Orbit, 2014; 33(4): 314–317 ! Informa Healthcare USA, Inc. ISSN: 0167-6830 print / 1744-5108 online DOI: 10.3109/01676830.2014.904381
C ASE REPORT
A Rare Case of Bilateral Orbital Castleman Disease Bipasha Mukherjee1, Mohammad Shahid Alam1, and S. Krishnakumar2 1
Orbit and Oculoplasty, Medical Research Foundation, Chennai, India and 2 Ocular Pathology, Sankara Nethralaya, Chennai, India
Orbit Downloaded from informahealthcare.com by Nyu Medical Center on 05/29/15 For personal use only.
ABSTRACT Castleman disease is a non-neoplastic cause of lymphadenopathy, first described in 1956 by Dr. Benjamin Castleman. Orbital involvement in Castleman disease is extremely rare. We report a case of bilateral orbital Castleman disease in a 48-year-old Asian male who presented with bilateral inferior dystopia. MRI revealed bilateral extraconal superior orbital mass. Histopathology and immunohistochemistry of the mass revealed features of Castleman disease of hyaline vascular type. Castleman disease should be a differential in suspected idiopathic orbital inflammatory disease and lymphoproliferative disorders. Keywords: Castleman disease, orbit, proptosis
of Hg in the right and left eye respectively. Fundus examination showed bilateral choroidal folds with normal optic discs. Magnetic Resonance Imaging (MRI) of the orbits revealed bilateral superior extraconal lobulated mass lesion, suggestive of lymphoma (Figure 2). The patient underwent incisional biopsy through lid crease approach in the right eye. Histopathological examination revealed a well-capsulated lesion composed of lymphoid follicles with germinal centers with vascular proliferation and hyalinization. Some follicular dendritic cells were also seen (Figure 3a and b). Immunohistochemistry was positive for CD3 and CD 43 (interfollicles), CD20 & CD79a (follicles), CD21 and CD 23 (dendritic cells). Histopathology and immunohistochemistry corroborated the diagnosis of Castleman disease (CD). Patient was advised about complete surgical removal of the orbital masses, along with consultation with hemato-oncologist for systemic evaluation to rule out multicentric disease. However, the patient was from a neighboring country, and he had to leave due to expiry of his visa. He was asked to renew his visa and return for further management as soon as possible.
Castleman disease (CD) is a non-neoplastic cause of lymphadenopathy. It was first described by Dr Benjamin Castleman in 1956.1 Since then, only eleven cases of orbital Castleman disease have been reported in the literature.2 Clinically, the disease can either be unicentric or multicentric with systemic involvement. We report a rare case of Castleman disease involving both orbits.
CASE REPORT A 48-year-old Asian male from the Indian subcontinent presented with painless, progressive mass lesions over the eyeballs for the past 3 years. There were no systemic complaints. On examination, there was bilateral gross proptosis with inferior dystopia (Figure 1). Best corrected visual acuity in both the eyes was 20/80 (Jaeger). Color vision was grossly abnormal in both the eyes and pupils were sluggish. Ocular movements were limited in all direction of gaze. Bilateral well-circumscribed, firm-to-hard, superior orbital masses were seen. There was no lymphadenopathy. Intraocular pressure was 22 and 24 mm
Received 10 December 2013; Revised 27 February 2014; Accepted 10 March 2014; Published online 14 May 2014 Correspondence: Bipasha Mukherjee, Orbit and Oculoplasty, Medical Research Foundation, Chennai, India. E-mail: [email protected]
314
Castleman Disease 315
Comment
Orbit Downloaded from informahealthcare.com by Nyu Medical Center on 05/29/15 For personal use only.
Castleman disease is a non-neoplastic abnormal follicular proliferation of uncertain pathogenesis.4 It is also known as angiofollicular or giant lymph node hyperplasia. Clinically it has two variants, a localized one with a good prognosis, and which is
FIGURE 1. Clinical photograph of the patient showing bilateral proptosis with inferior dystopia.
curable with complete surgical resection. And a multicentric variant with widespread lymphadenopathy and organomegaly, presenting with systemic symptoms like fever, chills, and night sweats. This variant usually has a poorer prognosis.5 Histopathologically Castleman disease has been classified into three subtypes. The hyaline vascular, plasma cell, and mixed cell type.4 Hyaline vascular Castleman disease characteristically consists of atrophic hyalinized follicular centre with onion skin arrangement of small lymphocytes and one or more penetrating blood vessels conferring a ‘‘lollipop on stick’’ appearance. The plasma cell type is characterized by hyperplastic germinal centers with sheets of plasma cells in the interfollicular areas. Paracortical hypervasuclarity and onion skin mantle zone of lymphocytes are absent.5 The mixed cell type has features of both.3 Of the previous 11 cases published in literature till date, the most common type has been reported to be of hyaline vascular type (7 cases); one each of plasma cell and mixed cell type; and in two, histopathological typing was not available.2
FIGURE 2. Coronal and axial MRI, T-1 weighted image showing well defined bilateral homogenously enhancing extraconal lobulated mass lesions in supero-lateral orbit.
FIGURE 3. (A, B) Histopathological picture showing lymphoid follicles, vascular proliferation with hyalinization and expansion of mantle zone. Few plasma cells and follicular dendritic cells are also seen (Hematoxylin-eosin stain). !
2014 Informa Healthcare USA, Inc.
18
61
70
Park et al.[5] (2002)
Ide M et al.11 (2003)
Venizelos et al.6 (2010)
Mukherjee et al. (This report) (2014)
2
3
4
5
M
M
M
F
M
Sex
Bilateral proptosis with orbital mass lesions
Bilateral lower lid swelling
Bilateral proptosis
Bilateral upper lid swelling
Bilateral upper lid swelling and diplopia.
Clinical presentation
SR-LPS = Superior rectus-levator palpebrae superioris. LR = Lateral rectus.
48
71
Age in yrs
Kurokawa et al.12 (1999)
Study
1
Case
Imaging studies
CT: Bilateral peri-optic orbital lesions with enlarged lacrimal glands MRI: Bilateral homogenously enhancing extraconal lobulated mass lesions in superolateral orbit
CT: Bilat orbital mass lesion surrounding SR-LPS; LR muscles MRI: Bilateral orbital soft tissue lesion
CT & MRI: Bilateral enlarged lacrimal glands with perioptic tissue swelling
TABLE 1. Bilateral Orbital Involvement in Castleman Disease: A summary.
Uni centric?
Multi centric
Multi centric
Uni centric
Multi centric
Clinical type
HPE
Hyaline vascular
Plasma cell
Hyaline vascular
Castleman Ds (Lymph node Biopsy): type not mentioned. Hyaline vascular
Orbit Downloaded from informahealthcare.com by Nyu Medical Center on 05/29/15 For personal use only.
Treated with surgical excision with no recurrence at 1 year of follow up Treated with radiotherapy as initial diagnosis was Lymphoma; then with Rituximab and oral steroids with no recurrence at 10 months of follow up Treated with systemic steroids with no recurrence at 6 months of follow up Underwent incisional biopsy. Complete excision of lesions planned
Treated with systemic steroids. Died of recurrence after 10 months.
Outcome
316 B. Mukherjee et al.
Orbit
Orbit Downloaded from informahealthcare.com by Nyu Medical Center on 05/29/15 For personal use only.
Castleman Disease 317 Recently, a new classification has been proposed by some authors which divides Castleman disease into four subtypes, namely, hyaline vascular, plasma cell, HHV-8 associated CD and a multicentric CD- not otherwise specified (NOS).6 The pathogenesis of Castleman disease is unclear. Aberrant production of IL – 6 secondary to stimulation by HHV – 8 or unidentified exogenous and endogenous factors leading to plasma cell proliferation and their resistance to apoptosis has been considered as a possible mechanism in multicentric CD.7,8 Castleman disease rarely involves sites lacking in lymphatic tissue such as the brain and orbit. Snead et al. had reported the first histopathologically proven case of orbital Castleman disease. The authors had also noted that it is impossible to differentiate this condition from orbital lymphoma without biopsy and histopathological examination.9 Orbital Castleman disease can also mimic idiopathic orbital inflammatory disease (IOID).10 Unlike unicentric involvement, where complete surgical excision is curative, there is no standard treatment protocol for multicentric disease. Various treatment modalities like surgical resection, steroids, chemotherapy, radiotherapy, immunotherapy (interferon a, all Trans retinoic acid, thalidomide), anti-viral therapy, and monoclonal antibodies have been tried with variable results.7 Ide et al. had reported a case of bilateral multicentric Castleman disease treated successfully with Rituximab.11 Orbital involvement in Castleman disease is relatively rare. To the authors’ knowledge, five cases of bilateral orbital Castleman disease have been reported in the literature till date (including the present study) (Table 1). The first case of bilateral orbital Castleman diseases was reported by Kurokawa et al. in 1999.12 We find that bilateral orbital involvement is seen more commonly in elderly males, usually of hyaline vascular type. They can present with lacrimal gland enlargement, peri-optic swelling, or orbital mass lesions. Multicentric involvement is a definite possibility and must be ruled out by systemic examination and appropriate investigations in this group of patients. In conclusion, Castleman disease is an
!
2014 Informa Healthcare USA, Inc.
important differential diagnosis to be considered among other orbital afflictions like IOID, IGG4 related sclerosing disease and lymphoproliferative disorders.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES 1. Cronin DMP, Warnke RA. Castleman disease. An update on classification and the spectrum of associated lesions. Adv Anat Pathol 2009;16:236–246. 2. Jones NW, Fountain TR, Thakral B, Eldibany M. Castleman’s disease in the orbit of a 17 year old girl: a case report. Ophthal Plast Reconstr Surg 2014;30:e17–e20. 3. Brubaker JW, Harrie RP, Patel BC, et al. CT and orbital ultrasound findings in a case of Castleman disease. Ophthal Plast Reconstr Surg 2011;27:e37–e43. 4. Alyahya GA, Prause JU, Heegard S. Castleman’s disease in the orbit. A 20 year follow up. Acta Ophthalmol Scand 2002; 80:540–542. 5. Park KS, Choi YJ, Song KS. Hyaline-vascular type Castleman’s disease involving both orbits. Acta Ophthalmol Scand 2002;80:537–539. 6. Venizelos I, Papathomas TG, Papathanasiou M, et al. Orbital involvement in castleman disease. Surv Ophthalmol 2010;55:247–255. 7. Casper C. The aetiology and management of castleman disease at 50 yrs: translating pathophysiology to patient care. Br J Haematol 2005;129:3–17. 8. Menke DM, Chadbum A, Cesarman E, et al. Analysis of the human herpes virus 8 (HHV 8) genome and HHV-8 v IL-6 expression in archival cases of castleman disease at low risk of HIV infection. Am J Clin Pathol 2002;117: 268–275. 9. Snead MP, James JN, Snead DRJ, et al. Orbital lymphomas and castleman’s disease. Eye 1993;7:84–88. 10. Intani M, Kashi S, Nosaka K, Arima N. Orbital pseudotumor as an initial manifestation of multicentric castleman’s disease. Jpn J Ophthalmol 2005;49:505–508. 11. Ide M, Ogawa E, Kasagi K, et al. Successful treatment of multicentric Castleman’s disease with bilateral orbital tumor using rituximab. Br J Haematol 2003;121:818–819. 12. Kurokawa T, Suzuki S, Kawaguchi K, et al. Castleman disease presenting with ophthalmic signs and symptoms. Am J Ophthal 1999;128:14–16.
C ASE REPORT
A Rare Case of Bilateral Orbital Castleman Disease Bipasha Mukherjee1, Mohammad Shahid Alam1, and S. Krishnakumar2 1
Orbit and Oculoplasty, Medical Research Foundation, Chennai, India and 2 Ocular Pathology, Sankara Nethralaya, Chennai, India
Orbit Downloaded from informahealthcare.com by Nyu Medical Center on 05/29/15 For personal use only.
ABSTRACT Castleman disease is a non-neoplastic cause of lymphadenopathy, first described in 1956 by Dr. Benjamin Castleman. Orbital involvement in Castleman disease is extremely rare. We report a case of bilateral orbital Castleman disease in a 48-year-old Asian male who presented with bilateral inferior dystopia. MRI revealed bilateral extraconal superior orbital mass. Histopathology and immunohistochemistry of the mass revealed features of Castleman disease of hyaline vascular type. Castleman disease should be a differential in suspected idiopathic orbital inflammatory disease and lymphoproliferative disorders. Keywords: Castleman disease, orbit, proptosis
of Hg in the right and left eye respectively. Fundus examination showed bilateral choroidal folds with normal optic discs. Magnetic Resonance Imaging (MRI) of the orbits revealed bilateral superior extraconal lobulated mass lesion, suggestive of lymphoma (Figure 2). The patient underwent incisional biopsy through lid crease approach in the right eye. Histopathological examination revealed a well-capsulated lesion composed of lymphoid follicles with germinal centers with vascular proliferation and hyalinization. Some follicular dendritic cells were also seen (Figure 3a and b). Immunohistochemistry was positive for CD3 and CD 43 (interfollicles), CD20 & CD79a (follicles), CD21 and CD 23 (dendritic cells). Histopathology and immunohistochemistry corroborated the diagnosis of Castleman disease (CD). Patient was advised about complete surgical removal of the orbital masses, along with consultation with hemato-oncologist for systemic evaluation to rule out multicentric disease. However, the patient was from a neighboring country, and he had to leave due to expiry of his visa. He was asked to renew his visa and return for further management as soon as possible.
Castleman disease (CD) is a non-neoplastic cause of lymphadenopathy. It was first described by Dr Benjamin Castleman in 1956.1 Since then, only eleven cases of orbital Castleman disease have been reported in the literature.2 Clinically, the disease can either be unicentric or multicentric with systemic involvement. We report a rare case of Castleman disease involving both orbits.
CASE REPORT A 48-year-old Asian male from the Indian subcontinent presented with painless, progressive mass lesions over the eyeballs for the past 3 years. There were no systemic complaints. On examination, there was bilateral gross proptosis with inferior dystopia (Figure 1). Best corrected visual acuity in both the eyes was 20/80 (Jaeger). Color vision was grossly abnormal in both the eyes and pupils were sluggish. Ocular movements were limited in all direction of gaze. Bilateral well-circumscribed, firm-to-hard, superior orbital masses were seen. There was no lymphadenopathy. Intraocular pressure was 22 and 24 mm
Received 10 December 2013; Revised 27 February 2014; Accepted 10 March 2014; Published online 14 May 2014 Correspondence: Bipasha Mukherjee, Orbit and Oculoplasty, Medical Research Foundation, Chennai, India. E-mail: [email protected]
314
Castleman Disease 315
Comment
Orbit Downloaded from informahealthcare.com by Nyu Medical Center on 05/29/15 For personal use only.
Castleman disease is a non-neoplastic abnormal follicular proliferation of uncertain pathogenesis.4 It is also known as angiofollicular or giant lymph node hyperplasia. Clinically it has two variants, a localized one with a good prognosis, and which is
FIGURE 1. Clinical photograph of the patient showing bilateral proptosis with inferior dystopia.
curable with complete surgical resection. And a multicentric variant with widespread lymphadenopathy and organomegaly, presenting with systemic symptoms like fever, chills, and night sweats. This variant usually has a poorer prognosis.5 Histopathologically Castleman disease has been classified into three subtypes. The hyaline vascular, plasma cell, and mixed cell type.4 Hyaline vascular Castleman disease characteristically consists of atrophic hyalinized follicular centre with onion skin arrangement of small lymphocytes and one or more penetrating blood vessels conferring a ‘‘lollipop on stick’’ appearance. The plasma cell type is characterized by hyperplastic germinal centers with sheets of plasma cells in the interfollicular areas. Paracortical hypervasuclarity and onion skin mantle zone of lymphocytes are absent.5 The mixed cell type has features of both.3 Of the previous 11 cases published in literature till date, the most common type has been reported to be of hyaline vascular type (7 cases); one each of plasma cell and mixed cell type; and in two, histopathological typing was not available.2
FIGURE 2. Coronal and axial MRI, T-1 weighted image showing well defined bilateral homogenously enhancing extraconal lobulated mass lesions in supero-lateral orbit.
FIGURE 3. (A, B) Histopathological picture showing lymphoid follicles, vascular proliferation with hyalinization and expansion of mantle zone. Few plasma cells and follicular dendritic cells are also seen (Hematoxylin-eosin stain). !
2014 Informa Healthcare USA, Inc.
18
61
70
Park et al.[5] (2002)
Ide M et al.11 (2003)
Venizelos et al.6 (2010)
Mukherjee et al. (This report) (2014)
2
3
4
5
M
M
M
F
M
Sex
Bilateral proptosis with orbital mass lesions
Bilateral lower lid swelling
Bilateral proptosis
Bilateral upper lid swelling
Bilateral upper lid swelling and diplopia.
Clinical presentation
SR-LPS = Superior rectus-levator palpebrae superioris. LR = Lateral rectus.
48
71
Age in yrs
Kurokawa et al.12 (1999)
Study
1
Case
Imaging studies
CT: Bilateral peri-optic orbital lesions with enlarged lacrimal glands MRI: Bilateral homogenously enhancing extraconal lobulated mass lesions in superolateral orbit
CT: Bilat orbital mass lesion surrounding SR-LPS; LR muscles MRI: Bilateral orbital soft tissue lesion
CT & MRI: Bilateral enlarged lacrimal glands with perioptic tissue swelling
TABLE 1. Bilateral Orbital Involvement in Castleman Disease: A summary.
Uni centric?
Multi centric
Multi centric
Uni centric
Multi centric
Clinical type
HPE
Hyaline vascular
Plasma cell
Hyaline vascular
Castleman Ds (Lymph node Biopsy): type not mentioned. Hyaline vascular
Orbit Downloaded from informahealthcare.com by Nyu Medical Center on 05/29/15 For personal use only.
Treated with surgical excision with no recurrence at 1 year of follow up Treated with radiotherapy as initial diagnosis was Lymphoma; then with Rituximab and oral steroids with no recurrence at 10 months of follow up Treated with systemic steroids with no recurrence at 6 months of follow up Underwent incisional biopsy. Complete excision of lesions planned
Treated with systemic steroids. Died of recurrence after 10 months.
Outcome
316 B. Mukherjee et al.
Orbit
Orbit Downloaded from informahealthcare.com by Nyu Medical Center on 05/29/15 For personal use only.
Castleman Disease 317 Recently, a new classification has been proposed by some authors which divides Castleman disease into four subtypes, namely, hyaline vascular, plasma cell, HHV-8 associated CD and a multicentric CD- not otherwise specified (NOS).6 The pathogenesis of Castleman disease is unclear. Aberrant production of IL – 6 secondary to stimulation by HHV – 8 or unidentified exogenous and endogenous factors leading to plasma cell proliferation and their resistance to apoptosis has been considered as a possible mechanism in multicentric CD.7,8 Castleman disease rarely involves sites lacking in lymphatic tissue such as the brain and orbit. Snead et al. had reported the first histopathologically proven case of orbital Castleman disease. The authors had also noted that it is impossible to differentiate this condition from orbital lymphoma without biopsy and histopathological examination.9 Orbital Castleman disease can also mimic idiopathic orbital inflammatory disease (IOID).10 Unlike unicentric involvement, where complete surgical excision is curative, there is no standard treatment protocol for multicentric disease. Various treatment modalities like surgical resection, steroids, chemotherapy, radiotherapy, immunotherapy (interferon a, all Trans retinoic acid, thalidomide), anti-viral therapy, and monoclonal antibodies have been tried with variable results.7 Ide et al. had reported a case of bilateral multicentric Castleman disease treated successfully with Rituximab.11 Orbital involvement in Castleman disease is relatively rare. To the authors’ knowledge, five cases of bilateral orbital Castleman disease have been reported in the literature till date (including the present study) (Table 1). The first case of bilateral orbital Castleman diseases was reported by Kurokawa et al. in 1999.12 We find that bilateral orbital involvement is seen more commonly in elderly males, usually of hyaline vascular type. They can present with lacrimal gland enlargement, peri-optic swelling, or orbital mass lesions. Multicentric involvement is a definite possibility and must be ruled out by systemic examination and appropriate investigations in this group of patients. In conclusion, Castleman disease is an
!
2014 Informa Healthcare USA, Inc.
important differential diagnosis to be considered among other orbital afflictions like IOID, IGG4 related sclerosing disease and lymphoproliferative disorders.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES 1. Cronin DMP, Warnke RA. Castleman disease. An update on classification and the spectrum of associated lesions. Adv Anat Pathol 2009;16:236–246. 2. Jones NW, Fountain TR, Thakral B, Eldibany M. Castleman’s disease in the orbit of a 17 year old girl: a case report. Ophthal Plast Reconstr Surg 2014;30:e17–e20. 3. Brubaker JW, Harrie RP, Patel BC, et al. CT and orbital ultrasound findings in a case of Castleman disease. Ophthal Plast Reconstr Surg 2011;27:e37–e43. 4. Alyahya GA, Prause JU, Heegard S. Castleman’s disease in the orbit. A 20 year follow up. Acta Ophthalmol Scand 2002; 80:540–542. 5. Park KS, Choi YJ, Song KS. Hyaline-vascular type Castleman’s disease involving both orbits. Acta Ophthalmol Scand 2002;80:537–539. 6. Venizelos I, Papathomas TG, Papathanasiou M, et al. Orbital involvement in castleman disease. Surv Ophthalmol 2010;55:247–255. 7. Casper C. The aetiology and management of castleman disease at 50 yrs: translating pathophysiology to patient care. Br J Haematol 2005;129:3–17. 8. Menke DM, Chadbum A, Cesarman E, et al. Analysis of the human herpes virus 8 (HHV 8) genome and HHV-8 v IL-6 expression in archival cases of castleman disease at low risk of HIV infection. Am J Clin Pathol 2002;117: 268–275. 9. Snead MP, James JN, Snead DRJ, et al. Orbital lymphomas and castleman’s disease. Eye 1993;7:84–88. 10. Intani M, Kashi S, Nosaka K, Arima N. Orbital pseudotumor as an initial manifestation of multicentric castleman’s disease. Jpn J Ophthalmol 2005;49:505–508. 11. Ide M, Ogawa E, Kasagi K, et al. Successful treatment of multicentric Castleman’s disease with bilateral orbital tumor using rituximab. Br J Haematol 2003;121:818–819. 12. Kurokawa T, Suzuki S, Kawaguchi K, et al. Castleman disease presenting with ophthalmic signs and symptoms. Am J Ophthal 1999;128:14–16.
