Using p16 immunohistochemistry to classify morphologic cervical intraepithelial neoplasia 2: correlation of ambiguous staining patterns with HPV subtypes and clinical outcome.

p16INK4a immunohistochemistry (IHC) is widely used to facilitate the diagnosis of human papillomavirus (HPV)-associated cervical precancerous lesions. Although most p16 results are distinctly positive or negative, certain ones are ambiguous: they meet some but not all requirements for the "block-positive" pattern. It is unclear whether ambiguous p16 immunoreactivity indicates oncogenic HPV infection or risk of progression. Herein, we compared HPV genotypes and subsequent high-grade squamous intraepithelial lesion (HSIL) outcomes among 220 cervical biopsies with a differential diagnosis of cervical intraepithelial neoplasia 2 based on hematoxylin and eosin morphology and varying degrees of p16 immunoreactivity. p16 results were classified as block positive (n=40, 18%), negative (n=130, 59%), or ambiguous (n=50, 23%), a category we further grouped into 3 patterns: strong/basal (n=18), strong/focal (n=15), and weak/diffuse (n=17). Seventy percent of ambiguous p16 lesions were negative for the most common low- and high-risk HPV types; the remaining 30% were positive for HPV 16, 18, 45, 58, 59, or 66. Three patterns revealed comparably low HPV detection rates (28%, 27%, and 35%). During 12-month surveillance, HSILs were detected in 35% of the p16 block-positive group, 1.5% of negative group, and 16% of the ambiguous group. The accuracy of ambiguous p16 immunoreactivity in predicting oncogenic HPV and HSIL outcome is significantly lower than that of the block-positive pattern but greater than negative staining. Specific guidelines for this intermediate category should prevent diagnostic errors and help implement p16 IHC in general practice.

Primary MALT Lymphoma of the Breast Treated with Definitive Radiation.

We are reporting a case of a 59-year-old woman, with a family history of breast cancer, who presented with extranodal marginal zone lymphoma (MALT) of the left breast. She received definitive radiation therapy and remains without evidence of disease. Here, we present a case and review the current literature to determine the optimal treatment of this rare presentation of MALT.

MALT Lymphoma of the Bladder: A Case Report and Review of the Literature.

The presentation of a MALT lymphoma in the bladder is exceedingly rare. Furthermore, the optimal treatment of primary MALT confined to the bladder remains to be defined. Here, we report a case of a 65-year-old female with primary MALT lymphoma treated with definitive radiation therapy. The patient received a total dose of 30 Gy in 20 equal daily fractions to the bladder and tolerated the treatment well. In addition, we have extensively reviewed the relevant literature to better define the optimal management of this rare disease. In conclusion, primary MALT lymphoma of the bladder represents a rare malignancy with excellent prognosis if detected at an early stage. For early stage disease, definitive radiation represents an excellent treatment modality with a minimal side-effect profile.

Non-emergency department interventions to reduce ED utilization: a systematic review.

OBJECTIVES: Recent health policy changes have focused efforts on reducing emergency department (ED) visits as a way to reduce costs and improve quality of care. This was a systematic review of interventions based outside the ED aimed at reducing ED use. METHODS: This study was designed as a systematic review. We reviewed the literature on interventions in five categories: patient education, creation of additional non-ED capacity, managed care, prehospital diversion, and patient financial incentives. Studies written in English, with interventions administered outside of the ED, and a comparison group where ED use was an outcome, were included. Two independent reviewers screened search results using MEDLINE, Cochrane, OAIster, or Scopus. The following data were abstracted from included studies: type of intervention, study design, population, details of intervention, effect on ED use, effect on non-ED health care use, and other health and financial outcomes. Quality of individual articles was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. RESULTS: Of 39 included studies, 34 were observational and five were randomized controlled trials. Two of five studies on patient education found reductions in ED use ranging from 21% to 80%. Out of 10 studies of additional non-ED capacity, four showed decreases of 9% to 54%, and one a 21% increase. Both studies on prehospital diversion found reductions of 3% to 7%. Of 12 studies on managed care, 10 had decreases ranging from 1% to 46%. Nine out of 10 studies on patient financial incentives found decreases of 3% to 50%, and one a 34% increase. Nineteen studies reported effect on non-ED use with mixed results. Seventeen studies included data on health outcomes, but 13 of these only included data on hospitalizations rather than morbidity and mortality. Seven studies included data on cost outcomes. According to the GRADE guidelines, all studies had at least some risk of bias, with four moderate quality, one low quality, and 34 very low quality studies. CONCLUSIONS: Many studies have explored interventions based outside the ED to reduce ED use in various populations, with mixed evidence. Approximately two-thirds identified here showed reductions in ED use. The interventions with the greatest number of studies showing reductions in ED use include patient financial incentives and managed care, while the greatest magnitude of reductions were found in patient education. These findings have implications for insurers and policymakers seeking to reduce ED use.