Vasitis Nodosa and Related Lesions: A Modern Immunohistochemical Staining Profile with Special Emphasis on Novel Diagnostic Dilemmas

Vasitis nodosa is a benign proliferation of vas deferens epithelium, thought to be a response to trauma or obstruction, usually vasectomy. Although histologic features mimic malignancy, diagnosis is usually straightforward due to the clinical context. We analyzed 21 specimens with vasitis or epididymitis nodosa with antibodies to PAX8, CD10, p63, alpha-methyl-acyl-coA-racemase (AMACR), GATA3, prostein, NKX3.1, and prostate-specific antigen (PSA). Two diagnostically problematic cases included 1) florid bladder muscle involvement after prostatectomy and 2) involvement of the ampulla and ejaculatory duct in a radical prostatectomy specimen. Vasitis nodosa was excluded in 3 additional histologic mimics (2 post-treatment prostate cancers and 1 bladder cancer). PAX8 yielded consistent positive (100%) nuclear staining in the proliferative glands of vasitis nodosa, often stronger and more uniform than native vas deferens. CD10 labeling was common but also labeled secretions and other structures. Labeling for p63 was often basally located in glands with a multilayered appearance, but often markedly attenuated or lacking in the proliferative glands compared to native epithelium. AMACR positivity was variable but often present (19/21). PSA, prostein, and NKX3.1 were consistently negative. Rare problematic cases of vasitis nodosa include “invasion” of the ejaculatory duct at the prostate and involvement of bladder muscle after prostatectomy. The proliferative vasitis nodosa glands often have a prostate cancer-like staining pattern with variable AMACR positivity and negative or patchy p63. However, reliable positivity for PAX8, patchy GATA3, and negative staining for PSA, NKX3.1, and prostein aid in distinguishing from prostate cancer and tubular variants of bladder cancer

Pathological Staging of Renal Cell Carcinoma: A Review of 300 Consecutive Cases

Aims: Pathological staging of renal cell carcinoma (RCC) can be challenging compared to other cancer types, as invasion often manifests as finger‐like protrusions into vascular spaces or renal sinus tissue. Although prior studies have shown larger tumour size to be correlated highly with renal sinus invasion, prospective data on evaluating pathological stage are limited. We evaluated a large series reported by one urological pathologist. Methods and results: Three hundred consecutive specimens were reviewed. Tumours larger than 5 cm were routinely sampled extensively or grossly re‐reviewed when no extrarenal extension was identified on initial examination. Apparent multifocal disease was assessed critically for intravascular spread. Retrograde venous invasion was reported in 15 of 300 (5%) cases, 13 of 15 of which were clear cell RCC. Of a total of 163 specimens with clear cell histology, only five of 34 (15%) tumours 7 cm or larger were reported as pT2, all of which had an explanatory comment indicating the absence of definitive extrarenal spread. In contrast, 15 of 20 (75%) pT2 tumours were non‐clear cell histology (papillary, chromophobe and translocation‐associated). Comparing pT3a or higher tumours, the median tumour size in cases with retrograde venous invasion was 8.0 cm, compared to 6.2 cm in cases without retrograde venous invasion (P = 0.005). ConclusionsOur findings support that retrograde venous invasion should be considered carefully before diagnosing multifocal clear cell RCC, which is rare in the sporadic setting. In the absence of vascular invasion, multifocal clear cell papillary RCC can be a mimic. pT2 occurs more frequently with non‐clear cell histology (particularly papillary or chromophobe RCC).https://scholarlycommons.henryford.com/merf2019basicsci/1002/thumbnail.jp

THE EFFECT OF A PERIPHERAL NOREPINEPHRINE PROTOCOL ON CENTRAL LINE UTILIZATION IN A SURGICAL ICU

INTRODUCTION: Central venous catheters (CVC) are associated with various complications. In several studies, the use of vasopressors through peripheral venous catheters (PVC) obviated the need for CVC insertion in 34-87% of patients. Although evidence indicates that the peripheral administration of vasopressors is safe, most health systems currently use protocols that favor the use of CVC over PVC. We proposed a quality improvement study evaluating the use of a protocol for the peripheral administration of a dilute norepinephrine solution (16 mcg/ml) in the surgical intensive care unit (SICU). METHODS: This was a retrospective quality improvement study conducted at Henry Ford Hospital in Detroit, MI. We included 100 patients that were admitted to the SICU between June and December 2021 and received dilute norepinephrine for any cause through a PVC under our prespecified protocol. Guidelines for CVC insertion were present in the protocol to assist clinicians. An extravasation protocol was instituted which included application of 2% nitroglycerin ointment. The primary endpoint evaluated was the number of patients in which a CVC was placed, regardless of the cause, within 24 hours of discontinuation of norepinephrine through the PVC. Secondary endpoints included the indication for central line placement, dose of norepinephrine infused, duration of norepinephrine infusions, gauge and location of the PVC, frequency of extravasation events, and tissue injury. RESULTS: Out of the 100 included in the study 51 patients (51%) did not receive a CVC, and 60 patients (60%) did not receive a CVC within the first 24 hours of discontinuation of peripheral norepinephrine. Norepinephrine extravasation was noted in 6 patients (6%). These incidents were successfully managed with nitroglycerin (2%) ointment. CONCLUSIONS: We demonstrated that administration of diluted norepinephrine through a PVC following a protocol in the SICU was associated with a reduction in CVC placement. The incidence of extravasation of norepinephrine was rare. Careful assessment of the PVC allowed for early treatment with topical nitroglycerine and no harm was identified to any patient

Seroprevalence of rubella in pregnant women

Background: Rubella is a droplet infection characterized by self-limiting illness. However infection during pregnancy may result in miscarriage, congenital birth defects leading to long term morbidity. The aim of the study was to estimate the seroprevalence of rubella immunity in pregnant women.Methods: Antenatal patients, irrespective of period of gestation, fulfilling the inclusion criteria were tested for rubella IgG antibodies.Results: A total of 258 pregnant women were included in the study. The estimated seroprevalence of immunity against Rubella infection was 70.5% (n=182) whereas 29.5% (n=76) were seronegative and thus susceptible to rubella infection. The distribution of seroprevalence of rubella immunity based on age group and gravidity were also evaluated.Conclusions: The results reveal high level of rubella sero positivity, which indicates continued transmission of rubella infection in the community.

Class III β-tubulin expression as a predictor of docetaxel-resistance in metastatic castration-resistant prostate cancer

About half of the patients treated with docetaxel in the setting of metastatic castration-resistant prostate cancer (CRPC) are non-responders. Therefore, a marker of response would be beneficial for clinical decision-making. We evaluated class III β-tubulin (βIII-tubulin) expression as a predictor of resistance in this setting, which previously has been correlated with lack of response to taxanes in other cancers. Patients with CRPC were included if they were treated with at least 3 cycles of docetaxel between 1990 and 2011. βIII-tubulin expression was assessed by immunostaining, which was performed in tissue samples obtained either via biopsy or prostatectomy at the time of diagnosis. Rates of prostate-specific antigen (PSA) response and overall survival (OS) following docetaxel treatment were compared between patients with high (2+ or 3+ staining) vs. low (0 or 1+ staining) βIII-tubulin expression. Of 73 patients, 26 (35%) had a high expression of βIII-tubulin. A PSA decline of 10% or greater occurred in 65% of patients with a high βIII-tubulin expression vs. 89% with a low βIII-tubulin expression (p = 0.0267). The median OS for patients with a high βIII-tubulin expression was 17.4 (95% CI 8.7-21.0) months vs. 19.8 (95% CI 16.6-23.6) months for patients with a low expression (p = 0.039). Our results show that a high βIII-tubulin expression is a negative prognostic factor in metastatic CRPC patients treated with docetaxel

Transcriptional network involving ERG and AR orchestrates Distal-less homeobox-1 mediated prostate cancer progression

Distal-less homeobox-1 (DLX1) is a well-established non-invasive biomarker for prostate cancer (PCa) diagnosis, however, its mechanistic underpinnings in disease pathobiology are not known. Here, we reveal the oncogenic role of DLX1 and show that abrogating its function leads to reduced tumorigenesis and metastases. We observed that ~60% of advanced-stage and metastatic patients display higher DLX1 levels. Moreover, ~96% of TMPRSS2-ERG fusion-positive and ~70% of androgen receptor (AR)-positive patients show elevated DLX1, associated with aggressive disease and poor survival. Mechanistically, ERG coordinates with enhancer-bound AR and FOXA1 to drive transcriptional upregulation of DLX1 in ERG-positive background. However, in ERG-negative context, AR/AR-V7 and FOXA1 suffice to upregulate DLX1. Notably, inhibiting ERG/AR-mediated DLX1 transcription using BET inhibitor (BETi) or/and anti-androgen drugs reduce its expression and downstream oncogenic effects. Conclusively, this study establishes DLX1 as a direct-target of ERG/AR with an oncogenic role and demonstrates the clinical significance of BETi and anti-androgens for DLX1-positive patients

Renal Cell Carcinoma with Angioleiomyoma-Like Stroma and Clear Cell Papillary Renal Cell Carcinoma: Exploring SDHB Protein Immunohistochemistry and the Relationship to Tuberous Sclerosis Complex

Renal cell carcinoma (RCC) with angioleiomyoma-like stroma appears to be molecularly distinct from clear cell RCC; however, its relationship to clear cell papillary RCC remains debated. Recent studies have found that similar tumors sometimes occur in patients with tuberous sclerosis complex (TSC), of which one study found unexpectedly negative succinate dehydrogenase (SDH) B immunostaining. We evaluated immunohistochemistry for SDHB in 12 apparently sporadic RCCs with angioleiomyoma-like stroma and correlated with clinical information for stigmata of TSC. Tumors were compared to a group of 16 clear cell papillary RCCs and 6 unclassified tumors with prominent stroma. With exception of 1 unclassified tumor, all exhibited at least focal cytoplasmic staining for SDHB protein, often requiring high magnification and better appreciated with increased antibody concentration. Detailed history information was available for 9/12 patients with smooth muscle-rich tumors, revealing no stigmata of undiagnosed TSC. Electron microscopy performed on 1 of these tumors revealed mitochondria to be very sparse, potentially accounting for the weak immunohistochemical labeling for SDHB protein. Weak SDHB immunostaining may represent another shared feature of RCC with angioleiomyoma-like stroma and clear cell papillary RCC, likely due to sparse mitochondria, strengthening the possible relationship of these entities. Although smooth muscle-rich tumors have been recently reported in patients with TSC, absence of staining in tumors with this pattern may not be specific for TSC. In tumors with pale or clear cytoplasm, immunohistochemical staining for SDHB should be interpreted with caution as evidence of abnormality in the SDH pathway

Pseudosarcomatous myofibroblastic proliferations of the genitourinary tract are genetically different from nodular fasciitis and lack USP6, ROS1 and ETV6 gene rearrangements

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145266/1/his13526_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145266/2/his13526.pd

The interplay of growth differentiation factor 15 (GDF15) expression and M2 macrophages during prostate carcinogenesis

M2 (tumor-supportive) macrophages may upregulate growth differentiation factor 15 (GDF15), which is highly expressed in prostate tumors, but the combined utility of these markers as prognostic biomarkers are unclear. We retrospectively studied 90 prostate cancer cases that underwent radical prostatectomy as their primary treatment and were followed for biochemical recurrence (BCR). These cases also had a benign prostate biopsy at least 1 year or more before their prostate cancer surgery. Using computer algorithms to analyze digitalized immunohistochemically stained slides, GDF15 expression and the presence of M2 macrophages based on the relative density of CD204- and CD68-positive macrophages were measured in prostate: (i) benign biopsy, (ii) cancer and (iii) tumor-adjacent benign (TAB) tissue. Both M2 macrophages (P = 0.0004) and GDF15 (P \u3c 0.0001) showed significant inter-region expression differences. Based on a Cox proportional hazards model, GDF15 expression was not associated with BCR but, in men where GDF15 expression differences between cancer and TAB were highest, the risk of BCR was significantly reduced (hazard ratio = 0.26; 95% confidence interval = 0.09-0.94). In addition, cases with high levels of M2 macrophages in prostate cancer had almost a 5-fold increased risk of BCR (P = 0.01). Expression of GDF15 in prostate TAB was associated with M2 macrophage levels in both prostate cancer and TAB and appeared to moderate M2-macrophage-associated BCR risk. In summary, the relationship of GDF15 expression and CD204-positive M2 macrophage levels is different in a prostate tumor environment compared with an earlier benign biopsy and, collectively, these markers may predict aggressive disease

Racial differences in the systemic inflammatory response to prostate cancer

Systemic inflammation may increase risk for prostate cancer progression, but the role it plays in prostate cancer susceptibility is unknown. From a cohort of over 10,000 men who had either a prostate biopsy or transurethral resection that yielded a benign finding, we analyzed 517 incident prostate cancer cases identified during follow-up and 373 controls with one or more white blood cell tests during a follow-up period between one and 18 years. Multilevel, multivariable longitudinal models were fit to two measures of systemic inflammation, neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR), to determine NLR and MLR trajectories associated with increased risk for prostate cancer. For both measures, we found no significant differences in the trajectories by case/control status, however in modeling NLR trajectories there was a significant interaction between race (white or Black and case-control status. In race specific models, NLR and MLR values were consistently higher over time among white controls than white cases while case-control differences in NLR and MLR trajectories were not apparent among Black men. When cases were classified as aggressive as compared to non-aggressive, the case-control differences in NLR and MLR values over time among white men were most apparent for non-aggressive cases. For NLR among white men, significant case-control differences were observed for the entire duration of observation for men who had inflammation in their initial prostate specimen. It is possible that, among white men, monitoring of NLR and MLR trajectories after an initial negative biopsy may be useful in monitoring prostate cancer risk