Faculty Bibliography

PURPOSE: To evaluate the clinical and immunopathologic features of two patients with bilateral dacryoadenitis associated with regional enteritis. DESIGN: Retrospective clinicopathologic study. METHODS: Clinical records, photographs, and imaging studies were reviewed and microscopic sections of lacrimal gland biopsies were critically re-evaluated. The microscopic slides were stained with hematoxylin and eosin, special stains for organisms, and a range of immunohistochemical biomarkers including CD3, CD4, CD5, CD8, CD20, CD68, CD138, CD1a, IgG, IgG-4, and IgA. RESULTS: Both cases involved a young female patient with a well-established diagnosis of regional enteritis. Histopathologic examination of biopsies disclosed moderate intraparenchymal fibrosis and lymphoplasmacytic infiltrates without lymphoid follicles. Small to medium-sized intraparenchymal, non-caseating granulomas lacking multinucleated giant cells, and in one case, CD68-positive and CD1a-negative palisading granulomas in widened interlobular fibrous septa were detected. IgG4 plasma cells and vasculitis were not observed. Additional immunohistochemical studies revealed that CD8 T-lymphocytes (suppressor/cytotoxic subset) predominated over CD4-positive T-lymphocytes (helper cells) surrounding the necrobiotic foci and were intermixed with the CD68-positive histiocytes in the absence of CD20 B-lymphocytes. Special stains for organisms were negative. CONCLUSIONS: Dacryoadenitis is the rarest form of ocular adnexal involvement in regional enteritis, which affects the orbit far more frequently than ulcerative colitis. It is a granulomatous process with the possibility of palisading necrobiotic foci. In contrast, ulcerative colitis causes an interstitial lymphocytic and non-granulomatous myositis. Sarcoidosis, Wegener granulomatosis and pseudorheumatoid nodules must be ruled out. Treatment options entail a wide variety of agents with selection based upon empirical considerations and tailored to the patient's symptoms.

PURPOSE:: This study was designed to better understand the biologic nature of optic nerve gliomas (ONGs) and to investigate staining techniques that might improve the pathologic interpretation of surgical margins. METHODS:: In this retrospective case series, clinical data on patient presentation, MRI, surgical visualization, and initial pathologic interpretation were gathered. Specimens were then reexamined using analysis of p53, isocitrate dehydrogenase 1 (IDH1), MIB-1, and B-rapidly accelerated fibrosarcoma (BRAF) duplication. RESULTS:: Six patients were studied. All were diagnosed with World Health Organization grade 1 ONGs on original pathology. On reexamination, BRAF tandem duplication was found in 2 patients with neurofibromatosis Type 1 association. P53 immunoreactivity was noted in a third case. No cases had IDH1 immunoreactivity. Focal elevations of MIB-1 up to 7.5% were noted in 2 cases. CONCLUSIONS:: ONGs are neoplasms with variable degrees of aggressiveness. As more is understood regarding their varied genetic underpinnings, improved pathologic classification and individualized treatment regimens may be achieved. The authors hope that this study helps guide the oculoplastic community toward a multi-institutional, prospective study of ONG genomic sequencing.

This case report describes a biopsy-proven metastasis of gestational choriocarcinoma to the medial rectus muscle. Patient evaluation and follow up included comprehensive ophthalmologic history and examination, external and fundus photography, immunohistochemistry preparations of the medial rectus muscle specimen, MRI, ultrasound of the abdomen and pelvis, comprehensive blood tests, and CT scans of the chest, abdomen, and pelvis. The tissue specimen was obtained via a medial perilimbal conjunctival peritomy. MRI revealed a mass intrinsic to the right medial rectus muscle. Immunohistochemical staining confirmed gestational choriocarcinoma metastasis in medial rectus muscle biopsy. The patient showed general and orbital improvement following 7 subsequent cycles of chemotherapy. In conclusion, gestational choriocarcinoma may metastasize to the orbit in addition to the previously reported ocular site, the choroid. A chemotherapy regimen of etoposide, methotrexate, actinomycin-D, cyclophosphamide, and vincristine can effectively treat the intraorbital component of the disease.

A 60-year-old man with stable bilateral thyroid eye disease (TED) underwent unilateral strabismus surgery. Within 1 month, he developed TED reactivation in only the contralateral orbit. At a later date, again after 6 months of inactive TED, he underwent bilateral strabismus surgery. Within 1 month of surgery, he developed bilateral TED reactivation. Surgical manipulation of orbital tissues may, in rare cases, provoke reactivation of TED.

OBJECTIVE: IgG4-related disease is an emerging clinical entity which frequently involves tissue within the orbit. In order to appreciate the implications of IgG4 immunostaining, we analyzed gene expression and the prevalence of IgG4- immunostaining among subjects with orbital inflammatory diseases. METHODS: We organized an international consortium to collect orbital biopsies from 108 subjects including 22 with no known orbital disease, 42 with nonspecific orbital inflammatory disease (NSOI), 26 with thyroid eye disease (TED), 12 with sarcoidosis, and 6 with granulomatosis with polyangiitis (GPA). Lacrimal gland and orbital adipose tissue biopsies were immunostained for IgG4 or IgG secreting plasma cells. RNA transcripts were quantified by Affymetrix arrays. RESULTS: None of the healthy controls or subjects with TED had substantial IgG4 staining. Among the 63 others, the prevalence of significant IgG4-immunostaining ranged from 11 to 39% depending on the definition for significant. IgG4 staining was detectable in the majority of tissues from subjects with GPA and less commonly in tissue from subjects with sarcoidosis or NSOI. The detection of IgG4+ cells correlated with inflammation in the lacrimal gland based on histology. IgG4 staining tissue expressed an increase in transcripts associated with inflammation, especially B cell-related genes. Functional annotation analysis confirmed this. CONCLUSION: IgG4+ plasma cells are common in orbital tissue from patients with sarcoidosis, GPA, or NSOI. Even using the low threshold of 10 IgG4+ cells/high powered field, IgG4 staining correlates with increased inflammation in the lacrimal gland based on histology and gene expression.

PURPOSE: To correlate clinical features, imaging and pathologic findings in recurrent Solitary Fibrous Tumor of the orbit (SFT) in order to predict long-term behavior. METHODS: Clinical features, imaging and pathologic findings of three patients with biopsy proven SFT are reported. Demographic and clinical features were recorded at presentation and at each consultation; imaging was performed as a diagnostic tool and for follow-up. A biopsy was performed at presentation and subsequently when symptoms worsened. Pathology specimens were reviewed retrospectively to corroborate diagnosis. Intraoperative and histopathologic features were recorded. A correlation was made between clinical, imaging and pathologic results to identify outcome predictors of recurrence, locally aggressive behavior and malignant transformation. RESULTS: All cases presented recurrent tumors with locally aggressive behavior over time. All were women in the fifth decade of life. Tumors induced proptosis, swelling of the lids and eye displacement at presentation and were diagnosed as other types of collagen-rich tumors before CD34 immunohistochemistry was available. Mean follow-up was 26.6 years (range 12-37). Relevant findings for all cases included a heterogeneous, irregular tumor containing cystoid spaces filled with mucoid material diffusely enhancing with imaging techniques. Intraoperative findings included a gelatinous matrix within the center of the tumor mass, which was not present at primary resection. Histopathology could not detect specific cellular patterns or immunological markers related to these changes. CONCLUSIONS: Recurrence and locally aggressive behavior was better predicted by imaging and surgical findings rather than histopathological characteristics. Cystoid degeneration in recurrent tumors may suggest malignant transformation over time.

PURPOSE: Outcome evaluation in ocular adnexal lymphoma (OAL) is based on clinical assessment and conventional volumetric changes in tumor size. The purpose of this retrospective study was to compare if changes in apparent diffusion coefficient (ADC) tumor values obtained by diffusion-weighted MRI corresponded to changes in enhancing tumor volume in the evaluation of early treatment response or failure in patients with OAL. METHODS: A retrospective case series analysis of conventional contrast-enhanced orbital MRI and diffusion-weighted sequences was performed on 8 pathologically confirmed OAL tumors before and after therapy. Mean ADC values and normalized ADC ratios were obtained using a region-of-interest analysis method on enhancing OAL lesions; tumor volumes were calculated using a manual segmentation method. Changes in tumor volume, mean ADC tumor values, and normalized ADC ratios were compared before and after therapy using a Wilcoxon rank-sum test. RESULTS: Overall, a significant difference was found in mean ADC values and normalized ADC ratios within OAL tumors before and after therapy (p < 0.05), irrespective of the type of therapy administered. There was a trend toward decreased mean enhancing tumor volume after therapy (p = 0.161). An increase in ADC values and a decrease in enhancing tumor volume after therapy correlated with a positive treatment response in 7 of 8 tumors; a decrease in ADC values and an increase in enhancing tumor volume after therapy correlated with a negative treatment response in 1 of 8 tumors. CONCLUSIONS: Tracking changes in tumor ADC values after various treatment regimens for OAL may be useful in predicting early treatment response or failure and can provide complementary information that corresponds to conventional volume changes in tumor size. Further validation of these preliminary results in larger prospective randomized trials is needed.

Subperiosteal orbital hemorrhage typically results from trauma. Spontaneous subperiosteal orbital hemorrhage (SSOH) is rare and has been reported with sudden elevation of cranial venous pressure, bleeding diathesis, and sinusitis. This article presents a series of 9 patients (11 orbits) with SSOH and review the associated systemic conditions. 10 out of 11 orbits (91%) underwent surgical intervention due to advanced orbital signs or poor vision.

PURPOSE: To determine the value of preoperative MRI in predicting the histopathologic margin of optic nerve glioma undergoing surgical resection. METHODS: Retrospective, noncomparative, multicenter case series of patients diagnosed with prechiasmal optic nerve glioma, using MRI, who underwent surgical resection. Clinical data were abstracted from patient medical records at 6 medical centers through a survey vehicle. Preoperative MRI findings were compared with intraoperative findings and postoperative histopathologic interpretations of the posterior margins of 13 surgically resected optic nerve gliomas. RESULTS: A total of 13 patient submissions qualified for study entry based on preoperative MRI having identified a unilateral optic glioma anterior to the optic chiasm. Of these, 2 cases (15%) demonstrated an abnormal macroscopic appearance of the chiasm intraoperatively and were surgically debulked rather than resected as planned preoperatively. The remaining 11 patients underwent resection posterior to the margins indicated by preoperative MRI. Of these, 3 (27%) demonstrated evidence of microscopically positive margins on histopathologic examination. Follow up ranged from 3 months to 21 years. One patient with involvement of the chiasm manifested tumor growth; no other recurrences or evidence of growth occurred in the remaining patients, including 1 other case with involvement of the chiasm and 3 cases with positive surgical margins. CONCLUSIONS: Unilateral optic nerve gliomas limited to the prechiasmatic nerve on MRI not infrequently extend beyond the MRI borders. This finding is of significance when considering management options, particularly surgical resection.