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Year : 2020  |  Volume : 2  |  Issue : 1  |  Page : 32

Orbital castleman disease and literature review

Department of Oculoplastics, Ophthalmology Institute “Conde de Valenciana”, Mexico City, Mexico

Date of Submission01-Apr-2020
Date of Decision09-Apr-2020
Date of Acceptance02-May-2020
Date of Web Publication23-Nov-2020

Correspondence Address:
Dr. Adriana Davila-Camargo
Paseo Del Tecnológico 909, Int 520 Col. Residencial Tecnológico, CP 27272 Torreón, Coahuila
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/PAJO.PAJO_15_20

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We present a case of an orbital mass confirmed as Castleman disease (CD) with the histopathological and immunohistochemical review. CD in the orbit is uncommon and has been seldom reported. The case we present justifies the review due to the abnormal location and clinical presentation. Variety of the differential diagnoses that can arise from an orbital mass with these characteristics are also discussed.

Keywords: Castleman disease, orbital Castleman disease, orbital disease, orbital neoplasms, orbital tumors

How to cite this article:
Davila-Camargo A, Ball-Burstein S, Tovilla-Canales JL. Orbital castleman disease and literature review. Pan Am J Ophthalmol 2020;2:32

How to cite this URL:
Davila-Camargo A, Ball-Burstein S, Tovilla-Canales JL. Orbital castleman disease and literature review. Pan Am J Ophthalmol [serial online] 2020 [cited 2021 Nov 27];2:32. Available from: https://www.thepajo.org/text.asp?2020/2/1/32/301331

  Introduction Top

The first report of Castleman disease (CD) was described in 1954 by Dr. Benjamin Castleman.[1] The first orbital CD report was described in 1993 in England by Dr. Martin P. Snead.[2] Since then, few reports of orbital CD have been described and are available in Pubmed search.[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14] CD can be classified histologically or clinically.[15],[16] The histopathological classification includes the hyaline vascular, plasma cell, or mixed type.[15] CD has two clinical variants: unicentric or multicentric.[16] A unicentric variant can be treated with surgical resection alone and holds a better clinical prognosis. A multicentric variant is usually associated with systemic symptoms such as fever, chills, night sweats, widespread lymphadenopathy, splenomegaly, polyneuropathy, and cytopenias.[16] It usually requires multisystemic workup, surgical resection, and treatments such as steroids, chemotherapy, immunotherapy, or radiotherapy.[5],[17],[18] It has been associated with herpesvirus 8 and holds a grim prognosis.[19] To the knowledge of the authors, this is the first CD case reported in Mexico.

  Case Report Top

A 54-year-old woman presented to the Oculoplastics Department in Mexico City with the main complaint of a palpable nodular mass on the upper left orbit inducing a mechanical ptosis [Figure 1]. She referred a 1-year evolution, with no pain, fever, or weight loss. Her medical history included the removal of an osseous cyst in her left jaw with the insertion of a titanium plaque during childhood. She had phacoemulsification surgery in both eyes a year before. No other known diseases were reported. On examination, bilateral best-corrected visual acuity was 20/20. Palpation of the superonasal orbit revealed a nonmobile, nonpulsatile, painless, and solid mass with inferior displacement of the globe. Valsalva maneuver caused no changes in the mass. The remaining ophthalmological examination was unremarkable. A computed tomography with contrast revealed a well enhancing circumscribed lesion in the superior aspect of the left orbit. No bone lysis was observed [Figure 2]. Blood tests and systemic examination were normal. An excisional biopsy through a lid crease approach was performed. A yellowish, well-circumscribed lesion, that appeared to arise from the supraorbital nerve measuring 25 mm × 10 mm × 10 mm was excised and sent for histological examination [Figure 3]. The biopsy showed lymphoid proliferation in a follicular pattern with atypical germinal centers [Figure 4]. Immunohistochemistry for CD20, CD3, CD21, CD138, CD68, and herpesvirus 8 was completed. CD20 and CD3 were diffuse and positive in B and T lymphocytes, CD21 was positive in dendritic follicular cells of the germinal centers, CD138 and CD68 were diffuse and intensely positive in plasmatic cells and dendritic plasmacytoid cells, respectively in the interfollicular stroma. The immunoreaction for herpesvirus 8 was negative [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]. These findings are consistent with the diagnosis of CD of the hyaline vascular type. The patient was referred to an oncologist for systemic workup and treatment. Tomography of the chest, abdomen, and pelvis was performed and reported as negative. The patient's laboratory findings (complete blood count, liver function test, metabolic panel, and HIV test) were normal. A year afterward, the patient had no evidence of disease recurrence or systemic involvement.
Figure 1: External photograph of patient 1 with increased volume in the left upper eyelid and inferolateral displacement of the globe

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Figure 2: Computed tomography scan of patient 1, showed a well circumscribed solid mass with moderate enhancement in the superonasal aspect of the orbit, without bony involvement

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Figure 3: Through a superior eyelid crease approach, a yellowish solid mass was excised. Due to its macroscopic aspect and location it was thought to be an orbital schwannoma

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Figure 4: Photomicrograph showing broad zones of follicle's mantle and concentric rings of small lymphocites which give the appearance of “onion skin” (H and E, ×40)

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Figure 5: Same as Figure 4, magnified to show better the “onion skin”

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Figure 6: Hyaline vascular changes (H and E)

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Figure 7: Positivity in lymphocytes B of mantle cells of lymphoid follicles (CD20, ×5)

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Figure 8: Positivity in T lymphocytes of the interfollicular areas and some cells of the follicular centers (CD3, ×10)

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Figure 9: Positivity in follicular dendritic cells of the germinal centers (CD21, ×10)

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Figure 10: Positivity in plasma cells in interfollicular areas (CD138, ×40)

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  Discussion Top

CD is a common cause of nonneoplastic lymphadenopathy.[15] Nearly 70% of CD cases are located in the thorax, 10%–15% in the abdomen, retroperitoneum, and pelvis, and 10%–15% in the neck.[20] It is atypical to find it in tissues depleted of lymphatics, such as the orbit or the brain.[21] It is believed that lymphatic tissue can be sequestrated within the orbit during embryonic development or that it may contain scattered lymphocytes, which could likely initiate reactive or neoplastic lymphoid proliferative lesions.[13]

The most common type of CD found in the orbit is hyaline vascular type and unicentric variant, like in our patient.[13] No gender predilection has been observed. It occurs mostly in the fourth decade of life. A single lymph node is involved with sizes ranging from 6 to 7 cm. It is characterized by the atrophic hyalinized follicular center with onion skin arrangement of small lymphocytes and one or more penetrating blood vessels conferring a “lollipop on stick” appearance. Pathogenesis of CD remains unclear, although the current model for CD pathogenesis is aberrant production of interleukin-6 by B cells in the lymph node mantle zone, stimulated by a viral infection.[17]

On radiological studies, it can be very difficult to differentiate this condition from orbital lymphoma without histopathological examination.[2],[20] Orbital CD can also mimic idiopathic orbital inflammatory disease.[6] It is important to acknowledge the unusual radiological characteristics this disease may present to suspect its diagnosis, but it cannot be diagnosed exclusively based on the radiological findings.[2],[20] Differential diagnosis should include all well-circumscribed orbital solid lesions such as cavernous hemangioma, neurilemoma, neurofibroma, fibrous histiocytoma, some metastatic lesions, and lymphoproliferative disorders.[22] It can also mimic immunoglobulin G4-related disease, systemic lupus erythematosus, acute Epstein-Barr virus infection, HHV8/KSHV infection, among others.[23] The presumed diagnosis for our case was a schwannoma of the supraorbital nerve, similar to a previous case reported of a CD misdiagnosed as an infraorbital nerve schwannoma.[10] This remarks the importance of histopathology and immunohistochemistry for a correct final diagnosis.

To the best of our knowledge, this is the first case of orbital CD reported in the Mexican population. Although orbital involvement in CD is very rare, ophthalmologists should consider it in the differential diagnosis of orbital masses.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Castleman B. Hyperplasia of mediastinal lymph node. N Engl J Med 1954;250:26-30.  Back to cited text no. 1
Snead MP, James JN, Snead DR, Robson DK, Rizk SN. Orbital lymphomas and Castleman's disease. Eye. 1993;7:84-88.  Back to cited text no. 2
Brubaker JW, Harrie RP, Patel BC, Davis DK, Mamalis N. CT and orbital ultrasound findings in a case of Castleman disease. Ophthalmic Plast Reconstr Surg 2011;27:e37-9.  Back to cited text no. 3
Gittinger JW Jr. Ocular involvement in Castleman's disease. Response to radiotherapy. Ophthalmology 1989;96:1646-9.  Back to cited text no. 4
Ide M, Ogawa E, Kasagi K, Kawachi Y, Ogino T. Successful treatment of multicentric Castleman's disease with bilateral orbital tumour using rituximab. Br J Haematol 2003;121:818-9.  Back to cited text no. 5
Inatani M, Kashii S, Nosaka K, Arima N. Orbital pseudotumor as an initial manifestation of multicentric Castleman's disease. Jpn J Ophthalmol 2005;49:505-8.  Back to cited text no. 6
Kang D, Lee J, Lee H, Baek S. Unicentric castleman′s disease in the orbit: A case report. Indian J Ophthalmol 2015;63:555.  Back to cited text no. 7
[PUBMED]  [Full text]  
Jáñez L, Taban M, Wong CA, Ranganath K, Douglas RS, Goldberg RA. Localized Intraorbital Castleman's disease: A case report. Orbit 2010;29:158-60.  Back to cited text no. 8
Jones NW, Fountain TR, Thakral B, Eldibany M. Castleman's disease in the orbit of a 17-year-old girl. Ophthalmic Plast Reconstr Surg 2014;30:e17-20.  Back to cited text no. 9
Kurokawa T, Suzuki S, Kawaguchi K, Fujisawa N, Yoshimura N. Castleman disease presenting with opthalmic signs and symptoms. Am J Ophthalmol 1999:128:114-6.  Back to cited text no. 10
Mukherjee B, Alam MS, Krishnakumar S. A rare case of bilateral orbital castleman disease. Orbit 2014;33:314-7.  Back to cited text no. 11
Park K, Choi Y, Song K. Hyaline-vascular type Castleman's disease involving both orbits. Acta Ophthalmol Scand 2002:80:537-9.  Back to cited text no. 12
Venizelos I, Papathomas TG, Papathanasiou M, Cheva A, Garypidou V, Coupland S. Orbital involvement in Castleman disease. Surv Ophthalmol 2010;55:247-55.  Back to cited text no. 13
Billagra A, Weil D, Vivante S, Croxatto J, Ferrerer D. Castleman's disease. Vis Pan Am 2015;14:110-1.  Back to cited text no. 14
Cronin DM, Warnke RA. Castleman Disease. Adv Anat Pathol 2009;16:236-46.  Back to cited text no. 15
Tarentino AL, Maley F. A comparison of the substrate specificities of endo-beta-N-acetylglucosaminidases from Streptomyces griseus and Diplococcus Pneumoniae. Biochem Biophys Res Commun 1975;67:455-62.  Back to cited text no. 16
Casper C. The aetiology and management of Castleman disease at 50 years: Translating pathophysiology to patient care. Br J Haematol 2005;129:3-17.  Back to cited text no. 17
Nishimoto N, Sasai M, Shima Y, Nakagawa M, Matsumoto T, Shirai T, et al. Improvement in Castleman's disease by humanized anti-interleukin-6 receptor antibody therapy. Blood 2000;95:56-61.  Back to cited text no. 18
Wang HW, Pittaluga S, Jaffe ES. Multicentric Castleman disease: Where are we now? Semin Diagn Pathol 2016;33:294-306.  Back to cited text no. 19
Ko SF, Hsieh MJ, Ng SH, Lin JW, Wan YL, Lee TY. Imaging Spectrum of Castleman's Disease. Am J Roentgenol 2004;182:769-75.  Back to cited text no. 20
Alyahya GA, Prause JU, Heegaard S. Castleman's disease in the orbit. A 20-year follow-up. Acta Ophthalmol Scand 2002;80:540-2.  Back to cited text no. 21
Karcioğlu Zeynel A. Orbital Tumors: Diagnosis and Treatment. New York: Springer; 2015.  Back to cited text no. 22
Fajgenbaum DC, Uldrick TS, Bagg A, Frank D, Wu D, Srkalovic G, et al. International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood 2017;129:1646-57.  Back to cited text no. 23


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]


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