Purpose
To investigate the discordance between original and central laboratories in estrogen receptor (ER) status, in tumors originally deemed to be ER-negative, and in HER2 status in a diverse ...population-based sample.
Methods
In a follow-up study of 1785 women with Stage I–III breast cancer diagnosed between 2005 and 2007 in the Detroit and Los Angeles County SEER registry catchment areas, participants were asked to consent to reassessment of ER (in tumors originally deemed to be ER-negative) and HER2 status on archival tumor samples approximately four years after diagnosis. Blocks were centrally prepared and analyzed for ER and HER2 using standardized methods and the guidelines of the American Society of Clinical Oncology and the College of American Pathologists. Analyses determined the discordance between original and central laboratories.
Results
132 (31%) of those eligible for ER reassessment and 367 (21%) eligible for HER2 reassessment had archival blocks reassessed centrally. ER discordance was only 6%. HER2 discordance by immunohistochemistry (IHC) was 26%, but final HER2 results—employing FISH in tumors that were IHC 2+ at the central laboratory—were discordant in only 6%. Half of the original laboratories did not perform their own assays.
Conclusions
Discordance between original and central laboratories in two large metropolitan areas was low in this population-based sample compared to previously reported patient samples. Centralization of testing for key pathology variables appears to be occurring in many hospitals. In addition, quality improvement efforts may have preceded the publication and dissemination of specialty society guidelines.
To present a case of facial disfigurement from an injectable permanent filler and describe the consequences to patients exposed to the same injector (common source outbreak).
Case report and ...discussion of a common source outbreak after a group of persons developed complications years after permanent filler given by one injector.
A 39-year-old transgender model underwent polymethylmethacrylate (Artefill) facial filler injections to the lips, cheeks, and chin in 2018. A year later, the patient presented to the emergency room with severe facial swelling and difficulty breathing. Treatments have included 4 surgeries to remove filler and scar tissue and chronic low-dose oral steroid therapy. Upon questioning the patient, 6 additional people suffered from similar facial swelling years after injection by the same injector. The injector cannot be located.
Care must be taken in giving all facial fillers, particularly permanent ones. When one source patient is identified, questioning the patient's knowledge of others affected is critical to help manage an epidemic problem and to report a rogue injector. Physicians have a duty to investigate and report such cases.
To review and summarize the existing literature on the clinical applications of amniotic membrane transplantation (AMT) in ophthalmic plastic and reconstructive surgery.
A literature review was ...conducted on the PubMed database using the following search terms: "amniotic membrane" and "eyelid" or "orbit" or "fornix" or "socket" or "lacrimal".
In total 516 articles resulted from the search, of which 62 were included. Numerous cases and case series have been published on the use of amniotic membrane transplantation for ocular surface reconstruction, eyelid and forniceal reconstruction, and cicatricial eyelid abnormalities. Surgical methods of securing the graft vary. Few comparative studies exist; some show a similar or improved result when compared to oral mucous membrane grafting for certain indications.
Amniotic membrane transplantation can be a useful tool for the oculoplastic surgeon when faced with a case requiring reconstruction of the posterior lamellae, particularly in patients without other graft donor sites available, and uses of AMT continue to expand. Additional studies directly comparing AMT to other reconstructive techniques would be helpful in choosing between the available surgical techniques and standardizing best practices.
Recent increases in incidence and survival of oropharyngeal cancers in the United States have been attributed to human papillomavirus (HPV) infection, but empirical evidence is lacking.
HPV status ...was determined for all 271 oropharyngeal cancers (1984-2004) collected by the three population-based cancer registries in the Surveillance, Epidemiology, and End Results (SEER) Residual Tissue Repositories Program by using polymerase chain reaction and genotyping (Inno-LiPA), HPV16 viral load, and HPV16 mRNA expression. Trends in HPV prevalence across four calendar periods were estimated by using logistic regression. Observed HPV prevalence was reweighted to all oropharyngeal cancers within the cancer registries to account for nonrandom selection and to calculate incidence trends. Survival of HPV-positive and HPV-negative patients was compared by using Kaplan-Meier and multivariable Cox regression analyses.
HPV prevalence in oropharyngeal cancers significantly increased over calendar time regardless of HPV detection assay (P trend < .05). For example, HPV prevalence by Inno-LiPA increased from 16.3% during 1984 to 1989 to 71.7% during 2000 to 2004. Median survival was significantly longer for HPV-positive than for HPV-negative patients (131 v 20 months; log-rank P < .001; adjusted hazard ratio, 0.31; 95% CI, 0.21 to 0.46). Survival significantly increased across calendar periods for HPV-positive (P = .003) but not for HPV-negative patients (P = .18). Population-level incidence of HPV-positive oropharyngeal cancers increased by 225% (95% CI, 208% to 242%) from 1988 to 2004 (from 0.8 per 100,000 to 2.6 per 100,000), and incidence for HPV-negative cancers declined by 50% (95% CI, 47% to 53%; from 2.0 per 100,000 to 1.0 per 100,000). If recent incidence trends continue, the annual number of HPV-positive oropharyngeal cancers is expected to surpass the annual number of cervical cancers by the year 2020.
Increases in the population-level incidence and survival of oropharyngeal cancers in the United States since 1984 are caused by HPV infection.
Importance
Although the most recent American Joint Committee on cancer staging guidelines for ocular surface squamous neoplasia place a heightened emphasis on biopsy and histopathologic analysis, the ...interpretation and clinical relevance of these staging criteria are not always clear. We address limitations of using histopathologic analysis to predict clinical outcomes and suggest less‐invasive assessments.
Background
To investigate the impact of histopathologic depth of invasion on outcomes for tumours with the common presentation of multiple structure involvement.
Design
Retrospective chart review at tertiary institution.
Samples
Of 41 eyes with ocular surface squamous neoplasia between 2012 and 2017, 27 tumours involving multiple ocular structures clinically were included.
Methods
Biopsied tumours were determined to be invasive beyond the basement membrane or non‐invasive; non‐biopsied tumours were clinically identified with unknown depth of invasion. Outcomes were compared using Fisher's exact or Student's t tests.
Main Outcome Measures
Proportion of tumours cured, recurred and/or persisting.
Results
Twelve tumours (44%) received primary excisional biopsy, 10 (37%) received chemotherapy without biopsy and 5 (19%) received chemotherapy and biopsy. Clinical diagnosis was correct in all biopsied cases. While there were no significant differences in outcomes between invasive vs non‐invasive tumours or treatments, there was a trend toward larger basal diameter in recurrent tumours regardless of treatment.
Conclusions and Relevance
When ocular surface squamous neoplasia tumours with similar clinical involvement were compared, histopathologic depth of invasion was not predictive of clinical outcomes. Future staging criteria may consider the potential of largest basal dimension for more accurate prognostication.
We describe a rare case of ocular surface squamous neoplasia (OSSN) with intraocular spread after excisional biopsy which presented as a postoperative anterior chamber (A/C) opacity, initially ...thought to be a hypopyon. A 60-year-old female with history of a right (OD) conjunctival mass involving the cornea, surgically excised and diagnosed as OSSN, presented 2 months postoperatively with an A/C opacity concerning for infection. The patient was prescribed prednisolone acetate and ofloxacin drops postoperatively; topical chemotherapy was not given. When the opacity did not respond to 3 weeks of topical treatment, they were referred to an ocular oncologist for management. Intraoperative records from biopsy were unavailable; use of cryotherapy is unknown. On presentation, the patient had reduced vision OD. On slit-lamp exam, a white plaque in the A/C was seen, obscuring the iris. Given concern for postoperative intraocular cancer spread and extent of disease, enucleation with extended conjunctival excision was done. Gross pathology revealed an A/C mass with a diffuse hazy membrane. Histopathology diagnosed moderately differentiated OSSN with extensive intraocular invasion; a full-thickness limbal defect was visualized. Disease was confined to the globe, without residual conjunctival malignancy. This case emphasizes the importance of taking surgical precaution when excising conjunctival lesions, especially large lesions which obscure ocular anatomy, to maintain scleral integrity and Bowman’s layer with limbal lesions. Intraoperative cryotherapy and postoperative chemotherapy should also be employed. If a patient with history of ocular surface malignancy displays symptoms concerning postoperative infection, this case highlights the importance of considering invasive disease.
GPR158 is a newly characterized family C G-protein-coupled receptor, previously identified in functional screens linked with biological stress, including one for susceptibility to ocular ...hypertension/glaucoma induced by glucocorticoid stress hormones. In this study, we investigated GPR158 function in the visual system.
Gene expression and protein immunolocalization analyses were performed in mouse and human brain and eye to identify tissues where GPR158 might function. Gene expression was perturbed in mice, and in cultures of human trabecular meshwork cells of the aqueous outflow pathway, to investigate function and mechanism.
is highly expressed in the brain, and in this study, we show prominent expression specifically in the visual center of the cerebral cortex. Expression was also observed in the eye, including photoreceptors, ganglion cells, and trabecular meshwork. Protein was also localized to the outer plexiform layer of the neural retina.
deficiency in knockout (KO) mice conferred short-term protection against the intraocular pressure increase that occurred with aging, but this was reversed over time. Most strikingly, the pressure lowering effect of the acute stress hormone, epinephrine, was negated in KO mice. In contrast, no disruption of the electroretinogram was observed. Gene overexpression in cell cultures enhanced cAMP production in response to epinephrine, suggesting a mechanism for intraocular pressure regulation. Overexpression also increased survival of cells subjected to oxidative stress linked to ocular hypertension, associated with TP53 pathway activation.
These findings implicate GPR158 as a homeostatic regulator of intraocular pressure and suggest GPR158 could be a pharmacological target for managing ocular hypertension.
Pancreatic cancer is the fourth leading cause of cancer death in the United States. Prognostic biomarkers are lacking, and treatment has limited effect on survival. Tissues from Surveillance, ...Epidemiology, and End Results registries (Iowa, Hawaii, and Los Angeles) were used to build a tissue microarray of 161 pancreatic tumors (113 resections and 48 biopsies). Proportional hazard models adjusted for age, race, sex, stage, time-period of diagnosis, and treatment. Associations were examined between markers (MUC1, MUC2, MUC5AC, synaptophysin, chromogranin, neuron specific enolase, epidermal growth factor receptor, HER2, CD5, CD138, CK5/6, CK19, CK20, and p53) and survival time from diagnosis. After adjusting for covariates, borderline statistically significant associations were seen between expression of each of the three mucins (MUC1, MUC2, and MUC5AC) and shorter survival time. The associations strengthened for 154 (96%) adenocarcinomas, particularly the 120 (75%) well-differentiated to moderately differentiated ductal adenocarcinomas, a tumor type that occurred more often in the cohort among White cases than cases of other racial origin (P<0.01). For differentiated ductal adenocarcinomas, associations with shorter survival time were seen for expression of all three mucins combined versus other mucin expression patterns (adjusted hazard ratio, 1.8; 95% confidence interval, 1.2-2.6) and for MUC2(+) versus MUC2(-) expression (adjusted hazard ratio, 1.6; 95% confidence interval, 1.1-2.4). Mucin gene expression, particularly MUC2 expression, may have prognostic value for differentiated adenocarcinomas. Tumor histologies differed in this and Japanese cohorts. The tissue microarray is available to evaluate other biomarkers. Tissue-based surveillance can be used to monitor tumor histology in populations and facilitate applied research.
Introduction: Anterior segment tumors can be difficult to detect until tumor growth is substantial enough to cause local signs or symptoms. Earlier detection may result in improved outcomes, ...particularly the ability to option for globe-conserving therapy. Multiple diagnostic modalities such as ultrasound or optical coherence tomography exist to aid for earlier detection of ciliary body tumors, but they also have limitations. Here we describe the potential for scleral angiography as an adjunctive modality to assist in evaluating anterior segment ciliary body tumors. Case Presentations: A 61-year-old Caucasian male and a 57-year-old Hispanic female presented for ciliary body tumor evaluation. The Caucasian male notably had abnormal scleral, episcleral, and conjunctival vessels in the affected eye. Scleral angiography was performed in both cases with the abnormal vasculature highlighted in the Caucasian male. The Hispanic female did not demonstrate abnormal scleral angiographic patterns. Notably, the Caucasian male also had regions of abnormal scleral angiography arising in locations of otherwise normal appearing sclera. Both patients had the affected eyes enucleated. Histology of the enucleated eyes demonstrated a ciliary body melanoma in the Caucasian male associated with abnormal vascular and tumor infiltration of the scleral bed. The Hispanic female had a pigmented ciliary body adenoma without involvement of the scleral bed. Conclusion: With limited sample size, scleral angiography has the potential to detect abnormal scleral vascular patterns in otherwise normal appearing sclera in cases of ciliary body tumor with scleral vascular invasion.
Human papillomavirus (HPV) is a major risk factor for specific cancers of the head and neck, particularly malignancies of the tonsil and base of the tongue. However, the role of HPV in the ...development of laryngeal cancer has not been definitively established. We conducted a population-based, cancer registry study to evaluate and characterize the genotype-specific prevalence of HPV in invasive laryngeal cancer cases diagnosed in the U.S.
The presence of genotype-specific HPV DNA was evaluated using the Linear Array HPV Genotyping Test and the INNO-LiPA HPV Genotyping Assay in formalin-fixed paraffin embedded tissue from 148 invasive laryngeal cancer cases diagnosed in 1993-2004 within the catchment area of three U.S. SEER cancer registries.
HPV DNA was detected in 31 of 148 (21%) invasive laryngeal cancers. Thirteen different genotypes were detected. Overall, HPV 16 and HPV 33 were the most commonly detected types. HPV was detected in 33% (9/27) of women compared with 18% (22/121) of men (p = 0.08). After adjustment for age and year of diagnosis, female patients were more likely to have HPV-positive laryngeal tumors compared to males (adjusted OR 2.84, 95% CI 1.07-7.51). Viral genotype differences were also observed between the sexes. While HPV 16 and 18 constituted half of HPV-positive cases occurring in men, among women, only 1 was HPV 16 positive and none were positive for HPV 18. Overall 5-year survival did not vary by HPV status.
HPV may be involved in the development of a subset of laryngeal cancers and its role may be more predominant in women compared to men.
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