Active Vitamin D3 (Calcitriol) Increases Adipose Graft Retention in a Xenograft Model.

BACKGROUND: Autologous fat grafting, although broadly indicated, is limited by unsatisfactory retention and often requires multiple procedures to achieve durable outcomes. Graft survival is strongly influenced by the magnitude and duration of post-engraftment ischemia. Calcitriol is a pleiotropic, safe nutrient with cell-specific influence on viability and metabolic flux. OBJECTIVES: Evaluate the efficacy of activated vitamin D3 (calcitriol) in improving grafting outcomes and examine its mechanisms. METHODS: Lipoaspirate was collected for ex vivo culture (7 unique donors), in vitro bioenergetic analysis (6 unique donors), and in vivo transplantation (5 unique donors). Ex vivo samples were incubated for up to 2 weeks before extraction of the stromal vascular fraction (SVF) for viability or flow cytometry. SVF was collected for Seahorse (Agilent; Santa Clara, CA) analysis of metabolic activity. Human endothelial cell lines were utilized for analyses of endothelial function. In vivo, samples were implanted into athymic mice with calcitriol treatment either (1) once locally or (2) 3 times weekly via intraperitoneal injection. Grafts were assessed photographically, volumetrically, and histologically at 1, 4, and 12 weeks. Hematoxylin and eosin (H&E), Sirius red, perilipin, HIF1α, and CD31 tests were performed. RESULTS: Calcitriol-treated lipoaspirate demonstrated dose-dependent increases in SVF viability and metabolic reserve during hypoxic stress. Calcitriol treatment enhanced endothelial mobility ex vivo and endothelial function in vitro. In vivo, calcitriol enhanced adipocyte viability, reduced fibrosis, and improved vascularity. Continuous calcitriol was sufficient to improve graft retention at 12 weeks (P < .05). CONCLUSIONS: Calcitriol increased fat graft retention in a xenograft model. Calcitriol has potential to be a simple, economical means of increasing fat graft retention and long-term outcomes.

Right Ventricular Involvement of an Aggressive Malignant Peripheral Nerve Sheath Tumor.

We present a case of a 58-year-old woman who had a painful right thigh mass for a few months. A transthoracic echocardiogram revealed no evidence of an intracardiac mass. She had a whole-body positron emission tomography/computed tomography scan two months later that revealed masses in her right lower extremity and a mass in her right ventricle that had not been initially reported. She had been initially diagnosed with an undifferentiated pleomorphic sarcoma, but this diagnosis was changed to a malignant peripheral nerve sheath tumor with repeat pathology. She was subsequently hospitalized. An echocardiogram showed a mass covering 80% of her right ventricle (RV). Serial cardiac magnetic resonance imaging revealed a 9.4 × 5.6 cm RV mass with vascular and avascular portions and inflow and outflow tract obstruction. Computed tomography showed no other metastases. Due to a delay in diagnosis and a decline in left ventricular ejection fraction, the patient could not undergo palliative chemotherapy or radiotherapy.

Significance of high-risk HPV detection in women with atypical glandular cells on Pap testing: Analysis of 1857 cases from an academic institution.

BACKGROUND: The role of high-risk human papillomavirus (hrHPV) testing in women with various types of atypical glandular cells (AGC) on Papanicolaou (Pap) test is undetermined. METHODS: Herein, the authors retrospectively searched their pathology database for cases of AGC with concurrent hrHPV testing and histological follow-up results within 1 year between January 2008 and December 2013. RESULTS: Among 3709 AGC cases occurring during the study period, 2287 had concurrent Hybrid Capture 2 HPV testing results. The overall rate of hrHPV positivity (hrHPV+) was 27.7%. Of these 2287 cases, 1857 cases (81.2%) had histological follow-up results within 1 year, including 529 hrHPV + cases and 1328 hrHPV-negative (hrHPV-) cases. Among the hrHPV + cases, 16.8% had cervical intraepithelial neoplasia 2/3 (CIN2/3), 5.7% had cervical adenocarcinoma in situ (AIS)/adenocarcinoma (ADC), and 1.1% had an endometrial carcinoma. Among the hrHPV- cases, 0.6% had CIN2/3, 0.2% had AIS/ADC, and 3.8% had an endometrial carcinoma. The rate of high-grade cervical lesions (CIN2/3, AIS, or ADC) was significantly higher in women who were hrHPV + compared with hrHPV- women for all age groups. Endometrial carcinoma was most commonly present in women aged ≥50 years. CONCLUSIONS: To the authors' knowledge, the current study is the largest follow-up study published to date regarding women with AGC cytology and HPV testing. The study data indicate that hrHPV testing is useful for predicting the risk of high-grade cervical neoplasia in women with AGC, but has no significant value in evaluating the risk of endometrial carcinoma. The combination of cytology, hrHPV testing, and patient age can significantly aid in the appropriate management of these individuals. Cancer Cytopathol 2017;125:205-211. © 2016 American Cancer Society.

Clinical significance of atypical glandular cells in Pap tests: An analysis of more than 3000 cases at a large academic women's center.

BACKGROUND: The interpretation of atypical glandular cells (AGC) in Papanicolaou (Pap) tests and screening for glandular neoplasia remain challenging. METHODS: Pap tests with an AGC interpretation from January 2008 to December 2013 were retrieved from a pathology database, and cases with histologic follow-up within 1 year were included in the study. RESULTS: There were 589,830 Pap tests during the study period, and 3709 cases (0.6%) were reported as AGC, which included the following: AGC, not otherwise specified (52.0%); atypical endocervical cells (28.0%); and other categories. There were 3007 cases (81.1%) with histologic follow-up results within 1 year. Cervical intraepithelial neoplasia 2/3 (CIN2/3), cervical adenocarcinoma in situ (AIS)/adenocarcinoma, and endometrial carcinoma were identified in 5.6%, 1.9%, and 5.5% of cases, respectively. Glandular neoplasia was more likely to be identified in cases with pure AGC subcategories than cases with AGC and squamous abnormalities. Endometrial neoplasia was more likely to be identified in cases with atypical endometrial cells than other categories. Overall, the most common severe abnormality on histologic follow-up was CIN2/3. Although CIN2/3 was the most common severe lesion in patients younger than 30 years (10.0%) and in patients aged 30 to 49 years (6.4%), endometrial carcinoma was the most common lesion in women who were 50 years old or older (13.7%). Endocervical glandular lesions (AIS and adenocarcinoma) occurred in only 1.9% of women. CONCLUSIONS: AGC subtypes and ages significantly affect histological follow-up results; 90.5% of cases with carcinoma on histologic follow-up were either endometrial or metastatic carcinoma. This study supports the recommendation that women with AGC Pap test results should be followed up with both endocervical and endometrial sampling. Cancer Cytopathol 2016;124:589-95. © 2016 American Cancer Society.

Diagnostic utility of arborizing stromal meshwork fragments in mucinous tumors.

INTRODUCTION: Arborizing stromal meshwork fragments (ASMFs) have been proposed as a useful clue to differentiate mucin associated with mucinous adenocarcinoma from contaminating mucus during endobronchial ultrasound-guided transbronchial needle aspiration. Our aim was to retrospectively review cytology cases with mucinous material to determine the utility of ASMFs in diagnosing mucinous tumors. MATERIAL AND METHODS: Diff-Quik stained smears from archival cytology cases (N = 40) were reviewed, including adenocarcinomas with mucinous features, cystic mucinous neoplasms, and control cases with mucin contamination. Specimens were procured by image-guided fine needle aspiration (FNA) (16 cases), endoscopic ultrasound-guided FNA (22 cases), pathologist-performed FNA (1 case), and fluid drainage (1 case). All cases were reviewed for ASMFs, which were defined as metachromatic, spidery extensions with frayed edges within a background of mucinous material. RESULTS: ASMFs were identified in 4 (10% of cases, 14% of adenocarcinomas) cases of metastatic gastrointestinal mucinous adenocarcinomas in various locations (liver, lymph node, lung, and bone), but absent in mucin contamination. ASMFs in Diff-Quik stained smears were magenta-colored and corresponded to intervening stroma between dissecting mucin in the tumor. Nonarborizing desmoplastic stroma, inspissated mucus, cartilage fragments, transgressing vessels in renal cell carcinoma, and mucus-like material in pancreatic pseudocysts can morphologically mimic ASMFs. CONCLUSION: These data show that ASMFs may be encountered in some (14%) cases of adenocarcinoma with mucinous differentiation. When present, ASMFs can be diagnostically helpful to differentiate adenocarcinoma with mucinous features from contaminating mucus, if reliably distinguished from mimics. Diagn. Cytopathol. 2016;44:805-810. © 2016 Wiley Periodicals, Inc.