Neoplastic angioendotheliomatosis. A variant of malignant lymphoma immunohistochemical and ultrastructural observations of three cases

Neoplastic angioendotheliomatosis (NAE) is a rare, fatal disease characterized by widespread intravascular proliferations of malignant cells of putative endothelial origin. Clinically, dermatologic and bizarre neurological manifestations predominate, but review of the reported cases of NAE reveals ophthalmic involvement to be frequent. To our knowledge, no reports of NAE have appeared in the ophthalmic literature. We describe three cases of NAE with the ocular manifestations of visual loss, cells in the vitreous, retinal artery occlusion, retinal vascular and pigment epithelial alterations, nystagmus, and cortical blindness. Autopsies (including eyes and central nervous system) revealed pancorporal involvement by intravascular anaplastic cells in each patient. In two patients massive extravascular involvement was also present. The tumor cells lacked ultrastructural features of endothelial cells and failed to stain for factor-VIII-related antigen. Common leukocyte antigen, a maker for hematopoietic cells, particularly lymphocytes, was detected on tumor cells in all cases, indicating that NAE is probably an extranodal lymphoma. The dramatic response of the central nervous system lesions to radiotherapy in one case supports this contention. It is suggested that this disorder be treated as a malignant lymphoma.     

眼眶原发性非何杰金淋巴瘤误诊教训和早期手术治疗

目的 探讨眼眶非何杰金淋巴瘤（ｎｏｎ－Ｈｏｄｇｋｉｎ ｍａｌｉｇｎａｎｔ ｌｙｍｐｈｏｍａ,ＮＨＬ）的早期诊断、常见误诊原因和早期手术的观点。方法 通过复习文献和结合３例眼眶ＮＨＬ临床资料进行分析。结果 眼眶ＮＨＬ起病较急,可表现为眼眶前段软组织炎症或炎性假瘤,Ｂ超和ＣＴ检查也易误诊为炎症,且用抗生素和糖皮质激素治疗症状可缓解而延误治疗。结论 眼眶ＮＨＬ早期可表现为炎症,如用足量,强力的广谱抗生素     

A case of primary non-Hodgkin lymphoma of the lacrimal sac

Malignant tumors of the lacrimal sac are uncommon, and primary non-Hodgkin lymphomas are rare. We report the case of an 80-year-old woman presenting with epiphora and swelling of the left lacrimal area. A dacryocystorhinostomy was programmed, but within few weeks a painful tumor appeared with cervical nodes. Pathological studies of the mass revealed diffuse malignant lymphoma with large B cells. The lymphoma was classified as stage IIE using Ann Arbor staging after clinical, biological and radiological examination. Six CHOP systemic chemotherapy were proposed. After 12 months and only 4 cures because of hematological complications and cardiac toxicity, the patient was disease-free. Primary non-Hodgkin lymphoma of the lacrimal sac is extremely rare. Collaboration between the ophthalmologist, anatomopathologist and oncologist allowed us to determine the type and the extension and to propose an aggressive but successful treatment in this highly malignant and very localized lymphoma.     

Oculocerebral non-Hodgkin's lymphoma with uveal involvement: development of an epibulbar tumor after vitrectomy

Primary ocular lymphoma is the ocular manifestation of primary oculocerebral non-Hodgkin's lymphoma. We describe a 79-year-old woman with a 7-year history of bilateral uveitis and subsequent central nervous system lymphomas. Repeated diagnostic vitrectomy during the following 5 years failed to demonstrate intraocular lymphoma cells. Within 9 months after the second vitrectomy, an epibulbar tumor developed in the limbal region of the left eye at the site of the sclerotomy. The eye, blind and painful due to secondary angle-closure glaucoma, was enucleated. Histopathologically, the globe showed a diffuse large B-cell non-Hodgkin's lymphoma extending from the ciliary body outward through the sclerotomy. We conclude that, following vitrectomy, a primary ocular lymphoma may extend through the sclerotomy lesion and present as an epibulbar tumor. Uveal involvement may occur in oculocerebral non-Hodgkin's lymphoma.     

Intraocular involvement as initial symptoms of non-Hodgkin lymphoma

BACKGROUND: The diagnosis of a intraocular lymphoma is often delayed because of a symptomatic pseudouveitis. CASE REPORT: We report on a 68-year-old female patient, who was referred because of a tumor of the optic disk in her right eye and bilateral uveitis with secondary glaucoma. The painful blind right eye was enucleated. The assumed diagnosis of a pseudouveitis as an initial manifestation of a B-cell lymphoma was confirmed histologically. She developed systemic extension and recurrence in the second eye despite polychemotherapy. The patient died from complications of her systemic tumor disease 15 months after initial symptoms. CONCLUSIONS: An initially unilateral and later bilateral uveitis in elderly patients which does not respond to steroid therapy could also be suspicious for an intraocular lymphoma. If the conjunctiva is not involved, the confirmation of the diagnosis requires a diagnostic viteous biopsy.     

Primary orbital malignant lymphoma: a clinicopathology study of 17 cases

We investigated the clinicopathologic characteristics of 17 patients (13 men and 4 women) with primary orbital malignant lymphoma using the Working Formulation. Most of the cases belonged to the low-grade malignancy group, and more women than men were in the histologically high-grade malignancy group. The phenotype of the tumor cells was investigated immunohistochemically. All cases showed the monoclonal feature of a B-cell lineage. All patients received chemotherapy with or without radiotherapy. Of 16 subjects, 15 achieved a complete remission; none of these patients has had a recurrence since the completion of the initial therapy (range of follow-up from 16 months to 10 years). One patient died. Offprint requests to: H.K. Mishima     

Two cases of malignant lymphoma complicated by hemophagocytosis resembling orbital cellulitis

Two patients with malignant lymphoma complicated by hemophagocytic syndrome (HPS) are reported. Their clinical signs at onset were similar to those of orbital cellulitis. Lymphoma complicated by hemophagocytosis is called lymphoma-associated hemophagocytic syndrome (LAHS) and its prognosis is reported to be very poor. As far as we know, this is the first report in the ophthalmological field. In our patients, we suspected that the lesions occurred from the orbit or skin of this area. The first patient was a 22-year-old man and the second patient a 16-year-old girl. The diagnosis was very difficult at the onset of disease. They died within. 6 months after the first ophthalmological examination. When orbital cellulitis is suspected and, antibiotic therapy is ineffective, we should suspect HPS and should examine serum ferritin, which is a good marker of HPS. Early biopsy and consultation with a hematologist are very important.     

A clinical study of intraocular malignant lymphoma

PURPOSE: We investigated whether vitreous cytology and the measurement of intravitreous cytokine were useful for the diagnosis of intraocular malignant lymphoma. SUBJECTS AND METHODS: 8 eyes of 5 patients with suspected intraocular malignant lymphoma during the past 15 months. 3 vitreous samples were collected from 3 patients at the time of pars plana vitrectomy. Polymerase chain reaction(PCR) amplification and flowcytometric analysis(FACS) of the vitreous samples were performed. Interleukin (IL)-10 and IL-6 concentrations were measured. RESULTS: Vitreous cytology showed increased atypical B lymphocytes. The vitreous IL-10/IL-6 ratio was higher than 1 in all cases. Monoclonal rearrangement of the immunoglobulin heavy chain gene and the light chain restriction of immunoglobulin were detected. CONCLUSION: The detection of the monoclonality of infiltrated cells into the vitreous by PCR amplification and FACS, and the measurements of IL-10 and IL-6 concentrations in the vitreous fluid may be useful in the diagnosis of intraocular malignant lymphoma.     

Sudden blindness in an AIDS patient. Simultaneous infection with cytomegalovirus and herpes simplex viruses and development of malignant non-Hodgkin lymphoma]

A 50 year old patient with non-diagnosed HIV-infection at onset of his illness developed impairment of vision and temporary double vision combined with severe hemianopsia. With normal fundus and suspicious Herpes simplex iritis therapy with Acyclovir was started. Primarily the patient showed a good response to the therapy and loss of vision could be prevented. After 4 weeks CMV-retinitis developed. In spite of Gancyclovir therapy manifestation of total loss of vision after 6 weeks. Autopsy demonstrated signs of simultaneous a CMV-infection of the retina and a herpes simplex-infection of the optic nerve combined with a Non-Hodgkin-Lymphoma of the optic tract.     

A case of primary B-cell type non-Hodgkin lymphoma originating in the iris

PURPOSE: To report a case of primary malignant B-cell type non-Hodgkin lymphoma originating in the iris. DESIGN: Interventional case report. METHODS: An 83-year-old woman presented with anterior uveitis resulting from primary malignant lymphoma in the iris. Ultrasound biomicroscopy and indocyanine green angiography using a scanning laser ophthalmoscope showed abnormalities in the iris. Diagnostic biopsy of the iris revealed B-cell type non-Hodgkin lymphoma. RESULT: The patient was treated with radiotherapy, and the tumorous lesion resolved. CONCLUSION: Primary lymphoma localized in the iris only is rare. In this case, diagnostic biopsy and radiotherapy of the iris lymphoma provided good results.     

眼附属器恶性淋巴瘤172例临床病理分析

目的初步探讨眼附属器恶性淋巴瘤的临床特点及病理学分类。方法 对172例187眼经组织病理学确诊的眼附属器恶性淋巴瘤患者的临床及病理资料进行回顾性分析。结果 患者年龄12～85岁,平均63岁,病程13d～25a,平均75个月。其中眼眶恶性淋巴瘤最多见,共98眼(52.33%),其次为结膜48眼(25.00%)及眼睑37眼(20.35%)、泪囊4眼(2.33%)。免疫组织化学染色146例159眼(84.88%)均为非霍奇金淋巴瘤,其中86例95眼(58.90%)确诊为低度恶性黏膜相关淋巴组织淋巴瘤(MALT淋巴瘤)。眼附属器恶性淋巴瘤以眼睑色块和结膜新生物128眼(69.77%)或眼球突出48眼(25.00%)为主要就诊原因。结论 眼附属器恶性淋巴瘤多为黏膜相关性淋巴组织淋巴瘤,免疫组织化学检测有助于诊断。准确的肿瘤病理学分类不仅能指导临床治疗,还能反映患者预后。     

Multifocal intraocular malignant melanoma: report of two cases and review of the literature.

PURPOSE: To describe two eyes from two patients with multifocal primary intraocular melanoma. DESIGN: Two case reports. METHODS: The history and histologic findings in the enucleated eyes of two patients with multifocal intraocular melanoma are described in comparison to previously reported cases. MAIN OUTCOME MEASURES: Pathologic examination of enucleated eyes. RESULTS: One of the two eyes contained mixed cell type melanomas, and one eye contained spindle cell type melanomas. Examination of serial sections showed no continuity between the intraocular melanomas. There were no associated ocular or systemic conditions with the multifocal intraocular melanomas. CONCLUSIONS: Multifocal primary intraocular melanoma is rare. There is no known predisposing factor to this condition.     

Trilateral malignant lymphoma: primary malignant B-cell lymphoma of the eyes and brain. Diagnosis by transvitreal retinochoroidal biopsy

A 59-year-old woman with therapy-resistant bilateral involvement of posterior uvea and retina of some months' duration was examined. Diagnostic vitrectomy was inconclusive, but subsequent transvitreal retinochoroidal biopsy gave ample material for the immunohistopathological diagnosis of a malignant B cell lymphoma. Despite systemic and intrathecal cytostatics and ocular X-ray therapy, central nervous system involvement was observed 2 months later. The ocular lesions regressed after treatment and have not recurred.     

A case of malignant lymphoma with various ocular manifestations

A case of malignant lymphoma with a variety of ophthalmological findings was reported. The patient was a 65-year-old man with malignant lymphoma in retro-peritoneum (stage IV). Uveitis with hypopyon and secondary glaucoma appeared in his right eye, optic neuritis in his left eye. We compared clinical observations with histopathological findings and found that glaucoma was due to direct obstruction in the trabecular space by tumor cells and optic neuritis was due to the tumor cell infiltration into optic nerve.