Respiratory Medicine CME 3 (2010) 235237

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Respiratory Medicine CME

journal homepage: www.elsevier.com/locate/rmedc

Case Report

Reactive lymphoid hyperplasia A case of castlemans disease reviewed

Jarrod Bruce a, *, Brian Goodman b, Patrick Ross Jr. b, Charles Hitchcock c, S. Patrick Nana-Sinkam a
a

Department of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University Medical Center, 201 Davis Heart and Lung Research Institute,
473 West 12th Avenue, Columbus, OH 43210, United States
b
Department of Thoracic Surgery, The Ohio State University Medical Center, N846 Doan Hall, 410 West 10th Ave, Columbus, OH 43210, USA
c
Department of Pathology, The Ohio State University Medical Center, 081 Davis Heart & Lung Research Institute, 473 West 12th Avenue, Columbus, OH-43210, USA

a r t i c l e i n f o

a b s t r a c t

Article history:
Received 5 October 2009
Accepted 30 October 2009

Reactive lymphoid hyperplasia is a common pathological nding from lung biopsy. It is frequently the
original pathologic interpretation from FNA or core biopsies of lesions that are ultimately determined to
be non-neoplastic pulmonary lymphoid disorders. One of these disorders is Castlemans Disease. We
present a case of a 35-year-old male who underwent multiple procedures to diagnose a posterior
mediastinal mass. This was eventually diagnosed as Castlemans Disease. We review the pathology of
reactive lymph node hyperplasia and the spectrum of non-neoplastic pulmonary lymphoid disorders. We
also review the Unicentric hyaline vascular variant form of Castlemans disease.
2009 Elsevier Ltd. All rights reserved.

Keywords:
Solitary lung mass
Castlemans disease
Non-neoplastic pulmonary lymphoid
disorders
Posterior mediastinal mass
Reactive lymph node hyperplasia

1. Introduction
Reactive lymphoid hyperplasia is a common pathologic nding
from ne needle aspirates and core biopsies of peripheral lymph
nodes. It is also a common nding from parenchymal lung and
mediastinal lymph node biopsies. This histological nding should
prompt the clinician to consider the spectrum of non-neoplastic
pulmonary lymphoid lesions. One cause of reactive lymphoid
hyperplasia is Castlemans disease which was the nal diagnosis in
our case. Herein we briey discuss the differential of reactive
lymphoid hyperplasia in the setting of pulmonary lymph node
biopsy and focus on non-neoplastic pulmonary lymphoid disorders.
We also provide a brief review of unicentric hyaline vascular variant
of Castlemans disease (U-HVV).
2. Case report
A 35 year-old Argentinean male was referred to pulmonary
clinic for work-up of an abnormal chest x-ray (Fig. 1). The patient
had a 15-year history of cough productive of brown sputum
without any hemoptysis. The patient immigrated from Argentina
ve years prior to presentation. He reported no exposure to
tuberculosis or placement of a PPD. He worked as a butcher for 15
years and denied smoking. Ten months prior to evaluation he
suffered a clavicular fracture due to a motor cycle accident. At that
* Corresponding author. Tel.: 1 614 293 4919; fax: 1 614 293 5503.
E-mail address: jarrod.bruce@osumc.edu (J. Bruce).
1755-0017/$36.00 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.rmedc.2009.10.005

time, he was noted to have a large posterior mediastinal mass on

chest x-ray. A chest CT revealed a heterogeneous 15  20 cm paraspinal mass (Fig. 2). He underwent a CT guided biopsy using an 18
G core biopsy needle. Pathology results demonstrated a paucity of
normal lung tissue, but prominent lymphoid tissue without
molecular evidence of a B-cell lymphoproliferative disorder.
Preoperative pulmonary function tests (PFTs), serum chemistries,
cell blood count, liver function tests and LDH were normal. A CT of
the abdomen was normal without evidence of lymphadenopathy.
A video assisted thoracoscopic (VATS) biopsy was performed at
which time the mass was noted to be 15  20 cm and extending to
the posterior parietal pleura adjacent to the vertebral bodies and
the esophagus. Grossly, the mass was very vascular and had
a thickened, white peel. Due to the vascularity and concern for
bleeding the patient underwent multiple Tru-cut core biopsies.
Intraoperative frozen section was concerning for lymphoma. His
postoperative course was uncomplicated and he was discharged to
home. Pathology revealed fragments of reactive appearing
lymphoid tissue. Given the lack of denitive diagnosis, location and
size of the mass, it was felt that complete surgical resection would
be required. Therefore, the patient underwent a right thoracotomy
with resection of the mass. Intraoperatively, there was concern for
extension to the T6 neural foramina and a neurosurgical consultation was obtained to assist with dissection of the mass from the
nerve root. The patients hospital course was uncomplicated and he
was discharged to home. Final pathology revealed Castlemans
disease, hyaline vascular type (Fig. 3). Molecular studies did identify a monoclonal T-cell proliferation of unknown signicance.

236

J. Bruce et al. / Respiratory Medicine CME 3 (2010) 235237

Fig. 1. A chest radiograph demonstrates a large posterior mediastinal mass.

3. Discussion
The incidence of reactive lymphoid hyperplasia from needle
guided biopsy of pulmonary parenchyma or thoracic lymphadenopathy has not been reported. In almost all cases this nding
prompts the clinician to obtain further surgical samples to dene
the process. Reactive lymphoid hyperplasia (RLH) has been
described as the benign and reversible enlargement of lymphoid
tissue secondary to antigen stimulus.1 There are four patterns
which can be seen in RLH: Follicular Pattern, Diffuse Paracortical
Hyperplasia, Sinus Histiocytosis and Mixed Pattern.1 Each of these
morphologic patterns has an associated differential diagnosis that
pathologists entertain for the etiology of reactive lymphoid
hyperplasia. Unfortunately, the ability to clearly distinguish these
patterns within the lymph node occurs in less than 10% of cases.1
More often, the primary goal becomes differentiating benign vs.
malignant potential of the tissue. It is often possible using immunohistochemical and molecular analysis to exclude clonality of the
tissue, which in the majority of cases excludes malignancy.2

Fig. 3. 400X magnication of a surgical pathology specimen obtained demonstrates

the characteristic atrophic germinal center surrounded by concentric zones of
lymphocytes. This appearance is referred to as onion-skin which is identied by the
arrow.

When faced with histological ndings of reactive lymphoid

hyperplasia the differential diagnosis can be narrowed to nonneoplastic lymphoid lesions. A table summarizing key features of
these disorders is listed below as Table 1.3,4 The chest physician can
use a basic algorithm to help narrow their differential diagnosis for
this pathological nding. The rst step is to critique the appearance
of the lesion on imaging and from surgical evaluation. If the lesion
has the appearance of a solitary lung mass then the differential can
be narrowed to an intrapulmonary lymph node, Plasma cell granuloma, pseudolymphoma or as in our case, Castlemans Disease.3,4
If the lesion has a poorly dened interstitial or alveolar appearance
then the etiology is typically follicular bronchiolitis or lymphocytic
interstitial pneumonia.3,4
A rare disease, also referred to as giant lymph node hyperplasia,
angiofollicular lymph node hyperplasia and benign lymph node
lymphoma, Castlemans Disease was rst described in 1959 by
Castleman5 and colleagues. A patient presented with fevers and
weakness and was found to have a mediastinal mass. Surgical
resection revealed lymphadenopathy whose characteristic architecture is still used to dene Castlemans disease.
There are three types of Castlemans disease: unicentric
hyaline vascular variant, unicentric plasma cell variant and multicentric plasma cell variant.6 Discussion will be limited to the

Table 1
Characteristics of non-neoplastic pulmonary lymphoid disorders.
Disease

Fig. 2. A CT scan of the chest demonstrated a large heterogeneously enhancing

posterior mediastinal mass.

Common features

Intrapulmonary
Solitary/multiple lung
lymph node
or mediastinal masses
Plasma cell
Solitary lung mass
granuloma
Pseudolymphoma
Solitary lung mass
Castlemans Disease Solitary mass in middle
U-HVV
or posterior mediastinum
Follicular
Bilateral reticular or
bronchiolitis
reticulonodular
inltrates
Lymphoid interstitial Ground glass opacities,
pneumonia
nodular lesions and
rarely cysts

Age at time Constitutional

of onset
signs
(years)
Any age

No

1030

No

3070
2030

No
No

Depends on Yes dyspnea,

underlying obstructive PFTs
cause
4070
Yes cough,
dyspnea, wt loss.

J. Bruce et al. / Respiratory Medicine CME 3 (2010) 235237

unicentric hyaline vascular variant (U-HVV). The multicentric

plasma cell variant has a much different presentation with
systemic symptoms. In U-HVV, the overall number of lymphoid
follicles is increased. The atrophic germinal centers are surrounded by concentric zones of small lymphocytes yielding an
onion-skin appearance6 seen in Fig. 3. Due to the similarity of
the histopathologic pattern to lymph nodes seen in viral or
inammatory disorders, the disease was originally attributed to
an undened inammatory process.5 The current thought is that
the pathogenesis of Castlemans Disease is multifactorial,
involving viral stimulation (HHV-8), angiogenesis and cytokine
(IL-6) production.6 There are no studies demonstrating a clonal
immunoglobin or T-cell receptor gene rearrangement in the
pathologic samples that were dened as CD7 thus enabling the
classication within the spectrum of non-neoplastic pulmonary
lymphoid disorders.
Clinically, the median age of presentation of U-HVV Castlemans Disease is 35 years with no predilection towards either
gender.8 There is typically a single node or chain of lymph nodes
involved. The most common locations are mediastinum, cervical,
abdominal and axillary lymph nodes.8 There are very few reports
of systemic symptoms (<10%) compared to symptoms of fevers,
night sweats that can be seen with the unicentric plasma cell or
the multicentric plasma cell variants. In U-VHH the symptoms
typically reect the compression of the mass against adjacent
structures.
Diagnosis is best achieved by excisional biopsy. Due to the
normal appearance of cells from the lymph node along with the
normal clonality of those cells, ne needle aspirates and core
biopsies typically fail to diagnose U-HVV Castlemans Disease.9 In
one case series, frozen section review revealed the correct diagnosis in only 50% of cases.10 Preserving the architecture of the entire
germinal center and interfollicular zone is paramount. In our case, it
was likely that the architecture was disrupted with the core needle
biopsies in the original two procedures and thus the diagnosis was
unable to be made.
Treatment of U-VHH Castlemans Disease is by surgical excision,
which is almost always curative.11 Due to the size at presentation
and the vascular appearance, surgical resection has been primarily
performed through thoracotomy. The 5 year survival rate is 100%

237

with only a few case reports documenting reoccurrence of U-VHH

Castlemans Disease.10
4. Summary
We provide a basic approach for the chest physician to formulate a differential diagnosis for reactive lymphoid hyperplasia from
lung biopsy. This differential focuses on the non-neoplastic
pulmonary lymphoid disorders. Castlemans disease is part of this
list and should be considered for any asymptomatic mediastinal
masses that are interpreted as reactive lymphoid hyperplasia from
FNA or core needle biopsy.
Conict of interest
The authors have no nancial conict of interest.
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