Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders.

BACKGROUND: Mikulicz's disease (MD) has been considered as one manifestation of Sjögren's syndrome (SS). Recently, it has also been considered as an IgG(4)-related disorder. OBJECTIVE: To determine the differences between IgG(4)-related disorders including MD and SS. METHODS: A study was undertaken to investigate patients with MD and IgG(4)-related disorders registered in Japan and to set up provisional criteria for the new clinical entity IgG(4)-positive multiorgan lymphoproliferative syndrome (IgG(4)+MOLPS). The preliminary diagnostic criteria include raised serum levels of IgG(4) (>135 mg/dl) and infiltration of IgG(4)(+) plasma cells in the tissue (IgG(4)+/IgG+ plasma cells >50%) with fibrosis or sclerosis. The clinical features, laboratory data and pathologies of 64 patients with IgG(4)+MOLPS and 31 patients with typical SS were compared. RESULTS: The incidence of xerostomia, xerophthalmia and arthralgia, rheumatoid factor and antinuclear, antiSS-A/Ro and antiSS-B/La antibodies was significantly lower in patients with IgG(4)+MOLPS than in those with typical SS. Allergic rhinitis and autoimmune pancreatitis were significantly more frequent and total IgG, IgG(2), IgG(4) and IgE levels were significantly increased in IgG(4)+MOLPS. Histological specimens from patients with IgG(4)+MOLPS revealed marked IgG(4)+ plasma cell infiltration. Many patients with IgG(4)+MOLPS had lymphocytic follicle formation, but lymphoepithelial lesions were rare. Few IgG(4)+ cells were seen in the tissue of patients with typical SS. Thirty-eight patients with IgG(4)+MOLPS treated with glucocorticoids showed marked clinical improvement. CONCLUSION: Despite similarities in the involved organs, there are considerable clinical and pathological differences between IgG(4)+MOLPS and SS. Based on the clinical features and good response to glucocorticoids, we propose a new clinical entity: IgG(4)+MOLPS.

[Three ocular sarcoidosis patients examined by indocyanine green angiography].

PURPOSE: To assess the findings of indocyanine green angiography(IA) in patients with ocular sarcoidosis. SUBJECTS AND METHODS: Three active ocular sarcoidosis patients with various retinochoroidal findings diagnosed by biopsy or systemic examination. Two patients were diagnosed pathologically and one patient was diagnosed clinically. IA & fluorescein angiography(FA) were performed before and after treatment with systemic steroid administration. RESULTS: IA revealed hyperfluorescence surrounding the presumed granulomatous lesions. This hyperfluorescence disappeared immediately after the treatment. FA showed hyperfluorescence continuing even after therapy. CONCLUSIONS: It is purposed that the ring-form hyperfluorescence in IA is due to accelerated vascular permeability in the active sarcoid granuloma. IA, which vividly reflects activity of sarcoid lesions, is an important tool for clinical evaluation of ocular sarcoidosis.

A case of orbital lymphoproliferative lesion diagnosed as malignant lymphoma after recurring 11 years later

Background: Most primary lymphoproliferative lesions in the ocular adnexa, including the eyelid, conjunctiva, and orbit, are diagnosed as low-grade malignant lymphomas. Recurrence and dissemination of these tumors are rare in Japan. The long-term prognosis for this disorder still remains to be clarified.Case and Method: A 53-year-old woman was first referred to us for right orbital tumor in 1986. After subtotal resection of the tumor, the patient received no additional treatment. She visited us in 1997 with the complaint of bilateral orbital tumor. Biopsied specimens were examined histologically using hematoxylin-eosin and immunohistological staining. Southern blot hybridization was used to detect immunoglobulin gene rearrangement. The paraffin-embedded specimen obtained in 1986 was also examined for immunoglobulin gene rearrangement using nested polymerase chain reaction technique. Findings: The specimens from 1997 and 1986 were both diagnosed as lymphoid type of inflammatory pseudotumor, based on polyclonal B cell immunohistological staining. Immunoglobulin gene rearrangement was present in both specimens.Conclusions: The orbital tumor resected in 1986 was a low-grade malignant lymphoma which disseminated systematically 11 years later. This case shows a long-term course of orbital lymphoproliferative lesion with positive immunoglobulin gene rearrangement. It also shows the importance of follow-up over 10 years in the case of low-grade malignant lymphoma of the ocular adnexa.

Activation of the TCL1 protein in B cell lymphomas.

The TCL1 gene, localized near the break point of chromosome 14q32.1 often involved in T cell leukemias, is also expressed in normal precursor T and B cells, and B cell lymphoma cell lines. We investigated the expression of the TCL1 protein in various types of B cell lymphomas according to the Revised European-American Classification of Lymphoid neoplasms. Paraffin-embedded tissue sections of lymphoma specimens were subjected to TCL1 immunohistochemistry, and positivity was scored on a three-tiered scale: - (< 25% cells), + (25-50% cells), and ++ (> 50% cells). The TCL1 protein was expressed in low-grade B cell lymphomas including mucosa-associated lymphoid tissue type in ocular adnexa (18/20, 90%). It was also expressed in follicular, lymphoplasmacytic, and mantle cell lymphoma, but not in high-grade diffuse large B cell lymphoma (2/11, 18%). These data suggest that the expression of the TCL1 gene characterizes low-grade B cell lymphomas, and may be involved in certain processes of lymphomatogenesis.

[A case of orbital lymphoproliferative lesion diagnosed as malignant lymphoma after recurring 11 years later].

BACKGROUND: Most primary lymphoproliferative lesions in the ocular adnexa, including the eyelid, conjunctiva, and orbit, are diagnosed as low-grade malignant lymphomas. Recurrence and dissemination of these tumors are rare in Japan. The long-term prognosis for this disorder still remains to be clarified. CASE AND METHOD: A 53-year-old woman was first referred to us for right orbital tumor in 1986. After subtotal resection of the tumor, the patient received no additional treatment. She visited us in 1997 with the complaint of bilateral orbital tumor. Biopsied specimens were examined histologically using hematoxylin-eosine and immunohistological staining. Southern blot hybridization was used to detect immunoglobulin gene rearrangement. The paraffin-embedded specimen obtained in 1986 was also examined for immunoglobulin gene rearrangement using nested polymerase chain reaction technique. FINDINGS: The specimens from 1997 and 1986 were both diagnosed as lymphoid type of inflammatory pseudotumor, based on polyclonal B cell immunohistological staining. Immunoglobulin gene rearrangement was present in both specimens. CONCLUSION: The orbital tumor resected in 1986 was a low-grade malignant lymphoma which disseminated systemically 11 years later. This case shows a long-term course of orbital lymphoproliferative lesion with positive immunoglobulin gene rearrangement. It also shows the importance of follow-up over 10 years in the case of low-grade malignant lymphoma of the ocular adnexa.

Ocular ischemic syndrome in diabetic patients.

PURPOSE: Diabetes mellitus aggravates carotid occlusive disease, that can manifest as ocular ischemic syndrome (OIS). Ocular manifestations and visual prognosis of OIS in diabetic patients were retrospectively analyzed. METHODS: Twenty-three consecutive diabetic patients with OIS were divided into two groups according to the presence of iris neovascularization, and the clinical features were reviewed. RESULTS: In the first group, 14 eyes of 12 diabetic patients (11 men and 1 woman) had no iris neovascularization. Two patients had bilateral OIS. The ages in this group ranged from 50-75 years. Four eyes with optic atrophy or ischemic optic neuropathy had severe visual loss. Six eyes with hypoperfusion retinopathy or retinal vein obstruction and 2 eyes with cataract had mild visual loss. Each eye with amaurosis fugax or retinal neovascularization had no visual deterioration. Asymmetrical retinopathy was observed in 2 patients. Carotid surgery stabilized and resolved amaurosis fugax and hypoperfusion retinopathy. In the second group, 11 eyes of 11 patients had iris neovascularization. The patients were all male and their ages ranged from 53-77 years. All eyes with iris neovascularization had severe visual deterioration. In 5 patients, asymmetrical ocular manifestation was observed. Carotid reconstruction surgery and ophthalmological treatment were not successful for recovering a satisfactory visual outcome in OIS. CONCLUSION: The features of OIS in diabetic patients mimic diabetic retinopathy and manifest with asymmetrical ocular findings. Iris neovascularization is an indicator of poor visual prognosis. It is essential to recognize the early stages of OIS associated with diabetes mellitus.

[A case of syringomatous carcinoma derived from the lid].

A 73-year-old male presented with a slowly growing tumor in the right lower eyelid of one year's duration. The condition had been diagnosed elsewhere as poorly differentiated squamous cell carcinoma by biopsy. The residual tumor progressed rapidly and metastatized to the ipsilateral preauricular lymph nodes. We performed orbital evisceration and radical neck resection. Microscopically, the tumor showed small epithelial nests, cords, and ductal structure buried in abundant collagenous stroma. Besides focal squamous differentiation with keratinization in the surface area, the tumor showed, as cardinal features, ductal differentiation possessing comma-like extensions identical to syringoma. Cellular atypia, invasive growth pattern, and remarkable perineural invasion were suggestive of malignancy. These features led to the diagnosis of syringomatous carcinoma. Immunohistologically, the tumor showed positive staining for cytokeratine and epithelial membrane antigen (EMA). It was mostly negative for S-100 and carcinoembryonic antigen (CEA).

Laser flare intensity in diabetics: correlation with retinopathy and aqueous protein concentration.

The laser flare intensity in diabetics, measured with the scattering of a light beam, was evaluated and compared with actual aqueous protein concentration obtained during surgery. Measurement of the laser flare intensity in 120 diabetics and 108 normal subjects was performed with the laser flare cell meter (FC1000 Kowa, Tokyo). Aqueous protein concentration in 26 diabetics and six controls who underwent intraocular surgery was measured by the method of Bradford. No significant difference in the laser flare intensity was found between normal subjects and diabetics without retinopathy. A significant increase in the laser flare intensity was observed after six decades in diabetics with background retinopathy and all with proliferative retinopathy. The laser flare intensity correlated with the duration of diabetes mellitus. There was a significant linear relation between the laser flare intensity and actual aqueous protein concentration. The linear regression formula was X = Y1.39 x 1.02 (X = protein concentration, mg/dl; Y = flare intensity, photon counts/ms). The precise value of the laser flare intensity provides a new indicator to evaluate the diabetic change in the function of the ocular barrier.