Clinicopathological features of peripheral nerve sheath tumors involving the eye and ocular adnexa.

Peripheral nerve sheath tumors (PNSTs) are known to occur in the orbit and comprise 4% of all orbital tumors, but have not been well studied in contemporary literature. Ninety specimens involving the eye and ocular adnexa (1979-2015) from 67 patients were studied. The mean age was 32.5years. Locations included orbit (58.9%), eyelid (60.0%), and other ocular adnexa. Most specimens were neurofibromas (70.0%), followed by schwannomas (11.1%), neuromas (11.1%), granular cell tumors (n=4), nerve sheath myxomas (n=2), and malignant PNST (n=1). Fifty-six (88.9%) neurofibroma cases were neurofibromatosis 1 associated. Among neurofibromas, 31.7% were localized, 38.1% were plexiform, 25.4% were diffuse, and 4.8% were diffuse and plexiform. These tumors involved skin (31.7%), soft tissue (11.1%), skeletal muscle (22.2%), peripheral nerve (63.0%), lacrimal gland (20.6%), and choroid (n=1). Other histologic findings included pseudo-Meissner corpuscles (27%), Schwann cell nodules (4.8%), prominent myxoid component (7.9%), melanin-like pigment (3.2%), and inflammation (14.3%). Available immunostains included S100 (+ in 15/15 cases), EMA (+ in 2/4 cases), CD34 (+ in 4/4 cases), and Ki-67 (<1% in 4/4 cases). Among 10 schwannomas, 8 were conventional and 2 were plexiform. Observed features included capsule (n=5), hyalinized vessels (n=5), Verocay bodies (n=7), and Antoni B pattern (n=5). Immunostaining included S100+ in 4 of 4 cases, and collagen IV+ and Ki-67 <1% in 3 of 3 cases. Neurofibromas are the most common PNST involving the eye and ocular adnexa, and the majority are associated with neurofibromatosis 1. Plexiform and diffuse patterns and the presence of pseudo-Meissner corpuscles are relatively frequent in this area.

Morphologists overestimate the nuclear-to-cytoplasmic ratio.

BACKGROUND: The Paris System for Reporting Urinary Cytology (TPS) has defined nuclear-to-cytoplasmic (N:C) ratio cutoff values for several of its risk-stratified diagnostic categories. However, because pathologists are not trained to recognize strict N:C ratio cutoff values, a previously designed survey was used to determine whether pathologists could accurately identify N:C ratios according to TPS standards. METHODS: Participants were instructed to estimate the N:C ratio of ideal (line drawing) and real (cell photograph) images presented via an online survey. Actual N:C ratios ranged from 0.3 to 0.8, and 3 answer choices were available: < 0.5, ≥ 0.5 and <0.7, and ≥0.7. The resulting data were analyzed to determine the accuracy and performance of the subgroups. RESULTS: A total of 137 individuals completed the survey. Approximately 24.1% were cytopathologists, 18.2% were pathologists without formal cytopathology training, 18.2% were cytotechnologists, 24.1% were pathology residents, and 15.3% were nonmorphologists. Overall, 70.0%, 67.6%, and 93.3% of responses, respectively, were correct for images with an N:C ratio of < 0.5, ≥0.5 and < 0.7, and ≥0.7. For images with an actual N:C ratio < 0.5 and ≥0.5 and < 0.7, 30.0% and 25.0% of responses, respectively, overestimated the N:C ratio. Furthermore, for images with an N:C ratio of 0.4 and 0.6, > 40.0% of responses overestimated the N:C ratio. As a whole, morphologists were significantly more accurate than nonmorphologists (P = .030). CONCLUSIONS: Morphologists tended to overestimate the N:C ratio, particularly at ratios close to TPS-recommended cutoff values. Additional training regarding N:C ratio estimation may help pathologists to adapt to this new system. Cancer Cytopathol 2016;124:669-77. © 2016 American Cancer Society.

Should the BK polyomavirus cytopathic effect be best classified as atypical or benign in urine cytology specimens?

BACKGROUND: According to The Paris System for Reporting Urinary Cytology (TPS), the category of atypical urothelial cells (AUC) should not be applied to specimens in which cellular changes can be entirely attributed to the polyoma (BK) virus cytopathic effect (CPE). Until recently, cases with BK CPE at The Johns Hopkins Hospital were categorized as atypical urothelial cells of uncertain significance (AUC-US), which is equivalent to the TPS AUC category. This study was performed to determine how significantly the rate of AUC-US specimens would decrease if specimens with only BK CPE were classified as benign. METHODS: Two reviewers and 1 adjudicator re-evaluated urinary tract specimens to determine whether sufficient cytological atypia justified an AUC-US diagnosis independent of the presence of BK CPE. For patients with surgical follow-up, the rate of high-grade urothelial carcinoma (HGUC) on tissue biopsy was tracked over a 5-year period. RESULTS: The reclassification rate of AUC-US cases with BK CPE as benign was 62.6%. The rate of subsequent HGUC was 6.0% for cases reclassified as benign and 10.0% for cases still classified as AUC-US. These rates were not significantly elevated in comparison with control cohorts among all-comers. However, for patients without a history of HGUC, the rate of HGUC on follow-up was significantly elevated in comparison with the rate for a benign control cohort and was similar to the rate for the AUC-US control cohort. CONCLUSIONS: Reclassification as benign would have decreased the rate of AUC-US from 24.8% to 20.7% during the study year. However, the high rate of subsequent HGUC among nonsurveillance patients suggests that the reclassification of specimens with BK CPE in these patients may be inappropriate. Cancer Cytopathol 2016;124:436-42. © 2016 American Cancer Society.

The cytomorphological features of low-grade urothelial neoplasms vary by specimen type.

BACKGROUND: Urinary tract (UT) cytology has been used successfully to diagnose high-grade urothelial carcinoma but is reported to have poor sensitivity for low-grade urothelial neoplasms (LGUNs). However, the literature has shown that LGUN may be associated with atypical findings in UT specimens. The authors determined which features were most commonly observed, and whether the method of specimen procurement had an effect. METHODS: A total of 326 specimens were identified over an 8-year period. One hundred fifty-three specimens were reviewed and graded for cellularity, number of tissue fragments (TFs), degeneration, inflammation, hyperchromasia, nuclear pleomorphism, nuclear border irregularity, nuclear size, cytoplasmic tails, nuclear eccentricity, and high-grade features. RESULTS: Of the 153 specimens, 86 specimens (56.2%) demonstrated cellular atypia; of those, 51.2% were voided urine (VU) and 31.4% were UT washing (UW) specimens. The majority of specimens had many cells (46.5%), many single cells (44.2%), few to moderate TFs (46.5% and 27.9%, respectively), mild hyperchromasia (52.3%), mild nuclear pleomorphism (51.2%), mild nuclear border irregularity (60.5%), cytoplasmic tails (51.2%), and few to moderate eccentric nuclei (37.2% and 36.1%, respectively). The presence of TFs, cytoplasmic tails, and eccentric and enlarged nuclei were significantly more common in UW versus VU specimens (P = .036, .012, .014, and .027, respectively) and in UW versus benign UW controls (P = .001, .002, .002, and .003, respectively). CONCLUSIONS: Approximately 50% of UT specimens with LGUN on follow-up demonstrated atypical features. Based on comparison with benign UW controls, TFs, cytoplasmic tails, nuclear eccentricity, and enlarged nuclei were more pronounced in neoplastic UW than VU specimens, suggesting that the method of urine specimen procurement affects the presence of certain low-grade features. Cancer Cytopathol 2016;124:552-64. © 2016 American Cancer Society.

Single vs multiple intraocular pressure measurements in glaucoma surgical trials.

IMPORTANCE: Little is known about the necessity of multiple same-day intraocular pressure (IOP) measurements in describing the effect of IOP-lowering surgical procedures, and such evidence could affect surgical trial recruitment and retention of participants. OBJECTIVE: To determine whether a single IOP measurement might adequately approximate the mean of several measurements in glaucoma surgical trials. DESIGN, SETTING, AND PARTICIPANTS: A prospective, multicenter, interventional cohort from the prerandomization phase of a randomized clinical trial evaluating use of a supraciliary implant for treatment of IOP was conducted at multiple ophthalmology clinics. A total of 609 patients (609 eyes) with primary open-angle glaucoma and cataract were included. INTERVENTIONS: One IOP measurement was made while patients were receiving their usual medications to lower IOP, and 3 IOP measurements were made at 8 am, 12 pm, and 4 pm after patients underwent washout of all IOP-lowering eyedrops. MAIN OUTCOMES AND MEASURES: The proportion of eyes in which the increase in IOP after washout, using the mean of the 3 measurements, differed by more than 0.5, 1.0, 1.5, or 2.0 mm Hg from the increase in IOP after washout using only 1 of the postwashout measurements. A proportion of 10% or less at the 1.5-mm Hg cutoff was considered clinically acceptable. The hypothesis was formulated after data collection but before the data were examined. RESULTS: The mean (SD) IOP before washout was 18.5 (4.0) mm Hg. The mean increase in IOP after washout, using the mean of the 3 measurements, was 5.3 (4.2) mm Hg. The percentage of eyes in which the increase in IOP using a single postwashout IOP differed from the increase in IOP using the mean of 3 measurements by more than 1.5 mm Hg was 35.1%, 25.6%, 34.2%, 30.0%, and 31.4% when the single measurement was made at 8 am, 12 pm, 4 pm, a randomly chosen single measure of those 3 times, and the time closest to that of the prewashout IOP, respectively. By logistic regression, the 12 pm postwashout IOP had the lowest proportion of eyes differing from the mean (P < .001) and thus most closely approximated the mean diurnal IOP. CONCLUSIONS AND RELEVANCE: Although eliminating multiple IOP measurements would simplify the conduct of surgical trials in glaucoma, our data show that using a single IOP measurement after washout does not adequately approximate the mean of multiple IOP measurements.