The utility of p63, CK7, and CAM5.2 staining in differentiating pagetoid intraepidermal carcinomas.

BACKGROUND: Extramammary Paget disease (EMPD), pagetoid squamous cell carcinoma in situ (PSCCIS), and Paget disease of the breast (PD) are intraepidermal carcinomas with overlapping histopathologic features. CK7 and CAM5.2 stains are frequently utilized to distinguish PSCCIS from EMPD and PD. However, some cases of PSCCIS can stain positively for CAM5.2 and CK7, indicating a potential pitfall with these stains. p63 has been shown to distinguish PSCCIS from EMPD. We assessed p63 staining in PD and compared it to p63 staining of PSCCIS and EMPD. METHODS: A retrospective search for 15 examples each of PSCCIS, EMPD, and PD with remaining tissue in the paraffin block was performed. The diagnosis was confirmed by a board-certified dermatopathologist and immunostaining for p63, CK7, and CAM5.2 was performed. Staining >55% was scored as positive. Staining <55% was scored as negative and an approximate percentage of positive cells was recorded. RESULTS: Diffuse nuclear expression for p63 was detected in 100% (15/15) of PSCCIS cases, 0% (0/15) of PD cases, and 0% (0/15) of EMPD cases. CK7 and CAM5.2 stains were positive in 100% of PD. CAM5.2 was positive in 100% of EMPD and CK7 was positive in 93% of EMPD. CAM5.2 was positive in 0% of PSCCIS biopsy specimens, but partial staining was seen in 20%. CK7 was positive in 13%, but partial staining was seen in 47%. CONCLUSIONS: p63 immunostaining is a highly sensitive and specific method for differentiating between PSCCIS and PD or EMPD. While CAM5.2 and CK7 are also useful ancillary stains in this differential diagnosis, false-positive and false-negative staining occurs with these two markers.

Validated transport conditions maintain the quality of washed red blood cells.

BACKGROUND: Washing red blood cell (RBC) units prior to transfusion is indicated for certain patients. In the United States, units stored at 1°C-6°C or transported at 1°C-10°C are available for issue up to 24 h, if not used immediately. The washing procedure commonly utilizes room temperature saline resulting in units starting out above the allowed temperature range. This leads to wastage if units are issued and returned too quickly before having a chance to equilibrate in a transport cooler. STUDY DESIGN AND METHODS: Here we performed an experimental study of washed RBC quality comparing "ideal" storage conditions in a blood bank refrigerator to a "real-world" simulation of unit transport, including holding in a transport cooler. Twelve RBC units were washed and allocated evenly into either condition. RESULTS: Measurements at 0, 1, 3, 6, 12, and 24 h post-washing revealed that placement in a transport cooler was associated with higher unit temperature prior to 12 h (p = .013) with a maximum difference of 9.3°C. Despite this difference, several measures of unit quality including extracellular potassium, pH, lactate, and free hemoglobin were indistinguishable between conditions (p = .382, .224, .286, .691, respectively). We selected half of the tested units from our irradiated inventory and confirmed increased potassium leak (p < .001) and accumulation of free hemoglobin (p = .012) in irradiated units. DISCUSSION: Washed units stored under approved transport conditions are acceptable to return to inventory up to 24 h after washing and we provide a prediction interval-based temperature threshold for rejecting these units, permitting reduced waste.

Langerhans cell histiocytosis limited to the female genital tract: A review of literature with three additional cases.

•LCH of the female reproductive tract has four patterns of involvement.•A comprehensive literature review revealed 35 cases of pure genital LCH.•We report two new cases of pure LCH lesions of the vulva and one of the cervix.•Treatment of LCH varies and there is no standard for pure genital involvement.•Prognosis of LCH confined to the gynecologic tract appears to be favorable.

Paraproteinemic keratopathy in monoclonal gammopathy of undetermined significance treated with primary keratoprosthesis: Case report, histopathologic findings, and world literature review.

RATIONALE: We report a case of paraproteinemic keratopathy associated with monoclonal gammopathy of undetermined significance, treated with keratoprosthesis as a primary penetrating procedure. Histopathological findings and a world literature review are presented. PATIENT CONCERNS: A 74 year old female recently diagnosed with monoclonal gammopathy undetermined significance presented with progressive blurry vision bilaterally. DIAGNOSES: Examination revealed corneal opacities consistent with paraproteinemic keratopathy. INTERVENTIONS: Corneal transplantation with the Boston Type I keratoprosthesis was performed on the right and, a year later, on the left. OUTCOMES: Visual outcomes were good. Histopathological staining of host corneal buttons were consistent with monoclonality, and electron microscopy revealed fibrillar extracellular aggregates within intervening normal stroma. LESSONS: Corneal deposits may be the only manifestation of monoclonal gammopathy of undetermined significance in patients who are otherwise systemically asymptomatic. Ophthalmologists who encounter corneal opacities may order the appropriate diagnostic studies to determine the presence of occult systemic disease. Risk of graft failure after penetrating keratoplasty from recurring opacities is high, so keratoprosthesis as a primary penetrating procedure may afford superior long-term outcomes. Host corneal buttons retrieved from penetrating keratoplasty or corneal biopsy may be sent for histopathological examination to confirm the diagnosis.

Vasodilatory effects of the selective GPER agonist G-1 is maximal in arteries of postmenopausal women.

G-protein-coupled estrogen receptors (GPERs) have been proposed to mediate estrogen-mediated vasodilation. The presence of GPER-dependent vasodilation in human resistance-sized arteries (HRAs) or its signal transduction pathways have not been investigated. HRAs in subcutaneous fat tissues (biopsies from postmenopausal women (PMW), age-matched men (M) and pregnant women (PGW)) were mounted for in vitro isometric force recording. Vasodilation induced by G-1 (selective GPER-agonist, 3 µM) from HRAs pre-contracted with norepinephrine amounted to 40±5% in PMW, significantly larger than those obtained from M (20±5%) or PGW (20±5%). L-NAME (nitric oxide (NO) synthase inhibitor) abolished these relaxations in PGW, attenuated them in PMW and had no effect in M. Immunohistochemical analysis confirmed the presence of GPER in both smooth muscle and endothelial cells of HRA with maximum expression in PGW. In cultured human umbilical vein endothelial cells (HUVECs), G-1 increased NO-synthesis concentration-dependently through higher expressions of endothelial NO-synthase (eNOS) and through enhanced phosphorylation of eNOS on Ser(1177). In conclusion, GPER vasodilates human resistance arteries through various activating mechanisms of the eNOS-signaling pathway.