14.8%, WBC 5700/cm3, platelet 94 000/mm3, positive direct and indirect Coombs
test, erythrocyte sedimentation rate 150 mm in first
hour and reticulocyte 3.2%. Fibrin degradation product (<500 ng/ml ), fibrinogen (4.25 g/l ), prothrombin
time (15.8 s, INR 0.98), partial thromboplastin time
(patient 30 s, control 28 s), bilirubin (18 mmol/l ),
ferritin (179 pmol/l ), folate (29.2 nmol/l ), B
12
(1259 pmol/l ), and serum iron (9.6 mmol/l ) were
normal. A peripheral blood film did not show any
abnormal cells but normocytic normochromic anaemia
and decreased number of platelets. The patient’s liver
function tests were normal and serum globulin was
54 g/l. Detailed microbiological, mycological, and serological studies were repeated, and showed positive
antinuclear factor of 1/40 dilution with negative antiDsDNA and normal complements. Further immunological evaluation revealed polyclonal hypergammaglobulinaemia, positive C-reactive protein, positive
rheumatoid factor, negative antineutrophil cytoplasmic
antibody, and negative infectious mononucleosis heterophil antibody. Anti-RNP and anti-SSA antibodies
were not detected. A test for lupus anticoagulant was
© 1998 European Renal Association–European Dialysis and Transplant Association
2374
(a)
M. R. N. Nampoory et al.
Fig. 2. Photomicrograph of the lymph node showing Castleman
disease. Vascular spaces (arrowheads) with plump endothelial cells
are surrounded by plasma cells in the interfollicular areas of the
lymph node (thin arrows) (H&E×185).
(b)
Fig. 1. (a) Photomicrograph of the skin lesion showing the Kaposi
sarcoma with numerous slit-like vascular spaces in the dermis. The
epidermis is unremarkable (H&E×75). (b) High-power view of the
Kaposi sarcoma lesion showing vascular lumina lined by plump
endothelial cells (arrows). Proliferating spindle cells are seen between
the vascular spaces (H&E×185).
negative, while anticardiolipin antibody (IgG) was
positive (30.7 g/l ). There was decrease in the helper to
suppressor T lymphocyte cell ratio (0.98, normal
1.2–4.7) with increase in helper T cells. The patient’s
CMV IgG was positive at a titre of 1/128, and EBV
IgM was 1/64. He was negative for HIV, hepatitis C,
and hepatitis B virus testing. Roentgenological studies
revealed multiple enlarged retroperitoneal lymph
nodes, while there were no mediastinal masses.
Biopsy of the skin revealed numerous vascular
lumina and slit-like spaces lined by prominent endothelial cells in the dermis ( Figure 1a, b). There was
proliferation of spindle-shaped cells peripheral to the
endothelial cells. The stroma contained extravasated
red cells and haemosiderin pigment. These findings
confirmed the diagnosis of Kaposi sarcoma. Lymphnode biopsy revealed prominent lymphoid follicles with
germinal centres. There was increased vascularity with
proliferation of blood vessels inside the follicles and in
the interfollicular tissue. Sheets of plasma cells were
seen in the interfollicular areas ( Figure 2). These features are characteristic of Castleman disease of the
Fig. 3. Photomicrograph showing a focus of Kaposi sarcoma in the
cortex of a lymph node. Note the proliferation of spindle cells
separated by slit-like spaces (arrowheads) similar to the skin lesion
shown in Fig. 1a. Part of a lymph-node follicle is shown (F )
(H&E×75).
plasma-cell type. In areas of the cortex and capsule of
the lymph node there was proliferation of spindle cells
separated by slit-like spaces containing red cells, while
intervening stroma contained haemosiderin pigment
( Figure 3). These features were similar to those of the
skin biopsy. Based on these findings a diagnosis of
multicentric giant lymph-node hyperplasia (multicentric form of Castleman disease) with foci of Kaposi
sarcoma in the lymph node was made.
Since the diagnosis of Kaposi sarcoma and
Castleman disease was confirmed, an oncologist was
consulted for further management. By this time
the patient’s general condition deteriorated and
he developed severe thrombocytopenia (platelet
11 000/mm3). Hence active supportive measures with
platelet and blood transfusions were undertaken and
chemotherapy was suspended. He expired 7 days after
the diagnosis despite adequate control of anaemia and
uraemia, and other supportive measures.
Castleman disease and Kaposi sarcoma in end-stage renal disease
Discussion
Castleman et al. first described a disorder of hyperplasia of mediastinal lymph nodes with its characteristic
histological picture in 1956 [7]. Since then giant lymphnode hyperplasia has been found in various locations
other than the mediastinum, either multicentric or as
localized [8]. The morphological features of both however are similar. Keller et al. [9] divided the reported
cases into two distinct categories: hyaline vascular type
comprising 91% of the cases and the remaining 9% as
plasma cell type. In our patient with generalized lymphadenopathy, the disease was multicentric and the lymph
node showed increased vascularity and proliferation of
numerous blood vessels inside the follicles (so-called
angiofollicular lesion) and interfollicular tissue. In
addition, sheets of plasma cells were seen in the interfollicular areas. This histological finding thus confirmed the diagnosis of multicentric form of Castleman
disease (multicentric giant lymph node hyperplasia) in
our patient. Chen [10] divided the multicentric form
of Castleman disease into two distinct types, namely
limited multicentric form and generalized form. The
limited multicentric form involves supradiaphragmatic
lymph nodes and is often self-limited with rare recurrences and a prolonged course. The generalized form
is irreversible, with two types of evolution: (i) long
survival up to 18 years with recurrent clinical exacerbations followed by temporary remissions, and (ii) rapid
progression with a fatal outcome. This rapid progressive type of generalized Castleman disease represents
the most severe form of the disease, in which patients
are prone to develop sepsis, opportunistic infections,
and Kaposi sarcoma, as in our patient.
Extrathoracic multicentric form of Castleman
disease are associated with several clinical entities
including heavy-chain disease, membranous, membranoproliferative, and crescentic glomerulonephritis,
temporal arteritis, Hashimoto thyroiditis, myasthenia
gravis, and antierythropoietic factor anaemia that are
highly suggestive of disorders of immune status [8].
Our patient had several features of immunological
disturbances like hypergammaglobulinaemia, Coombspositive anaemia and positive ANA. He had thrombocytopenia which could not be explained by any
infection, drugs, intravascular coagulation or bonemarrow abnormality. So an autoimmune thrombocytopenia seems the most likely possibility. Autoimmunity
is a known aetiological factor for anaemia and thrombocytopenia in these group of patients [10]. There
have been only a few attempts to study the immunological features in Castleman disease. Altered T-cell
function with impaired lymphocyte responsiveness in
mixed lymphocyte cultures and reversed helper to
suppressor T-cell ratio have been reported [8,11,12].
A low T4/T8 ratio in our patient is thus explainable.
A low T4/T8 ratio is regularly seen in patients with
acquired immune deficiency syndrome (AIDS) [8].
AIDS is a recognized cause of Castleman disease. Our
patient, however, did not have AIDS.
2375
Other than advanced age [13], the patient in this
report did not have any predisposing factors. The
immunocompromised state of patients with ESRD on
regular dialysis could possibly form the only immunoregulatory disturbance in our patient predisposing to
the development of Castleman disease. There are only
two previous reports of patients with Castleman disease
requiring dialysis [14,15] which was needed for acute
renal failure due to associated kidney disease.
Kaposi sarcoma is well known to occur in immunocompromised patients like transplant recipients and in
patients with AIDS. We could not find any report of
Kaposi sarcoma developing in patients with ESRD on
regular dialysis treatment in the English medical literature. Our patient had had no immunosuppressive
therapy previously, nor AIDS.
The association of Castleman disease and Kaposi
sarcoma, two rather rare disorders, appears too frequently to be due to chance alone [1,8,13,16 ]. Chen
[10] reviewed the literature of this combination and
found 10 cases including two of his own. Since then
only three more cases have been reported with a
combination of multicentric Castleman disease and
Kaposi sarcoma [8,10,18]. This combination have
never been reported in subjects with ESRD. The salient
clinicopathological features of these 13 reported cases
included elderly age, generalized lymphadenopathy,
anaemia, constitutional symptoms like fever, hepatosplenomegaly and dysproteinaemia [1,8,10]. Our patient
had all the above features. The lymph-node involvement in Kaposi sarcoma in most of the above-reported
cases was focal and only few of the enlarged lymph
nodes were involved, as in the present case. There have
been reports of Castleman disease (multicentric variety)
transforming to malignant lymphoma [17]. In addition
it is reported that when angiofollicular lesions are
noted in AIDS, the patient may be at risk of developing
Kaposi sarcoma [18]. There could be three explanations for these rare diseases occurring together:
(1) Castleman disease occurs in patients with AIDS,
Kaposi sarcoma, and immunosuppression. Production
of (a) vasoproliferative factor(s) in these immunosuppressed or immunodeficient patients could explain
the occurrence of both diseases together [13]. (2) They
may represent related diseases or the same disease with
slightly different manifestations. There have been
reports of elevated CMV antibodies in subjects with
Kaposi sarcoma to support the suggestion that Kaposi
sarcoma could be due to an infective agent [19].
Frequent involvement of lymph nodes in Kaposi sarcoma is well documented. Castleman disease could
represent a slightly different tissue reaction to an
identical causative agent. (3) It is established that
the incidence of Hodgkin disease, non-Hodgkin
lymphoma, and Mycosis fungoides is higher in patients
with Kaposi sarcoma [20]. Castleman disease may also
be viewed as a lymphoproliferative disorder whose
incidence is increased in patients with Kaposi sarcoma.
We prefer the first or second hypothesis, since CMV
and EBV antibodies were positive in our patient.
Further studies on epidemiological, clinical, viro-
2376
logical, immunological, and histological aspects of
these diseases are required, to look for possible transition changes between Kaposi sarcoma and Castleman
disease. It would also help to elucidate the reasons for
the curious occurrence of these two rare diseases
together. In addition, the disease should be suspected
in elderly patients with ESRD who present with prolonged fever, lymphadenopathy, skin lesions, and
anaemia.
Acknowledgements. We wish to express our thanks to Mr George
Varghese for his secretarial assistance in preparing this manuscript.
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Received for publication: 8.1.98
Accepted in revised form: 7.5.98