T-cell and T/natural killer-cell lymphomas involving ocular and ocular adnexal tissues: a clinicopathologic, immunohistochemical, and molecular study of seven cases

OBJECTIVE: Lymphomas of the eye and its adnexa are frequently of B lineage. This study aims to characterize the clinical and histopathologic features of the rare non-B-cell non-Hodgkin lymphomas (NHL) of these locations. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Seven cases of T- and T/NK-cell lymphomas involving the ocular and ocular adnexal tissues. METHODS: A morphologic, immunohistochemical, and molecular analysis (polymerase chain reaction) of each of the tumors was undertaken. The lesions were classified according to the Revised European-American Lymphoma (REAL) classification. The clinical and follow-up data were collected. RESULTS: The patients included four women and three men ranging in age from 32 to 88 years (mean, 63 years). The presenting ophthalmic symptoms varied from a small nodule on the upper eyelid and conjunctival swellings to dramatic loss of vision associated with gross protrusion of the globe. Five of the cases presented were secondary manifestations of a systemic lymphoma in ocular tissues; two cases represented primary disease. Three cases were "peripheral T-cell lymphomas (PTCL), unspecified" with positivity for CD3, CD8, and betaF1 and negativity for CD56. Two cases were CD3+, CD30+, and CD56- and were classified as "anaplastic large-cell lymphomas of T-cell type" (T-ALCL). The remaining two cases showed an immunophenotype of CD3+, CD56+, and betaF1- and proved to contain Epstein-Barr virus (EBV) by in situ hybridization, consistent with "T/natural killer (NK)-cell lymphoma of nasal type." Clonal T-cell populations were shown in all three of the PTCLs by Southern blot (n = 1) and polymerase chain reaction (n = 2) for the T-cell receptor gamma and beta genes in one case of ALCL but not in the T/NK-cell lymphomas. Five patients died within 2 years; only two patients (one primary PTCL and one cutaneous T-ALCL) were disease free at 4 and 5 years' follow-up, respectively. CONCLUSION: This study shows that a heterogeneous group of T-cell lymphomas can involve the eye and its adnexal tissue. Most T-cell neoplasms are secondary manifestations of systemic disease and carry a poor prognosis. These findings, in conjunction with published data on ocular B-NHL, also indicate that immunophenotypic differentiation between T- and B-NHL in these locations is of clinical importance.     

Rapidly fatal nasal natural killer/T-cell lymphoma: orbital and ocular adnexal presentations

Nasal natural killer/T-cell lymphoma (NKTL) is an aggressive malignancy that may initially present with orbital and/or ocular adnexal symptoms. We describe the case of a 27-year-old female with nasal NKTL, who initially presented with epiphora and died 4 months thereafter.     

Primary vitreoretinal natural killer/T-cell lymphoma with breast involvement: A case report and review of the literature

A 50-year-old woman developed recurrent vitreous opacities in her left eye. The first diagnostic vitrectomy revealed no significant abnormality. Optical coherence tomography showed multiple high-density reflective nodules. The ratio of interleukin-6 to interleukin-10 was over 1 in her aqueous humor, and Epstein-Barr virus was present. A conventional immunohistochemistry examination of vitrectomy specimens was diffusely positive for CD2, CD3, and Ki-67. Highly metabolic nodules were found in her right breast on positron emission tomography-computed tomography scan. Immunohistochemistry of the breast biopsy was suggestive of natural killer/T-cell lymphoma. Considering the homology between the two lesions, combined with ancillary cytokine, cytology, and flow cytometry findings, the final diagnosis was primary vitreoretinal natural killer/T-cell lymphoma with involvement of the breast. The lymphoma resolved with chemotherapy, intravitreal injection of methotrexate, and ocular radiotherapy. This case shows that primary vitreoretinal natural killer/T-cell lymphoma can present with concomitant systemic involvement. We reviewed relevant published literature and summarized some new approaches that make the diagnosis easier and faster; however, the cytopathologic analysis of intraocular fluid is irreplaceable. An effective treatment strategy is still a matter of speculation.     

Ocular involvement in nasal natural killer T-cell lymphoma

Purpose To describe the clinical, morphologic, and immunohistochemical features of a case of paranasal natural killer/T-cell lymphoma (NKTL) with ocular involvement. Case report In March 2005 the patient presented with a maxillary sinusitis and upper nasal obstruction. In July she underwent a nasal computed tomography (CT) scan and multiple biopsies of the granulomatous tissue in the nasal fossae. The diagnosis was NK/T non-Hodgkin’s lymphoma nasal type, stage IV A. Afterwards she presented anterior uveitis. In September after the diagnosis of lymphoma the patient underwent a bone marrow biopsy and thoracic and abdominal CT scan. An ophthalmic examination including visual acuity assessment and fundoscopic examination was made. In October she started chemotherapy cycles. Maxillary CT scan and ophthalmic examinations were performed during the cycles. In January 2006 after severe recurrences of panuveitis a diagnostic vitrectomy was performed. Results A diagnosis of T-lymphoma cells in the vitreous was made; the tumor was most likely originating from her paranasal NKTL. The condition of the patient deteriorated rapidly and she expired on February 2006. Conclusions Nasal and paranasal sinus lymphomas are rare, but aggressive diseases with a tendency to invade tissues and spread to CNS, including the eye. Ocular manifestations prior to systemic ones may be useful to monitor the response to therapy.     

Intraocular involvement of a nasal natural killer T-cell lymphoma: a case report

Herein, we report a case of nasal natural killer T-cell lymphoma (NKTL) with intraocular involvement. A 57-year-old woman was referred due to a three-day history of photophobia and diplopia in the left eye. One-month previously, she was diagnosed with nasal NKTL of the right nasal cavity. Ophthalmic examination revealed conjunctival injection and ptosis. The left pupil was fully dilated and non-reactive to light. Ocular motion was restricted on left-upper gaze. Five days later, anterior uveitis developed and persisted despite topical steroid treatment. An orbital magnetic resonance imaging was without specific findings, however, ophthalmoplegia, vitreous opacity, and an iris mass were observed. A diagnostic anterior chamber aspiration was performed. Aqueous humor aspiration revealed 35% morphologically atypical lymphocytes. After an intravitreal triamcinolone injection, radiotherapy and chemotherapy were administered; this resolved the uveitis and iris mass. When refractory uveitis or orbital pseudotumor occurs in patients with nasal NKTL, ocular and orbital involvement of the NKTL should be considered.     

Primary ocular Epstein-Barr virus-associated non-Hodgkin's lymphoma in a patient with AIDS: a clinicopathologic report

OBJECTIVE: To report an unusual case of chronic multifocal chorioretinitis with vitritis in a patient with acquired immunodeficiency syndrome (AIDS) that was resistant to antiviral and antitoxoplasmic medication and required a retinal biopsy for definitive diagnosis. METHODS: Vitreous biopsy, pars plana vitrectomy, and retinal biopsy were performed. The vitreous biopsy material was sent for bacterial, fungal, and viral culture, and the vitreous cassette was sent for cytology. The retinal biopsy material was divided and sent for polymerase chain reaction testing for toxoplasmosis and virology and pathologic tissue analysis. RESULTS: Vitreous cytology showed a mixed population of lymphocytes and histiocytes, but all other microbiologic and virologic studies were negative. Tissue analysis revealed an infiltrate of atypical mononuclear cells extending from the inner limiting membrane through the outer plexiform layer characteristic of a B cell, non-Hodgkin's lymphoma of the central nervous system (NHL-CNS). In situ hybridization for the Epstein-Barr virus (EBV) was positive. An extensive systemic evaluation did not show evidence of extraocular tumor. CONCLUSION: Although rare, primary ocular NHL-CNS can be seen in patients with AIDS, and its clinical presentation often closely resembles other disorders. To our knowledge, this case represents the first ocular NHL in which EBV is shown to be associated.     

Regulation of the metastasis of murine ocular melanoma by natural killer cells

In the current study we examine parameters affecting the metastasis of ocular tumors of in vivo derived B16F10 melanoma. In C57BL/6J beige (bg/bg) mice, with low NK activity, metastasis to the lungs was increased and survival time decreased. In C57BL/6J normal (+/+) mice treatment with PK136, a highly specific monoclonal anti-NK antibody (Ab), caused a depletion of NK cytotoxic activity, as demonstrated using a standard 51Cr release assay. In animals bearing ocular tumors, treatment with PK136 Ab resulted in significantly increased pulmonary metastasis and an altered pattern of metastasis. The effect of combined treatment protocols using LS2616 (linomide) and cyclophosphamide (Cy) was examined in enucleated and unenucleated animals. Treatment with LS2616 and Cy resulted in a significant decrease in mean pulmonary metastases (MPM), a decreased frequency of metastasis to the submandibular lymph nodes and an increase in mean survival time. In enucleated mice this combined treatment protocol resulted in apparent cures, the lowest MPM and the longest survival time observed. When tumor-bearing mice were treated with either silica, carrageenan or sublethal gamma irradiation, no effect on metastasis or survival was observed. This study demonstrates the importance of the NK cell as a primary effector cell for the control of metastasis from in vivo derived ocular B16F10 melanoma.     

Recurrent natural killer/T-cell lymphoma of the lacrimal sac and nasolacrimal duct in a 59-year-old Caucasian woman

A 59-year-old Caucasian woman with past medical history significant for Natural Killer (NK)/T-cell lymphoma of the right nasal septum in remission for nine months presented after surveillance PET-CT imaging revealed increased metabolic activity in the right nasolacrimal duct. She also reported ipsilateral epiphora starting around this time. The lacrimal sac and nasolacrimal ductal mucosa were biopsied via an external approach. Pathologic evaluation revealed a proliferation of lymphoid cells with necrotic tissue. Immunohistochemical staining demonstrated predominantly CD3+, EBER+, and CD56+ cells indicating recurrent NK/T-cell lymphoma. This case describes an unusual presentation of recurrent NK/T-cell lymphoma involving the lacrimal excretory system in a Caucasian adult. Recurrent malignancy should be considered in the differential of any patient with a history of a lymphoproliferative disorder near the lacrimal drainage system who presents with new onset epiphora.     

Natural killer/T-cell lymphoma masquerading as orbital cellulitis

We describe 3 cases of natural killer/T-cell lymphoma that presented by masquerading as orbital cellulitis. All of the patients were examined for pain, fever, proptosis, and motility restriction. Computed tomography of the orbits and sinuses revealed orbital soft-tissue swelling without focal abscess in all 3 cases. Bacterial and fungal cultures were negative in each case and all of the patients had initial improvement on systemic antibiotics, only to relapse several days later. Diagnosis of natural killer/T-cell lymphoma was then made based on biopsy of the orbit or sinus. Natural killer/T-cell lymphoma should be considered in cases of orbital cellulitis or sinusitis that fail to respond to traditional management. Biopsy of the affected region should be performed expeditiously to diagnose this condition. Repeat biopsy may be needed.     

Primary intraocular lymphoma (ocular reticulum cell sarcoma) diagnosis and management

The authors retrospectively reviewed the diagnosis and management of 20 intraocular lymphoma patients who initially presented with either ocular or central nervous system (CNS) disease. As the ophthalmic community has become more aware of this entity, the interval between symptoms and diagnosis has significantly shortened. Diagnosis can usually be made on cytopathologic examination of vitreous cells. However, in three cases more than one vitreous biopsy was necessary. Results of cytologic examination appeared to be more accurate than those of conventional lymphocyte surface marker studies in the diagnosis of an intraocular lymphoma. Long-term survival occurred in some patients treated with a combination of intrathecal chemotherapy and ocular/CNS irradiation.     

GM1 Gangliosidosis,type 2: ocular clinicopathologic correlation

The clinical and pathological manifestations of a case of juvenile GM₁ gangliosidosis are presented and the pathological findings compared with those previously reported for GM₁ gangliosidosis in man and in animal models. The most striking finding in the present case was the marked degeneration of the retinal ganglion cell and nerve fiber layers. Although such extensive ganglion cell loss was not observed in any of the other cases reviewed, the presence of multimembranous inclusion bodies in retinal ganglion cells strongly suggests that the pathological process was similar in all cases. Much remains to be learned about the function of gangliosides in the healthy retina and about the pathophysiological consequences of deranged ganglioside metabolism. The many parallels, including those observed in pathological studies, between the human and animal forms of GM₁ gangliosidosis allow an optimistic appraisal of the value of further research using the animal models.     

Primary graft failure : a clinicopathologic and molecular analysis

OBJECTIVE: Primary graft failure (PGF) corneal tissues were analyzed for herpes simplex virus (HSV) and varicella-zoster virus (VZV). DESIGN: Retrospective, noncomparative case series. MATERIALS: Formalin-fixed, paraffin-embedded tissue of 21 donor corneas and 14 recipient corneas of PGF cases, as well as 10 control corneas. METHODS: Clinical, histologic, immunohistochemical, polymerase chain reaction (PCR), and, in selected cases, transmission electron microscopic characteristics were studied. MAIN OUTCOME MEASURES: Evidence of HSV or VZV in donor tissues. RESULTS: Median patient age was 65 years, and median donor age was 48 years. Donor cornea parameters, including endothelial cell counts, death-to-preservation time, and time in storage, were generally within accepted standards. Stromal edema was found in all 21 donor corneas with PGF. Eighteen donor corneas demonstrated severely reduced or absent endothelium and mild to moderate lymphocytic infiltration without necrosis. Three donor corneas (14%) had necrotizing stromal keratitis (NSK) with keratic precipitates. Positive immunohistochemical staining of keratocytes for HSV was present in two of two donor corneas with NSK and was negative in 18 other donor corneas. Polymerase chain reaction analysis revealed the DNA of HSV type 1 (HSV1) in all donor corneas with NSK and in four donor corneas without NSK (33%). Recipient corneal tissue was negative for HSV1 DNA in three patients with NSK and positive in two of the four other PCR-positive patients. Transmission electron microscopy analysis showed viral particles in two donor corneas with NSK. Polymerase chain reaction analysis revealed no evidence of HSV type 2 or VZV in any cornea. All control corneas were negative for viral DNA. Sixteen corneas remained clear and two had failed after regraft for PGF, with a median follow-up of 3.6 years. CONCLUSIONS: Herpes simplex virus type 1 DNA was present in 33% of patients of PGF. Herpetic stromal keratitis was found in some failed corneas; the lack of HSV in the paired recipient suggests importation within the donor cornea. The overall prognosis for regrafting after PGF is good.     

Systemic lupus erythematosus: Systemic and ocular features

Systemic lupus erythematosus is one of a group of diseases believed to have an auto immune basis. It presents in a diversity of clinical forms, making its diagnosis difficult and often delayed. Ocular signs are common and may be the first manifestations of the disease. Recognition of the underlying cause can assist in more appropriate treatment of the systemic signs and symptoms. This review examines the epidemiology, aetiology, systemic and ocular signs, together with suggested medical and optometrical management strategies.