Multipurpose ultrasonographic characteristics of primary uveal MALT lymphoma.

PURPOSE: To investigate the ultrasonographic features in patients with primary uveal mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: Medical records of 12 patients (13 eyes) diagnosed with primary uveal MALT lymphoma between September 2014 and September 2021 were retrospectively reviewed. Ultrasonography, B-scan ultrasonography, color Doppler flow imaging, and ultrasound biomicroscopy findings were retrieved from the medical records. RESULTS: Mean age of the included patients was 59.4 ± 8.6 years. Typical ultrasonographic features of the choroidal infiltrates were flat, diffuse, and thickened, with low and homogenous internal reflectivity and with rich arterial blood flow from posterior ciliary arterioles. The mean thickness of the choroidal infiltrates was 1.34 ± 0.68 mm (n = 13). Most of the affected eyes had posterior episcleral extensions, with a mean thickness of 1.66 ± 1.21 mm (n = 12). Typical crescent-like posterior episcleral extensions were detected in nine eyes (69.2%). In six eyes, the blood flow from the choroidal infiltrates communicated with the episcleral extensions. In the ciliary body, the mean thickness of the infiltrates was 1.08 ± 0.43 mm (n = 9), and seven eyes (77.8%) had 360° ring-like infiltrations. The initial best-corrected visual acuity (BCVA) was significantly correlated with the final BCVA after treatment (p < 0.001). CONCLUSION: Multipurpose ultrasonographic imaging revealed the unique characteristics of the primary uveal MALT lymphoma and is helpful in the diagnosis of this rare disease.

Neurosarcoidosis presenting as CRVO combined CRAO: a biopsy-proven case report of a Chinese patient.

BACKGROUND: Neurosarcoidosis is a rare systemic disorder that can affect the eye and other organs, including the central nervous system. Neurosarcoidosis infiltrating the optic nerve presenting as central retinal vein occlusion combined with artery ischaemia has not been reported in the literature previously. We describe a Chinese patient presenting with acute monocular vision loss, in whom an optic nerve biopsy confirmed the diagnosis of neurosarcoidosis. CASE PRESENTATION: A 47-year-old woman complained of acute decreased vision in her left eye over the course of 1 month. She reported that her vision deteriorated quickly within first 3 days of consulting an ophthalmologist at a local hospital. She was diagnosed with central retinal vein occlusion after funduscopic examination and fundus fluorescein angiography, and the vision in her left eye further deteriorated to no light perception. An orbital magnetic resonance imaging showed an abnormal T1-weighted image of the optic nerve after contrast enhancement. She was referred to a neuro-ophthalmologist for further evaluation. After routine blood tests ruled out infectious and metastatic diseases, she was prescribed 500 mg/d methylprednisolone for 5 days, but her vision did not improve. As she could still not perceive light, an optic nerve biopsy was performed, and the histopathology revealed non-necrotising granuloma that was consistent with neurosarcoidosis. CONCLUSIONS: Isolated optic nerve infiltration by neurosarcoidosis without the involvement of the central nervous system or other systemic organs is challenging to diagnose. Biopsy of the optic nerve sheath is crucial for the final diagnosis of neurosarcoidosis. Therefore, a comprehensive ophthalmologic and systemic examination and work-up for inflammation of the eye, chest, and central nervous system should be conducted for atypical cases.

Hard Palate Mucoperiosteal Transplantation for Defects of the Upper Eyelid: A Pilot Study and Evaluation.

PURPOSE: To use hard palate mucoperiosteum to reconstruct the upper eyelid wisely and to evaluate its function and outcome. METHODS: In this case series, medial or lateral defects of the upper eyelid were reconstructed with a hard palate mucoperiosteum graft and a bandage contact lens to protect the cornea. Slit-lamp examinations, in vivo confocal microscopy, patient surveys, and pathologic examinations were performed as evaluations. RESULTS: Seven patients were included in this study. The average follow-up time was 21.9 months. Postoperatively, all patients maintained their preoperative corneal transparency, and the best-corrected visual acuities remained stable. Postoperative corneal examination by in vivo confocal microscopy was similar to the normal contralateral eye in all cases. All hard palate mucoperiosteal grafts merged smoothly with the normal tarsoconjunctiva. The mean ratio of the graft length to the upper eyelid decreased from 48.6% during the operation to 32.2% during the follow-up; the average shrinkage rate was 16.3% ± 7.1%. Both in vivo confocal microscopy and the pathologic examinations showed that stratified squamous epithelium comprised the main part of the hard palate graft. All patients could blink normally and had a relatively normal appearance. All patients were satisfied with the overall outcome of this therapy. Main complications included loss of eyelashes (100%), abnormal curvature of the eyelid (28.5%), mild lagophthalmos (14.3%), trichiasis (14.3%), and slight exfoliation of the corneal epithelium (42.8%). CONCLUSIONS: not only effectively reconstructs the upper eyelid but also provides protection for the cornea.

A Staged Procedure in the Treatment of Primary Lacrimal Sac Epithelial Malignancy: A Retrospective Cases Analysis.

PURPOSE: To determine the effect of a staged procedure in the treatment of primary lacrimal sac epithelial malignancy. METHODS: This is a retrospective case series of 18 consecutive patients with primary lacrimal sac epithelial malignancy treated at an orbital tumor referral center between 2002 and 2017. Study was conducted in compliance with the Declaration of Helsinki. All patients underwent biopsy of the mass to confirm the diagnosis pathologically. Chemotherapy concurrent with radiotherapy was delivered to the patients to reduce and concrete the tumor prior to surgery. En bloc resection of the lacrimal sac malignancy and nasolacrimal duct was followed. RESULTS: Eleven patients were male and 7 patients were female. The median follow-up time was 72.2 months. Nine patients had squamous cell carcinoma, 7 poorly differentiated carcinoma, 1 transitional cell carcinoma, and 1 adenoid cystic carcinoma. After chemotherapy and radiotherapy, the tumor volume was reduced significantly (p < 0.0001). En bloc resection of the lacrimal sac malignancy was performed in all patients with concurrent partial ethmoidectomy in 8 patients and medial maxillectomy in 5 patients. One patient (5.6%) suffered from adenoid cystic carcinoma died of metastatic disease. Two patients (11.1%) with local recurrence received reoperation, and 1 patient (5.6%) with pulmonary metastasis received gamma knife radiosurgery. These patients are alive with no evidence of tumor. Other patients are alive without evidence of disease at last follow up. No patient had new onset of lymph node enlargement during and after the treatment. CONCLUSIONS: The staged procedure is a promising method for the treatment of primary lacrimal sac epithelial malignancy with no postoperative lymph node metastasis.

Novel GPR34 and CCR6 mutation and distinct genetic profiles in MALT lymphomas of different sites.

Mucosa-associated lymphoid tissue (MALT) lymphoma originates from a background of diverse chronic inflammatory disorders at various anatomic sites. The genetics underlying its development, particularly in those associated with autoimmune disorders, is poorly characterized. By whole exome sequencing of 21 cases of MALT lymphomas of the salivary gland and thyroid, we have identified recurrent somatic mutations in 2 G-protein coupled receptors (GPR34 and CCR6) not previously reported in human malignancies, 3 genes (PIK3CD, TET2, TNFRSF14) not previously implicated in MALT lymphoma, and a further 2 genes (TBL1XR1, NOTCH1) recently described in MALT lymphoma. The majority of mutations in GPR34 and CCR6 were nonsense and frameshift changes clustered in the C-terminal cytoplasmic tail, and would result in truncated proteins that lack the phosphorylation motif important for ß-arrestin-mediated receptor desensitization and internalization. Screening of these newly identified mutations, together with previously defined genetic changes, revealed distinct mutation profiles in MALT lymphoma of various sites, with those of salivary gland characterized by frequent TBL1XR1 and GPR34 mutations, thyroid by frequent TET2, TNFRSF14 and PIK3CD mutations, and ocular adnexa by frequent TNFAIP3 mutation. Interestingly, in MALT lymphoma of the salivary gland, there was a significant positive association between TBL1XR1 mutation and GPR34 mutation/translocation (P=0.0002). In those of ocular adnexa, TBL1XR1 mutation was mutually exclusive from TNFAIP3 mutation (P=0.049), but significantly associated with IGHV3-23 usage (P=0.03) and PIK3CD mutation (P=0.009). These findings unravel novel insights into the molecular mechanisms of MALT lymphoma and provide further evidence for potential oncogenic co-operation between receptor signaling and genetic changes.

Significant association between TNFAIP3 inactivation and biased immunoglobulin heavy chain variable region 4-34 usage in mucosa-associated lymphoid tissue lymphoma.

Both antigenic drive and genetic change play critical roles in the development of mucosa-associated lymphoid tissue (MALT) lymphoma, but neither alone is sufficient for malignant transformation, and lymphoma development critically depends on their cooperation. However, which of these different events concur and how they cooperate in MALT lymphomagenesis is totally unknown. To explore this, we investigated somatic mutations of 17 genes and immunoglobulin heavy chain variable region (IGHV) usage in 179 MALT lymphomas from various sites. We showed that: (1) there was a significant association between the biased usage of IGHV4-34 (binds to the carbohydrate I/i antigens) and inactivating mutation of TNFAIP3 [encoding a global negative regulator of the canonical nuclear factor-κB (NF-κB) pathway] in ocular adnexal MALT lymphoma; (2) IGHV1-69 was significantly overrepresented (54%) in MALT lymphoma of the salivary gland, but was not associated with mutation in any of the 17 genes investigated; and (3) MALT lymphoma lacked mutations that are frequently seen in other B-cell lymphomas characterized by constitutive NF-κB activities, including mutations in CD79B, CARD11, MYD88, TNFRSF11A, and TRAF3. Our findings show, for the first time, a significant association between biased usage of autoreactive IGHV and somatic mutation of NF-κB regulators in MALT lymphoma, arguing for their cooperation in sustaining chronic B-cell receptor signalling and driving oncogenesis in lymphoma development. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Ocular juvenile xanthogranuloma.

PURPOSE: To report the clinical and histopathologic characteristics and prognoses of three ocular juvenile xanthogranuloma (JXG) cases. CASE REPORTS: Three cases were included in this study. The first case involved a 5-year-old girl with an enlarging yellowish mass at the limbus with corneal involvement. Ultrasound biomicroscopy showed a poorly demarcated mass involving the underlying cornea and sclera. The mass was excised in combination with a lamellar keratoplasty procedure. No recurrence was seen at the 2-year follow-up. The second case involved a 2-year-old boy with an enlarging yellowish mass on the conjunctiva, without limbal involvement. The mass was excised with no recurrence noted 1 year later. The third case involved a 7-month-old girl with unilateral eye redness and photophobia combined with multiple orange-red, raised nodular lesions on the skin. Examination under general anesthesia revealed a gray-yellow mass in the inferior and temporal iridocorneal angles. The intraocular pressure and corneal diameter were normal. Examination using ultrasound biomicroscopy showed a high-level echo lump in the inferior and temporal angles. There was no treatment for this case. At the 1-year follow up, the eye symptoms had resolved and the skin lesions were flat. Histopathologic examinations were completed on all three cases. The presence of Touton giant cells in hematoxylin-eosin staining, positive CD68 staining, and negative S-100 and CD1a staining confirmed the diagnosis of JXG. CONCLUSIONS: We report three histopathologically confirmed ocular JXG cases involving the corneoscleral limbus, conjunctiva, and iris with angle involvement, respectively. Ultrasound biomicroscopy performed on two cases demonstrated no obvious division between the mass and the surrounding structures. The cases with ocular surface involvement were successfully treated by excision and the case with iris involvement spontaneously regressed without any treatment. Early excision may be the better choice for ocular surface lesions, especially when corneal involvement is a possibility.

Intraocular medulloepithelioma clinical features and management of 11 cases.

AIMS: To describe the clinical features, imaging characteristics, histopathology, treatment and outcomes of intraocular medulloepithelioma. METHODS: Medical records of 11 patients with clinically or histopathologically confirmed medulloepithelioma were retrieved and reviewed. Clinical features, diagnostic challenges, imaging characteristics, management, histopathology and prognosis were assessed. RESULTS: The median age of the patients at initial diagnosis was 4 years, with the most common manifestations being leukocoria (five eyes), loss of vision (four eyes), ocular pain (one eye) and ophthalmic screening (one eye). The clinical signs include a grey-white ciliary body lesion, cataract or lens subluxation, secondary glaucoma and evident cysts. The ultrasound biomicroscopy (UBM) imaging most commonly displays ciliary body mass with intratumoural cysts (nine eyes). Three patients underwent surgery for cataract or glaucoma while the tumours were incidentally found. Two of the three patients managed by eye preserve treatments eventually required enucleation because of local tumour recurrence or phthisis. One patient treated with intra-arterial chemotherapy and cryotherapy had successful tumour regression and globe salvage. CONCLUSIONS: Initial misdiagnosis, delay in diagnosis and subsequent misdirected management is not uncommon in medulloepithelioma. The presence of multiple cysts in the tumour and retrolental neoplastic cyclitic membrane detected by UBM can offer certain information. Selective intra-arterial melphalan may prevent further tumour growth, but longer follow-up is necessary until treatment efficacy is fully evaluated.

Malignant transformation of orbital solitary fibrous tumor.

Orbital solitary fibrous tumor (SFT) is a rare tumor and may recur or undergo malignant transformation without complete excision. We present a case of orbital SFT which recurred twice and underwent malignant transformation. The patient was treated with en bloc excision via a lateral orbitotomy. The postoperative histopathologic diagnosis of this case was an adult fibrosarcoma. Postoperative adjuvant radiation therapy was given. In 18 months of further follow-up, there has been no evidence of recurrence, both clinically and in regular imaging studies.

A novel A20 (TNFAIP3) antibody (Ber-A20) can be used to detect unmutated A20 by immunohistology.

AIMS: A20 (TNFAIP3) is a nuclear factor-κB (NF-κB)-inducible component of tumour necrosis factor and Toll-like receptor intracellular signal transduction. It negatively regulates NF-κB, and has been identified as a tumour suppressor. Several studies have described A20 inactivation by deletion of the A20 locus at 6q23, inactivating mutations, and/or methylation of the A20 promoter in various lymphoma entities. METHODS AND RESULTS: We generated a monoclonal antibody against the C-terminus of A20 (Ber-A20) and investigated full-length A20 expression of normal lymphoid tissue and lymphomas for the first time. We identified loss of A20 expression in tumour cells of 24% of classical Hodgkin lymphoma, 27% of diffuse large B-cell lymphoma, 20% of chronic lymphocytic leukaemia, 19% of follicular lymphoma, 13% of mantle cell lymphoma and 8% of primary mediastinal B-cell lymphoma cases by immunohistology. Loss of A20 expression rarely occurred in T-cell non-Hodgkin lymphoma. CONCLUSIONS: Our data are in agreement with cytogenetic and molecular analyses. Among 21 cases of ocular adnexal marginal zone lymphomas with known A20 mutation status, we detected complete absence of A20 expression, whereas cases with wild-type A20 were weakly A20-positive. We demonstrate that A20 loss can be detected by immunohistology with a sensitivity similar to that of complex molecular and genetic methods.

A20 inactivation in ocular adnexal MALT lymphoma.

Recent studies showed A20 inactivation by deletion, mutation and promoter methylation in ocular adnexal mucosa-associated lymphoid tissue lymphoma. However, the incidences of A20 abnormalities and their clinical impact remain for the most part unknown. It is also unknown whether ABIN-1 and ABIN-2, the components of the A20 NF-κB inhibitor complex, are inactivated by genetic changes in ocular adnexal mucosa-associated lymphoid tissue lymphoma. A total of 105 cases were investigated for A20 mutation/deletion, ABIN-1/2 mutation, MALT1 and IGH involved translocation. Somatic mutation was seen frequently in A20 (28.6%) but rarely in ABIN-1 (1%) and ABIN-2 (1%). A20 mutations were significantly associated with A20 heterozygous deletion, and both were mutually exclusive from the MALT1 or IGH involved translocations. A20 mutation/deletion was also significantly associated with increased expression of the NF-κB target genes CCR2, TLR6 and BCL2. The cases with A20 mutation/deletion required significantly higher radiation dosages to achieve complete remission than those without these abnormalities.

TIPARP is involved in the regulation of intraocular pressure.

Elevated intraocular pressure (IOP) is the major risk factor for glaucoma. The molecular mechanism of elevated IOP is unclear, which impedes glaucoma therapy. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible Poly-ADP-ribose Polymerase (TIPARP), a member of the PARP family, catalyses mono-ADP-ribosylation. Here we showed that TIPARP was widely expressed in the cornea, trabecular meshwork, iris, retina, optic nerve, sclera, and choroid of human eyes. The expression of TIPARP was significantly upregulated in the blood and trabecular meshwork of patients with primary open angle glaucoma compared with that of healthy controls. Transcriptome analysis revealed that the expression of genes related to extracellular matrix deposition and cell adhesion was decreased in TIPARP-upregulated human trabecular meshwork (HTM) cells. Moreover, western blot analysis showed that collagen types I and IV, fibronectin, and α-SMA were increased in TIPARP-downregulated or TIPARP-inhibited HTM cells. In addition, cross-linked actin networks were produced, and vinculin was upregulated in these cells. Subconjunctival injection of the TIPARP inhibitor RBN-2397 increased the IOP in Sprague-Dawley rats. Therefore, we identified TIPARP as a regulator of IOP through modulation of extracellular matrix and cell cytoskeleton proteins in HTM cells. These results indicate that TIPARP is a potential therapeutic target for ocular hypertension and glaucoma.

Primary Mucoepidermoid Carcinoma of the Lacrimal Apparatus.

PURPOSE: In this study, we evaluated the clinicopathologic and molecular characteristics of lacrimal apparatus mucoepidermoid carcinoma (MEC) to define its typical diagnostic features. DESIGN: Retrospective observational case series. METHODS: Institutional pathology records between 2011 and 2021 were searched for all cases of lacrimal apparatus MEC. RESULTS: A total of 2 male and 6 female patients ranging in age from 18 to 83 years (median 56, mean 54) were included. Six lacrimal apparatus MECs were found in the lacrimal gland, and 2 cases occurred in the lacrimal sac and nasolacrimal duct. Histologically, there were 6 cases of conventional MEC, 1 clear-cell variant of MEC, and 1 oncocytic variant of MEC for a total of 8 cases. There were 3 low-grade cases and 5 high-grade cases. All 8 cases were evaluated via immunohistochemistry, and the results were positive (scores 1-4) for pankeratin, 34betaE12, p63, p40, CK7, CK8, and CK19, with a relatively higher expression of p63 observed in high-grade MEC. The presence of human papillomavirus (HPV) type 6 DNA was found in 4 patients. MAML2 fluorescence in situ hybridization was positive for MAML2 rearrangement in 3 lacrimal gland tumors (2 low-grade and 1 high-grade). Six tumors were managed with radical resection, and 2 patients underwent orbital exenteration. Postoperative radiation therapy was delivered to 6 patients, and chemotherapy was administered to 1 patient. CONCLUSIONS: MECs of the lacrimal apparatus are rare tumors, and the rate of MAML2 translocations is lower than that in salivary MECs. Lacrimal gland and lacrimal sac MECs may not be of the same subtypes intrinsically because of the difference in MAML2 translocation, anatomy, and clinical course. The etiologic function of HPV type 6 infection should be explored in lacrimal apparatus MECs. Radical surgery is the treatment of choice. The description of these unique findings may assist in the definitive diagnosis of and improve our understanding of lacrimal apparatus MEC.

Lacrimal sac lymphoma: a case series and literature review.

AIM: To study the clinical and pathological characteristics of the lacrimal sac lymphoma, which is rare but it is the major type of non-epithelial malignant tumor in the lacrimal sac region. METHODS: Sixty-four cases of malignant lacrimal sac tumors in our hospital from 1986 to 2020 were retrospectively reviewed. Eight cases of lacrimal sac lymphoma were carefully reviewed. RESULTS: There were five mucosal-associated lymphoid tissue (MALT) lymphomas, one diffused large B-cell lymphoma, one NK/T cell lymphoma, and one mantle cell lymphoma. All eight patients represented symptoms of epiphora with swelling in the lacrimal sac for a certain period of time and showed no signs of systemic involvement at the first time of clinical visits. They had received either chemotherapy or radiotherapy after surgery. Long-term follow-up (from 11 to 220mo) showed that, except one patient with MALT lymphoma died for unknown reasons at 104mo after surgery, the other 7 patients were all alive with no signs of local recurrence, neither in other organs. CONCLUSION: Non-epithelial malignant tumors of the lacrimal sac are rare and lymphoma is the major subtype.

Giant Cell Arteritis Presenting With Ocular Symptoms: Clinical Characteristics and Multimodal Imaging in a Chinese Case Series.

Purpose: To evaluate demographic and clinical characteristics of a Chinese population with giant cell arteritis using multimodal imaging focusing on ophthalmic examinations. Design: Retrospective observational case series. Materials and Methods: In the neuro-ophthalmology division of the Eye, Ear, Nose, and Throat Hospital, Shanghai, we evaluated the demographic and clinical characteristics of patients diagnosed with giant cell arteritis between January 2016 and June 2021. Results of routine ophthalmic examinations including fundus examination, optical coherence tomography, color duplex ultrasonography of ocular and superficial temporal arteries, orbital magnetic resonance imaging, and superficial temporal artery biopsy were evaluated. Results: A total of 15 patients (22 eyes; ten male and five female) were evaluated with a mean age of 77.0 ± 8.5 years. Among them, seven had bilateral involvement that occurred simultaneously or sequentially. Twelve patients presented with arteritic anterior ischemic optic neuropathy, two with arteritic anterior ischemic optic neuropathy combined with cilioretinal artery occlusion, and one with cotton-wool spots. In acute stages of optic neuropathy and retinopathy, optical coherence tomography revealed optic disc edema, thickening of the inner retinal nerve fiber layer and ganglion cell layer, and loss of layer structure. In late stages, optical coherence tomography revealed diffuse atrophy of the inner retina. The "halo" sign was observed in 12 patients in the superficial temporal artery ultrasound, and seven out of eight patients who underwent biopsy demonstrated classic giant cell arteritis pathological changes. Most patients having poor visual acuity but ability to perceive light; 10/22 eyes had permanent vision loss. Conclusion: Although rare in Asians, giant cell arteritis may be underdiagnosed among elderly Chinese patients presenting with anterior ischemic optic neuropathy. Non-invasive superficial temporal artery ultrasound detecting inflammatory thickening of the intima as the "halo" sign combined with routine elevated erythrocyte sedimentation rate and C-reactive protein may be helpful in diagnosing patients with a high probability of having giant cell arteritis.

A Novel and Easy-to-Promote Prognostic Model for Patients With Uveal Melanoma.

Purpose: To establish an easy and widely applicable prognostic prediction model for uveal melanoma (UM) based on a Chinese population. Patients and Methods: A total of 295 consecutive cases treated at the Eye & ENT Hospital of Fudan University were included as the primary cohort, and 256 cases were included in the validation cohorts from two external Caucasian databases. Clinicopathological data were collected retrospectively, and nomogram models were formulated based on multivariable analysis. The concordance index (C-index), AUC (area under the Receiver Operating Characteristic, ROC curve), and Brier score were calculated and compared. Results: Based on the training cohort, a nomogram model was established with five relevant variables: age, tumor size, ciliary body involvement, non-spindle cell type and extra-scleral extension. The C-index was 0.737, the 3- and 5-year AUCs were 0.767 and 0.742, and the Brier scores for 3- and 5-year survival were 0.082 and 0.129, respectively, which showed superior prediction compared to that of the Tumor, Node and Metastasis staging system. The model also displayed good discrimination and calibration in the external validation cohorts. By risk stratification, patients could be divided into low- and high-risk groups, and the overall survival curves displayed significant differences in the training and validation cohorts. Conclusion: Our nomogram model was simple and accurate at predicting the overall survival of patients with UM. It was established based on Asian patients and proved suitable for Caucasian patients; thus, it has a wide range of potential applications, especially for patients living in less medically developed countries and regions.

[Clinicopathologic features of retinoblastoma and expression of VEGF and Ki-67 after comprehensive treatment].

OBJECTIVE: To investigate the clinic pathologic features of retinoblastoma (RB) after comprehensive treatment, and study the expression of vascular endothelial growth factor (VEGF) in retinoblastoma treated with chemotherapy prior to enucleation. METHODS: Retrospective analysis was performed on retinoblastoma specimens obtained consecutively between 2006 and 2008 by enucleation, and patients' clinical information and clinic pathologic features were also collected. Immunohistochemical staining and real-time PCR were performed for the expression of VEGF. Immunohistochemical staining was also performed for Ki-67. RESULT: Among the 9 chemotherapy-treated cases, six belonged to group D and three to group E of IIRC. The reasons for enucleation included extensive vitreous seeds, RB recurrence, extensive subretinal fluid/seeds, vitreous hemorrhage and total tractional detachment of the retina. During the comprehensive treatment, the main tumors regressed in all eyes. The main tumors showed a mean decrease of 43.7% in the largest basal diameter and a mean decrease of 57.9% in thickness. The average interval between the end of chemotherapy and enucleation was 5.7 months. The reason for enucleation was the recurrence of main tumor, recurrence of new tumors, recurrent vitreous seed or subretinal seed. Three eyes showed a type 1 regression pattern, one eye showed a type 2 pattern, and the other five eyes showed type 3 clinical regression patterns. The expression of VEGF was lower in eyes that underwent planned enucleation than eyes that suffered from RB recurrence. CONCLUSIONS: The main reason for enucleation was extensive subretinal fluid/seeds after the comprehensive treatment. The type 3 clinical regression patterns were most common. In retinoblastoma, higher expression of VEGF may play an important role in the recurrence of retinoblastoma after comprehensive treatment.

Thyroid MALT lymphoma: self-harm to gain potential T-cell help.

The development of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is driven by chronic inflammatory responses and acquired genetic changes. To investigate its genetic bases, we performed targeted sequencing of 93 genes in 131 MALT lymphomas including 76 from the thyroid. We found frequent deleterious mutations of TET2 (86%), CD274 (53%), TNFRSF14 (53%), and TNFAIP3 (30%) in thyroid MALT lymphoma. CD274 was also frequently deleted, together with mutation seen in 68% of cases. There was a significant association between CD274 mutation/deletion and TNFRSF14 mutation (p = 0.001). CD274 (PD-L1) and TNFRSF14 are ligands for the co-inhibitory receptor PD1 and BTLA on T-helper cells, respectively, their inactivation may free T-cell activities, promoting their help to malignant B-cells. In support of this, both the proportion of activated T-cells (CD4+CD69+/CD4+) within the proximity of malignant B-cells, and the level of transformed blasts were significantly higher in cases with CD274/TNFRSF14 genetic abnormalities than those without these changes. Both CD274 and TNFRSF14 genetic changes were significantly associated with Hashimoto's thyroiditis (p = 0.01, p = 0.04, respectively), and CD274 mutation/deletion additionally associated with increased erythrocyte sedimentation rate (p = 0.0001). In conclusion, CD274/TNFRSF14 inactivation in thyroid MALT lymphoma B-cells may deregulate their interaction with T-cells, promoting co-stimulations and impairing peripheral tolerance.

[Clinical therapeutic efficiency of chemoreduction and local therapy for children with retinoblastoma].

OBJECTIVE: To evaluate the therapeutic efficiency of customized combined therapy for retinoblastoma. METHODS: Retrospective case series. Twenty nine patients (40 eyes) with retinoblastoma were accepted customized combined therapy between Jan. 2005 and Dec. 2007 in our hospital. The combined therapy included chemoreduction using vincristine, etoposide, and carboplatin (VEC) combined with local cryotherapy and/or transpupillary thermotherapy (TTT). The average follow-up duration was 38 months and ranging from 12 to 50 months. RESULTS: Twenty five patients had bilateral retinoblastoma, 4 patients had unilateral retinoblastoma. The stages of 40 eyes were classified according to the International Intraocular Retinoblastoma Classification, 14 eyes (35%) were group A, 9 eyes (22.5%) were group B, 4 eyes (10%) were group C, 10 eyes (25%) were group D, and 3 eyes (7.5%) were group E. Seventeen eyes had vitreous and/or subretinal seeds. The overall globe preservation rate was 75% (30/40); and was 100% (14/14) in group A, 100% (9/9) in group B, 75% (3/4) in group C, 40% (4/10) in group D and 0% (0/3) in group E. A progressive decrease of globe preservation rate was observed in eyes with advanced stages. Tumor recurrence was detected in 4 eyes after chemoreduction, leading to the enucleation. Ten eyes were enucleated in the present series, with 1 eye in group C, 6 eyes in group D and 3 eyes in group E. None of 29 patients died during the follow-up. No patients had any serious side effect of chemotherapy such as leukemia. CONCLUSIONS: The customized combined therapy can effectively preserve certain patients' eyeballs and even obtain useful visual function. The International Intraocular Retinoblastoma Classification is useful in the clinical management of retinoblastoma.