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Journal Name: Journal of Case Reports and Images in Oncology
Type of Article: Case Report
Title: An unusual cause of neck swelling - Unicentric castleman’s disease: Case report
and review of literature
Authors: Komaranchath Ashok S, AH Rudresh., Kuntegowdenahalli Lakshmaiah C,
Chennagiri S Premalata., Dasappa Loknatha, Jacob Linu A
doi: To be assigned
Early view version published: July 7, 2015
How to cite the article: Komaranchath A.S, Rudresh AH, Kuntegowdenahalli L.C,
Chennagiri S.P., Dasappa L, Jacob L. A, An unusual cause of neck swelling - Unicentric
castleman’s disease: Case report and review of literature. Journal of Case Reports and
Images in Oncology Forthcoming 2015.
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TYPE OF ARTICLE: Case Report
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TITLE: An unusual cause of neck swelling - Unicentric castleman’s disease: Case
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report and review of literature
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AUTHORS:
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Dr. Komaranchath Ashok S MD, MRCP(UK)1, Dr. AH Rudresh. MD, DM2 , Dr.
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Kuntegowdenahalli Lakshmaiah C. MD, DM3, Dr. Chennagiri S Premalata. MD4, Dr.
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Dasappa Loknatha5, Dr. Jacob Linu A5
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AFFILIATIONS:
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DM Medical Oncology Resident, Dept. of Medical Oncology, Kidwai Memorial
Institue of Oncology, Bangalore-29, INDIA. e-mail: komaranchath@gmail.com
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Assistant Professor, Dept. of Medical Oncology, Kidwai Memorial Institue of
Oncology, Bangalore-29, INDIA. e-mail: rudresha.ah@gmail.com
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Professor and HOD, Dept. of Medical Oncology, Kidwai Memorial Institue of
Oncology, Bangalore-29, INDIA. e-mail: kcluck@gmail.com
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Associate Professor, Dept. of Pathology, Kidwai Memorial Institue of Oncology,
Bangalore-29, INDIA. e-mail: prema_venka@hotmail.com
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Associate Professor, Dept. of Medical Oncology, Kidwai Memorial Institue of
Oncology, Bangalore-29, INDIA. e-mail: drlok61@gmail.com
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CORRESPONDING AUTHOR DETAILS
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Dr. Ashok S Komaranchath
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Dept. of Medical Oncology, Kidwai Memorial Insitute of Oncology
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Dr. M. H. Marigowda Road, Bangalore – 560029 , Karnataka, INDIA
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Phone number: +919880565471
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Email: komaranchath@gmail.com
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Short Running Title: Unicentric Castleman’s Disease: A Case report
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TITLE: An unusual cause of neck swelling - Unicentric castleman’s disease: Case
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report and review of literature
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ABSTRACT
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Introduction
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Castleman’s disease is a rare disorder in which there is a benign proliferation of
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lymphoid tissue. There are two clinical entities; namely, unicentric castleman’s
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disease with the disease confined to a single anatomic lymph node and a
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multicentric castleman’s disease characterized by generalized lymphadenopathy,
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constitutional symptoms, a more aggressive clinical course and relatively poorer
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prognosis. The most common histopathological subtype is the hyaline vascular
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variant
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Case Report
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We present the case of an 18-year-old girl who presented to us with a painless right-
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sided neck swelling which was completely excised and diagnosed to have hyaline
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vascular variant of unicentric castleman’s disease. This disorder carries an excellent
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prognosis and does not require further therapy if complete excision of the involved
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lymph node has been done.
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Conclusion
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Unicentric castleman’s disease is a rare cause of unilateral neck swelling albeit with
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an excellent prognosis. Diagnosis by excision biopsy can double up as the treatment
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as well in cases of solitary lymph node involvement
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Keywords:
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Immunocompetent
Castleman’s
Disease,
Unicentric,
Hyaline
Vascular
variant,
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CONSENT: Written informed consent was obtained from the subject before
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preparation of the manuscript
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TITLE: An unusual cause of neck swelling - Unicentric castleman’s disease: Case
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report and review of literature
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INTRODUCTION
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The term Castleman’s disease is used to describe a group of related
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lymphoproliferative disorders. There are several forms of idiopathic Castleman’s
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disease that can be classified either anatomically (unicentric or multicentric) or by
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morphology (hyaline-vascular, plasma cell, or mixed histology). With the discovery of
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KSHV, it was recognized that this virus causes a plasmablastic variant of multicentric
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Castleman’s disease (MCD). Unicentric Castleman’s disease (UCD) most often
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presents as a localized disease with a solitary, slow-growing lymph node. There are
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two main histologic subtypes of unicentric Castleman’s disease: the hyaline vascular
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variant, and the plasma cell variant. The hyaline vascular form is much more
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common and almost always involves only one site. It accounts for around 90% of all
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unicentric cases.[1] In contrast to multicentric Castleman’s disease, which is most
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commonly seen in the setting of immunocompromise (usually in HIV infected
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patients); unicentric castleman’s disease is seen in immunocompetent patients. Also,
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UCD can be treated with simple excision alone and usually does not require
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systemic therapy.
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CASE REPORT
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An 18 year old girl with no co-morbidities, presented with a swelling in the right side
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of the neck for the past two years, which had increased over the past one month.
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There was no pain over the swelling, no complaints of difficulty in eating or
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swallowing food. There was no history of fever, night sweats, or weight loss. There
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was no history of any other such swellings in any part of her body. Physical
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examination revealed a firm level II cervical lymph node in the right side of her neck.
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Contrast enhanced CT scan of the neck showed a well-defined right cervical lymph
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node of 4 x 3 cm size.(Figure 1) She underwent excision biopsy of the lymph node at
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another institution and was referred to our center for further evaluation and
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management. CT scan of the thorax, abdomen and pelvis showed no other
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significant lymphadenopathy. HIV, HBsAg and Anti-HCV antibodies were negative.
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Bone marrow aspiration and biopsy were normal. Histopathology of the same
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showed a characteristic onion skin appearance of follicles with two germinal centres
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within the same follicle surrounded by a marked mantle layer hyperplasia.(Figure 2)
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There was also presence of the pathognomonic “Lollipop Lesions” (Figure 3) which
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are formed due to penetration of sclerotic blood vessels into the atrophic germinal
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centers. These features were consistent with the diagnosis of the hyaline vascular
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variant of Unicentric Castleman’s Disease. As whole node excision was done and
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she had no evidence of disease elsewhere in the body, she was kept under follow-
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up.
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DISCUSSION
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The clinico-pathological features of castleman’s disease was described by Benjamin
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Castleman in 1956. He reported a series of 13 patients with hyperplastic lymph
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nodes in the mediastinum which contained small, hyalinized follicles and increased
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vascular proliferation between the lymph node follicles. [2] It is a rare tumour that
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usually presents as a slowly growing, solitary painless mass.[3] The most common
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site involved is the mediastinum and involvement of cervical lymph nodes is rare. In
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an early series by Keller et.al., 86%of cases were confined to the mediastinum and
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only 6% of cases involved the neck.[1] A more recent series in 2003 by Bond et.al.
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showed that the neck was involved in only 14% of all cases, with the mediastinum
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being the most common site, accounting for 60% of cases. [4] Within the head and
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neck region, the most common sites were cervical and submandibular areas. [5]
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Unicentric Castleman’s disease: It most commonly occurs in young adults with a
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median age of 35 years. [1,3,6] In most series, there was an equal incidence seen in
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males and females. [1,3] The most common histological variant was that of hyaline
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vascular variant which was seen in around 90% of all unicentric castleman’s
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disease.[1] Of those patients with the plasma cell variant, 50% had systemic findings
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of anemia, an elevated ESR count, hypergammaglobulinemia, and marrow
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plasmacytosis. [1]
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Multicentric Castleman’s Disease: It is a systemic disease with multiple sites of
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involvement. Almost all cases are that of the plasma cell variant. It may be
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associated with or without HHV-8 infection. There was a male preponderance, and
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occurs in older patients.[7,8,9] It is most commonly seen in the setting of HIV
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infection.[3] MCD usually presents with constitutional symptoms like fever, night
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sweats and arthralgia as well as peripheral lymph node enlagement and
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hepatosplenomegaly.[3,8,10]
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Pathogenesis: The histopathological features of Castleman’s disease like increase
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in plasma cells and immunoblasts, germinal centre hyperplasia and increased
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vascularity are seen as exaggerations of responses to normal antigenic stimuli.
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Studies in the early 1990’s have found a correlation between the systemic
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manifestations of UCD and local production of Interleukin-6. [11,12] The exact cells
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which seem to produce IL-6 has not been elucidated yet [13] but candidate cells
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include follicular dendritic cells, germinal centre B Cells or the interfollicular cells.
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[11,12] Also, IL-6 receptor polymorphisms have been identified in HIV-negative CD
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and are associated with increased soluble IL-6 receptor levels. [14]
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Diagnosis: Most patients with unicentric Castleman’s disease (UCD) are
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asymptomatic and are diagnosed when an enlarged lymph node was noted on
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physical examination or imaging. UCD may be suspected when there is a single
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persistently enlarged mass, especially a nodal mass associated with moderate to
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intense post-contrast enhancement on a CT scan.
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The hyaline vascular variant of Castleman’s disease is characterized by the
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presence of abnormal follicles with atrophic germinal centers surrounded by wide
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mantle zones consisting of small lymphocytes. [2] A Characteristic feature is the
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presence of two adjacent germinal centres surrounded by a single, wide mantle
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zone. These are called double germinal centers.(Figure 2) The germinal centres are
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usually depleted of lymphocytes and are replaced with follicular dendritic cells
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arranged in a concentric manner producing an onion-skin appearance. (Figure 2)
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The interfollicular tissue contains many small sclerotic blood vessels These are often
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seen penetrating upto the centre of the regressed germinal centers, producing a
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pathognomonic "lollipop lesion".(Figure 3) [1,2,13]
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Prognosis: The prognosis for patients with unicentric disease, regardless of the
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histologic variant, is generally excellent, as surgical excision is curative.[7] There has
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been no reported recurrence of the hyaline vascular variant in literature following
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complete excision. Multicentric disease is more aggressive and carries a poorer
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prognosis and shorter survival.[9] Treatment recommendations for multicentric
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Castleman’s disease have been difficult to establish because the literature contains
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mostly small series. Numerous therapies have been tried for multicentric disease,
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including
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antibodies and single-agent and combination chemotherap.[15] Immune modulators
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like steroids, Interferon, ATRA and Thalidomide have been used with varying
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success. Antiviral therapy directed against HHV-8 (Ganciclovir, Foscarnet, cidofovir)
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as well as HIV (combination Anti Retroviral Therapy – cART) have been tried as well.
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Since plasma cells in the mantle zone of some patients may express CD20,
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Rituximab has also been tried which gave durable complete remissions in three out
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of five patients who were subjected to treatment with this antibody. [16] Two
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monoclonal antibodies against IL-6 are also available, Siltuximab and Tocilizumab,
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of which the former is approved for HIV/HHV8 negative MCD in USA and the latter
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is approved for use only in Japan. [17,18]
surgery,
radiotherapy,
immune
modulators,
antivirals,
monoclonal
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CONCLUSION
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Unicentric castleman’s disease is a rare cause of unilateral neck swelling albeit with
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an excellent prognosis. Diagnosis by excision biopsy can double up as the treatment
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as well if there are no other involved sites. The characteristic arrangement of
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follicular dendritic cells and lollipop lesions clinches the diagnosis. No further therapy
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is required after complete excision of the lymph node.
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CONFLICT OF INTEREST
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The authors report no conflicts of interest
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AUTHOR’S CONTRIBUTIONS
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Dr. Ashok S Komaranchath
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Group 1 - Conception and design, Acquisition of data, Analysis and interpretation of
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data
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Group 2 - Drafting the article, Critical revision of the article
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Group 3 - Final approval of the version to be published
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Dr. AH Rudresh. MD, DM2
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Group 1 - Conception and design
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Group 2 - Critical revision of the article
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Group 3 - Final approval of the version to be published
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Dr. Kuntegowdenahalli Lakshmaiah C. MD, DM3
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Group 1 - Conception and design
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Group 2 - Critical revision of the article
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Group 3 - Final approval of the version to be published
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Dr. Chennagiri S Premalata. MD4
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Group 1 - Conception and design
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Group 2 - Critical revision of the article
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Group 3 - Final approval of the version to be published
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Dr. Dasappa Loknatha5
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Group 1 - Conception and design
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Group 2 - Critical revision of the article
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Group 3 - Final approval of the version to be published
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Dr. Linu A Jacob
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Group 1 - Conception and design
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Group 2 - Critical revision of the article
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Group 3 - Final approval of the version to be published
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ACKNOWLEDGEMENTS
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NONE
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REFERENCES
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1. Keller AR, Hochholzer L, Castleman B. Hyaline-vascular and plasma-cell types of giant
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lymph node hyperplasia of the mediastinum and other locations. Cancer 1972; 29 (3):
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670-83.
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2. Castleman B, Iverson L, Menendez VP. Localized mediastinal lymphnode hyperplasia
resembling thymoma. Cancer 1956; 9 (4): 822-30.
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3. Sherman JA, Birtwhistle CJ, Davies HT. A rapidly expanding lesion in the neck: Unusual
presentation of Castleman's disease. Int J Oral Maxillofac Surg 2001; 30 (5): 458-60.
4. Bond SE, Saeed NR, Palka I, Carls FP. Castleman's disease presenting as a midline neck
mass. Br J Plast Surg 2003; 56 (1): 62-4.
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5. Maruyama S, Hao N, Cheng J, et al. Castleman's disease of the buccal mucosa: Report of
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a case and review of the literature of head and neck cases. Oral Surg Oral Med Oral
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Pathol Oral Radiol Endod 2002; 93 (3): 305-10.
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6. Talat N, Belgaumkar AP, Schulte KM. Surgery in Castleman's disease: a systematic
review of 404 published cases. Ann Surg 2012; 255:677.
7. Frank DK, Charney D, Kashani A. Plasma cell variant of Castleman's disease occurring
concurrently with Hodgkin's disease in the neck. Head Neck 2001; 23 (2): 166-9.
8. Peterson BA, Frizzera G. Multicentric Castleman's disease. Semin Oncol 1993; 20 (6):
636-47.
9. McCarty MJ, Vukelja SJ, Banks PM, Weiss RB. Angiofollicular lymph node hyperplasia
(Castleman's disease). Cancer Treat Rev 1995; 21 (4): 291-310
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10. Yi AY, deTar M, Becker TS, Rice DH. Giant lymph node hyperplasia of the head and
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neck (Castleman's disease): A report of five cases. Otolaryngol Head Neck Surg 1995;
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113 (4): 462-6.
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11. Yoshizaki K, Matsuda T, Nishimoto N, et al. Pathogenic significance of interleukin-6 (IL6/BSF-2) in Castleman's disease. Blood 1989; 74:1360.
12. Leger-Ravet MB, Peuchmaur M, Devergne O, et al. Interleukin-6 gene expression in
Castleman's disease. Blood 1991; 78:2923.
13. Frizzera G. Atypical lymphoproliferative disorders. In: Neoplastic Hematopathology,
Knowles DM (Ed), Lippincott, Williams and Wilkins, Philadelphia 2001. p.595.
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14. Stone K, Woods E, Szmania SM, et al. Interleukin-6 receptor polymorphism is prevalent
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in HIV-negative Castleman Disease and is associated with increased soluble interleukin-6
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receptor levels. PLoS One 2013; 8:e54610.
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15. Casper C. The aetiology and management of Castleman disease at 50 years: Translating
pathophysiology to patient care. Br J Haematol 2005; 129 (1): 3-17
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16. Marcelin, A.-G., Aaron, L., Mateus, C., Gyan, E., Gorin, I., Viard, J.-P., Calvez, V. &
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Dupin, N. (2003) Rituximab therapy for HIV-associated Castleman disease. Blood, 102,
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2786–2788.
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17. Van Rhee F, Fayad L, Voorhees P, Furman R, Lonial S, Borghaei H et.al. Siltuximab, a
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novel anti-interleukin-6 monoclonal antibody, for Castleman's disease. J Clin Oncol.
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2010;28(23):3701
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18. Matsuyama M, Suzuki T, Tsuboi H, Ito S, Mamura M, Goto D et.al. Anti-interleukin-6
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receptor antibody (tocilizumab) treatment of multicentric Castleman's disease. Intern
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Med. 2007;46(11):771.
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FIGURE LEGENDS
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Figure 1: CECT scan of neck showing enlarged right cervical lymph node
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Figure 2: Histopathology showing Classical “Lollipop Lesion” (Black arrow)
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Figure 3: Characteristic histopathological appearance of two germinal centers
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(Arrows) within a single follicle, surrounded by marked mantle cell hyperplasia.
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FIGURE
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Figure 1: CECT scan of neck showing enlarged right cervical lymph node
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Figure 2: Histopathology showing Classical “Lollipop Lesion” (Black arrow)
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Figure 3: Characteristic histopathological appearance of two germinal centers
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(Arrows) within a single follicle, surrounded by marked mantle cell hyperplasia.
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