Immunohistochemical Expression of Lymphatic Endothelial Markers in Blue Rubber Bleb Nevus Syndrome.

INTRODUCTION: Blue rubber bleb nevus syndrome (BRBNS) is an uncommon vascular anomaly characterized by multifocal cutaneous, visceral, and other soft tissue or solid organ venous malformations. We observed that BRBNS lesions express immunohistochemical markers of lymphatic differentiation. METHODS: BRBNS histopathologic specimens assessed at our institution during the past 27 years were reviewed. Slides from 19 BRBNS lesions were selected from 14 patients (9 cutaneous, 9 gastrointestinal, and 1 hepatic). We recorded the involved anatomical compartments and presence/absence of thrombi or vascular smooth muscle. Immunohistochemical endothelial expression of PROX1 (nuclear) and D2-40 (membranous/cytoplasmic) was evaluated semi-quantitatively. RESULTS: Endothelial PROX1 immunopositivity was noted in all specimens; the majority (89.5%) demonstrated staining in more than 10% of cells. D2-40 immunopositivity was present in one-third (33%) of cutaneous lesions and only 1 gastrointestinal lesion. CONCLUSION: Endothelial cells in BRBNS almost always express 1 or more immunohistochemical markers of lymphatic differentiation.

Large Malignant Testicular/Paratesticular Tumors in Adolescence: Assessment of Gross Tumor Size in a Vulnerable Age Group.

OBJECTIVE: We hypothesized that reticence to address a groin mass may result in late presentation of testicular/paratesticular malignancy in early puberty through adolescence. METHODS: Malignant testicular and paratesticular tumors (malignant germ cell tumors and rhabdomyosarcomas) diagnosed at our institution from 1994-2023 for patients aged 11-20 were included. Clinicopathologic features were recorded, and statistically analyzed. RESULTS: Eighty-five cases were identified. Patient ages ranged from 11 to 20 years (mean 17 years, median 16 years). The greatest tumor dimension ranged from 0.8 to 18.0 cm (mean 4.4 cm, median 3.5 cm). Ten tumors (11.8% of cases) were ≥10.0 cm. In the 11-13-year-old age group, 100% of tumors (3/3) were ≥10 cm. The proportion of tumors ≥10 cm was significantly higher in the 11-13-year-old age group than in either the 14-16-year-old (P<0.001) or 17-20-year-old (P<0.001) age groups. CONCLUSION: This adolescent cohort with malignant testicular and paratesticular tumors showed a high proportion (11.8%) of very large (≥10 cm) tumors. Although the reasons are unknown and likely multifactorial, this study suggests that adolescents, particularly the 11-13 year age group, are a vulnerable population.

Loss of KLK4::KLKP1 pseudogene expression by RNA chromogenic in-situ hybridization is associated with PTEN loss and increased risk of biochemical recurrence in a cohort of middle eastern men with prostate cancer.

BACKGROUND: KLK4::KLKP1 fusion is a recently described pseudogene that is enriched in prostate cancer (PCa). This new biomarker has not been characterized in the Middle Eastern population. OBJECTIVE: To establish the incidence and prognostic value of KLK4::KLKP1 fusion in a cohort of Middle Eastern men with PCa and explore the relationship of this marker to other relevant biomarkers (PTEN, ERG, SPINK1). DESIGN, SETTING, AND PARTICIPANTS: We interrogated a cohort of 340 Middle Eastern men with localized PCa treated by radical prostatectomy between 2005 and 2015. KLK4::KLKP1 fusion status was assessed by RNA Chromogenic in situ hybridization (CISH) and correlated to pathological and clinical parameters. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: RNA-CISH expression of KLK4::KLKP1 was correlated with prognostic factors, ERG, PTEN, and SPINK1 expression, and biochemical recurrence (BCR) following prostatectomy. RESULTS AND LIMITATIONS: 51.7% of patient samples showed positive KLK4::KLKP1 expression; more commonly in cores of PCa (38%) versus non-cancer (20.6%) (p < 0.0001) and in lower Gleason Grade Group tumors (1-3) vs (4-5). KLK4::KLKP1 expression positively correlated with ERG positivity and inversely associated with PTEN loss. No significant association was found with SPINK1 expression, seminal vesicle invasion, positive surgical margin, pathological stage, or patient age (< 50 or ≥ 50). The association between PTEN loss and BCR increased when combined with KLK4::KLKP1 negativity (HR 2.31, CI 1.03-5.20, p = 0.042). CONCLUSIONS: KLK4::KLKP1 expression is more common in this cohort of Middle Eastern men than has been reported in North American men. It is associated with ERG positivity and inversely correlated with PTEN loss. In isolation, KLK4::KLKP1 expression was not significantly associated with clinical outcome or pathological parameters. However, its expression is associated with certain molecular subtypes (ERG-positive, PTEN-intact) and as we demonstrate may help further stratify the risk of recurrence within these groups.

The Association between Cyclin Dependent Kinase 2 Associated Protein 1 (CDK2AP1) and Molecular Subtypes of Lethal Prostate Cancer.

Prostate cancer (PCa) is one of the most commonly diagnosed types of malignancy and is the second leading cause of cancer-related death in men in developed countries. Cyclin dependent kinase 2 associate protein 1(CDK2AP1) is an epigenetic and cell cycle regulator gene which has been downregulated in several malignancies, but its involvement in PCa has not yet been investigated in a clinical setting. We assessed the prognostic value of CDK2AP1 expression in a cohort of men diagnosed with PCa (n = 275) treated non-surgically by transurethral resection of the prostate (TURP) and studied the relationship between CDK2AP1 expression to various PCa molecular subtypes (ERG, PTEN, p53 and AR) and evaluated the association with clinical outcome. Further, we used bioinformatic tools to analyze the available TCGA PRAD transcriptomic data to explore the underlying mechanism. Our data confirmed increased expression of CDK2AP1 with higher Gleason Grade Group (GG) and metastatic PCa (p <0.0001). High CDK2AP1 expression was associated with worse overall survival (OS) (HR: 1.62, CI: 1.19−2.21, p = 0.002) and cause-specific survival (CSS) (HR: 2.012, CI 1.29−3.13, p = 0.002) using univariate analysis. When compared to each sub-molecular type. High CDK2AP1/PTEN-loss, abnormal AR or p53 expression showed even worse association to poorer OS and CCS and remained significant when adjusted for GG. Our data indicates that CDK2AP1 directly binds to p53 using the Co-Immunoprecipitation (Co-IP) technique, which was validated using molecular docking tools. This suggests that these two proteins have a significant association through several binding features and correlates with our observed clinical data. In conclusion, our results indicated that the CDK2AP1 overexpression is associate with worse OS and CSS when combined with certain PCa molecular subtypes; interaction between p53 stands out as the most prominent candidate which directly interacts with CDK2AP1.

Isolated Pulmonary Emergomycosis in an Immunocompetent Patient in Alberta, Canada.

Emergomyces canadensis pulmonary infection was incidentally diagnosed in an asymptomatic patient suspected to have metastatic osteosarcoma. Molecular diagnosis was imperative to fungal identification given overlapping histopathological features with histoplasmosis. This report documents a case of isolated pulmonary emergomycosis in an otherwise immunocompetent patient while discussing diagnostic and management pitfalls of this emerging and underdiagnosed infection.

Adipocyte-rich CTNNB1-mutated Intramuscular Gardner Fibroma Progressing to Desmoid Fibromatosis.

Gardner fibroma (GF) is a benign soft-tissue tumor that is associated with Gardner syndrome and can progress to, or co-occur with, desmoid fibromatosis (DF). Herein, we report a unique case of an 11-year-old boy who presented with a rapidly growing soft-tissue mass after biopsy of a stable fat-rich lesion present in the calf muscles since infancy, with Magnetic resonance imaging findings suggesting an intramuscular adipocytic tumor. The resection showed GF and DF. DF arising from a preexisting GF (the so-called "GF-DF sequence") is a well-documented phenomenon. Although immunohistochemistry was negative for nuclear ß-catenin expression, a CTTNB1 S45F mutation, which has been associated with aggressive behavior in DF, was identified in both components using a next-generation sequencing-based molecular assay. This is the first time a mutation in CTNNB1 has been identified in GF and the GF-DF sequence, thus expanding our knowledge of the molecular pathogenesis of the GF-DF sequence and highlighting the role of molecular testing in pediatric soft-tissue tumors. The histologic findings of an adipocyte-rich intramuscular GF also are unique, expanding the morphological spectrum of GF and adding GF to the differential diagnosis of intramuscular lesions with an adipocytic component.