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71 NMMJ | Volume 5 | Number 2 | July-December 2024
Nepal Mediciti Medical JournalNepal Mediciti Medical Journal
Acharya Shoshan1*, Aryal Gopi2 Basnet Sunila3 Rana Reena4, Pandey Kricha5, Thakur Nikki6
Department of Laboratory Medicine and Pathology
Nepal Mediciti Hospital, Bhaisepati, Lalitpur, Nepal
Castleman disease: A single-center case series in
Nepal Mediciti Hospital
BACKGROUND
In 1954, Castleman Disease (CD), was rst described and is also known as angiofollicular lymph node hyperplasia or giant
lymph node hyperplasia . Among many sites where lesion occurs, commonest is in the thorax (60%), abdomen (11%), neck
(14%), and axilla (4%)
MATERIALS AND METHOD
We analyzed ve cases of Castleman disease we received in Nepal Mediciti during ve-year period from 2020 to 2024.
Demographics, clinical variables, anatomical site, centricity, histopathology, immunochemistry, and surgical approach were
reviewed.
RESULTS
Among ve cases, anatomical location of two cases from retroperitoneum, two from inguinal region and one is from cervical
lymph node. Three cases were male and two were female. Age group of these ve cases shows three were adult and two were
children. All of them underwent surgical resection and under continuous follow up. One of the cases from retroperitoneum had
got recurrence.
CONCLUSION
Castleman disease is a diagnosis of exclusion. Case should be evaluated on the basis of proper clinical ndings, blood
parameters, HIV and HHV-8 test, imaging along with biopsy and IHC. Lymphoma and Kaposi sarcoma may mimic on radiology
and histologically with Castleman disease.
KEYWORDS
Unicentric Castleman disease, Hyaline vascular, Lymphoma
ABSTRACT
*Corresponding Author |
Dr. Shoshan Raj acharya
Email: acharyashoshan6@gmail.com
Department of Laboratory Medicine and Pathology,
Nepal Mediciti Hospital, Sainbu, Lalitpur, Nepal
This work is licensed under a Creative
Commons Attribution 4.0 Unported License.
Case Report
72
NMMJ | Volume 5 | Number 2 | July-December 2024
Castleman disease: A single-center case series | Case Report
INTRODUCTION
In 1954 , Castleman Disease (CD), was rst described and
is also known as Angio follicular lymph node hyperplasia or
giant lymph node hyperplasia1. Among many sites where
lesion occurs, commonest is in the thorax (60%), abdomen
(11%), neck (14%), and axilla (4%).2 Pathologically it can be
classied as hyaline vascular type (HV-CD), plasma cell type,
mixed type, and human herpes virus (HHV)-8 associated
Castleman disease.3 Surgery is the primary treatment and
has good long-term prognosis. Multicentric Castleman
Disease (MCCD) is a more serious systemic condition, often
associated with constitutional symptoms. Exaggerated
systemic inflammatory response secondary to “Cytokine
storm” involving Interleukin-6 (IL-6) may cause multi-organ
dysfunction4. Most important the histopathological features
encountered in the various forms of Castleman disease are
diverse, and for the most part, lack specicity, because they
are seen to varying degrees in different clinical variants of
Castleman disease, and in reactive (autoimmune/infectious)
and malignant (lymphoma) contexts.5 POEMS syndrome is a
paraneoplastic syndrome. The important features, other than
those in its previously listed acronym, include papilledema,
extravascular volume overload, sclerotic bone lesions,
thrombocytosis, elevated vascular endothelial growth factor
(VEGF), and abnormal pulmonary function. TAFRO syndrome
is an acute or subacute systemic inflammatory disorder
characterized by the conditions previously listed in the
acronym. Of note, the anasarca includes pleural effusion and
ascites and the organomegaly includes hepatosplenomegaly
and lymphadenopathy.6
After literature review, we analyzed all reported cases
of association CD-NHL and CD-HD. NHL is more often
associated with multicentric CD, its diagnosis being
concurrent with CD diagnosis or occurring within 2 years.
B-NHL is predominant (71%), and mantle cell lymphoma
represents 40% of these B-NHL cases.7 Incidence of CD
based of anatomical location sites based on literature
review. Table (1.1)(8). Surgical removal of a unicentric mass
of hyaline-vascular or hyaline-vascular/plasma cell type
is curative. Partial resection, radiotherapy, or observation
alone may avoid the need for excessively aggressive therapy.
Patients with multicentric disease, either hyaline-vascular or
plasma cell type, do not benet from surgical management
and should be candidates for multimodality therapy. 8
In one study, the incidence of Kaposi's-sarcoma- associated,
HHV 8-related non-Hodgkin's lymphoma in a cohort of HIV-
positive patients with multicentric Castleman’s disease was
15-fold higher than the incidence in the general HIV-positive
population. 9
Collectively, we were involved in the diagnosis of 5 patients
with Castleman's disease. Among ve patients three were
treated in Nepal Mediciti Hospital and two were treated in
another center. All 5 patients had the localized form and the
hyaline-vascular type of Castleman's disease as determined
by surgical lymph node biopsy. Follow-ups were conducted by
telephone calls. In this article, we describe these 5 cases, and
we review the entire course of Castleman's disease, including
its clinical features at presentation, its histopathological
characteristics, and the diagnostic and treatment challenges
it poses.
CASE REPORTS
Patient 1
A 46-year-old woman presented with a 2-year history of a
persistent, enlarging left lateral neck mass. The patient also
complained of right-sided neck numbness and tingling. The
remainder of her medical history was unremarkable. On
magnetic resonance imaging (MRI) the mass measured 4.2
x 2.2 cm. Fine-needle aspiration cytology was not done. Core
biopsy was performed which shows lymphoid follicles with
interspersed sclerotic vessels. IHC ndings were negative
for diagnosis of lymphoma. The patient was referred to the
surgery department and excision biopsy was performed.
Patient 2
A 53-year-old male presented with enlarged lymph node in
cervical region for one month associated with pain. CT-Scan
shows homogeneously enhancing and necrotic lymph node
with septal thickening and ground glass opacities. Excision
biopsy was received which shows greyish brown lobulated
surface. On Microscopic examination shows follicular
architecture of lymphoid architecture is replaced by diffuse
proliferation of lymphoid cells, with concentric arrangement
of dilated vessels with interspersed plasma cells. Differential
diagnosis of lymphoproliferative neoplasm and Castleman
disease was made. IHC ndings ruled out lymphoproliferative
neoplasm.
Patient 3
A 13-year-old male with asymptomatic heterogeneous
mass in mesentery in right iliac fossa with minimal internal
vascularity. USG features suggestive of conglomerate
lymph node with differential diagnosis of lymphoma
and tuberculosis. Core biopsy performed from mass
microscopically shows diffuse sheets of plasma cells along
Table 1.1 Incidence of Castleman disease by location
Location Percentage of cases
Thorax 60
Neck 14
Abdomen 11
Axilla 04
Other 11
73 NMMJ | Volume 5 | Number 2 | July-December 2024
with thick-walled blood vessels with areas of hemorrhage
and brosis. Diagnosis was conformed as plasma cell variant
of Castleman disease by IHC.
Patient 4
A 74-year female with previously biopsy proven case of
Castleman disease presented with enlarged lymph node
in hypogastrium and multiple skin lesions. USG-features
suggestive of recurrence of Castleman disease with
differential of conversion to lymphoma. On microscopic
examination there is diffuse component of polymorphous
population of lymphoid cells coursed by conspicuous
vascular proliferation with hyalinized wall and prominent
endothelial vessels. Plasma cells are noted but not in sheets.
Final diagnosis of hyalinized vascular type Castleman
disease was made on H and E examination
Patient 5
A 24-year old female with left retroperitoneal mass. CECT-
features suggestive of extra- adrenal pheochromocytoma.
Excision biopsy microscopically shows lymphoid follicles
with thickened mantle zone. Sclerotic arterioles penetrate
most of the thyroid follicles. Nodular inltrate of lymphocytes
surrounded by broad band of collagen is seen at places.
Scattered large cells with vesicular nuclei were also identied.
Microscopic differentials were Castleman lymphadenopathy,
diffuse large cell lymphoma and Hodgkin lymphoma
S.N. Age Sex Diagnosis
146 Female Unicentric Castleman disease
253 Male Unicentric Castleman disease
313 Male Unicentric Castleman disease
474 Female Unicentric Castleman disease
524 Female Unicentric Castleman disease
Fig 1. CECT shows enhancing soft tissue density mass
Fig 2. Gross picture showing well circumscribed light grey
soft to rm mass
Fig 3. Microscopic image showing onion skin pattern, sclerotic
vessels entering into germinal center of lymphoid follicle
Fig 4. Microscopic image showing sclerotic vessels with
increased vascularity in lymphoid follicles
Nepal Mediciti Medical Journal
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NMMJ | Volume 5 | Number 2 | July-December 2024
DISCUSSION
1. Etiology
Conditions that result in Castleman disease is associated with
chronic low-grade inflammation, lymphoid-hamartomata’s
hyperplasia, viral infections, abnormal modulation of
cytokines, and angiogenesis. HIV and human herpes
virus (HHV)-8 has also been associated with multicentric
Castleman disease. Advances in diagnosis, classication,
pathogenesis, and therapy are substantial since the original
description of UCD by Benjamin Castleman in 1954.10
2. Pathogenesis
Overexpression of Interleukin (IL)-6 and some epidermal
growth factor receptor is seen on signaling pathways involved
in patient with UCD. FDCs (Follicular dendritic cells role in
lymphocyte trafcking is largely mediated through secretion
of chemokine ligand 13 also known as B lymphocytic
chemoattractant .11
3. Diagnosis
Castleman's disease can pose several diagnostic dilemmas.
Most often it manifests as an asymptomatic, unifocal, soft-
tissue mass without any trademark signs or symptoms.
4. Imaging test
X-ray, CT, MRI, PET scan can allow health care provider to
locate the enlarged lymph node. 12 Vascularity within the
lymphoid follicles can be studied by the imaging technique.
Denite diagnosis of Castleman is always not possible but
differentials can be listed out. In our cases also imaging
technique have listed differentials of paraganglioma and
lymphoma as differentials.
5. Blood parameters
Castleman disease is mostly presented with low red blood
cell count. Thrombocytosis or thrombocytopenia. HHV-8,
test and HIV test must be performed to rule out multicentric
Castleman disease (MCD). We have ruled out MCD in our all
cases.13
6. FNAC
FNAC have been very low helpful in case of diagnosis of
Castleman disease. Differentials of reactive lymphadenopathy
and lymphoma could only be made as in FNAC we see
lymphoid population only. In our cases we have made
reactive lymphadenopathy as diagnosis in cases where we
have performed FNAC.
7. Biopsy
Biopsy is the gold standard for diagnosis of Castleman
disease. Hyperplastic lymphoid follicle with sclerotic blood
vessels entering into germinal center along with twinning
of germinal center is most common histological nding we
have encountered in our cases. IHC markers along with HHV-
8, and HIV test is co- performed to rule out lymphoma and
multicentric Castleman disease, which we have performed in
our cases.
8. Treatment
Corticosteroids, low dose chemotherapy oral etoposide,
cyclophosphamide has been used in most cases. Recent
development of monoclonal antibodies is also been widely
used now. Surgical excision remains the gold standard
followed by chemotherapy.14 MCD and recurrent cases of
UCD should be in close follow up as there is always risk of
conversion into lymphoma.
CONCLUSION
Among ve cases we received, three were female and two
were male. Two among ve were of younger age children. All
of them were diagnosed as UC Castleman disease. So, we
can conclude that Castleman disease can occur in any age,
irrespective of gender and is most common type is UC type.
Castleman disease is a diagnosis of exclusion. Case should
be evaluated on the basis of proper clinical ndings, blood
parameters, HIV and HHV-8 test, imaging along with biopsy
and IHC. Lymphoma and Kaposi sarcoma may mimic
on radiology and histologically with Castleman disease.
Diagnosis of Castleman disease is insufcient we should
separate into HV and PC (HHV8- or HHV-8 +) as they have
different prognosis. We should perform HHV8 IHC on all
cases with plasma cell CD, HHV-8 – (differentiate with
autoimmune disease, IG4 related disease). HHV8+ should be
carefully evaluated for KS and Lymphoma.
Castleman disease: A single-center case series | Case Report
75 NMMJ | Volume 5 | Number 2 | July-December 2024
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