1648 CASE REPORT DAY ET AL Ann Thorac Surg

CASTLEMAN’S DISEASE ASSOCIATED WITH MYASTHENIA GRAVIS 2003;75:1648 –50

References
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2. Woodruff JM, Chernik NL, Smith MC, Millett WB, Foote FW.
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triton tumor. Cancer 1991;67:1076 –83.
5. Otani Y, Morishita Y, Yoshida I, et al. A malignant Triton
tumor in the anterior mediastinum requiring emergency
CASE REPORTS

surgery: report of a case. Surg Today 1996;26:834 –6.

6. Daimaru Y, Hashimoto H, Enjoji M. Malignant Triton tumors:
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8. Bose AK, Deodhar AP, Duncan AJ. Malignant Triton tumor of
the right vagus. Ann Thorac Surg 2002;74:1227–8.
9. Downey RJ, Mc Cormack P, Lo Cicero J III. Dissemination of
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111:954 – 60. show the lobular pattern with paler areas surrounded by a congested
rim of tissue.

Castleman’s Disease Associated

With Myasthenia Gravis
Jonathan R. S. Day, MRCS, Duncan Bew, MBBS,
Mark Ali, FRCS, Roberto Dina, FRC(Path),
and Peter L. C. Smith, FRCS
Departments of Cardiothoracic Surgery and Pathology,
Hammersmith Hospital, London, United Kingdom
Castleman’s disease presents as a peculiar type of lymph
node hyperplasia. Traditionally, the disease has been
classified on clinical grounds (solitary or multicentric)
and by histologic appearance (hyaline vascular pattern,
plasma cell predominance, or mixed lesions). It is now
increasingly clear that there are different etiologies for
each of these different subtypes. Reported associations
include POEMS syndrome (polyneuropathy, organo-
megally, endocrinopathy, monoclonal gammopathy, and
skin changes), paraneoplastic pemphigus, Hodgkin’s dis-
ease, and follicular dendritic cell sarcoma. We present a
case of Castleman’s disease associated with myasthenia
gravis, the third reported case in the literature. We
discuss Castleman’s disease and review the literature.
(Ann Thorac Surg 2003;75:1648 –50)
© 2003 by The Society of Thoracic Surgeons
Accepted for publication Nov 1, 2002.
Address reprint requests to Dr Day, Department of Cardiothoracic
Surgery, Hammersmith Hospital, Du Cane Rd, London W12 0HS, UK;
e-mail: j.day@ic.ac.uk.
C astleman’s disease is a distinct lymphoproliferative
disorder of uncertain origin, with more than 70% of
lesions being located in the chest. It is commonly asso-
ciated with POEMS syndrome, paraneoplastic pemphi-
gus, Hodgkin’s disease, and follicular dendritic cell sar-
come, but very rarely with myasthenia gravis.
A previously healthy, 39-year-old woman was trans-
ferred to our hospital for thymectomy. She initially pre-
sented with mild speech impairment, a decreased swal-
lowing reflex, and a right-sided ptosis, and had recently
been diagnosed with acetylcholine receptor–positive my-
asthenia gravis. A computed tomogram (CT) and mag-
netic resonance imaging scan (MRI) had been performed
and revealed a mass in the left anterior mediastinum,
thought to be a thymoma. Before transfer, she underwent
60% plasmaphoresis, 5 days of immunoglobulin therapy,
and was started on pyridostigmine 60 mg qid.
At operation, through a median sternotomy, the thy-
mus was removed intact and separate from a mass in the
left side of the chest. The mass was a pinkish nodule (Fig
1) adherent to adjacent structures, particularly the pul-
monary artery, aortic arch, and the lung. Running
through it was the vagus nerve, and over it was the left
phrenic nerve. The left phrenic nerve was identified and
preserved, and the mass was carefully dissected from the
pulmonary artery and the aorta. The left vagus nerve was
electively sacrificed as it ran through the tumor. After
successfully removing the mass and gaining adequate

© 2003 by The Society of Thoracic Surgeons 0003-4975/03/$30.00

Published by Elsevier Science Inc PII S0003-4975(02)04963-9
Ann Thorac Surg
2003;75:1648 –50 CASTLEMAN’S DISEASE ASSOCIATED WITH MYASTHENIA GRAVIS
Fig 2. At high magnification (hematoxylin & eosin, ⫻400), the hya-
line vascular pattern is recognizable. The pale follicles, containing a
central irregular area with a peripheral cuff of lymphocytes, are
readily apparent.
hemostasis, the chest was closed. Postoperative recovery
was uneventful, although as anticipated she developed a
hoarse voice.
Tissue samples were sent for histologic analysis. The
thymus was extensively replaced by fat, surrounding
islands of thymic tissue. A thin peripheral strip of epi-
thelial cells represented the cortex, whereas the medulla
contained Hassall’s corpuscles and a few germinal cen-
ters. Due to the low ratio of thymic-to-fat tissue, the
findings were considered consistent with thymic atrophy
and mild thymitis. Lymph nodes removed together with
the thymus and from the left mediastinum showed vari-
able features of sinus histiocytosis and sinusoidal dila-
tion, with no evidence of vascular proliferation. Some of
these features were interpreted as evidence of lymphos-
tasis. The removed mass consisted of lymphoid tissue
with follicles containing multiple capillaries surrounded
by hyaline sheaths (CD 21⫹). Postcapillary venules were
prominent at the periphery of the follicles, which were
surrounded by concentric cuffs of lymphocytes arranged
in an onion skin pattern (Fig 2). Only a small number of
plasma cells and eosinophils were present in the para-
cortex. The changes were consistent with the diagnosis of
mediastinal solitary Castleman’s disease, of the hyaline
vascular type. Immunohistochemical detection of endo-
thelial markers (CD 31, CD 34) highlighted the vascular
nature of the lesion. No evidence of involvement by
Castleman’s disease was noted beyond the boundaries of
the tumor.
Comment
Castleman’s disease, also referred to as giant lymph node
hyperplasia or angiofollicular lymph node hyperplasia, is
a distinct lymphoproliferative disorder of uncertain ori-
gin that was first described by Castleman in 1956 [1].
CASE REPORT DAY ET AL 1649
More than 70% of lesions are located in the chest, along
the tracheobronchial tree, in the mediastinum or lung
hilus. Other sites commonly involved include the neck,
pelvis, retroperitoneum, and axilla [2]. There is no sig-
nificant gender predominance or identifiable risk factors
in the development of the disease [2]. Patients are usually
asymptomatic or have nonspecific complaints, often due
to tracheobronchial compression, such as cough, dyspnoea,
chest pain, respiratory infection, and back pain [2].
The disease has been classified on clinical grounds
(solitary or multicentric) and histologic appearance.
Three histologic types have been described: hyaline
vascular, plasma cell, and a mixed type [3]. It is now
CASE REPORTS
increasingly clear that there are different aetiologies for
each of these different subtypes. Reported associa-
tions with Castleman’s disease include POEMS syn-
drome (polyneuropathy, organomegally, endocrinopa-
thy, monoclonal gammopathy, and skin changes) [4],
paraneoplastic pemphigus [5], Hodgkin’s disease [6], and
follicular dendritic cell sarcoma [7]. The multicentric
plasma cell variant is strongly associated with infection
by human herpes virus 8 (HHV 8), and patients have
an increased risk for the development of other HHV
8 –associated neoplasms, including Kaposi’s sarcoma
and extranodal B-cell lymphoma [8]. The solitary
plasma cell variant of Castleman’s disease is often
seen in patients with a history of lymphoma [6]. Over-
production of the cytokine interleukin 6 (IL-6), either
native or virally encoded, has been hypothesized to drive
plasma cell proliferation in these subtypes [9]. The patho-
genesis of the hyaline vascular variant of Castleman’s
disease is currently unknown; however, vascular and
dendritic cell proliferations are common in this disorder
[10]. Localized clonal proliferations of stromal elements,
particularly follicular dendritic cells, occur in hyaline
vascular Castleman’s disease and possibly explain the
increased incidence of follicular dendritic cell sarcomas in
this subtype [10].
Simple excision of solitary nodules is usually curative,
especially in the hyaline vascular type [9]. The plasma
cell type is frequently associated with systemic manifes-
tations, such as amyloidosis, and is often refractory
to systemic therapy with corticosteroids and chemo-
therapy, particularly in the multicentric form [9]. Over-
production of IL-6 from affected lymph nodes is
thought to be responsible [9]. Therefore, interference
with IL-6 signaling may constitute a new therapeutic
strategy for this disease. In one study immediately
after administration of rhPM-1 (an anti-IL-6 receptor
antibody), fever and fatigue disappeared, and anemia
as well as serum levels of C-reactive protein (CRP),
fibrinogen, and albumin started to improve. After 3
months of treatment, hypergammaglobulinemia and
lymphadenopathy were remarkably alleviated, as were
renal function abnormalities in patients with amyloid-
osis. Treatment was well tolerated with only transient
leukopenia. Histopathological examination revealed
reduced follicular hyperplasia and vascularity after
rhPM-1 treatment [9].
Two previous cases of Castleman’s disease associated
 1650 CASE REPORT SWELSTAD ET AL
AN UNUSUAL PRESENTATION OF GORHAM’S SYNDROME
with myasthenia gravis have been reported in the liter-
ature. The first, by Emson [11] in 1973, described a
14-year-old girl with solitary retroperitoneal Castleman’s
disease of the hyaline vascular type. The second, by
Pasaoglu at el [12] in 1994, reported a 15-year-old girl
with multicentric extrathoracic Castleman’s disease with
features of both the hyaline vascular and plasma cell
types. The finding of thymus showing mild follicular
hyperplasia is relatively common in myasthenia gravis,
being the only thymic abnormality in approximately 65%
of cases. Such a finding is often present in other autoim-
mune diseases [13], however not with Castleman’s dis-
ease, and is therefore most likely associated with myas-
CASE REPORTS
thenia gravis. It is possible that the association between
Castleman’s disease and myasthenia gravis is more than
coincidental, and an underlying autoimmune mechanism
may be involved.
References
1. Castleman B, Iverson L, Menendez VP. Localized mediasti-
nal lymphonode hyperplasia resembling thymoma. Cancer
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2. Keller AR, Hochholzer L, Castleman B. Hyaline-vascular and
plasma-cell types of giant lymph node hyperplasia of the
mediastinum and other localizations. Cancer 1972;29:670 –6.
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min Diagn Pathol 1988;5:346 –64.
4. Adelman HM, Cacciatore ML, Pascual JF, Mike JM, Alberts
WM, Wallach PM. Case report: Castleman disease in asso-
ciation with POEMS. Am J Med Sci 1994;307:112–4.
5. Caneppele S, Picart N, Bayle-Lebey P, Paul J-L, Irsutti M,
Oksman F, Joly P, Bazex J. Paraneoplastic pemphigus asso-
ciated with Castleman’s tumour. Clin Exp Dermatol 2000;25:
219 –21.
6. Abdel-Reheim FA, Koss W, Rappaport ES, Arber DA. Coex-
istence of Hodgkin’s disease and giant lymph node hyper-
plasia of the plasma-cell type (Castleman’s disease). Arch
Pathol Lab Med 1996;120:91–6.
7. Chan ACL, Chan KW, Chan JKC, Au WY, Ho WK, Ng WM.
Development of follicular dendritic cell sarcoma in hyaline-
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evolution by sequential biopsies. Histopathology 2001;38:
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9. Nishimoto N, Sasai M, Shima Y, et al. Improvement in
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tor antibody therapy. Blood 2000;95:56 –61.
10. Pauwels P, Dal Cin P, Vlasveld LT, Aleva RM, van Erp WF,
Jone D. A chromosomal abnormality in hyaline vascular
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11. Emson HE. Extrathoracic angiofollicular lymphoid hyper-
plasia with coincidental myasthenia gravis. Cancer 1973;21:
241–5.
12. Pasaoglu I, Dogan R, Topcu M, Gungen Y. Multicentric
angiofollicular lymph-node hyperplasia associated with my-
asthenia gravis. Thorac Cardiovasc Surg 1994;42:253–6.
13. Okabe H. Thymic lymph follicles: a histopathological study
of 1,356 autopsy cases. Acta Pathol Jpn 1966;16:109 –30.
© 2003 by The Society of Thoracic Surgeons
Published by Elsevier Science Inc
Ann Thorac Surg
2003;75:1650 –2
Chylotamponade: An Unusual
Presentation of Gorham’s
Syndrome
Matthew Reed Swelstad, MD, Carmine Frumiento, MD,
Alice Garry-McCoy, MD, Rashmi Agni, MD, and
Tracey L. Weigel, MD
Department of Surgery, University of Wisconsin, Madison,
Wisconsin
Gorham’s Syndrome, also known as massive osteolysis
or “vanishing bone disease” results from lymphangioma-
tosis with adjacent bone resorption. Chylothorax is a
common complication in cases of mediastinal involve-
ment. We report a case of Gorham’s Syndrome present-
ing as chylotamponade successfully treated with pericar-
dial drainage, early parenteral nutritional support,
bilateral pleurodesis for chylous effusions, and adjuvant
external beam radiation.
(Ann Thorac Surg 2003;75:1650 –2)
© 2003 by The Society of Thoracic Surgeons
G orham’s Syndrome, also known as massive osteoly-
sis or “vanishing bone disease,” results from lym-
phangiomatosis and is often fatal secondary to malnutri-
tion. Nearly 20% of cases are complicated by chylothorax,
yet there are only three reported cases of asymptomatic
chylopericardium. The following is a report of Gorham’s
Syndrome presenting as chylous pericardial tamponade.
A healthy 31-year-old woman presented with new-onset
heartburn, wheezing, chest heaviness, and shortness of
breath. She was treated with oral ranitidine, steroids, and
albuterol, and her heartburn and wheezing resolved. She
returned 3 weeks later to the emergency room with an
increase in dyspnea and chest pressure.
A chest roentgenogram demonstrated an enlarged
cardiac silhouette and a right pleural effusion (Fig 1).
Echocardiogram confirmed a large pericardial effusion
with tamponade, and a pigtail catheter inserted percuta-
neously into the pericardial space drained approximately
1.5 L of chylous fluid. The patient was placed on bowel
rest and total parenteral nutrition. Chest computed to-
mographic scan demonstrated osteolytic right posterior
ribs 3, 4, and 5 and T7 and T8 vertebral bodies, and a right
pleural effusion. A chest tube was placed and drained
1,500 mL of chylous effusion. Lymphangiogram demon-
strated a broad plexus of severely ectatic lymphatic
ductules running along the posterior chest walls bilater-
Accepted for publication Oct 27, 2002.
Address reprint requests to Dr Weigel, 600 Highland Ave, CSC Room
4-346, University of Wisconsin Medical Center, Madison, WI 53792;
e-mail: weigel@surgery.wisc.edu.
0003-4975/03/$30.00
PII S0003-4975(02)04776-8