Cutaneous pleomorphic adenoma of the periocular region - a case series.

Mixed tumour of the skin is a rare entity also known as chondroid syringoma and pleomorphic adenoma. These usually present as slow-growing skin nodules with a smooth surface, clear boundaries, and no ulceration. Case series exist describing pleomorphic adenomas in the periocular region including the lids and orbit, separate to the more familiar lacrimal gland pleomorphic adenoma. These may arise from accessory or ectopic lacrimal gland tissue but in the eyelids are more likely to arise from sweat glands in the skin. Histopathological analysis of these lesions is important to identify complete excision, minimising recurrences and in identifying rare but potential malignant transformation. We describe the clinical features and outcomes in three cases of pleomorphic adenoma with two at the medial canthus (including one recurrence) and one in the brow region.

Validation of ROS1 by immunohistochemistry against fluorescent in situ hybridisation on cytology and small biopsy samples in a large teaching hospital.

OBJECTIVE: Rearranged ROS1, present in 1%-2% of non-small cell lung cancer (NSCLC) patients, usually young, never or light smokers, is assessed by fluorescence in situ hybridization (FISH) to determine eligibility for tyrosine kinase inhibitors (TKI). Immunohistochemistry (IHC) for the protein product of ROS1 rearrangement, a cost-effective alternative, is validated on cytology and small biopsy samples. METHODS: From 1 March to 31 December 2019, cytology cell blocks and small biopsy samples from a selected cohort of NSCLC patients were concurrently tested for ROS1 gene rearrangement by Vysis 6q22 Break Apart FISH probe and IHC using Cell Signalling D4D6 antibody. Mismatch cases were tested by an RNA fusion next generation sequencing (NGS) panel. RESULTS: In a prospective population of 95 cases, 91 were negative and two were positive by both FISH and IHC. Both dual positive cases were female never smokers and benefited from TKI treatment. Another two cases were positive by FISH but negative by IHC and repeat by NGS showed one to be negative but one failed. Turnaround time for IHC was 0 to 8 days from request to authorisation, whilst that of FISH was 9 to 42 days at a cost of £51 and £159 respectively. CONCLUSION: IHC to assess for the protein product of ROS1 gene rearrangement on cytology cell blocks and small biopsy samples in a routine setting is a promising screening method to assess eligibility for TKI treatment with positive and indeterminate cases confirmed by FISH or NGS as it has good negative predictive value, faster turnaround time and is cost effective, with proven technical and clinical validation.

A rare case of orbital angioleiomyoma.

A 65-year old woman presented with 3-year history of painless, gradual swelling of the right upper eyelid associated with proptosis. Computed tomography (CT) and magnetic resonance imaging (MRI) of the orbit showed a well circumscribed soft tissue mass in the supero-lateral orbit. An excision biopsy of the lesion was performed via lateral orbitotomy. Histopathology examination and immunochemistry staining confirmed the diagnosis of cavernous angioleiomyoma. The tumour was excised completely. Orbital angioleiomyoma is a rare benign tumour and the lesion can cause visual morbidity, particularly when intraconal. Despite sophisticated imaging modalities, histopathological analysis is essential for diagnosis. Angioleiomyoma should be included in the differential diagnosis of well-defined orbital lesions. Complete surgical excision carries a low risk of recurrence.

Polymicrobial Keratitis With Cryptococcus curvatus, Candida parapsilosis, and Stenotrophomonas maltophilia After Penetrating Keratoplasty: A Rare Case Report With Literature Review.

OBJECTIVES: To report the first case of fungal keratitis caused by Cryptococcus curvatus after penetrating keratoplasty (PK) in an immunocompetent patient and to describe its therapeutic challenge and long-term outcome. METHODS: An interventional case report. RESULTS: A 54-year-old female patient underwent right PK for lattice dystrophy. At 5-year post-PK, she developed a polymicrobial keratitis caused by Candida parapsilosis, and Stenotrophomonas maltophilia at the peripheral graft, which was successfully treated with topical antibiotic and antifungal drops. One year later, another fungal keratitis occurred which apparently resolved with antifungal treatment but recurred in an unusual fashion and required a repeat PK revealing the diagnosis of C. curvatus keratitis. This was confirmed by microbiological culture on Sabouraud dextrose agar, nuclear ribosomal repeat regional sequencing of the D1-D2 and internal transcribed spacer regions, and histopathological examination. Various topical, intracorneal, and systemic antifungal treatments had been attempted but failed to resolve the infection completely, necessitating a subsequent third PK. A further recurrence was noted 16-month post-third PK, which was eradicated with multiple topical and intracorneal antifungal treatment, and direct cryotherapy to the corneal abscess. No further recurrence of C. curvatus was noted at 4-year follow-up. CONCLUSIONS: Cryptococcus curvatus should be added to the known list of organisms capable of causing fungal keratitis. Our experience suggests that this type of organism could cause low-grade, grumbling infection, which may however be exceptionally difficult to treat. Long-term eradication of this rare fungal keratitis could be potentially achieved by intensive ocular and systemic antifungal treatment, repeat therapeutic keratoplasties, and focal cryotherapy.

Live porcine thirty days delayed recovery surgery: Qualitative findings with the hypersonic vitrectomy.

INTRODUCTION: Qualitatively assess the possible delayed structural, macroscopic and microscopic changes in the neuro-retina, retinal vasculature, retinal pigment epithelium (RPE) and optic nerve head (ONH) after pars plana vitrectomy (PPV) surgery using a new hypersonic vitrector (HV). MATERIALS AND METHODS: Eight live porcine eyes underwent PPV using either the HV or a conventional pneumatic guillotine vitrector (GV). The un-operated fellow eye from each pig was used as an external control. The pigs were post-operatively kept alive for 30 days before termination and enucleation of the eyes. Prior to enucleation, all eyes underwent examination of the lens and indirect ophthalmoscopy. Enucleated eyes were fixed in formalin, examined macroscopically and processed for histological assessment. Microscopic analysis included assessment of neuro-retina, retinal vasculature, RPE and ONH, as well as observation for any morphological intraocular changes. Comparison was made between: (1) treated and untreated areas of the same eye (internal control) (2) different areas within the same eye operated on using different vitrector settings (3) eyes operated on with the HV and GV (4) eyes receiving surgery and the fellow un-operated eye (external control, same pig). RESULTS: All lenses had remained clear at 30 days into the postoperative period. On indirect ophthalmoscopy, the retina had remained attached in all eyes with no visible changes to the neuro-retina, retinal vasculature, RPE or ONH. Two eyes showed localized RPE depigmentation secondary to previously documented intraoperative retinal touch. The Morphological changes in the retinal layers above depigmented RPE were no different from retinal change elsewhere. There were mild and similar microscopic changes observed in the neuro-retina, retinal vasculature, RPE or ONH associated with either the HV or GV PPVs. Preliminary histological findings revealed no significant differences between eyes operated on with the HV and those operated on the GV. DISCUSSION: At 30 days into the postoperative period, there seemed to be similar morphological changes attributable to the use of HV and GV. Therefore, the HV promises to be a new alternative to the currently commercially available GV for PPV.

Chronic Lymphocytic Leukaemia/ Small-Cell Lymphocytic Lymphoma of the Lacrimal Sac: A Case Series.

BACKGROUND: Lymphomas of the lacrimal sac are rare, accounting for less than 10% of lacrimal sac malignant tumours. They may present with symptoms typical of secondary acquired nasolacrimal duct obstruction and are thus often misdiagnosed. METHODS: Case series and literature review. RESULTS: Herein we describe 3 cases of chronic lymphocytic leukaemia (CLL)/small-cell lymphocytic lymphoma (SLL) of the lacrimal sac with immunohistochemical and in 1 case molecular confirmation. CONCLUSION: Lymphomas of the lacrimal sac should be suspected in patients with known CLL presenting with epiphora and dacryocystitis. During dacryocystorhinostomy, an incisional biopsy of the lacrimal sac is essential for confirming CLL/SLL involvement and may guide treatment.

Gamma-delta T-cell lymphoma of skin, eye and brain presenting with visual loss.

A young man presented with rapid, predominantly right-sided visual loss with a background of multifocal skin lesions. Visual acuity was right hand movements, left 6/5 Snellen, deteriorating to 6/38. He showed panuveitis with bilateral multifocal retinal infiltrates and retinal vasculitis. Multifocal brain lesions were identified. Biopsy of both skin and vitreous showed atypical lymphocytes, and immunohistochemistry confirmed T-cell lymphoma of gamma-delta subtype. Management with the CODOX-M/IVAC polychemotherapy regimen achieved rapid response including resolution of intraocular changes and substantial improvement of visual acuity to right 6/7.5, left 6/6. However, he relapsed before planned stem cell transplantation. Salvage with the gemcitabine/dexamethasone/cisplatin regimen, although temporarily effective, was followed by further relapse including widespread brain involvement, and he succumbed 10 months after presentation.

Retinal and vitreous metastases from hepatocholangiocarcinoma.

BACKGROUND: To report a case of metastatic hepatocholangiocarcinoma to the vitreous and retina. CASE PRESENTATION: A 70-year-old male, who was recently diagnosed with hepatocholangiocarcinoma, was complaining of floaters in his right eye over the past 5 months and was referred to the Liverpool Ocular Oncology Centre. On presentation, his visual acuity in the right eye was 6/24. Fundus exam revealed a whitish, unilateral, full-thickness retinal lesion at the inferotemporal arcade of his right eye, with vitreous infiltration and subretinal fluid. The patient underwent 25G pars plana vitrectomy with biopsy, resection of the lesion and intravitreal bevacizumab injection. Histopathology testing of the surgical specimens confirmed the diagnosis of metastatic carcinoma to the eye. Two months postoperatively his visual acuity had improved to 6/7.5 and there was no sign of active disease in his right eye, while 9 months postoperatively his visual acuity decreased to 6/9.5 due to developing nuclear sclerotic cataract in his right eye. CONCLUSION: The current report presents the first case of a hepatocholangiocarcinoma metastasis to the vitreous and retina.

Ultrastructural and histopathologic findings after pars plana vitrectomy with a new hypersonic vitrector system. Qualitative preliminary assessment.

PURPOSE: Preliminary assessment of a new prototype ultrasound-based hypersonic vitrector (HV) by qualitatively examining the histopathological changes in the retina and vitreous body after pars plana vitrectomy (PPV) and its ability to fragment vitreous collagen. METHODS: Fourteen porcine cadaveric eyes, 20 eyes in live swine and six human cadaveric eyes underwent PPV using the HV or a pneumatic guillotine vitrector (GV). An additional 4 porcine crystalline lenses were touched with either the HV or GV for 1 minute. Following PPV, human vitreous was removed and processed for electron microscopy (EM). Eyes and lenses were fixed and sectioned for light microscopy (LM). RESULTS: There were no macroscopic retinal or optic nerve defects associated with either HV or GV PPVs. Cadaveric retinal specimens showed separation of the inner limiting membrane (ILM) and vacuolization and fragmentation at the nerve fiber layer (NFL) and the ganglion cell layer (GCL). ILM fragmentation and separation were found after PPV in live swine with both vitrectors. Small disruptions of the posterior capsule or structural lens defects were found after HV touch. The EM analysis revealed more fragmentation of human vitreous collagen fibrils after HV compared to GV PPV. CONCLUSIONS: LM and EM analysis of retina, vitreous, and crystalline lens after PPV showed similar morphological changes using the HV or the GV. Vitreous fragmentation appeared more effective with the HV. Overall this study suggests that the HV may be a promising new technology. More work is needed to quantitatively assess its safety and efficacy.

Lacrimal duct cyst abscess.

Cystic dilatation within the lacrimal gland is thought to be related to chronic inflammation and scarring of the lacrimal gland ductules. We review the literature and discuss a case and of lacrimal duct cyst suppuration presenting with visual loss, external ophthalmoplegia, proptosis and ptosis. To our knowledge, only one other report of a lacrimal ductal cyst abscess has been reported in the literature so far.

Amyloidosis of the orbit and adnexae.

PURPOSE: To present a series of patients with orbital and adnexal amyloidosis and illustrate the diversity of disease and the challenges of managing such cases. METHODS: Descriptive case series of ten patients with biopsy proven amyloidosis involving the orbit, conjunctiva and eyelids. The presentation, clinical findings and management are discussed for each case. RESULTS: All patients had some form of eyelid abnormality or malposition. Presenting complaints included ptosis, epiphora and ocular discomfort. Other clinical findings included conjunctival lesions and proptosis. The majority of patients had localised amyloidosis and one patient had systemic disease. Conservative management included lubrication and the use of bandage contact lenses. Surgical management included debulking, ptosis or other lid surgery. CONCLUSION: Amyloidosis can present to an Occuloplastic clinic in a wide variety of ways. Definitive diagnosis is based on the histopathological findings. Management is often challenging. Multi-disciplinary team involvement is critical in view of its systemic associations.

Donor preparation using pneumatic dissection in endothelial keratoplasty: DMEK or DSEK?

PURPOSE: To determine if residual stroma remains on the Descemet membrane when pneumatic dissection is used to prepare donor tissue for endothelial keratoplasty. METHODS: Pneumatic dissection using a posterior peripheral needle insertion was carried out on 5 eye bank corneas. Samples were then sent for histological analysis. RESULTS: A thin layer of stroma remained on the Descemet membrane in all the samples. The average central stromal thickness was 12.4 µm (range 6.5-20.0 µm). CONCLUSIONS: Endothelial keratoplasty using pneumatic dissection to prepare donor tissue should be considered a form of Descemet stripping endothelial keratoplasty and not Descemet membrane endothelial keratoplasty. If future studies show excellent visual results using pneumatic dissection for endothelial keratoplasty, then removal of all donor stroma may be unnecessary.

Residual corneal stroma in big-bubble deep anterior lamellar keratoplasty: a histological study in eye-bank corneas.

AIM: To determine if residual corneal stroma remains on the recipient posterior lamella in big-bubble deep anterior lamellar keratoplasty (DALK). METHODS: Pneumodissection using the big-bubble technique was carried out on eye-bank corneas mounted on an artificial anterior chamber. Samples that had a successful big-bubble formation were sent for histological evaluation to determine if any residual stroma remained on the Descemet membrane (DM). RESULTS: Big-bubble formation was achieved in 32 donor corneas. Two distinct types of big-bubble were seen: the bubble had either a white margin (30 corneas) or a clear margin (two corneas). The posterior lamellae of all the white margin corneas showed residual stroma on DM with a mean central thickness of 7.0 µm (range 2.6-17.4 µm). The clear margin corneas showed no residual stroma on DM. CONCLUSION: It should no longer be assumed that big-bubble DALK, where the bubble has a white margin, routinely bares DM. True baring of DM may only occur with the less commonly seen clear margin bubble.

Darier disease: beware the cyst that smells.

A 32-year-old woman presented with cystic eyelid lesions accompanied by foul-smelling discharge. Excision biopsy showed that she had Darier disease, and she was referred to dermatology for further management. Despite clinically indolent-looking lesions, biopsy and histology allowed the diagnosis of this rare condition to be made.

Severe mitral and aortic regurgitation in association with ankylosing spondylitis.

Aortic disease and aortic valve regurgitation are well documented in association with ankylosing spondylitis, although involvement of the mitral valve occurs more rarely. We report a case of severe mitral and aortic regurgitation in association with ankylosing spondylitis. We then discuss the characteristic cardiac manifestations that may occur in association with ankylosing spondylitis and the associated echocardiographic features.

Angiogenesis in non-small cell lung cancer: microvessel area in needle biopsy in vascular tumor density.

OBJECTIVE: To evaluate angiogenesis in non-small cell lung cancer (NSCLC) through immunohistochemistry with CD34 and computerized image analysis comparing the microvessel area in needle biopsies and surgical specimens. STUDY DESIGN: Core biopsies and surgical specimens from 28 patients with NSCLC were reviewed. Microvessels were highlighted by immunohistochemistry with anti-CD34. Tumor microvessel area was measured in digital photographs from hot spots of all samples. RESULTS: Average microvessel area among core samples was 5,093.6 microm2 (range, 233.4-17,916.8) and among surgical specimens was 3,599.3 microm2 (range, 376.9-9,514.0). There was strong correlation between overall microvascular area in biopsies and surgical specimens (r = 0.7; p = 0.0001). Mean area of core specimens was used to divide cases into groups of low and high vascular areas. A slightly stronger correlation was observed between biopsies and surgical specimens with low vascular areas (r = 0.84; p = 0.0001). CONCLUSION: There is strong correlation of microvessel area in core biopsies and respective surgical specimens in NSCLC. These data indicate that core specimens could be used to assess the extent of angiogenesis in NSCLC in the pretreatment phase.