Arthrographis kalrae Keratitis Complicated by Endophthalmitis: A Case Report With Literature Review.

OBJECTIVES: To report the first case of Arthrographis kalrae keratitis complicated by endophthalmitis in the UK and to review the current literature. METHODS: A case report with literature review. RESULTS: A 65-year-old male patient, with a background of treated B-cell lymphoma and herpes simplex virus-related neurotrophic keratopathy, presented with a large infiltrative corneal ulcer in the right eye. The patient was immediately commenced on empirical antifungal treatment in view of the clinical suspicion of fungal keratitis (FK). The initial corneal scrape identified the organism as nonspecific "mold," and the identity of A. kalrae was subsequently confirmed using matrix-assisted laser/desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS). During the clinical course, the patient received topical, intrastromal, intracameral, and systemic antifungal treatment, repeat therapeutic corneal cross-linking treatment, and three penetrating keratoplasties. Although a temporary improvement was achieved with therapeutic corneal cross-linking treatment, the FK progressed relentlessly and was ultimately complicated by an endophthalmitis despite maximum medical and surgical treatment, eventuating in an enucleation. CONCLUSIONS: A. kalrae keratitis is an exceptionally rare clinical entity that poses significant therapeutic challenges. MALDI-TOF-MS serves as a useful diagnostic technique in identifying this rare organism. Although the literature suggested that A. kalrae keratitis may sometimes be controlled with antifungal medical treatment alone, this approach was proven to be futile in our immunocompromised patient with pre-existing neurotrophic keratopathy, suggesting that early surgical intervention such as therapeutic keratoplasty may be required in these cases.

Multicenter Evaluation of the Idylla GeneFusion in Non-Small-Cell Lung Cancer.

Targeted therapy in lung cancer requires the assessment of multiple oncogenic driver alterations, including fusion genes. This retrospective study evaluated the Idylla GeneFusion prototype, an automated and ease-of-use (<2 minutes) test, with a short turnaround time (3 hours) to detect fusions involving ALK, ROS1, RET, and NTRK1/2/3 genes and MET exon 14 skipping. This multicenter study (18 centers) included 313 tissue samples from lung cancer patients with 97 ALK, 44 ROS1, 20 RET, and 5 NTRKs fusions, 32 MET exon 14 skipping, and 115 wild-type samples, previously identified with reference methods (RNA-based next-generation sequencing/fluorescence in situ hybridization/quantitative PCR). Valid results were obtained for 306 cases (98%), overall concordance between Idylla and the reference methods was 89% (273/306); overall sensitivity and specificity were 85% (165/193) and 96% (108/113), respectively. Discordances were observed in 28 samples, where Idylla did not detect the alteration identified by the reference methods; and 5 samples where Idylla identified an alteration not detected by the reference methods. All of the ALK-, ROS1-, and RET-specific fusions and MET exon 14 skipping identified by Idylla GeneFusion were confirmed by reference method. To conclude, Idylla GeneFusion is a clinically valuable test that does not require a specific infrastructure, allowing a rapid result. The absence of alteration or the detection of expression imbalance only requires additional testing by orthogonal methods.

Multi-center real-world comparison of the fully automated Idylla™ microsatellite instability assay with routine molecular methods and immunohistochemistry on formalin-fixed paraffin-embedded tissue of colorectal cancer.

Microsatellite instability (MSI) is present in 15-20% of primary colorectal cancers. MSI status is assessed to detect Lynch syndrome, guide adjuvant chemotherapy, determine prognosis, and use as a companion test for checkpoint blockade inhibitors. Traditionally, MSI status is determined by immunohistochemistry or molecular methods. The Idylla™ MSI Assay is a fully automated molecular method (including automated result interpretation), using seven novel MSI biomarkers (ACVR2A, BTBD7, DIDO1, MRE11, RYR3, SEC31A, SULF2) and not requiring matched normal tissue. In this real-world global study, 44 clinical centers performed Idylla™ testing on a total of 1301 archived colorectal cancer formalin-fixed, paraffin-embedded (FFPE) tissue sections and compared Idylla™ results against available results from routine diagnostic testing in those sites. MSI mutations detected with the Idylla™ MSI Assay were equally distributed over the seven biomarkers, and 84.48% of the MSI-high samples had ≥ 5 mutated biomarkers, while 98.25% of the microsatellite-stable samples had zero mutated biomarkers. The concordance level between the Idylla™ MSI Assay and immunohistochemistry was 96.39% (988/1025); 17/37 discordant samples were found to be concordant when a third method was used. Compared with routine molecular methods, the concordance level was 98.01% (789/805); third-method analysis found concordance for 8/16 discordant samples. The failure rate of the Idylla™ MSI Assay (0.23%; 3/1301) was lower than that of referenced immunohistochemistry (4.37%; 47/1075) or molecular assays (0.86%; 7/812). In conclusion, lower failure rates and high concordance levels were found between the Idylla™ MSI Assay and routine tests.

Eyelid skin trichilemmoma and underlying local malignancy: is an aggressive treatment necessary?

OBJECTIVE: Trichilemmoma is a benign tumour derived from the outer root sheath of hair follicles. Trichilemmoma can be associated with basal cell carcinoma (BCC), either as a collision lesion or from malignant transformation. This study evaluates malignancy associated with eyelid trichilemmoma and principles of treatment. METHODS AND ANALYSIS: Retrospective study involving biopsy-proven eyelid trichilemmoma cases over 14 years encountered at a tertiary referral centre. Presenting features, differential diagnosis, type and number of operations required and histopathological features including coexisting BCC were analysed. RESULTS: We identified 36 cases with an average age of 66 years. The clinical differential diagnoses were mainly BCC (44%), papilloma (36%) and squamous cell carcinoma (SCC) (3%). Three patients (8%) had trichilemmoma with associated BCC. Of the 19 cases (53%) of trichilemmomas without BCC with equivocal surgical margins, seven patients (19%) opted for further excision while 12 patients (33%) opted for observation and were discharged. A patient re-presented two years later with invasive BCC. Overall, 11% of our biopsy-proven eyelid trichilemmoma cases were associated with BCC. CONCLUSION: Patients should be informed that a proportion of incompletely excised eyelid trichilemmomas may conceal underlying BCC. Therefore, further surgery to achieve clear surgical margins should be offered. Patients who opt for observation should be offered 6-monthly follow-up for three to five years. Alternatively, they can be discharged with advice to report any recurrence of lumps, skin changes or loss of lashes at the site of previous lesion.

Staged excision of primary periocular basal cell carcinoma: absence of residual tumour in re-excised specimens: a 10-year series.

AIMS: The aim is to study staged periocular basal cell carcinoma (BCC) excision in a tertiary oculoplastic referral centre in Sheffield, UK. In particular, we examined patients with close or positive margins and no tumour seen on re-excision to identify demographics and tumour characteristics in this population. METHODS: A retrospective review of medical records of 437 cases of staged periocular BCC excisions over a 10-year period (2007-2017) was carried out. Patients had surgical excision with 3 mm clinically clear margins. Staged excision was performed for all cases included in this study. Standard reconstruction techniques were employed. Histopathology was analysed for tumour type, subtype and stage. RESULTS: Over the 10-year period, of the 437 periocular BCCs, 156 had close or involved margins. Residual tumour was found in 29 (18.6%), whereas in 122 eyelids of 120 patients (78.2%) no residual tumour was identified on histological examination. Micronodular (54.1%) and nodular (23.7%) growth patterns of BCC, as well as lower eyelid location (72.1%), were the most prevalent in this population. Two patients (1.6%) had recurrence of BCC over a mean follow-up of 57 months (range 1-125 months). CONCLUSIONS: A significant proportion of BCCs transected on initial excision show no residual tumour in the re-excision specimens. In the interval between initial excision and re-excision, there may be eradication of the residual tumour. The exact mechanisms for this are unclear, however, and re-excision remains the appropriate recommended course in the presence of involved surgical margins of periocular BCC, particularly when high-risk tumour subtypes are encountered.

Contact Lens-Related "Keratoschisis"-An Unusual Case of Corneal Stroma Lamellar Trauma.

PURPOSE: To describe the clinical, imaging, and histopathological features of a highly unusual, postcontact lens removal scenario in a 29-year-old woman. Most documented cases recover good vision but differ significantly from our case. METHODS: A 29-year-old woman presented to the Eye Casualty Department as she was unable to remove her right soft contact lens after having inadvertently slept wearing soft contact lenses. During removal, extensive axial corneal epithelial sloughing occurred. Examination immediately after lens removal revealed keratitis and hypopyon, and she was administered intensive topical antibiotics. During her treatment course, a raised crescent of edematous tissue was noted centrally. This persisted at 6 weeks after presentation, so exploration under anesthesia and superficial keratectomy were performed. The preoperative optical coherence tomography (OCT) image showed a thickened inferior cornea with a "tent" of epithelium growing over it. The operative findings identified a flap of the cornea, reflected back on itself and a corresponding stromal depression superior to the flap, correlating well with the OCT findings. The flap was removed and sent for histopathological examination. RESULTS: Histology revealed stromal tissue without the Bowman layer. The corneal stroma was scarred and chronically inflamed. Immunohistochemistry for pan-cytokeratins revealed epithelial cells on both sides of the flap, confirming that regenerative epithelial hyperplasia had occurred over the stromal flap and concurring well with the "tent" of epithelium observed on the OCT. CONCLUSIONS: We have described a highly unusual case of an inferiorly displaced stromal lamellar corneal traumatic flap associated with a soft contact lens removal, which we have termed lens-associated keratoschisis.