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• W2112325767 abstract "Signet-ring cell lymphoma (SRCL) is a rare morphologic variant of non-Hodgkin lymphoma with a “signet-ring cell” appearance. It has been described in both B-cell and T-cell lymphomas.1Nagasaki A. Oshiro A. Miyagi T. et al.Signet ring cell lymphoma.Int Med. 2003; 42: 1055-1056Crossref PubMed Scopus (4) Google Scholar We report an orbital SRCL of diffuse large B-cell type in a 60-year-old male, which, to the best of our knowledge, is only the second case to be described in the literature. A 60-year-old male presented to our clinic with complaints of painless, gradually progressive protrusion of his left eye for 18 months. External examination of the left eye showed a firm swelling superomedial and inferomedial to the globe associated with lid swelling (Fig. 1A). The distinct masses were nodular, and the posterior extent could not be ascertained. Orbital rims were intact and the overlying skin was normal. The masses were not freely mobile. Anterior segment evaluation, visual acuity, and fundus examination were normal. Computed tomography showed a well-defined hypodense to isodense, lobulated soft tissue lesion on the left side extending from the preseptal plane to the mid-orbit nasally and into the extraocular muscle cone. Anteriorly the mass extended up to the bridge of the nose; the bony orbit showed no change, and there was no involvement of the nose or sinuses (Fig. 1B, 1C). Microscopic examination of the incision biopsy from the orbital mass showed a diffusely infiltrating cellular tumour composed of large, noncohesive cells in a sclerotic stroma with foci of necrosis. Many of the tumour cells had large, round, cytoplasmic vacuoles and eccentrically placed atypical nuclei (Fig. 2A). Immunostaining was positive for leukocyte common antigen (Fig. 2B) and CD20 (Fig. 2C) in all tumour cells. Fifty-three percent of the cells were immunoreactive for Bcl-6. A positive reaction was seen for lambda light-chain restriction. Ki-67 activity was 70% to 80% (Fig. 2D). The tumour cells were negative for CD5, CD10, CD23, HMB45, pancytokeratin, S100, epithelial membrane antigen, smooth muscle actin, cytokeratin 7, and cytokeratin 20. They were also negative on periodic acid–Schiff (PAS) and Alcian blue staining. Systemic examination and bone marrow examination were normal. Our patient was thus categorized as Ann Arbor stage I and American Joint Committee on Cancer stage T3N0M0. He was started on a CHOP regimen composed of cyclophosphamide, hydroxydaunorubicin, Oncovin (Vincristine), and prednisolone. In addition, external beam radiotherapy (EBRT) of 4000 cGy was also given. A marked reduction in size of the tumour was seen after the first cycle, and a CT scan at the end of third cycle did not show any residual tumour. Ocular adnexal lymphomas are rare, accounting for only 1% to 2% of all lymphomas.2Barry O. Kremer I. Rakowsky E. Hadar H. Shaklai M. Orbital and adnexal involvement in systemic non-Hodgkin’s lymphoma.Cancer. 1994; 73: 2395-2399Crossref PubMed Scopus (85) Google Scholar Diffuse large B-cell lymphoma (DLBCL) is a high-grade lymphoma that commonly presents with systemic involvement.3Gedik S. Gur S. Maral T. Akova Y.A. Demirhan B. Bilateral synchronus primary orbital lymphoma.Adv Ther. 2006; 23: 433-438Crossref PubMed Scopus (3) Google Scholar Most ocular adnexal lymphomas are low-grade extranodal marginal zone lymphomas of B-cell type. Morphologic variants of DLBCL include centroblastic, immunoblastic, T-cell/histiocyte-rich and anaplastic subtypes.4Gatter K.C. Warnke R.A. Diffuse large cell lymphoma.WHO classification of tumours of hemopoietic and lymphoid tissues. International Agency for Research of Cancer, Lyon, France2008: 171-174Google Scholar SRCL, most commonly described as a variant of follicular lymphoma, has been rarely described in DLBCL.5Dardick I. Srinivasan R. Al-Jabi M. Signet-ring cell variant of large cell lymphoma.Ultrastruct Pathol. 1983; 5: 195-200Crossref PubMed Scopus (24) Google Scholar To date, only about 50 cases of SRCL have been described in the literature.6Cross P.A. Eyden B.P. Harris M. Signet-ring cell lymphoma of T-cell type.J Clin Pathol. 1989; 42: 239-245Crossref PubMed Scopus (41) Google Scholar Most commonly affecting the lymph nodes, SRCLs have been described to involve the skin, stomach, thyroid,1Nagasaki A. Oshiro A. Miyagi T. et al.Signet ring cell lymphoma.Int Med. 2003; 42: 1055-1056Crossref PubMed Scopus (4) Google Scholar small bowel, and bone marrow.7Kim H. Dorfman R.F. Rappaport H. Signet ring cell lymphoma: a rare morphologic and functional expression of nodular (follicular) lymphoma.Am J Surg Pathol. 1978; 12: 119-132Crossref Scopus (136) Google Scholar, 8Grogan T.M. Payne C.M. Richter L.C. Rangel C.S. Signet ring cell lymphoma of T-cell origin: an immunohistochemical and ultrastructural study relating giant vacuole formation to Cytoplasmic sequestration of surface membrane.Am J Surg Pathol. 1985; 9: 684-692Crossref PubMed Scopus (48) Google Scholar, 9Tungekar M.F. Gastric signet ring lymphoma with alpha heavy chains.Histopathology. 1986; 10: 725-733Crossref PubMed Scopus (25) Google Scholar, 10Allevato P.A. Kini S.R. Rebuck J.W. Miller J.M. Hamburger J.L. Signet-ring cell lymphoma of the thyroid: a case report.Hum Pathol. 1985; 16: 1066-1068Abstract Full Text PDF PubMed Scopus (27) Google Scholar, 11Basir N. Bickle I.C. Telisinghe P.U. Abdullah M.S. Chong V.H. Signet ring cell lymphoma of the small bowel: a case report.Oman Med J. 2012; 27: 491-493Crossref PubMed Scopus (7) Google Scholar, 12McCluggage W.G. Bharucha H. el-Agnaf M. Toner P.G. B cell signet-ring cell lymphoma of bone marrow.J Clin Pathol. 1995; 48: 275-278Crossref PubMed Scopus (25) Google Scholar Orbital SRCL is rare, with only 1 such case described previously in the literature.13Dolman P.J. Rootman J. Quenville N.F. Signet ring cell lymphoma in the orbit: a case report and review.Can J Ophthalmol. 1986; 21: 242-245PubMed Google Scholar Our case represents the second reported case of orbital SRCL. Based on the morphologic and immunohistochemical features, SRCLs are classified into 3 subtypes: clear vacuole type, Russell body type, and hyaloplasmic deposit type.11Basir N. Bickle I.C. Telisinghe P.U. Abdullah M.S. Chong V.H. Signet ring cell lymphoma of the small bowel: a case report.Oman Med J. 2012; 27: 491-493Crossref PubMed Scopus (7) Google Scholar Our patient has the clear vacuole type of SRCL. SRCLs have been described in both B-cell and T-cell lymphomas.6Cross P.A. Eyden B.P. Harris M. Signet-ring cell lymphoma of T-cell type.J Clin Pathol. 1989; 42: 239-245Crossref PubMed Scopus (41) Google Scholar, 7Kim H. Dorfman R.F. Rappaport H. Signet ring cell lymphoma: a rare morphologic and functional expression of nodular (follicular) lymphoma.Am J Surg Pathol. 1978; 12: 119-132Crossref Scopus (136) Google Scholar, 8Grogan T.M. Payne C.M. Richter L.C. Rangel C.S. Signet ring cell lymphoma of T-cell origin: an immunohistochemical and ultrastructural study relating giant vacuole formation to Cytoplasmic sequestration of surface membrane.Am J Surg Pathol. 1985; 9: 684-692Crossref PubMed Scopus (48) Google Scholar, 9Tungekar M.F. Gastric signet ring lymphoma with alpha heavy chains.Histopathology. 1986; 10: 725-733Crossref PubMed Scopus (25) Google Scholar, 10Allevato P.A. Kini S.R. Rebuck J.W. Miller J.M. Hamburger J.L. Signet-ring cell lymphoma of the thyroid: a case report.Hum Pathol. 1985; 16: 1066-1068Abstract Full Text PDF PubMed Scopus (27) Google Scholar, 11Basir N. Bickle I.C. Telisinghe P.U. Abdullah M.S. Chong V.H. Signet ring cell lymphoma of the small bowel: a case report.Oman Med J. 2012; 27: 491-493Crossref PubMed Scopus (7) Google Scholar Although more commonly associated with follicular type non-Hodgkin lymphoma, SRCL has been described rarely in large B-cell lymphoma.5Dardick I. Srinivasan R. Al-Jabi M. Signet-ring cell variant of large cell lymphoma.Ultrastruct Pathol. 1983; 5: 195-200Crossref PubMed Scopus (24) Google Scholar Our case was an SRCL of diffuse, large, B-cell type. The tumour cells in SRCL have been described to contain immunoglobulins, as was in our case.11Basir N. Bickle I.C. Telisinghe P.U. Abdullah M.S. Chong V.H. Signet ring cell lymphoma of the small bowel: a case report.Oman Med J. 2012; 27: 491-493Crossref PubMed Scopus (7) Google Scholar Ultrastructural examination of SRCL has revealed giant multivesicular bodies and electron-dense crystalloids enclosed within expanded segments of rough endoplasmic reticulum.5Dardick I. Srinivasan R. Al-Jabi M. Signet-ring cell variant of large cell lymphoma.Ultrastruct Pathol. 1983; 5: 195-200Crossref PubMed Scopus (24) Google Scholar, 14Eyeden B.P. Cross P.A. Harris M. The ultrastructure of signet-ring cell non-Hodgkin’s lymphoma.Virchows Arch A Pathol Anat Histopathol. 1990; 417: 395-404Crossref PubMed Scopus (22) Google Scholar Mucin is absent in SRCL, as opposed to a signet-ring cell adenocarcinoma, with which it can be confused morphologically, and PAS and Alcian blue staining were both negative in our patient. No known associations or risk factors predisposing to SRCL exist. Clinical manifestations of SRCL are similar to non-SRCL.11Basir N. Bickle I.C. Telisinghe P.U. Abdullah M.S. Chong V.H. Signet ring cell lymphoma of the small bowel: a case report.Oman Med J. 2012; 27: 491-493Crossref PubMed Scopus (7) Google Scholar The diagnosis relies on morphological findings and immunohistochemical features. The treatment for SRCL is similar to other lymphomas consisting of chemotherapy and/or radiotherapy depending on the location and stage of the tumour. Our patient was given EBRT and chemotherapy composed of a CHOP regimen. He responded significantly to the treatment administered. In conclusion, this is an unusual case of orbital SRCL, a rare variant of DLBCL. It is important to know the morphologic and immunohistochemical features of this variant, and thus differentiate it from a metastatic signet-ring carcinoma and orbital liposarcoma, both of which can be confused with and have different behaviour and management protocols. ErratumCanadian Journal of OphthalmologyVol. 49Issue 1PreviewIn the article “Orbital signet-ring cell lymphoma of diffuse, large, B-cell type” by Kaustubh Mulay, Akshay G. Nair, Ekta Aggarwal, Valerie A. White, Santosh G. Honavar in the December 2013 issue of the Canadian Journal of Ophthalmology (2013;48:e156), the author names appeared wrongly in the online version. The correct names are as mentioned above. Full-Text PDF" @default.
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