Salomão, Diva R.

A 68-year-old man with a history of keratoconus was referred for evaluation of a choroidal lesion in his left eye. Fundus autofluorescence demonstrated hyperautofluorescence in a leopard-spotting pattern. What would you do next?

Purpose: To review clinical presentations of periocular sebaceous carcinoma (SC) and introduce standardized nomenclature for multicentric and multifocal disease presentation. Methods: A comprehensive PubMed/Medline search was conducted to identify all articles reporting periocular multicentric or multifocal SC presentations. The authors also highlight an additional case of SC presenting with 2 clinically distinct tumor foci and complete secondary invasion of the lacrimal gland. Results: This review summarizes clinical presentations of periocular SC exhibiting discrete foci of microinvasion reported in the literature. Discrete microinvasion was associated with high rates of misdiagnosis (80%), simultaneous involvement of both upper and lower eyelids (80%), pagetoid spread (80%), multinodular growth (33%), local tumor spread (60%), previous eyelid manipulation (40%), and local recurrence (40%). Eyelid multifocality with clinically discrete nodules (42%) was associated with more advanced disease including orbital extension and regional invasion (80%). Conclusions: Despite previous reported associations with poorer outcomes, there is no consensus in the definition or nomenclature for discrete microinvasive or clinical disease presentations in periocular SC. The authors recommend defining multicentric disease as discrete foci of microinvasive tumor with basement membrane disruption and multifocal disease as discrete clinically evident nodules involving both the upper and lower eyelids. Differentiating between discrete microinvasive (multicentric) and clinically nodular (multifocal) disease may improve risk stratification to most accurately identify patients who require more aggressive management and surveillance.

Purpose: The purpose of this study was to describe an exceedingly rare presentation of secondary vitreoretinal involvement by the uncommon entity “indolent T-cell lymphoproliferative disorder of the gastrointestinal tract” and illustrate the utility of fluorescence in situ hybridization for diagnosis. Methods: This is a case report. Results: A 57-year-old woman with presumed iritis on chronic topical prednisolone acetate presented with increased vitreous opacities in the right eye. She had a history of biopsy-confirmed indolent T-cell lymphoproliferative disorder of the gastrointestinal tract involving the stomach and duodenum, JAK2-rearrangement positive, controlled on maintenance oral methotrexate. Vitreous biopsy was unremarkable with small CD3-positive and CD4-positive and CD20-negative lymphocytes, along with histiocytes and fibroblasts. Immunostains showed CD4 positivity, and fluorescence in situ hybridization revealed a JAK2 gene rearrangement, consistent with the patient's previously diagnosed indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. Intravitreal methotrexate injections were started in the right eye. MRI of the brain and lumbar puncture with cytology, MYD88, IL10, and flow cytometry performed at the time of right eye vitreoretinal lymphoma diagnosis revealed no evidence of central nervous system lymphoma, but subsequent bone marrow biopsy demonstrated 5% involvement by indolent T-cell lymphoproliferative disorder of the gastrointestinal tract, JAK2-rearrangement positive, with a lung nodule on PET computed tomography. She returned 4 months later with fatigue, night sweats, and blurry vision in the left eye with vitreous and anterior chamber cellular infiltration and retinal vasculitis. Conclusion: T-cell vitreoretinal lymphoma is rare, and diagnosis can be challenging. Despite inconclusive cytology in this case, interphase fluorescence in situ hybridization detected a JAK2 gene rearrangement, which confirmed the involvement by indolent T-cell lymphoproliferative disorder of the gastrointestinal tract and prompted appropriate treatment and workup for recurrent systemic or central nervous system lymphoma.

Sarcina ventriculi is a rare gram-positive coccus increasingly reported in patients with a history of delayed gastric emptying or gastric outlet obstruction and is sometimes seen in association with emphysematous gastritis and perforation. We report a case of a 67-year-old male who presented with epigastric pain. CT imaging and cholangiopancreatography were concerning for pancreatic neoplasia. Upper endoscopic ultrasound-guided fine needle aspiration cytology of a perigastric lymph node confirmed metastatic adenocarcinoma of pancreatic origin, and cocci arranged in a tetrad fashions characteristic of Sarcina ventriculi were noted. To our knowledge, this is the first reported case of Sarcina ventriculi in an FNA of metastatic pancreatic carcinoma in a perigastric lymph node. These organisms likely represent carry-through contaminants from the transgastric approach of the endoscopic FNA.

Abstract Introduction Little has been published about the choroidal vascular changes that occur years after radiation exposure. The aim of this study was to review the histological changes observed in the choroidal vasculature following radiotherapy for uveal melanoma. Methods Records from a single institution were retrospectively reviewed from June 7, 2007 to June 7, 2017; 101 patients with a diagnosis of uveal melanoma that underwent enucleation had their records reviewed. Out of these, a total of 26 eyes had undergone plaque brachytherapy prior to enucleation, which had been performed at a mean time of 7.2 years (range from 0 years to 30 years) after the initial plaque placement. A histopathologic analysis was conducted on all 26 eyes with special emphasis on the choroidal changes. Of these 26 eyes, 18 demonstrated evidence of radiation-induced vasculopathy. Results Of the 18 eyes, 10/18 (55%) had radiation retinopathy and 16/18 (89%) had radiation choroidal vasculopathy. One patient had a phthisical eye, and the choroid could not be evaluated because the characteristics of the vasculature could not be determined. Nine cases had vitreous hemorrhage (50%), all cases had radiation retinopathy, and 8/9 (89%) had radiation choroidopathy. Of the 16 cases with radiation choroidal vasculopathy, 3/16 (19%) had only intratumoral radiation choroidal vasculopathy, 3/16 (19%) had only extratumoral radiation choroidal vasculopathy, and, thus, 10/16 (32%) had both intratumoral and extratumoral radiation choroidal vasculopathy. In patients with radiation choroidal vasculopathy, 2/16 (13%) had hyalinization of the choroidal vessels. Another 3/16 (19%) cases with radiation choroidal vasculopathy had ectatic vessels. The other 11/16 (68%) had evidence of both hyalinization of the choroidal vessels as well as ectatic vessels in the choroid. Histological evidence of radiation retinopathy and choroidopathy were seen in 69% of eyes enucleated after receiving radiation therapy, which, in some cases, also had vitreous hemorrhage. Polypoidal choroidal vasculopathy, choroidal neovascularization, and retinal choroidal anastomoses (RAP-type lesions) were seen in 12 of the 16 eyes (75%). Discussion/Conclusion Irradiation of malignant tumors of the eye causes not only radiation retinopathy but also radiation choroidopathy. The role of radiation choroidopathy in the subsequent visual loss following radiotherapy and the role of anti-VEGF therapy needs to be recognized and distinguished from radiation retinopathy. Our data adds to the prior limited knowledge that radiation affects the choroid and can induce specific phenotypes similar to the clinical spectrum of CNV, PCV, and RAP.

Purpose: We aimed to describe the clinical and histologic findings in a few enucleation cases with intraocular lymphoma. Methods: Retrospective review of pathology files from a 22-year period identified cases with intraocular lymphoma among all enucleation specimens. Patient demographics, clinical findings, laboratory results, radiographic studies, and indication for enucleation were abstracted from electronic health records; slides were reviewed. Results: Four patients (three women and one man; age range, sixth through eighth decades of life) underwent enucleation with a final diagnosis of intraocular lymphoma. Two patients with primary vitreoretinal large B-cell lymphomas had been treated for refractory uveitis. Specimens showed retinal and subretinal infiltrates by atypical large B-lymphocytes and rare neoplastic cells in the vitreous. The remaining two patients had systemic lymphoproliferative disorders. One patient had chronic lymphocytic leukemia and floaters in his eye; vitreoretinal lymphoma developed, consistent with intraocular Richter transformation. The other had diffuse large B-cell lymphoma in remission; however, blurred vision developed, she was treated for panuveitis without improvement, and was later found to have ocular involvement by diffuse large B-cell lymphoma. Conclusion: Our series details the unusual circumstances when an eye is removed for intraocular lymphoma. Different patterns of ocular tissue involvement were observed when we compared primary and secondary lymphomas.

Abstract Introduction. Vitreoretinal lymphoma (VRL) is a rare ocular malignancy. Diagnosis and optimal treatment remain a challenge for clinicians. We present clinical characteristics and outcome of a cohort of 69 patients affected by vitreoretinal diffuse large B-cell (DLBCL) lymphoma treated at Mayo Clinic over a 28-year period. Methods. We accessed the Mayo Clinic Lymphoma Data Base to identify all patients > 18 years old with VRL diagnosed between 01/01/1990 and 01/31/2018. Only patients with DLBCL, confirmed at pathological review, were included. Clinical characteristics, therapies, response, relapse patterns and follow up status were collected and analyzed in the cohort and in the different subgroups: primary (PVRL, localized only in eye at diagnosis) vs concurrent (CVRL) vs secondary VRL (SVRL). Chi-squared test, Fisher's exact test and Wilcoxon's signed-rank test were used for analysis. Failure-free survival (FFS), overall survival (OS), central nervous system (CNS) and eye relapse-free survival were analyzed according to Kaplan Meier method. Differences between subgroups were compared with log-rank test. Since the group of SVRL can be affected by a survivorship selection bias, it was investigated separately for the outcome analysis. Results. A total of 69 patients with vitreoretinal DLBCL were included. At diagnosis, 33 (48%) were PVRL, 18 (26%) CVRL (eye plus CNS (N=17) or systemic (N=1) disease) and 18 (26%) had SVRL (9 primary CNS lymphomas, 9 systemic at diagnosis, among which 4 were primary testicular lymphomas). Unilateral intraocular involvement was observed in 16 (23%) cases. Clinical characteristics are reported in Table I. At diagnosis, patients received a systemic treatment in 35 (50%, including high-dose systemic MTX (HD-MTX, N 14, 20%), MTR (HD-MTX, Temozolomide and Rituximab) (N 7, 10%) and CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) with or without Rituximab (N 10, 15%)), combined systemic plus intraocular treatment in 15 (22%), local radiotherapy in 10 (14%) and intraocular therapy (intraocular injections of rituximab or MTX or steroids or a combination of these) in 9 (13%) cases. Systemic Rituximab, autologous stem cell transplantation (ASCT) and therapeutic vitrectomy/enucleation were performed in 36 (53%), 20 (29%) and 5 (7%) patients, respectively. The median number of treatments was 2 (range 0-10). Among PVRL and CVRL (N=51), median FFS, CNS relapse-free survival, eye relapse-free survival and OS were: 1.8 y, 4.9 y, 3.8 y and 4.1 y, respectively (Fig 1). Among PVRL they were: 2.6 y, not reached (NR), 5.2 y and 9.3 y, respectively. No CNS relapse occurred beyond 4 years in the PVRL subgroup. The median OS for patients diagnosed between 1990 and 1999, in contrast to 2000 and 2018 was 1.5 y vs 9.4 y respectively (p= 0.0002). OS was significantly higher in PVRL, as compared to CVRL (p= 0.04). Previous immunosuppression and poor performance status were predictive of worse outcome (p=0.04), while ASCT correlated with higher OS (p= 0.009). In PVRL, a combined systemic + intraocular therapy was associated with higher FFS (p=0.002) and CNS-relapse free survival (p= 0.003), but no difference in OS was observed. Among 18 SVRL, at a median follow-up of 1.1 y after vitreoretinal relapse, median FFS and OS were 0.3 y and 1.3 y, respectively. Systemic toxicities included 8 (11.6%) acute renal failures, 8 (11.6%) infections, and 3 (4.3%) hemorrhages. Intraocular toxicities included cataract in 11, vitreal detachment in 3 , ocular hypertension in 5, retinal vessel occlusion in 3 and keratitis in 2 cases. Of 69 patients, 39 (56.5%) died secondary to lymphoma (N=21, 53.8%), infectious toxicity (N=2, 5.2%), unrelated (N=3, 7.7%) or unknown (N=13, 33.3%) causes. Conclusions. VR DLBCL is a rare disease, which can occur as primary, concurrent with systemic, or in relapsed disease. OS over the decades has significantly improved. In PVRL, no late CNS relapses were observed, while late intraocular relapses can occur. A combined approach with intraocular + systemic HD-MTX based treatment at diagnosis was associated with a higher FFS and CNS-relapse free survival in PVRL and is recommended in bilateral involvement, even though no differences in OS were observed. Treatment consolidation with ASCT can be considered in cases with concurrent systemic disease. Further studies are needed to confirm these results and to better define the role of new drugs in treatment of this uncommon malignancy. Disclosures Witzig: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.