CDX-2 Expression in Esophageal Biopsies Without Goblet Cell Intestinal Metaplasia May Be Predictive of Barrett's Esophagus.

BACKGROUND: CDX-2 is a nuclear homeobox transcription factor not normally expressed in esophageal and gastric epithelia, reported to highlight intestinal metaplasia (IM) in the esophagus. Pathological absence of goblet cells at initial screening via hematoxylin and eosin (HE) and alcian blue (AB) staining results in patient exclusion from surveillance programs. AIMS: This study aimed to determine whether non-goblet cell IM, as defined by CDX-2 positivity, can be considered to be a precursor to Barrett's esophagus (BE). METHODS: This study received IRB approval (17,284). Patients with gastroesophageal reflux disease (n = 181) who underwent upper-gastrointestinal endoscopy with biopsies of the distal esophagus to rule out BE using HE/AB staining and CDX-2 immunostaining were followed for 3 years. Initial and follow-up staining results were evaluated for age/sex. RESULTS: Differences between development of goblet cell IM in CDX-2-negative and CDX-2-positive groups were evaluated. A Kaplan-Meier curve showed that, out of the 134 patients initially positive for CDX-2, 25 (18.7%) had developed goblet cell IM after 2 years and 106 (79.1%) after 3 years. Conversely, of the 47 patients initially negative for CDX-2, 8 (17.9%) developed goblet cell IM after 24 months and only 11 (23.8%) after 40 to 45 months (P = .049; age-adjusted Cox proportional hazard regression model). CONCLUSION: In cases that are initially AB negative and CDX-2 positive, CDX-2 was demonstrated to have a potential prognostic utility for early detection of progression to BE. CDX-2 expression is significantly predictive for risk of goblet cell IM development 40 to 45 months after initial biopsy.

Renal Function Is Associated with Changes in Bone Mineral Density in Postmenopausal Osteoporotic Women Treated with Denosumab: Data From a Retrospective Cohort Study.

Background/Objectives: Renal function influences bone metabolism, as kidney failure can increase the risk of fractures. Denosumab is an approved osteoporosis treatment, but its efficacy in relation to renal function has not yet been studied in real-life scenarios. This study aimed to investigate the denosumab-induced change in bone mineral density (BMD) according to kidney function. Methods: A retrospective analysis was conducted at the outpatient clinic in postmenopausal women receiving denosumab (60 mg subcutaneously administered every 6 months). The glomerular filtration rate (eGFR) was measured by the 2021 CKD-EPI equation and patients were stratified for eGFR categories. BMD was measured by dual-energy X-ray absorptiometry. Results: 128 women (mean age 70.3 ± 9.4 years) were recruited. The mean denosumab treatment duration was 3.9 ± 1.4 years and all the participants had improved BMD values. In stepwise multiple regression analysis-after controlling for age, BMI, and treatment duration-the eGFR value (ß = -0.11, SE 0.04, p = 0.01) was independently associated with the lumbar spine BMD change. The same association remained when the eGFR categories were considered (ß = 3.564, SE 1.29, p = 0.007). In addition, after controlling for BMI and the duration of denosumab treatment, age (ß = -0.7915, SE 0.37, p = 0.03) and eGFR (ß = -0.3257, SE 0.1567, p = 0.04) were found to be associated with femoral neck BMD change. The association remained when considering eGFR categories (ß = 8.7339, SE 4.29, p = 0.04). Conclusions: This retrospective study suggests that eGFR is associated with denosumab efficacy in postmenopausal women treated for osteoporosis.

Bax-interacting factor-1 expression in prostate cancer.

BACKGROUND: Bax-interacting factor (Bif)-1 protein is a member of the endophilin B family that binds to and activates the proapoptotic Bax protein in response to apoptotic signals. Loss of Bif-1 suppresses the intrinsic pathway of apoptosis and promotes tumorigenesis. We examined the expression levels of Bif-1 protein in human prostate cancer. MATERIALS AND METHODS: Thirty-nine archival tissue specimens of human prostate cancer, and a human prostate cancer tissue microarray containing 19 samples of normal prostate, 26 samples of benign prostatic hyperplasias (BPHs), 30 samples of high-grade prostatic intraepithelial neoplasia (PIN), and 153 samples of prostate cancer, were selected for immunohistochemical staining with Bif-1 antibody. The slides were scored by 2 independent observers. RESULTS: Nontissue microarray samples: moderate to strong Bif-1 staining was identified in 38 of 39 prostate cancer samples. In 32 cases, foci of PIN were identified adjacent to prostate cancer samples. Of these, 29 samples (90.6%) showed strong and diffuse Bif-1 staining. Benign prostatic hyperplasias, identified in 27 cases, was weakly Bif-1 positive in 88.9% of cases. Tissue microarray samples: 38.6% (59 of 153) of prostate cancer samples showed moderate to strong Bif-1 expression, and 21.6% (33 of 153) were Bif-1 negative. Bif-1 expression was moderate to strong in 76.7% (23 of 30) of PIN. Bif-1 was weak to moderate in 53.8% (14 of 26) of BPH and negative in 46.2% (12 of 26) of them. Low to moderate Bif-1 was seen in 89.5% of normal prostate samples. CONCLUSION: The loss of Bif-1 expression in a subset of prostate cancer samples is in agreement with the proapoptotic function of Bif-1. The significance of the increased Bif-1 in a subgroup of prostate cancer samples and in PIN remains to be determined. It seems that Bif-1 has a role in prostate cancer, providing the rationale for using Bif-1 as a target for prostate anticancer therapy.

Aneurysmal bone cyst of the temporal bone associated with reversible hemifacial paralysis.

Aneurysmal bone cyst (ABC) is an uncommon lesion of the temporal bone (TB), with only 20 cases reported. Facial paralysis is a rare complication (2 cases); however, no cases have been reported with preoperative reversal of paralysis. We report a 60-year-old man with a history of remote head trauma, who presented with serious otitis media and right hemifacial paralysis, which resolved with nonsurgical therapeutic measures. Magnetic resonance imaging and computed tomography showed a destructive and expansile lesion of the TB. The lesion was surgically removed, and ABC was diagnosed histologically. The patient had an uneventful recovery and demonstrated no recurrence at 1 year of follow-up. This report presents an unusual presentation of ABC in the TB, with a review of the clinical, radiological, pathological, and therapeutic features of this entity.

Actin expression in purely nodular versus nodular-infiltrative basal cell carcinoma.

BACKGROUND: The prognosis of basal cell carcinoma (BCC) correlates with its histological subtype. Actin is a microfilament that contributes to cell motility and invasiveness of cancer cells. Actin has been found to be more prominently expressed in the tumor cells and stroma of the more aggressive BCC subtypes. Here we compare actin expression in purely nodular (N-BCC) versus nodular-infiltrative (NI-BCC) tumors. METHODS: We studied seven cases of N-BCC and 13 cases of NI-BCC with immunohistochemistry for alpha-smooth muscle actin (SMA) and common muscle actin (CMA) within the tumor cells and stroma. A semiquantitative method was used to determine the degree of actin present in the tumor aggregates (on a scale of 0-4). RESULTS: Actin was present in the nodular component of 2/7 (28%) purely N-BCC and 11/13 (85%) mixed NI-BCC (p = 0.001). Actin was present in the infiltrative component of 13/13 (100%) NI-BCC. The average SMA score was 0.57 within the N-BCC compared with 1.77 within the nodular component of NI-BCC (p = 0.04); and 2.46 within the infiltrative component of the NI-BCC. The CMA score was 0.57 within the N-BCC, 1.54 within the nodular component of NI-BCC, and 1.92 within the infiltrative component of the NI-BCC. Actin was not found in the stroma of any of the N-BCC, while it was present in 8/13 (62%) of the NI-BCC (p = 0.0009). CONCLUSIONS: Actin expression is more prominent in the nodular component of mixed NI-BCC when compared with purely N-BCC. This suggests that the nodular components of NI-BCC and N-BCC are different, and that actin expression in the nodular component may be associated with potential invasiveness. This finding may be relevant when examining incompletely sampled nodular BCC.

Melanocytic matricoma: case confirmation of a recently described entity.

BACKGROUND: In 1999, Carlson et al. reported two cases of a matrical neoplasm that recapitulates the bulb of the anagen hair follicle, which they designated as melanocytic matricoma. METHODS: Here we report a similar case in a 78-year-old white male, who presented with a 0.4 cm purple-black firm papule in the left preauricular area. RESULTS: Histologically, the tumor is composed of a dual cell population including admixed epithelial matrical and supramatrical cells with "shadow" cell formation and pigmented dendritic melanocytes. Immunohistochemical studies for cytokeratin highlighted the epithelial component and studies for S-100 protein, HMB-45, and vimentin confirmed the melanocytic component. The differential diagnosis considered includes pigmented variants of pilomatricoma, matrical carcinoma, basal cell carcinoma and malignant melanoma. CONCLUSIONS: The case reported herein is the first confirmation of melanocytic matricoma, a distinctive adnexal neoplasm with characteristic clinical and pathologic features, which differentiate it from pigmented pilomatricoma.