Papillary Lesions Research Articles

PT1 Subclassification Predicts Progression-Free Survival in En Bloc Resection of Bladder Tumor Specimens.

The pathologic diagnosis of pT1 substage in conventional transurethral resection of bladder tumor specimens is inaccurate and has low interobserver reproducibility owing to fragmentation and cauterization of the specimens. En bloc resection of bladder tumor is a novel surgical procedure that improves diagnostic feasibility and accuracy in the pathologic diagnosis of bladder cancer, including depth and extent of invasion. To examine the prognostic value of multiple pT1 subclassification methods, using only en bloc resection specimens. We examined 106 patients with T1 bladder cancer who underwent en bloc resection. The pT1 substages were assigned by 3 different subclassification methods by using the muscularis mucosae or stalk of the papillary lesion as diagnostic landmarks or millimetric depth of invasion. Intergroup differences in progression-free survival and recurrence-free survival rates were analyzed. The prognostic values of clinicopathologic factors for progression/recurrence were analyzed by using multivariate analysis. The pT1 substage was evaluable in all cases. Tumors with invasion into/beyond the muscularis mucosae and those beyond the stalk of the papillary lesion were associated with worse progression-free survival (P = .002 and P = .01, respectively). Notably, no patient with invasion confined to the stalk had disease progression during the 23-month median follow-up period. Only the pT1 subclassification method using the muscularis mucosae was an independent prognosticator of progression in multivariate analysis (P = .03). Precise pathologic subclassification of invasion using en bloc resection specimens may enable accurate prognosis and assessment in patients with bladder cancer with suspicious shallow invasion.

Intracranial squamous papillary lesion.

Intracranial lesions with squamous differentiation raise a diagnostic challenge, which can include benign or malignant, primary and metastatic lesions. Here is the case of a 49‐year‐old woman, in which intraoperative cytology helped the differential and final diagnosis.

Subtypes of high-grade breast ductal carcinoma in situ (DCIS): incidence and potential clinical impact

ObjectiveThe purpose of this study was to investigate and classify the molecular subtypes of high-grade ductal carcinoma in situ (DCIS) and identify possible high-risk subtypes. The heterogenicity of DCIS with variable clinical and histopathological presentations has been recognized. Nevertheless, only histopathological grading and diameter are currently implemented in clinical decision-making following the diagnosis of DCIS. The molecular subtypes of DCIS and their IHC surrogate markers have not been defined in conventional treatment guidelines and recommendations. We applied the definitions of molecular subtypes according to the IHC surrogate markers defined for IBC and subclassified high-grade DCIS, accordingly.MethodsHistopathological specimens were collected, revised, and regraded from 494 patients diagnosed with DCIS between 1996 and 2018. Other in situ and papillary lesions observed in breast biopsies were excluded from this study. 357 high-grade DCIS cases were submitted to IHC analysis. The markers investigated were ER, PR, HER2, and Ki67.Results45 cases were classified as grade 1, 19 as grade 2, and 430 as grade 3. Sixty patients with high-grade DCIS had an additional invasive component in the surgical specimen. Thirty-three patients were diagnosed with recurrent DCIS or invasive cancer (minimum one year after their primary DCIS diagnosis). The proportions of luminal A and luminal B HER2-negative subtypes varied depending on whether 2011 or 2013 St. Gallen Consensus Conference guidelines were adopted. Luminal A was the most prevalent subtype, according to both classifications. The luminal B HER2-positive subtype was found in 22.1% of cases, HER2-enriched subtype in 21.8%, and TPN subtype in 5.6%. There were strong indications that HER2-enriched subtype was significantly more frequent among DCIS with invasive component (p = 0.0169).ConclusionsHigh-grade DCIS exhibits all the molecular subtypes previously identified in IBC, but with a somewhat different distribution in our cohort. HER2-enriched subtype is substantially related to the presence of an invasive component in DCIS; consequently, it is regarded as a high-risk entity.

Effect of differences in O-RADS lexicon interpretation between senior and junior sonologists on O-RADS classification and diagnostic performance

PurposeTo assess the consistency of Ovarian-Adnexal Reporting and Data System (O-RADS) lexicon interpretation between senior and junior sonologists and to investigate its impact on O-RADS classification and diagnostic performance.MethodsWe prospectively studied 620 patients with adnexal lesions, all of whom underwent transvaginal or transrectal ultrasound performed by a senior sonologist (R1) who selected the O-RADS lexicon description and O-RADS category for the lesion after the examination. Meanwhile, the junior sonologist (R2) analyzed the images retained by R1 and divided the lesion in the same way. Pathological findings were used as a reference standard. kappa (к) statistics were used to assess the interobserver agreement.ResultsOf the 620 adnexal lesions, 532 were benign and 88 were malignant. When using the O-RADS lexicon, R1 and R2 had almost perfect agreement regarding lesion category, external contour of solid lesions, presence of papillary inside cystic lesions, and fluid echogenicity (к: 0.81–1.00). Substantial agreement in solid components, acoustic shadow, vascularity and O-RADS categories (к: 0.61–0.80). Consistency in classifying classic benign lesions in the O-RADS category was only moderate (к = 0.535). No significant difference in diagnostic performance between them using O-RADS (P = 0.1211).ConclusionThere was good agreement between senior and junior sonologists in the interpretation of the O-RADS lexicon and in the classification of O-RADS, except for a moderate agreement in the interpretation and classification of classic benign lesions. Differences in O-RADS category delineation between sonologists had no significant effect on the diagnostic performance of O-RADS.

Clinicopathologic Features of Noninvasive Inverted Urothelial Papillary Tumor.

Clinicopathologic features and recurrence rates of inverted noninvasive urothelial papillary tumors have been poorly characterized to date with few larger studies evaluating long-term outcomes. The spectrum of histomorphology, clinical features, and prognosis of inverted lesions of the urinary bladder are retrospectively reviewed. Archived paraffin-embedded urothelial tumor samples from patients diagnosed with inverted urothelial papillary lesions between January 2005 and June 2020 were collated. A matched control population of patients with exophytic papillary lesions of the urothelium diagnosed during the same time period was randomly selected. The conventional clinicopathologic features of inverted urothelial papillary tumor were evaluated retrospectively and patient demographics, tumor characteristics, recurrence, and survival information were recorded. Lower recurrence rates were observed for inverted papillary urothelial neoplasm of low malignant potential (IPUNLMP) relative to papillary urothelial neoplasms of low malignant potential and for low-grade papillary urothelial carcinoma with an inverted growth pattern (LG-PUCI) relative to low-grade papillary urothelial carcinomas. No recurrence was found among the inverted urothelial papilloma cases. The 2- and 5-year disease-free survival rates were 100.0% and 85.2% for IPUNLMP patients; 94.4% and 80.4% for papillary urothelial neoplasms of low malignant potential; 89.5% and 82.0% for LG-PUCI; 73.7% and 54.6% for low-grade papillary urothelial carcinoma; 40.0% and 20.0% for high-grade papillary urothelial carcinoma with an inverted growth pattern patients and 26.7% and 26.7% for high-grade papillary urothelial carcinoma. Multivariate Cox regression analysis of IPUNLMP and LG-PUCI/high-grade papillary urothelial carcinoma with an inverted growth pattern indicated that tumor number (hazard ratio=4.356; 95% CI: 1.145-16.570; P =0.031) was a powerful prognostic factor for disease-free survival. Noninvasive, papillary urothelial lesions of the bladder tend to have lower recurrence and a better outcome if an inverted growth pattern is shown.

Second opinion (external specialist referral) practice of breast pathology: the Nottingham experience.

Breast pathology is a challenging field, and discrepancies in diagnoses exist and can affect patient management. This study aims to review a breast referral practice and assess the pattern and frequency of breast lesions sent for an external expert review and evaluate potential impacts on patients' care. Seven hundred and forty cases that were referred to Nottingham City Hospital for a second opinion between 2019 and 2022 which have slides and reports were retrieved and reviewed. Reasons for referral, initial diagnosis, proffered specialist opinion and any discrepancy or potential impacts of management were assessed. The most frequent entities were papillary lesions (19%), fibroepithelial lesions (17%), invasive carcinomas that were sent for confirmation of the invasive diagnosis or subtyping of the invasive tumour (17%), intraductal epithelial proliferation with atypia (9%) and spindle cell lesions (8%). Other entities included biphasic tumours such as adenomyoepithelioma, as well as vascular and nipple lesions. Few cases were sent for prognostic classification or comments on the management, and in occasional cases no initial diagnosis was offered. After reviewing the cases by the expert pathologists, the initial diagnosis was confirmed or one of the suggested diagnoses was preferred in 79% of cases, including 129 cases (17%) in which the opinion resulted minor changes in the management. Significant changes in the classification of lesions were made in 132 cases (18%) which resulted in significant change in the patient management recommendation. In 14 cases (2%) a final classification was not possible, and further specialist opinion was obtained. Comments on the differential diagnosis and advice on further patient management were provided in most cases. This study demonstrates the value of external referral of challenging, rare and difficult to classify breast lesions. It also highlights the most common breast lesions that are likely to be challenging, and specialist opinion can refine their classification to improve patient care.

ELF3 suppresses gallbladder cancer development through downregulation of the EREG/EGFR/mTOR complex 1 signalling pathway.

The prognosis of gallbladder cancer (GBC) remains poor, and a better understanding of GBC molecular mechanisms is important. Genome sequencing of human GBC has demonstrated that loss-of-function mutations of E74-like ETS transcription factor 3 (ELF3) are frequently observed, with ELF3 considered to be a tumour suppressor in GBC. To clarify the underlying molecular mechanisms by which ELF3 suppresses GBC development, we performed in vivo analysis using a combination of autochthonous and allograft mouse models. We first evaluated the clinical significance of ELF3 expression in human GBC tissues and found that low ELF3 expression was associated with advanced clinical stage and deep tumour invasion. For in vivo analysis, we generated Pdx1-Cre; KrasG12D ; Trp53R172H ; Elf3f/f (KPCE) mice and Pdx1-Cre; KrasG12D ; Trp53R172H ; Elf3wt/wt (KPC) mice as a control and analysed their gallbladders histologically. KPCE mice developed larger papillary lesions in the gallbladder than those developed by KPC mice. Organoids established from the gallbladders of KPCE and KPC mice were analysed in vitro. RNA sequencing showed upregulated expression of epiregulin (Ereg) in KPCE organoids, and western blotting revealed that EGFR/mechanical targets of rapamycin complex 1 (mTORC1) were upregulated in KPCE organoids. In addition, ChIP assays on Elf3-overexpressing KPCE organoids showed that ELF3 directly regulated Ereg. Ereg deletion in KPCE organoids (using CRISPR/Cas9) induced EGFR/mTORC1 downregulation, indicating that ELF3 controlled EGFR/mTORC1 activity through regulation of Ereg expression. We also generated allograft mouse models using KPCE and KPC organoids and found that KPCE organoid allograft tumours exhibited poorly differentiated structures with mTORC1 upregulation and mesenchymal phenotype, which were suppressed by Ereg deletion. Furthermore, EGFR/mTORC1 inhibition suppressed cell proliferation and epithelial-mesenchymal transition in KPCE organoids. Our results suggest that ELF3 suppresses GBC development via downregulation of EREG/EGFR/mTORC1 signalling. EGFR/mTORC1 inhibition is a potential therapeutic option for GBC with ELF3 mutation. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

ORAL VERRUCIFORM XANTHOMA: REPORT OF TWO CASES

Oral verruciform xanthoma (VX) is a benign lesion of unknown etiology, usually found in the gingiva and palate. This study reports on two cases of this uncommon lesion. The first is a nodule in the upper gingiva of an adult man, with the clinical diagnosis of squamous papilloma. The second is a white plaque on the tongue of a 64-year-old man, clinically diagnosed as leukoplakia or reactive hyperkeratosis. After excisional biopsy, both lesions presented a proliferation of squamous epithelium, with elongated rete ridges and numerous foamy macrophages (CD68+) within the connective tissue papillae, classified respectively as flat and verrucous. The first patient died during follow up, but the second showed no signs of recurrence one year after the biopsy. In a 60-year period, we have only 4 cases of VX (0.025%), a lesion that could be clinically misguided as other papillary or verrucous lesions. Oral verruciform xanthoma (VX) is a benign lesion of unknown etiology, usually found in the gingiva and palate. This study reports on two cases of this uncommon lesion. The first is a nodule in the upper gingiva of an adult man, with the clinical diagnosis of squamous papilloma. The second is a white plaque on the tongue of a 64-year-old man, clinically diagnosed as leukoplakia or reactive hyperkeratosis. After excisional biopsy, both lesions presented a proliferation of squamous epithelium, with elongated rete ridges and numerous foamy macrophages (CD68+) within the connective tissue papillae, classified respectively as flat and verrucous. The first patient died during follow up, but the second showed no signs of recurrence one year after the biopsy. In a 60-year period, we have only 4 cases of VX (0.025%), a lesion that could be clinically misguided as other papillary or verrucous lesions.

Bladder Postoperative Spindle Cell Nodule: Malignant Mimicry in the Postoperative Setting

Bladder Postoperative Spindle Cell Nodule: Malignant Mimicry in the Postoperative Setting

Papillary Endothelial Hyperplasia

A man in his 30s had a unilateral mass of the epididymis. There was no prior history of local trauma, and ultrasonographic imaging did not reveal the presence of any other testicular abnormality. A 1.4-cm unilocular cystic lesion was excised. Histopathologic examination showed the presence of blood vessels with organizing thrombi adjacent to the epididymis (Figure 1A, B ). On microscopic examination, several foci of proliferative clusters of cells with epithelioid to vaguely spindled morphology were identified (Figure 1C, D). What is the lineage of the epithelioid cells, and is this lesion benign or malignant?a.Vascular lineage, malignant (angiosarcoma)b.Carcinoma, malignantc.Vascular lineage, benign (papillary endothelial hyperplasia)d.Melanoma, malignant Answer: c. Vascular lineage, benign (papillary endothelial hyperplasia) The images show the presence of an intravascular lesion with organizing thrombus that is broken down into collagenized clumps admixed with hemorrhagic material (Figure 2A, B ). These collagenized clusters are lined by vascular endothelial cells, and immunohistochemistry for ERG and CD31 confirms vascular lineage (Figure 2C, D). These findings are consistent with papillary endothelial hyperplasia.1Akdur N.C. Donmez M. Gozel S. Ustun H. Hucumenoglu S. Intravascular papillary endothelial hyperplasia: histomorphological and immunohistochemical features.Diagn Pathol. 2013; 8: 167Crossref PubMed Scopus (51) Google Scholar Papillary endothelial hyperplasia is thought to represent breakdown of intravascular thrombi with accompanying ingrowth of vascular endothelial cells along the edges of thrombotic material. In late stages, as in this case, these lesions may impart an appearance of a papillary lesion with an anastomotic network of vascular endothelial cells that is frequently misinterpreted as an angiosarcoma. However, in contrast to angiosarcoma, these lesions are almost always exclusively intravascular and lack infiltrative growth. Infrequently, papillary endothelial hyperplasia may be recognized in an extravascular location secondary to rupture or as part of organization of an extravascular hematoma. These lesions exhibit minimal nuclear pleomorphism, mitotic activity, or necrosis. Finally, papillary endothelial hyperplasia has an excellent prognosis and does not recur when completely excised.

(388) Primary Penile Squamouse Cell Cancer Related Malignant Priapism In A Cystectomized Patient: A Case Report

Abstract Introduction Priapism is a prolonged (> 4 hours) and unintended erection without sexual stimulation or sexual desire. Priapism due to neoplasms is called malignant priapism, which is a rare condition that tends to occur with corporeal metastasis of other pelvic area malignancies. Priapism due to primary penile malignancies is extremely rare. Objective In this article, we present the case of a patient who underwent total penectomy and bilateral inguinal lymphadenectomy due to malignant priapism related to primary penile squamous cell cancer (SCC), and who also underwent radical cystectomy (RC) and total urethrectomy due to urothelial carcinoma 19 and 2 years prior, respectively. Methods We prepared the patient's information to present. Results An 82-year-old male patient presented to an outpatient clinic with unintended erection and penile pain of about 48 hours’ duration and was on follow-up in our clinic because of urothelial carcinoma history. The patient’s history indicated that he underwent RC and orthotopic neobladder due to muscle-invasive urothelial cancer (UC) in the bladder. No tumor was observed in the final cystectomy pathology; therefore, no adjuvant therapy was given. Seventeen years after the RC operation, he presented with hematuria and a papillary lesion detected in the mid-urethra during cystourethroscopy. Since the biopsy result from this region was compatible with high-grade UC, he underwent total urethrectomy, neobladder resection, and ileal conduit. Urethrectomy pathology results were reported as UC invading the subepithelial stroma and lymphovascular area. Adjuvant MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) chemotherapy was administered. On follow-up 2 years after the urethrectomy operation, he presented with prolonged priapism. On examination, a cold and erect penis with a 1 cm diameter ulcerated lesion on the glans penis were observed. Hypoxia and hypercarbia were observed on the cavernosal blood gas examination, which was compatible with ischemic priapism. The hemogram was normal. On the emergent penile duplex Doppler ultrasound showed decreased blood flow and a mass on the proximal part of the penis. Subsequently, pelvic magnetic resonance imaging was performed and a mass was observed that was fully destructive to the cavernosal bodies and had irregularly circumscribed borders (Figure 1). Afterward, the patient underwent a total penectomy and bilateral inguinal lymphadenectomy. The pathology report from the penectomy material suggested that the tumor was compatible with moderately differentiated SCC. No sign of metastasis was observed in the lymph nodes. Extensive sampling of the tumor did not reveal any UC in situ, nor SCC in situ. The penis shaft was fully infiltrated by the tumor, with SCC morphology starting from the surgical margin and damaging all the structures of the penile body (Figure 2). The patient was transferred to the oncology clinic for additional treatment planning. Conclusions Despite being the most common primary malignancy of the penis, to the best of our knowledge priapism due to primary penile SCC has been reported only once in the literature. Although metastatic disease is typically thought to be the cause, when a patient with a history of pelvic malignancy presents with malignant priapism, it should be kept in mind that primary malignancies of the penis may also cause this condition. Disclosure No

Detection and endoscopic classification of intraductal neoplasms of the bile duct by peroral cholangioscopy with narrow-band imaging (with videos).

Indirect diagnostic modalities are unsatisfactory for detecting intraductal neoplasm of the bile duct (IN-B), which can be detected by peroral cholangioscopy (POC) with narrow-band imaging (NBI). We investigated the POC findings of IN-B and developed a feasible endoscopic classification system. Four hundred seventy-one patients who underwent direct POC from April 2008 to July 2020 were enrolled. Intraductal superficial lesions of the bile duct (ISL-Bs) were classified according to surface structure and microvascular pattern on POC with NBI and correlated to histologic findings after POC-guided forceps biopsy sampling (POC-FB) or surgery. The primary outcome was the detection rate of IN-Bs, and the secondary outcomes were the associations of POC findings with IN-B, technical success rates of POC and POC-FB, and adverse events. Direct POC was successful in 458 of 471 patients (97.2%). Among the patients, 131 (27.8%) exhibited ISL-Bs. The technical success rate of POC-FB was 94.7% (124/131). Among the 124 patients who underwent POC-FB, IN-B was revealed in 54 (43.5%), for a detection rate of 11.8% (54/458). Papillary lesions (P= .041), nodular lesions (P= .044), and irregularly or regularly dilated and tortuous vessels (P= .004 and P= .006, respectively) were POC findings associated with IN-B. The area under the receiver-operating characteristic curve of the novel classification system was .899. POC with NBI can be useful for the detection of IN-Bs. Our novel classification system based on both surface structure and microvascular pattern may allow differentiation of IN-B from ISL-Bs.

Ultrasound Guided Core Needle Biopsy in The Diagnosis of Suspicious Breast Lesions: Radiologist’s perspectives

Background: Ultrasound guided core needle biopsy is becoming a gold standard in the work up of suspicious breast lesion. In Iraq, radiologists are not taking the lead in core needle biopsy performance. Objectives: To evaluate the radiologist performance of core needle biopsy highlighting the precession and accuracy of the procedure, the concordance of ultrasound and histopathology, and identifying challenges facing the radiologist during the procedure. Subjects and Methods: A prospective study involving a total of 50 patients with ultrasound (US) BIRADS IV or V. Ultrasound guided core needle biopsy was performed for each patient. Surgical pathology diagnosis was available for 40 patients. core needle biopsy results were correlated with Breast Imaging-Reporting and Data System (BI-RADS) categories and validity of the test was evaluated. Results: Malignancy was confirmed by histopathology in 76% of the cores. Concordance between BI-RADS(US) and histopathology for benignity and malignancy was achieved in all cores. Borderline lesions constituted 10% of total cores taken. Surgical resection of these lesions upgraded 3/5 (60%): two atypical ductal hyperplasia and an intraductal papillary lesions diagnosed by core needle biopsy found to be invasive ductal carcinoma after surgical resection. Sensitivity of core needle biopsy in this study was 91.4% with 100% specificity. Positive and negative predictive values were 100% and 62.5% respectively. The underestimation rate in high-risk group was 3/5 (60%). No significant complication was reported. Conclusion: Ultrasound guided core needle biopsy is a safe, efficient and relatively inexpensive method in diagnosing suspicious breast lesions. Radiologists can produce high sensitivity and specificity results. Radio pathological correlation is of paramount in achieving accurate results.

Genomic Profiling of Urothelial Carcinoma in Situ of the Bladder

BACKGROUND AND AIMS Urothelial carcinoma in situ (CIS) of the bladder is an intra-epithelial, high grade, malignant neoplasm characterised by flat (non-papillary) growth, with high probability of disease progression.1,2 CIS has histologic features similar to invasive cancer and is often a precursor to and associated with invasive cancer. Molecularly, bladder cancer can be broadly categorised into luminal and basal subtypes.1-7 However, the molecular features that are unique to CIS, as compared to other high-grade lesions, including papillary Ta and T1 tumours, are underexplored. Bulk RNA expression profiling is a standard for molecularly characterising bladder cancer, and RNA-sequencing protocols utilising formalin-fixed paraffin-embedded (FFPE) tumours are well established. However, CIS presents challenges for RNA sequencing due to the inability to reliably detect, the low incidence rate, and the quality of RNA derived from FFPE samples. While enhanced cystoscopy and narrow band imaging have improved the ability to detect CIS, sampling acquisition techniques still limit the optimisation of RNA sequencing. Furthermore, the authors determined that established dual nucleic acid extraction protocols for FFPE samples were not feasible due to small biopsy sample sizes, and that protocols should be optimised for either RNA or DNA. This study attempts to overcome above stated challenges to understand the molecular landscape of CIS by contrasting against papillary tumours and normal urothelium using RNA-sequencing on FFPE samples, as well as whole exome sequencing, and immunohistochemical and immunofluorescent analyses, with an intent to identify unique molecular signatures associated with CIS. MATERIALS AND METHODS The authors performed whole transcriptome profiling with RNA sequencing of FFPE specimens from 15 CIS, nine high-grade papillary Ta/T1 tumours, and eight normal urothelial samples (Cohort A). Wilcoxon test was used to filter differentially expressed genes and The Cancer Genome Atlas (TCGA) single sample classifier was used to assign molecular subtypes. Whole exome sequencing was performed for 19 patients with matched CIS and papillary tumour samples (Cohort B). Using multiplex immunofluorescence and immunohistochemistry analyses, 24 samples from 15 patients were analysed for the presence of cytotoxic T cells, T helper cells, regulatory T cells, B cells, M1 and M2 macrophages, and programmed cell death protein 1 and programmed death-ligand 1-expressing cells. RESULTS The authors performed molecular subtyping applying the UROMOL classification and as previously shown for CIS, the majority were Class 2a and 2b, with four Class 3 and one Class 1. They applied the TCGA single patient classifier and the majority were luminal with a breakdown of two luminal, five luminal infiltrated, seven luminal papillary, three basal, and one neuronal subtype (Figure 1). A 46-gene signature of differentially expressed genes in CIS samples was identified and included known druggable targets that were selectively upregulated (MTOR, TYK2, AXIN1, CPT1B, GAK, and PIEZO1) or downregulated (BRD2 and NDUFB2; p<0.05). An independent dataset was used to assess the robustness of these markers. High expression of MTOR, GUSBP11, KMT2D, and URB1 was significantly associated with CIS in this independent dataset.Additionally, mutational analysis of 34 matched CIS and 33 papillary tumours revealed a clonal origin of the lesions with mutations shared between both synchronous and metachronous tumours. Inter- and intra-patient mutational heterogeneity was also observed. The most frequently mutated gene was KDM6A, which was observed in 53% of the patient samples. Analysis of the immunological landscape of 24 CIS and papillary tumour lesions showed higher levels of immune cells in stromal compartments compared to carcinoma regions. Furthermore, more programmed cell death protein 1 positive cells were observed in CIS lesions compared with papillary tumours (p=0.03). CONCLUSION Collectively, this study identifies a molecular signature that distinguishes CIS lesions from papillary tumours in terms of gene expression levels, mutational landscape, and proportion of programmed cell death protein 1 positive cells that may contribute to an aggressive feature of progressive disease phenotype of the bladder cancer.

Percutaneous vacuum-assisted excision (VAE) of breast lesions of uncertain malignant potential (B3 lesions): a preliminary single-centre Italian experience.

In recent years vacuum-assisted excision (VAE) has been described as an alternative treatment for some B3 lesions. This study aims to assess the effectiveness of using VAE to manage selected B3 lesions by quantifying the number of B3 lesions undergoing VAE, the malignant upgrade rate, and the complications encountered. Our department evaluated all B3 lesions diagnosed between January 2019 and October 2021 and treated them with VAE. The data were collected during the initial biopsy and final histology based on VAE image guidance, also considering initial lesions and complications. The exclusion criteria were: B3 lesion of size > 20mm, presence of a concomitant malignant lesion, lesion < 5.0mm distant from the skin, nipple or pectoral muscle, phyllodes tumours or indeterminate B3 lesions. Lesions that upgraded to malignancy underwent surgical excision, while benign lesions performed radiological follow-ups. From 416 B3 lesions diagnosed, 67 (16.1%) underwent VAE. VAE was performed under X-ray (50/67) or ultrasound guidance (17/67). Five cases (7.5%) upgraded to a malignant lesion, 2 ADH, 2 LIN and one papillary lesion that underwent surgery. No malignancy or new lesions has occurred at the site of the VAE, with an average radiological follow-up of 14.9months. VAE could be a safe and effective pathway for managing selected B3 lesions. Lesions initially subjected to CNB with ADH and LN outcome, before undergoing VAE, should perform a VAB for better tissue characterization and management.

MP63-14 PRELIMINARY RESULTS OF FIRST-IN-HUMAN CRYOTHERAPY FOR NON MUSCLE INVASIVE BLADDER CANCER

You have accessJournal of UrologyCME1 Apr 2023MP63-14 PRELIMINARY RESULTS OF FIRST-IN-HUMAN CRYOTHERAPY FOR NON MUSCLE INVASIVE BLADDER CANCER Gilad Amiel, Omri Falik-Nativ, Kamil Malshy, Omer Sadeh, Michael Mullerad, Eyal Kochavi, and Azik Hoffman Gilad AmielGilad Amiel More articles by this author , Omri Falik-NativOmri Falik-Nativ More articles by this author , Kamil MalshyKamil Malshy More articles by this author , Omer SadehOmer Sadeh More articles by this author , Michael MulleradMichael Mullerad More articles by this author , Eyal KochaviEyal Kochavi More articles by this author , and Azik HoffmanAzik Hoffman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003321.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Initial treatment for Non-Muscle Invasive Bladder Cancer (NMIBC) mostly remains unchanged in recent decades. Utilizing cryotherapy with CO2 is commonly used to treat superficial papillary lesions of the skin for many years. Recently, we have proven its potential in treating urinary epithelial lesions in an animal model. In this study we present our preliminary phase 1 clinical experience and results in treating low grade papillary lesions of the bladder with cryoablation. METHODS: Following local IRB and Ministry of Health approval, 10 patients with up to 3 papillary lesions and a maximum of 10 mm in size were recruited. Exclusion criteria included previous high-grade disease and/or positive cytology. Following an initial routine cystoscopy, the bladder irrigation medium was replaced with CO2 insufflation, and each lesion was treated with 2 cycles of direct spraying of liquid CO2. Each cycle lasted 15 seconds, with 10 seconds of thawing between the treatment cycles. Follow-up cystoscopy and mandatory treatment site biopsy were performed 4-6 weeks after treatment. Routine surveillance with office cystoscopy was performed every 3 months for 1 year thereafter. RESULTS: 8 men and 2 women were included (age 57—89 years). Overall, 14 lesions were treated. No complications were noted during treatment or during follow-up (range 2-14 months). Pathological analysis of the treatment site 4-6 weeks after treatment detected residual low grade TCC only in the very first patient, attributed to suboptimal lesion freezing due to our initial learning curve. The other 13/14 biopsy sites were negative for cancer (93%). CONCLUSIONS: Initial results of cryotherapy utilizing CO2 spraying for small low grade NMIBC is safe and feasible. Pathological analysis confirms efficacy in tumor eradication. This novel treatment may be used as an office procedure and therefore, after further validation studies, offers a potential paradigm shift in the treatment of NMIBC. Source of Funding: Biotechnological Incubator Trendlines, Misgav, Israel © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e876 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Gilad Amiel More articles by this author Omri Falik-Nativ More articles by this author Kamil Malshy More articles by this author Omer Sadeh More articles by this author Michael Mullerad More articles by this author Eyal Kochavi More articles by this author Azik Hoffman More articles by this author Expand All Advertisement PDF downloadLoading ...

MP08-15 THE ROLE OF FLEXIBLE BLUE LIGHT CYSTOSCOPY IN SURVEILLANCE OF NON-MUSCLE INVASIVE BLADDER CANCER. RESULTS FROM A NORDIC REGISTRY

You have accessJournal of UrologyCME1 Apr 2023MP08-15 THE ROLE OF FLEXIBLE BLUE LIGHT CYSTOSCOPY IN SURVEILLANCE OF NON-MUSCLE INVASIVE BLADDER CANCER. RESULTS FROM A NORDIC REGISTRY Karsten Egbert Arnold Zieger, Kristine Young-Halvorsen, and Per-Uno Malmström Karsten Egbert Arnold ZiegerKarsten Egbert Arnold Zieger More articles by this author , Kristine Young-HalvorsenKristine Young-Halvorsen More articles by this author , and Per-Uno MalmströmPer-Uno Malmström More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003223.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bladder cancer is one of the most prevalent cancers in the world. Approximately 75% of bladder cancers are non-muscle invasive (NMIBC) with a high tendency of recurrence and progression. Thus, patients undergo regular surveillance cystoscopies, often life-long. Blue light cystoscopy (BLC) improves the diagnosis of papillary and flat lesions, and may play a role in the surveillance setting by reducing the risk of missing significant lesions, refuting suspicious changes, and strengthening confidence in recurrence-free cystoscopies. This study aims to evaluate the impact of BLC in a surveillance setting. METHODS: The Nordic Blue Light Flexible Cystoscopy (BLFC) registry is a prospective, observational, multi-center study including patients undergoing BLFC for suspicion or surveillance of NMIBC in an outpatient setting. The registry is approved by local ethics committees. Data recorded are patient demographics, bladder cancer history, findings under WLC and BLC, patient preference, discomfort and treatment. RESULTS: We performed 436 BLFC in 319 patients in surveillance of NMIBC. The EAU risk group distribution was 172 (54%) high risk, 136 (43%) intermediate risk and 11 (3%) low risk. 147 (34%) cases underwent adjuvant therapy with BCG or chemotherapy prior to BLFC. 318 (73%) cystoscopies revealed suspicious lesions using white light or blue light. We took biopsies from 452 lesions, showing malignancy in 126/409 (31%) lesions positive for blue light, while 7/43 (16%) lesions negative for blue light. In 86 cases (20%), lesions were identified only by blue light. Pathology showed malignancy in 37/104 biopsies (36%), including 18 CIS. Patients with small recurrences underwent office fulguration, 45 patients (10%) were referred to TURBT, and 82 patients subsequently received adjuvant intravesical therapy. 34 patients expressed discomfort during BLFC, due to bladder distension or the associated biopsy and/or fulguration. Physicians reported benefit of BLC in 367/436 (84%) of the cystoscopies, with a stronger confidence in confirming or refuting a suspicious lesion as the main advantage (28%). CONCLUSIONS: Flexible BLC as an adjunct to white light cystoscopy for surveillance of NMIBC improves the detection of malignant lesions. Furthermore, it improves surgeons’ confidence on identifying clinical important lesions. The combination of BLC with immediate fulguration of tumours in an outpatient setting may positively affect the patients’ burden in NMIBC. The impact on patients overall outcome is target of future evaluations. Source of Funding: Photocure ASA © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e100 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Karsten Egbert Arnold Zieger More articles by this author Kristine Young-Halvorsen More articles by this author Per-Uno Malmström More articles by this author Expand All Advertisement PDF downloadLoading ...

The Upgrade Risk of B3 Lesions to (Pre)Invasive Breast Cancer After Diagnosis on Core Needle or Vacuum Assisted Biopsy. A Belgian National Cohort Study

IntroductionFlat epithelial atypia (FEA), lobular neoplasia (LN), papillary lesions (PL), radial scar (RS) and atypical ductal hyperplasia (ADH) are lesions of uncertain malignant potential and classified as B3 lesions by the European guidelines for quality assurance in breast cancer screening and diagnosis. Current management is usually wide local excision (WE), surveillance may be sufficient for some. We investigated the upgrade rate of B3 lesions to breast malignancy in a subsequent resection specimen after diagnosis on core needle–or vacuum assisted biopsy (CNB–VAB) in a national population-based series. MethodsUsing data from the Belgian Cancer Registry (BCR) between January 1, 2013 and December 31, 2016, inclusion criteria were new diagnosis of a B3 lesion on CNB or VAB with subsequent histological assessment on a wider excision specimen. Histological agreement between first- and follow-up investigation was analyzed to determine the upgrade risk to ductal adenocarcinoma in situ (DCIS) or invasive breast cancer (IC) according to the type of B3 lesion. ResultsOf 1855 diagnosed B3 lesions, 812 were included in this study: 551 after CNB–261 after VAB. After diagnosis on CNB and VAB, we found 19.0% and 14.9% upgrade to malignancy respectively. Upgrade risks after CNB and VAB were: FEA 39.5% and 17.6%; LN 40.5% and 4.3%; PL 10.4% and 12.5%; RS 25.7%and 0.0%; ADH 29.5% and 20.0%. ConclusionBased on the observed upgrade rate we propose three recommendations: first, resection of ADH, and FEA with WE; second, resection of RS and classical LN with therapeutic VAB and further surveillance when radio-pathological correlation is concordant; third, surveillance of PL.

Condilomatosis oral en niña de 9 años. Reporte de un caso clínico

A clinical case of a 9-year-old patient who seeks care for elevated lesions of the oral mucosa is presented. A disease caused by HPV was diagnosed. This case might potentially involve child abuse due to modes of disease transmission. On clinical examination, an ulcerated papillary lesion of approximately 0.5 cm was observed in the right lip corner. Multiple raised warty lesions were seen on both cheeks and the lower labial mucosa. We conclude about the importance of a good clinical history and a complete oral examination to implement the right treatment and follow-up of pathologies.

Frequent Telomerase Reverse Transcriptase Promoter and Fibroblast Growth Factor Receptor 3 Mutations Support the Precursor Nature of Papillary Urothelial Hyperplasia of the Urinary Bladder

The precursor nature of papillary urothelial hyperplasia of the urinary bladder is uncertain. In this study, we investigated the telomerase reverse transcriptase (TERT) promoter and fibroblast growth factor receptor 3 (FGFR3) mutations in 82 patients with papillary urothelial hyperplasia lesions. Thirty-eight patients presented with papillary urothelial hyperplasia and concurrent noninvasive papillary urothelial carcinoma, and 44 patients presented with de novo papillary urothelial hyperplasia. The prevalence of the TERT promoter and FGFR3 mutations is compared between de novo papillary urothelial hyperplasia and those with concurrent papillary urothelial carcinoma. Mutational concordance between papillary urothelial hyperplasia and concurrent carcinoma was also compared. The TERT promoter mutations were detected in 44% (36/82) of papillary urothelial hyperplasia, including 23 (23/38, 61%) papillary urothelial hyperplasia with urothelial carcinoma and 13 (13/44, 29%) de novo papillary urothelial hyperplasia. The overall concordance of TERT promoter mutation status between papillary urothelial hyperplasia and concurrent urothelial carcinoma was 76%. The overall FGFR3 mutation rate of papillary urothelial hyperplasia was 23% (19/82). FGFR3 mutations were detected in 11 patients with papillary urothelial hyperplasia and concurrent urothelial carcinoma (11/38, 29%) and 8 patients with de novo papillary urothelial hyperplasia (8/44, 18%). Identical FGFR3 mutation status was detected in both papillary urothelial hyperplasia and urothelial carcinoma components in all 11 patients with FGFR3 mutations. Our findings provide strong evidence of a genetic association between papillary urothelial hyperplasia and urothelial carcinoma. High frequency of TERT promoter and FGFR3 mutations suggests the precursor role of papillary urothelial hyperplasia in urothelial carcinogenesis.