Peripheral hypertrophic subepithelial corneal degeneration: nomenclature, phenotypes, and long-term outcomes.

PURPOSE: To describe the long-term outcomes of peripheral hypertrophic subepithelial corneal degeneration. DESIGN: Retrospective case series. PARTICIPANTS: Twenty-two patients under the care of the External Disease Service, Moorfields Eye Hospital. METHODS: All patients matching clinical diagnostic criteria were included. Symptomatic patients were managed either conservatively or were offered superficial keratectomy in progressive cases where symptom control was inadequate. All excised tissue was examined histologically. MAIN OUTCOME MEASURES: Clinical phenotype, symptoms, recurrence rate after surgery, and histopathologic results. RESULTS: Twenty-two white patients (20 women and 2 men; age range, 27-88 years; median age, 42 years) had peripheral, usually bilateral (20/22 [91%]), elevated circumferential peripheral subepithelial corneal opacities and adjacent abnormal limbal vasculature, with or without pseudopterygia in 9 patients (41%), among whom 7 (32%) patients had bilateral disease. Apart from the abnormal vasculature, there were no signs of chronic ocular surface inflammation. Symptoms were ocular surface discomfort in 10 patients (45%), reduced vision in 4 patients (18%), and both of these in 5 patients (23%). Three patients (14%) were asymptomatic. There was no treatment in 6 patients (27%), topical lubricants in 8 patients (36%), spectacles in 1 patient (5%), and superficial keratectomy in 7 patients (32%; 5 bilateral), which was repeated for incomplete primary excision in 1 eye of 2 patients (9%) and for a bilateral recurrence in 1 patient (5%). Median follow-up after excision was 5 years (range, 1-11 years). Histopathologic changes were similar to those observed in pterygia (vascular component) and Salzmann's nodular degeneration (corneal component). CONCLUSIONS: Peripheral hypertrophic subepithelial corneal degeneration is an uncommon, usually bilateral, idiopathic disorder, occurring mostly in white women with a distinct phenotype. The condition was first described in 2003. Further cases among some patients have been described in more recent case series of Salzmann's nodular degeneration and diffuse keratoconjunctival proliferation, as well as in the previously described familial pterygoid corneal degeneration. Surgical excision was required in 30% of patients in this series, with infrequent short-term recurrences. The cause is uncertain. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Orbital plasmablastic lymphoma--comparison of a newly reported entity with diffuse large B-cell lymphoma of the orbit.

OBJECTIVES: To describe two cases of orbital plasmablastic lymphoma (PBL), a recently defined aggressive large-cell lymphoma with a plasmacytic immunophenotype, typically occurring in the oral cavity of HIV+ patients. To compare their presentation, management, immunohistochemistry and prognosis with orbital diffuse large B-cell lymphoma (DLBCL). DESIGN: Consecutive, comparative case series of patients presenting to a specialist orbital service with histologically proven PBL or DLBCL. RESULTS: Two cases of PBL and 14 cases of DLBCL were identified. The former were 40-49-year-old men, one HIV+, presenting with marked orbital/sinonasal tumour without oral involvement. Both tumours were negative for B-cell markers (CD20, CD79a), showed a plasmacytic immunophenotype (positive for CD 138, Vs38c), and displayed a Ki67 index of 100%. Despite chemotherapy, both patients died within 1 year. Of the 14 patients with DLBCL, 57% were female, mean age 65 yrs, and none were immunocompromised. Only 7 (50%) had sinus involvement and 3 (21%) had prior systemic lymphoma. All were positive for B-cell markers, with a Ki67 index of 55%-80%. None died within 1 year of diagnosis. CONCLUSIONS: PBL can present in the orbit and is more aggressive than DLBCL. It must be considered in the differential of orbital large-cell lymphoid tumours showing plasmablastic morphology or immunophenotype.

PRDM10-rearranged Soft Tissue Tumor: A Clinicopathologic Study of 9 Cases.

Gene fusion transcripts containing PRDM10 were recently identified in low-grade undifferentiated pleomorphic sarcomas (UPS). Here, we describe the morphologic and clinical features of 9 such tumors from 5 men and 4 women (age: 20 to 61 y). Three cases had previously been diagnosed as UPS, 3 as superficial CD34-positive fibroblastic tumor (SCD34FT), 2 as pleomorphic liposarcoma, and 1 as pleomorphic hyalinizing angiectatic tumor. The tumors were located in the superficial and deep soft tissues of the thigh/knee region (4 cases), shoulder (2 cases), foot, trunk, and perineum (1 case each) ranging in size from 1 to 6 cm. All showed poorly defined cellular fascicles of pleomorphic cells within a fibrous stroma with frequent myxoid change and a prominent inflammatory infiltrate. All displayed highly pleomorphic nuclear features, but a low mitotic count. Most tumors were well circumscribed. One of 9 tumors recurred locally, but none metastasized. Immunohistochemically, all were CD34 and showed nuclear positivity for PRDM10; focal positivity for cytokeratins was seen in 5/6 cases. PRDM10 immunoreactivity was evaluated in 50 soft tissue tumors that could mimic PRDM10-rearranged tumors, including 4 cases exhibiting histologic features within the spectrum of SCD34FT. Except for 2/6 pleomorphic liposarcomas and 1/4 myxofibrosarcomas, other tumors did not show nuclear positivity but displayed weak to moderate cytoplasmic immunoreactivity. In conclusion, PRDM10-rearranged soft tissue tumor is characterized by pleomorphic morphology and a low mitotic count. Its morphologic spectrum overlaps with SCD34FT. Clinical features of this small series suggest an indolent behavior, justifying its distinction from UPS and other sarcomas.

Bicanalicular obstruction in lichen planus: a characteristic pattern of disease.

PURPOSE: Lichen planus, an idiopathic mucocutaneous inflammatory disease, has only once been reported to cause lacrimal drainage obstruction. The authors present a series of patients with epiphora resulting from systemic lichen planus and describe the characteristic pattern of lacrimal canalicular blockage. DESIGN: Retrospective noninterventional case series. PARTICIPANTS: Eight patients (5 women, 3 men) with a median presenting age of 49 years (range, 39-60 years). METHODS: A retrospective review of case notes for patients attending the lacrimal clinic between 1998 and 2005 was performed to identify patients with nontraumatic lacrimal canalicular obstruction. In addition to demographic information, the data collected included a history of periocular herpetic infection, administration of systemic 5-fluorouracil, other causes of canalicular obstruction, the extent of proximal and distal canalicular obstruction (noted during surgery), the type of surgery, and the surgical outcomes. MAIN OUTCOME MEASURES: Identification of patients with biopsy-proven systemic lichen planus who had conjunctival and canalicular disease and documentation of the extent and severity of canalicular obstruction. RESULTS: Of the 184 patients with canalicular obstruction identified during the study period, 8 had lichen planus. Bilateral, bicanalicular involvement was present in 7 of 8 lichen planus patients, with 3 of 8 patients having completely obstructed canaliculi. Primary dacryocystorhinostomy (DCR) with retrograde canaliculostomy was performed in 4 of 8 patients, but all required secondary placement of Lester Jones canalicular bypass tubes. The other 4 patients had either primary DCR alone (both eyes in 1 patient, with solely canalicular stenosis) or DCR with primary placement of Jones tubes (6 eyes in 3 patients). Histologic examination of pericanalicular tissues in 2 patients showed features consistent with lichen planus. CONCLUSIONS: Lacrimal involvement in lichen planus is characterized by severe bilateral bicanalicular occlusion involving most of the length of affected canaliculi, and placement of a Jones canalicular bypass tube is generally required to control symptoms.

Ex vivo expansion and transplantation of limbal epithelial stem cells.

OBJECTIVE: To determine, using objective measures, the outcome of ex vivo cultured limbal epithelial stem cell (LESC) transplantation performed in compliance with good manufacturing practice using a novel culture system without 3T3 feeder cells. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Ten eyes of 10 patients with profound LESC deficiency arising from chemical injury (4 eyes), aniridia (3 eyes), ectodermal dysplasia (1 eye), Reiger's anomaly with Pax6 haploinsufficiency (1 eye), and unknown cause (1 eye). METHODS: Allogeneic (7 eyes) or autologous (3 eyes) corneal LESCs were cultured on human amniotic membrane. Tissue was transplanted to the recipient eye after superficial keratectomy. Impression cytology and confocal microscopy were performed 6 months after surgery with clinical follow-up to 13 months. Success was defined as an improvement in the defined clinical parameters of LESC deficiency, an improvement in visual acuity, the restoration of a more normal corneal phenotype on impression cytology, and the appearance of a regular hexagonal basal layer of cells on corneal confocal microscopy. MAIN OUTCOME MEASURES: Clinical parameters of LESC deficiency (loss of epithelial transparency, superficial corneal vascularization, epithelial irregularity, and epithelial breakdown), visual acuity, impression cytology and cytokeratin expression profiles, and in vivo confocal corneal confocal microscopy. RESULTS: The success rate using this technique was 60% (autografts 33%, allografts 71%). All patients with a successful outcome experienced an improvement in visual acuity of >/=2 lines Snellen acuity. Preoperatively, CK3+ and CK19+ cells accounted for 12+/-2.4% (mean +/- standard error of the mean) and 80+/-2.15% of cells, respectively, whereas postoperatively these accounted for 69+/-6.43% (P<0.0001) and 30+/-6.34% (P<0.0001) of cells, respectively. Goblet cells accounted for 8+/-1.19% of cells preoperatively and 1+/-0.35% of cells postoperatively (P<0.0001). CONCLUSIONS: These data demonstrate that it is possible to culture LESCs ex vivo in compliance with good manufacturing practice regulations. A set of objective outcome measures that confirm the efficiency of this technique in treating LESC deficiency is described. The widespread use of such standardized and objective outcome measures would facilitate a comparison between the different culture methods in use.

Superior oblique myositis as an early feature of orbital Wegener's granulomatosis.

A 66-year-old female presented with a 6-month history of increasing right-sided facial pain and diplopia. Right ocular movements were restricted in adduction and downgaze. Superior oblique (SO) enlargement was seen on an initial MRI scan, and subsequent diffuse infiltration was seen on a repeat scan. An elevated cANCA and biopsy of SO confirmed Wegener's granulomatosis (WG). We report a case of SO myositis as a predominant early feature of WG granulomatosis and review the literature regarding extraocular muscle involvement in WG. To our knowledge, early SO involvement has not been reported.

The use of radiotherapy for the treatment of localized orbital amyloidosis.

OBJECTIVE: To describe two patients with localized orbital amyloidosis and the response of their condition to surgical debulking followed by external beam radiotherapy. DESIGN: Retrospective noncomparative interventional case series. OUTCOME MEASURES: Stabilization or regression of orbital signs after treatment. METHODS: Patients with biopsy-proven diagnosis of localized progressive orbital amyloidosis received 34 and 30 Gy fractionated external beam radiotherapy. The clinical case notes and histopathology for the two patients were reviewed. RESULTS: A 69-year-old man with orbital amyloid deposition in association with localized MALT lymphoma had a marked improvement in orbital signs following surgical debulking and radiotherapy, with no recurrence over two years. A 59-year-old woman with localized orbital amyloidosis showed regression of disease after surgical debulking and radiotherapy, with no evidence of recurrence after six years of follow-up. CONCLUSION: External beam radiotherapy following surgical debulking appears to halt the progression of localized orbital amyloidosis. Radiotherapy may be used in conjunction with surgical debulking of disease.

Gliomatosis of the brain and spinal cord masquerading as infective lesions.

BACKGROUND: Gliomatosis of the brain or spinal cord is an infiltrating glial neoplasm that shows widespread invasion of the central nervous system with relative sparing of the underlying cytoarchitecture. Acceptance of the idea that the condition represents a distinct entity remains controversial in the absence of conclusive pathogenetic data. The clinico-pathological problems and difficulties in the ante-mortem diagnosis as well as the clinical and pathological similarities to infective lesions are evaluated. METHODS AND RESULTS: Three cases of cerebral and spinal gliomatosis are presented that clinically mimicked infective lesions and were diagnosed and treated as such. The correct diagnosis in each case was only made at post-mortem examination. The ante-mortem diagnosis of this rare tumor remains difficult owing to poor correlation of clinical, neuroradiological, and neuropathological findings. CONCLUSION: Gliomatosis of the brain and spinal cord may simulate infective lesions owing to difficulty in ante-mortem diagnosis because of vagueness of physical, radiological, and pathological findings. It is a diagnostic pitfall particularly in our setting where there is a high incidence of HIV/AIDS and patients often present with opportunistic infections such as mycobacterial, fungal, and/or viral infections, which show an atypical clinical picture and radiological findings. Multifocal neurologic deficit with noncontrast enhancing lesions that show diffuse contiguous involvement with overall preservation of the spinal or cerebral architecture and do not respond to infective treatment could suggest a diagnosis of gliomatosis cerebri.

Merkel cell carcinoma of the eyelid: management and prognosis.

IMPORTANCE: The literature on Merkel cell carcinoma (MCC) of the eyelid remains scarce, and there has yet to be a study using the most up-to-date TNM staging system for this rare but aggressive tumor. OBJECTIVE: To analyze the TNM stage, management, and outcomes of patients with MCC of the eyelid. DESIGN, SETTING, AND PARTICIPANTS: Retrospective case series of 21 patients from 5 tertiary referral centers in the United Kingdom and Australia with primary MCC of the eyelid presenting at a median age of 77 years, with median follow-up of 54 months. Tumors were staged according to the American Joint Committee on Cancer, 7th edition, TNM criteria for eyelid carcinoma and MCC. MAIN OUTCOMES AND MEASURES: TNM stage, treatment modalities, and clinical outcome. RESULTS: The eyelid carcinoma TNM stages were T2aN0M0 for 5 patients, T2bN0M0 for 7 patients, T3aN0M0 for 4 patients, T3bN0M0 for 3 patients, T2bN1M0 for 1 patient, and T3aN1M0 for 1 patient. The MCC TNM stages were T1N0M0 for 12 patients, T2N0M0 for 7 patients, T1N1M0 for 1 patient, and T2N1M0 for 1 patient. One patient had a sentinel lymph node biopsy, and 8 patients underwent head/neck imaging. Eighteen patients underwent a wide local excision, 12 with a paraffin section and 6 with a frozen section. Two patients underwent Mohs surgery, 1 of whom required an orbital exenteration. Twelve patients (57%) received adjuvant radiotherapy, and 2 patients received chemotherapy. The local recurrence rate was 10%, the regional nodal recurrence rate was 10%, and the distant metastatic recurrence rate was 19%. The lowest T category tumor metastasizing to both regional nodes and distant locations was a T2a (eyelid TNM)/T1 (Merkel TNM) tumor measuring 8 mm. Two patients with T3a (eyelid TNM)/T2 (Merkel TNM) tumors died of metastatic MCC. CONCLUSIONS AND RELEVANCE: The majority of patients with MCC of the eyelid present with localized eyelid disease of T category T2 (eyelid TNM)/T1 (Merkel TNM). A wide local excision with margin control remains the mainstay of treatment, whereas the use of radiotherapy is institution specific. Tumors with a low T category are associated with regional nodal and distant metastatic disease. It may therefore be reasonable to consider a sentinel lymph node biopsy or strict regional lymph node surveillance for all MCCs of the eyelid, regardless of T category or size.

Giant cell angiofibroma of the orbit with periosteal adherence.

We report a case of orbital giant cell angiofibroma, an unusual, recently reported benign spindle cell neoplasm. Preoperative clinical assessment and radiology suggested a benign mass and early operative findings were in concordance with this. Surgical excision was however, hampered by periosteal adhesion and lack of distinct encapsulation in the posterior part of the lesion. The histology of giant cell angiofibroma and its principle pathological differential diagnoses is discussed. As with some lymphangiomas, this is another benign orbital tumour which may present difficulties in complete surgical excision that are not anticipated based on the preoperative findings.