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 Table of Contents  
Year : 2021  |  Volume : 1  |  Issue : 3  |  Page : 608-610

Acute orbital presentation in an activated B-cell subtype, diffuse large B-cell lymphoma: clinicoradiological, histopathological and immunohistochemical correlation

1 Ophthalmic Plastics, Orbit and Ocular Oncology Services, LV Prasad Eye Institute, MTC Campus, Patia, Bhubaneswar, Odisha; Operation Eyesight Universal Institute for Eye Cancer, Hyderabad, Telengana, India
2 Kanupriya Dalmia Ocular Pathology Laboratory, LV Prasad Eye Institute, MTC Campus; Department of Pathology, Kalinga Institute of Medical Sciences, Patia, Bhubaneswar, Odisha, India

Date of Submission26-Aug-2020
Date of Acceptance30-Dec-2020
Date of Web Publication02-Jul-2021

Correspondence Address:
Dr. Ruchi Mittal
Consultant Pathologist, Kanupriya Dalmia Ocular Pathology Laboratory, LV Prasad Eye Institute, MTC Campus and Professor, Department of Pathology, Kalinga Institute of Medical Sciences, Patia, Bhubaneswar - 751 024, Odisha
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_2773_20

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Non-Hodgkin's lymphoma is the most common ocular adnexal neoplasm in adults. Involvement of the ocular adnexae can be primary in origin or secondary resulting from systemic disease. We report a 66-year-old male patient with an acute onset of orbital lymphoma with several atypical clinicoradiological features in the absence of any clinical signs of systemic disease at presentation. A histopathological diagnosis of diffuse large B-cell lymphoma was made and immunophenotyping revealed it to be an activated B-cell (ABC) subtype with a “non-double-expressor” phenotype. Rapid progression of disease was noted and resulted in a poor outcome. Clinicoradiological, histopathological, and immunohistochemical correlation is critical for accurate diagnosis in such situations. Additional immunophenotyping to delineate the subtype of DLBCL may have an important role in decision-making regarding the choice of treatment, and may contribute to the prognostication of disease outcome.

Keywords: Activated B-cell (ABC) subtype, germinal center B-cell (GCB) subtype, immunophenotyping, orbital diffuse large B-cell lymphoma (DLBCL)

How to cite this article:
Tripathy D, Pradhan A, Mittal R. Acute orbital presentation in an activated B-cell subtype, diffuse large B-cell lymphoma: clinicoradiological, histopathological and immunohistochemical correlation. Indian J Ophthalmol Case Rep 2021;1:608-10

How to cite this URL:
Tripathy D, Pradhan A, Mittal R. Acute orbital presentation in an activated B-cell subtype, diffuse large B-cell lymphoma: clinicoradiological, histopathological and immunohistochemical correlation. Indian J Ophthalmol Case Rep [serial online] 2021 [cited 2021 Jul 26];1:608-10. Available from: https://www.ijoreports.in/text.asp?2021/1/3/608/320012

Dr. Tripathy and Dr. Pradhan have contributed equally as first authors

Non-Hodgkins lymphoma (NHL) is the most common ocular adnexal malignancy in adults comprising about 10% of all orbital mass lesions.[1] Ocular adnexal lymphoma (OAL) comprises 1-2% of all NHLs[2] and 5–10% of all extranodal NHLs.[3],[4] The most common OAL type is the extranodal marginal zone B-cell lymphoma (EMZL) followed by diffuse large B-cell lymphoma (DLBCL).[5] Herein, we report a case of DLBCL with widespread systemic disease that presented acutely as an orbital mass lesion. We discuss its clinicoradiological, pathological, and immunohistochemical features. This study adhered to all tenets of the declaration of Helsinki.

  Case Report Top

A 66-year-old man presented with sudden onset drooping of the right upper eyelid, binocular diplopia, and pain in the right eye of 10 days' duration. There was no visual complaint and color vision was normal in both eyes. The right eye had complete ptosis [Figure 1]a, conjunctival chemosis, grossly restricted ocular motility [Figure 1]b and minimal proptosis (3 mm). The left eye had cortical cataract. Posterior segment details were unremarkable in both eyes. Regional lymph node involvement was absent. Blood investigations showed a moderately raised ESR. There was no systemic immunosuppression. MRI showed an intraconal soft tissue mass around the right optic nerve, hypointense on T1W [Figure 1]c and slightly hyperintense on T2W images. Intralesional or optic nerve sheath calcification was absent on CT [Figure 1]d. Based on the presentation, a presumptive diagnosis of orbital inflammatory disease was considered, and an oral corticosteroid trial was initiated. A week later, no improvement was evident. The color vision had dropped significantly by this time, but vision remained unaffected and an afferent pupillary defect could not be detected. Incisional biopsy with histopathology revealed infiltration of orbital soft tissue and fat by sheets of dyscohesive medium to large lymphoid cells in a diffuse pattern. The cells had scant to mild amount of pale eosinophilic to amphophilic cytoplasm, large nuclei with irregular nuclear membranes, fine chromatin, and 1-3 small para-central to peripheral nucleoli. Multiple mitotic figures were noted. Morphological features were suggestive of a high-grade diffuse lymphoid neoplasm [Figure 2]a. The lymphoid cells showed strong cytoplasmic expression of CD20 [Figure 2]b and negativity for CD3 [Figure 2]c. Negative staining with cyclin D1 [Figure 2]d and CD5 ruled out a mantle cell lymphoma (blastoid and pleomorphic variants). The Ki-67 proliferation index was 93% [Figure 3]a. The tumor cells did not express CD10 [Figure 3]b and additional staining with CD23 did not highlight any follicular dendritic cells. Further, the cells expressed BCL6 (56%) [Figure 3]c and BCL2 (100%) [Figure 3]d, thus excluding Burkitt lymphoma. Expression of MUM 1 was noted in 61% of cells [Figure 3]e and MYC was negative [Figure 3]f. A diagnosis of DLBCL, centroblastic type, non-germinal center B-cell (non-GCB) or ABC subtype with a “non-double-expressor” phenotype was confirmed.[6] Serum LDH levels were found to be elevated and PET-CT demonstrated involvement of the nasal cavity, right cervical, mediastinal and retroperitoneal lymph nodes, the liver, and the spinal canal. Disease was judged as Stage IV (AJCC 8th Ed, 2018). Systemic chemotherapy with R-CHOP was initiated. After one cycle, the patient developed severe lower spinal pain with paraplegia. Palliative systemic and intrathecal chemotherapy with spinal irradiation was initiated but the patient ultimately succumbed to his disease within 2 months.
Figure 1: A middle-aged male patient presented with severe ptosis of the right eye (a) and near-total external ophthalmoplegia (b) MRI showed a well-defined, ovoid, intraconal soft tissue mass in the right mid-posterior orbit around the optic nerve that was hypointense on the T1W image (c) On CT, no intralesional or optic nerve sheath calcification was evident. Moderate contrast enhancement was noted (d)

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Figure 2: Histopathology showed replacement of orbital soft tissue and fat by dyscohesive/poorly cohesive medium-sized lymphoid cells in a diffuse pattern. The cells had scant to mild amount of pale eosinophilic to amphophilic cytoplasm, large nuclei with irregular nuclear membrane, small 1–3 nucleoli and brisk mitoses (hematoxylin and eosin, X 400) indicative of a high-grade lymphoma (a). On immunohistochemistry, a diffuse and strong cytoplasmic expression of CD20 was noted (b). Tumor cells were negative for both CD3 (c) and cyclin D1 (d)

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Figure 3: The Ki-67 showed a proliferation index of 93% (a). On immunohistochemistry to identify the cell-of-origin, the cells were negative for CD10 (b) and positive for BCL6 (56%; c), BCL2 (100%; d), and MUM 1 (61%; e). Further immunophenotyping revealed them to be negative for MYC (f) confirming a “non-double-expressor” DLBCL phenotype

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  Discussion Top

Orbital lymphoma has been discussed in the literature from the perspective of “primary” disease (arising in the orbit),[7] and “secondary” disease (orbital involvement in a known case of systemic disease).[7],[8] Primary DLBCLs are reported to be either the second[5] or the third[4] most common lymphoma subtypes amongst the OALs. Overall, they form about 8% of the total cases of OALs.[9]

Several series in the literature report between 5.3% and 29.7% of secondary orbital involvement in systemic DLBCL with a consistently high mortality rate.[2],[4],[8],[9],[10],[11] Stacy et al. evaluated the clinicopathological, immunohistochemical, and prognostic features in a series of 20 cases of orbital DLBCLs.[9] A typical histological feature described by them was infiltration of the orbital fat which was also seen in the current case. Using immunostaining algorithms for immunophenotyping and classification, in four of their patients with stage IV disease (similar to our case), one had an ABC and three had a GCB subtype. C-MYC testing was done for only one case and was negative. The authors concluded that clinical staging correlated better with disease outcome as compared to immunohistochemical features or ABC/GCB immunophenotypes.[9]

The current case had some atypical features compared to those described in the literature for secondary orbital DLBCLs.[2],[4],[8],[9],[10] It was unilateral rather than bilateral at presentation, and had no associated vision loss or afferent pupillary defect in spite of an intraconal location in close relation to the optic nerve.[8],[10] Ptosis, external ophthalmoplegia, and chemosis seen in this case are uncommon presenting features in orbital lymphomas.[5] The widespread systemic disease involvement, the poor response to treatment with rapid progression and a fatal outcome was consistent with reports in the literature. Progression-free survival rates over 3–5 years in systemic DLBCL treated with combination immunochemotherapy is reported to be 63–76% for the GCB immunophenotype and 31–40% for the non-GCB/ABC immunophenotype.[12],[13] Treatment outcomes are significantly worse for the latter, especially with R-CHOP chemotherapy,[13] and this was well illustrated in the present case.

Gene expression profiling of DLBCL classifies it into two main molecular subgroups – the GCB subtype and the ABC subtype – based on the cell of origin. Though they may appear histomorphologically similar, they have different genetic and immunohistochemical characteristics, and exhibit significant differences in clinical behavior, response to therapy, and disease outcomes. Immunohistochemistry plays a key role in classifying the subtype by virtue of being a surrogate for gene expression profiling. It provides an efficient method of differentiating the two subtypes by using a stepwise analysis of specific markers.[9],[14]

This case also demonstrates the potential perils associated in opting for a systemic steroid trial based on a presumptive clinicoradiological diagnosis under certain circumstances. It is critical to consider a biopsy with histopathological and immunohistochemical evaluation as a first-line approach specifically when confronted with situations where the clinical presentation is atypical.

  Conclusion Top

To summarize, secondary ocular adnexal/orbital DLBCLs may present acutely with atypical clinicoradiological features, without overt signs of systemic disease at presentation and can have an aggressive clinical course. Our patient did not have any previous known history of affliction with a hematolymphoid malignancy. Secondary orbital disease can precede, be concurrent with or follow the occurrence of systemic lymphoma. Literature recommends that it should be considered in any older adult presenting with proptosis, eyelid fullness, diplopia, or ocular irritation, regardless of whether any established lymphohematopoietic disorder has been documented.[9] In such situations, clinicoradiological, histopathological, and immunohistochemical correlation contributes critically to an accurate diagnosis as illustrated in the presented case. Immunophenotyping to delineate the cell-of-origin may have an increasingly important role in the choice of treatment[14] and may also contribute to the prognostication of disease outcome. The authors suggest that this should routinely be performed for all cases of ocular adnexal DLBCLs.

Declaration of patient consent

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

Financial support and sponsorship

This work was supported by the Hyderabad Eye Research Foundation (HERF).

Conflicts of interest

There are no conflicts of interest.

  References Top

Shields J, Shields C, Scartozzi R. Survey of 1,264 patients with orbital tumors and simulating lesions. Ophthalmology 2004;111:997-1008.  Back to cited text no. 1
Bairey O, Kremer I, Rakowsky E, Hadar H, Shaklai M. Orbital and adnexal involvement in systemic non-Hodgkin's lymphoma. Cancer 1994;73:2395-9.  Back to cited text no. 2
Sjo LD. Ophthalmic lymphoma: Epidemiology and pathogenesis. Acta Ophthalmol 2009;87:1-20.  Back to cited text no. 3
Ferry JA, Fung CY, Zukerberg L, Lucarelli MJ, Hasserjian RP, Preffer FI, et al. Lymphoma of the ocular adnexa: A study of 353 cases. Am J Surg Pathol 2007;31:170-84.  Back to cited text no. 4
Olsen TG, Heegaard S. Orbital lymphoma. Surv Ophthalmol 2019;64:45-66.  Back to cited text no. 5
Smith SM, Riedell PA. Double hit and double expressors in lymphoma: Definition and treatment. Cancer 2018;124:4622-32.  Back to cited text no. 6
Jakobiec FA. Ocular adnexal lymphoid tumors: Progress in need of clarification. Am J Ophthalmol 2008;145:941-50.  Back to cited text no. 7
Esmaeli B, Ahmadi MA, Manning J, McLaughlin PW, Ginsberg L. Clinical presentation and treatment of secondary orbital lymphoma. Ophthal Plast Reconstr Surg 2002;18:247-53.  Back to cited text no. 8
Stacy RC, Jakobiec FA, Herwig MC, Schoenfield l, Singh A, Grossniklaus HE. Diffuse large B-cell lymphoma of the orbit: Clinicopathologic, immunohistochemical, and prognostic features of 20 cases. Am J Ophthalmol 2012;154:87-98.  Back to cited text no. 9
Madge SN, McCormick A, Patel I, Hatef E, Menon V, Prabhakaran VC, et al. Ocular adnexal diffuse large B-cell lymphoma: Local disease correlates with better outcomes. Eye 2010;24:954-61.  Back to cited text no. 10
McKelvie PA, McNab A, Francis IC, Fox R, O'Day J. Ocular adnexal lymphoproliferative disease: A series of 73 cases. Clin Exp Ophthalmol 2001;29:387-93.  Back to cited text no. 11
Lenz G, Staudt LM. Aggressive lymphomas. N Engl J Med 2010;362:1417-29.  Back to cited text no. 12
Gutiérrez-García G, Cardesa-Salzmann T, Climent F, Gonzalez-Barca E, Mercadal S, Mate JL, et al. Gene-expression profiling and not immunophenotypic algorithms predicts prognosis in patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Blood 2011;117:4836-43.  Back to cited text no. 13
Nowakowski GS, Czuczman MS. ABC, GCB, and double-hit diffuse large b-cell lymphoma: Does subtype make a difference in therapy selection? Am Soc Clin Oncol Educ Book 2015;e449-57.  Back to cited text no. 14


  [Figure 1], [Figure 2], [Figure 3]


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