Papillary Urothelial Carcinoma Research Articles

The clinical relevance of cut-off percentage for high-grade urothelial carcinoma within low-grade urothelial carcinoma: A determining factor?

AimsThe aim of the study was to analyze the cut-off value for the percentage of the high-grade (HG) component that has clinical significance in urothelial carcinoma (UC). Material and MethodsThe study included a total of 362 patients, mixed-grade UC (MGUC) patients were classified as Combine Group (CG) 1 based on the presence of less than 5% HG areas. High-grade papillary UC (HGPUC) patients were grouped based on HG component proportions: CG2 (≥5%–<50% HG), CG3 (≥50%–<100% HG), and pure HGPUC (PHGPUC) for 100% HG components. ResultsThere was a statistically significant difference between low-grade papillary UC (LGPUC) and CG1, CG2, or CG3, as well as LGPUC and PHGPUC, in terms of cancer-specific survival (CSS) (hazard ratio (HR) = 19.85, 95% confidence interval (CI) = 2.30–171.10 P = 0.007, HR = 28.38, 95% CI = 3.50–229.97 P = 0.002, HR = 18.64, 95% CI = 2.26–153.64 P = 0.007, and HR = 35.41, 95% CI = 4.61–271.72 P < 0.001, respectively). There was no statistically significant difference between PHGPUC and CG1, CG2, or CG3 in terms of CSS. ConclusionsThese findings suggest that even the presence of less than 5% HGPUC within LGPUC significantly impacts CSS. Furthermore, the increase in the percentage of HGPUC beyond 5% does not substantially influence the CSS. Based on these findings, disclosing the percentage of the high-grade component may be crucial for future patient management and treatment.

Validation of Keratin 17 as a Tissue Biomarker in the Diagnosis of Upper Tract Urothelial Carcinoma.

Upper tract urothelial carcinoma (UTUC) has a relatively low incidence but presents significant surveillance and treatment challenges. Therefore, novel biomarkers for the accurate detection of upper tract urothelial tumors are urgently needed. We evaluated the expression of Keratin 17 (KRT17), an oncoprotein implicated in the cell cycle progression of multiple human cancers and previously studied in bladder urothelial carcinoma, by immunohistochemistry in 139 UTUC cases, including noninvasive, invasive papillary urothelial carcinoma and urothelial carcinoma in situ. KRT17 expression pattern (basal/negative vs. nonbasal) and H-score were evaluated. The expression pattern was significantly different in normal (NL) compared to malignant urothelium. Nonbasal KRT17 expression was significantly higher in pTa (p<0.001) and invasive (pTinv) (p=0.0023) urothelial carcinoma compared to NL, and in pTinv compared to pTa (p=0.0391). Sensitivity and specificity for distinguishing benign from malignant tumors were 85% and 82, respectively, with an area under the curve of 0.83 (p <0.001). The KRT17 H-score was significantly higher in pTa and pTinv compared to NL (p < 0.001 and p=0.0035, respectively). Sensitivity and specificity for distinguishing benign from malignant carcinoma were 91% and 69%, respectively, with an AUC of 0.81 (p=0.0010). KRT17 was not associated with tumor site, grade, or stage. In summary, K17 is a sensitive and specific marker of neoplastic upper tract urothelium, and its potential use in routine diagnostics should be explored in larger studies.

5179 Uncommon Benign Mimics Of Suspicious Adrenal Nodules

Abstract Disclosure: L. Zhu: None. L. Loh: None. V. Gan: None. P. Kek: None. Introduction: Adrenal incidentaloma is often detected in imaging studies. In addition to biochemical testing, imaging plays a key role in guiding the management of such lesions. We describe two uncommon cases of benign lesions masquerading as suspicious adrenal nodules. Case 1. A 54-year-old man with hypertension, diabetes, dyslipidaemia, ischaemic heart disease and atrial fibrillation (on warfarin) underwent CT scan to exclude malignancy when he presented with thigh DVT, and was found to have a right 3.2cm adrenal nodule. Adrenal hormone profile was unremarkable. CT contrast characterization showed attenuation of 30, 35, and 32 HU on pre-contrast, venous and 10-minute delayed phase respectively. Given the minimal enhancement in high density areas, possible haemorrhage was considered and he was put on imaging surveillance. CT scans over the following 5 years showed stability of the lesion, resolution of high-density areas, and pre-contrast attenuation of -35HU, suggestive of myelolipoma. Further follow-up over the next 2 years then revealed tumour enlargement to 8.5cm, progressive predominance of dense areas (58 HU), and development of compressive symptoms. In view of mass effect, growing heterogeneity and possibility of a collision tumour, right adrenalectomy was performed. Histopathology revealed myelolipoma with extensive haemorrhage and no evidence of malignancy. Case 2. A 65-year-old woman had hypertension, ischaemic heart disease, dialysis-dependent end-stage renal disease secondary to glomerulonephritis, and oncological history of left renal cell carcinoma (RCC) and low-grade papillary urothelial carcinoma, both surgically resected 10 years ago. A new 1.6cm right adrenal nodule was seen on her surveillance CT scan for RCC. It was not present in a CT scan 7 years ago. The nodule displayed suspicious features such as nodular avid rim enhancement, persistent enhancement on delayed phase of contrast washout and central cystic change. Biochemical screening revealed plasma free metanephrine of 0.33 nmol/L (NR: &amp;lt;0.33) and plasma free normetanephrine of 0.99 nmol/L (NR: &amp;lt;0.71). Other adrenal hormone profiles were unremarkable. Cystic phaeochromocytoma was suspected and she underwent right adrenalectomy and nephrectomy following alpha blockade. Histopathology revealed a well-circumscribed nodule in the supra-renal adipose tissue, with vascular proliferation and features of anastomosing haemangioma. The right kidney was reported to have acquired cystic disease associated RCC. She was well post-operatively and remained on follow-up with the urologist for her RCC. Discussion: Haemorrhagic adrenal myelolipoma and supra-renal anatomosing haemangioma are benign lesions that may have CT characteristics similar to those of sinister lesions. Pre-operative diagnosis can be challenging. Surgical excision may be required to confirm diagnosis and exclude malignancy. Presentation: 6/3/2024

8062 Uncommon Presentation of Multiple Myeloma as a Rapidly Growing Thyroid Goiter Initially Thought to be Hashimoto's Thyroiditis

Abstract Disclosure: M.S. Shah: None. S. Humayon: None. K.P. Sanu: None. C. Peñaherrera: None. We present a unique case of an 85-year-old female with rapidly growing anterior neck swelling and subclinical hyperthyroidism, initially suggestive of Hashimoto's thyroiditis. The goiter initially responded well to steroids but rebounded back in size despite two courses of prednisone. This prompted further diagnostic workup which revealed unexpected findings, ultimately leading to the diagnosis of multiple myeloma involving the thyroid parenchyma and lymph nodes. The patient had no history of thyroid disorders or recent upper respiratory tract infections. She exhibited sudden neck swelling, mild subclinical hyperthyroidism, and positive TPO antibodies. Initial fine needle aspiration suggested lymphoid tissue with Hurthle cell differentiation, raising suspicion of Hashimoto's thyroiditis. Flow cytometry supported this diagnosis, but the potential for a Hurthle cell neoplasm persisted. Prednisone temporarily reduced thyroid size, but disease recurrence necessitated surgical excisional and incisional biopsies. Subsequent biopsies revealed plasma cell neoplasms consistent with multiple myeloma. The pathologic report confirmed MYC rearrangement, indicative of multiple myeloma involvement in lymph nodes and thyroid tissue. Protein electrophoresis revealed two restricted bands migrating in the gamma globin region. The patient experienced subclinical hyperthyroidism that evolved into euthyroidism over a month. Incidental findings included non-invasive, low grade papillary urothelial carcinoma. Disease progression was evident in a follow-up PET/CT, prompting oncology consultation. The patient initiated Revlimid with chemotherapy. Levothyroxine was prescribed for postoperative hypothyroidism, with adjustments based on thyroid panel results. This case report illustrates the intricate diagnostic challenges posed by multiple myeloma masquerading as a thyroid disorder. The unexpected evolution of the disease, marked by MYC rearrangement and metastatic spread, emphasizes the need for heightened vigilance in managing such cases. Clinicians should consider alternative diagnoses when treatment efforts fail to provide adequate response. This will ensure timely and appropriate management in clinical practice. This report contributes valuable insights into the diagnostic complexities and multidisciplinary considerations for addressing similar presentations in endocrine and oncology settings. Presentation: 6/1/2024

8062 Uncommon Presentation Of Multiple Myeloma As A Rapidly Growing Thyroid Goiter Initially Thought To Be Hashimoto's Thyroiditis

Abstract Disclosure: M.S. Shah: None. S. Humayon: None. K.P. Sanu: None. C. Peñaherrera: None. We present a unique case of an 85-year-old female with rapidly growing anterior neck swelling and subclinical hyperthyroidism, initially suggestive of Hashimoto's thyroiditis. The goiter initially responded well to steroids but rebounded back in size despite two courses of prednisone. This prompted further diagnostic workup which revealed unexpected findings, ultimately leading to the diagnosis of multiple myeloma involving the thyroid parenchyma and lymph nodes. The patient had no history of thyroid disorders or recent upper respiratory tract infections. She exhibited sudden neck swelling, mild subclinical hyperthyroidism, and positive TPO antibodies. Initial fine needle aspiration suggested lymphoid tissue with Hurthle cell differentiation, raising suspicion of Hashimoto's thyroiditis. Flow cytometry supported this diagnosis, but the potential for a Hurthle cell neoplasm persisted. Prednisone temporarily reduced thyroid size, but disease recurrence necessitated surgical excisional and incisional biopsies. Subsequent biopsies revealed plasma cell neoplasms consistent with multiple myeloma. The pathologic report confirmed MYC rearrangement, indicative of multiple myeloma involvement in lymph nodes and thyroid tissue. Protein electrophoresis revealed two restricted bands migrating in the gamma globin region. The patient experienced subclinical hyperthyroidism that evolved into euthyroidism over a month. Incidental findings included non-invasive, low grade papillary urothelial carcinoma. Disease progression was evident in a follow-up PET/CT, prompting oncology consultation. The patient initiated Revlimid with chemotherapy. Levothyroxine was prescribed for postoperative hypothyroidism, with adjustments based on thyroid panel results. This case report illustrates the intricate diagnostic challenges posed by multiple myeloma masquerading as a thyroid disorder. The unexpected evolution of the disease, marked by MYC rearrangement and metastatic spread, emphasizes the need for heightened vigilance in managing such cases. Clinicians should consider alternative diagnoses when treatment efforts fail to provide adequate response. This will ensure timely and appropriate management in clinical practice. This report contributes valuable insights into the diagnostic complexities and multidisciplinary considerations for addressing similar presentations in endocrine and oncology settings. Presentation: 6/1/2024

A RARE CASE OF COEXISTING BLADDER SMALL CELL NEUROENDOCRINE CARCINOMA AND PROSTATE ADENOCARCINOMA: CASE REPORT AND LITERATURE REVIEW

Objective: We present a case of synchronous malignancies of rare bladder small cell neuroendocrine carcinoma (SCNC) and prostate adenocarcinoma and provide literature review of bladder SCNC. Case(s) presentation: A 72-year-old male smoker presented with 3 months history of gross hematuria. Ultrasonography showed a large hypoechoic mass in the right bladder. TURBT was performed and histopathology of the TURBT specimen showed a high-grade papillary urothelial carcinoma. Abdominal contrast-enhanced computed tomography (CECT) demonstrated an isodense heterogenous undefined mass, with irregular border at right anterolateral side of bladder wall. Radical cystoprostatectomy, bilateral radical lymph node dissection and bilateral ureterocutaneostomy was performed. Histopathology and immunohistochemical examination after radical cystoprostatectomy revealed bladder small cell neuroendocrine carcinoma coexisting with prostate adenocarcinoma (Gleason score 3+3=6, group 1). The patient eventually succumbed to disease after having symptomatic disease progression and metastatic disease five months after the surgery. Discussion: Bladder SCNC is a rare malignancy with an incidence of 1–9/1,000,000 reported. This tumor has an aggressive clinical course with high incidence of metastasis, and it tends to confer dismal prognosis. No specific clinical symptom exists. Histopathological recognition and immunohistochemistry is required to differentiate this rare entity. Conclusion: Clinicians and pathologists should be alert to the possibility of bladder SCNC despite extremely scarce incidence. Keywords: Bladder cancer, small cell neuroendocrine carcinoma, synchronous malignancy, case report.

Immunophenotypic and molecular changes during progression of papillary urothelial carcinoma.

Urothelial carcinoma has various molecular subtypes, each with different tumor characteristics. Although it is known that molecular changes occur during tumor progression, little is known about the specifics of these changes. In this study, we performed transcriptional analysis to understand the molecular changes during tumor progression. Formalin-fixed, paraffin-embedded tumor tissues were obtained from 12 patients with muscle-invasive bladder cancer (MIBC). The invasive and non-invasive papillary areas were identified in papillary urothelial carcinoma specimens. Immunohistochemistry (IHC) and mRNA sequencing were performed for each tumor area. Patients with CK5/6-negative and CK20-positive non-invasive papillary areas were selected and classified into the IHC switch subgroup (CK5/6-positive and CK20-negative in the invasive area) and the IHC unchanged subgroup (CK5/6-negative and CK20-positive in the invasive area) according to the IHC results of the invasive area. We identified differences in the mRNA expression between the non-invasive papillary and invasive areas of the papillary MIBC tissue samples. In both the non-invasive papillary and invasive areas, the IHC switch subgroup showed basal subtype gene expression, while the IHC unchanged subgroup demonstrated luminal subtype gene expression. The non-invasive papillary area showed a gene expression pattern similar to that of the invasive area. Therefore, even if the non-invasive papillary area exhibits a luminal phenotype on IHC, it can have a basal subtype gene expression depending on the invasive area.

KRT18 as a Novel Biomarker of Urothelial Papilloma while Evaluating Low-Grade Papillary Urothelial Neoplasms: Bi-Center Analysis.

Although urothelial papilloma (UP) is an indolent papillary neoplasm that can mimic the morphology of low-grade papillary urothelial carcinoma (PUC), there is no immunomarker to differentiate reliably these two entities. In addition, the molecular characteristics of UP are not fully understood. We conducted an in-depth proteomic analysis of papillary urothelial lesions (n = 31), including UP and PUC along with normal urothelium. Protein markers distinguishing UP and PUC were selected with machine learning analysis, followed by internal and external validation using immunohistochemistry. In the proteomic analysis, UP and PUC showed overlapping proteomic profiles. We identified EHD4 and KRT18 as candidate diagnostic biomarkers of UP. Through immunohistochemical validation in two independent cohorts (n = 120), KRT18 was suggested as a novel UP diagnostic marker, able to differentiate UP from low-grade PUC. We also found that 3.5% of patients with UP developed urothelial carcinoma in subsequent resections, supporting the malignant potential of UP. KRT18 downregulation was significantly associated with UPs subsequently progressing to urothelial carcinoma, following their initial diagnosis. This is the first study that successfully revealed UPs comprehensive proteomic landscape, while it also identified KRT18 as a potential diagnostic biomarker of UP.

PAX8 expression in cancerous and non-neoplastic tissue: a tissue microarray study on more than 17,000 tumors from 149 different tumor entities

PAX8 plays a role in development of the thyroid, kidney, and the Wolffian and Mullerian tract. In surgical pathology, PAX8 immunohistochemistry is used to determine tumors of renal and ovarian origin, but data on its expression in other tumors are conflicting. To evaluate PAX8 expression in normal and tumor tissues, a tissue microarray containing 17,386 samples from 149 different tumor types and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. PAX8 results were compared with previously collected data on cadherin 16 (CDH16). PAX8 positivity was found in 40 different tumor types. The highest rate of PAX8 positivity was found in thyroidal neoplasms of follicular origin (98.6–100%), gynecological carcinomas (up to 100%), renal tumors (82.6–97.8%), and urothelial neoplasms (2.3–23.7%). Important tumors with near complete absence of PAX8 staining (< 1%) included all subtypes of breast cancers, hepatocellular carcinomas, gastric, prostatic, pancreatic, and pulmonary adenocarcinomas, neuroendocrine neoplasms, small cell carcinomas of various sites, and lymphomas. High PAX8 expression was associated with low tumor grade in 365 non-invasive papillary urothelial carcinomas (p < 0.0001) but unrelated to patient outcome and/or tumor phenotype in clear cell renal cell carcinoma, high-grade serous ovarian cancer, and endometrioid endometrial carcinoma. For determining a renal tumor origin, sensitivity was 88.1% and specificity 87.2% for PAX8, while sensitivity was 85.3% and specificity 95.7% for CDH16. The combination of PAX8 and CDH16 increased specificity to 96.8%. In conclusion, PAX8 immunohistochemistry is a suitable diagnostic tool. The combination of PAX8 and CDH16 positivity has high specificity for renal cell carcinoma.

The effect of intravesical chemohyperthermia with mitomycin in non-muscle-invasive bladder tumour patients who cannot tolerate BCG treatment or recur after treatment and refuse cystectomy.

Many patients receiving intravesical BCG treatment for non-muscle-invasive bladder cancer experience high recurrence rates despite initial adequate response. In this study, the effectiveness of intravesical chemohyperthermia (CHT) with mitomycin C (MMC) was evaluated in patients who developed relapse after intravesical BCG treatment or could not tolerate the treatment and could not undergo radical cystectomy for any reason. 59 patients who underwent complete bladder tumour resection, who had a T1 high-grade tumour and no variant histology was observed in the pathology, and who had previously received intravesical BCG treatment were included in the study. Adjuvant treatment with intravesical CHT-MMC was applied. As a treatment protocol, induction was applied once a week for 6weeks, followed by maintenance treatment 6 times at 4-week intervals. Each treatment session, it involved bladder wall hyperthermia with a temperature of up to 42℃ ± 2 and intravesical administration of 20mg/50ml MMC solution twice at 30-min intervals. Recurrence-free survival after warm mitomycin was 58.7 and 48%, respectively, at 24months and 44months, and progression-free survival was 72.6 and 66.2%, respectively. In the subgroup analysis performed according to the number of tumours at diagnosis (single, 2-5, more than 5), recurrence-free survival rates were 81.8%, 48.2% and 11%, respectively, during the median follow-up period of 44months. Intravesical CHT-MMC can be considered as an alternative treatment in selected well-informed patients with non-muscle-invasive papillary urothelial carcinoma who are unresponsive to BCG or intolerant to BCG. Prospectively designed studies with larger number of patients are needed.

Quantitative proteomics and immunohistochemistry uncover NT5DC2 as a diagnostic biomarker for papillary urothelial carcinoma

The accurate diagnosis of papillary urothelial carcinoma (PUC) is frequently challenging due to benign mimickers. Other than morphology-based diagnostic criteria, reliable biomarkers for differentiating benign and malignant papillary urothelial neoplasms remain elusive, so we sought to discover new markers to address this challenge. We first performed tandem mass spectrometry-based quantitative proteomics using diverse papillary urothelial lesions, including PUC, urothelial papilloma (UP), inverted urothelial papilloma, and cystitis cystica. We prioritized potential diagnostic biomarkers using machine learning, and subsequently validated through immunohistochemistry (IHC) in two independent cohorts. Metabolism, transport, cell cycle, development, and immune response functions were differentially enriched between malignant and benign papillary neoplasms. RhoB and NT5DC2 were shortlisted as optimal candidate markers for PUC diagnosis. In our pilot study using IHC, NT5DC2 was subsequently selected as its expression consistently differed in PUC (p = 0.007). Further validation of NT5DC2 using 49 low-grade (LG) urothelial lesions, including 15 LG-PUCs and 17 UPs, which are the most common mimickers, concordantly revealed lower IHC expression levels in LG-PUC (p = 0.0298). Independent external validation with eight LG-PUCs and eight UPs confirmed the significant downregulation of NT5DC2 in LG-PUC (p = 0.0104). We suggest that NT5DC2 is a potential IHC biomarker for differentiating LG-PUC from its benign mimickers, especially UP.

Low-Grade Urothelial Neoplasia

This chapter reviews the clinical, histopathologic, and cytologic features of low-grade urothelial neoplasia, including urothelial papilloma, papillary urothelial neoplasm of low malignant potential, and low-grade papillary urothelial carcinomas. An overview of various surgical pathology and cytology classification systems, diagnostic criteria, and common molecular alterations will be reviewed.

Cytomorphological characteristics of low-grade papillary urothelial carcinoma in voided urine samples: Distinction from benign and high-grade papillary urothelial carcinoma.

Given its frequent recurrence and the potential for high-grade transformation, accurate diagnosis of low-grade papillary urothelial carcinoma (LGPUC) in urine cytology is clinically important. We attempted to identify cytomorphologic features in urine samples, which could be helpful for the identification of LGPUC. We conducted a retrospective review of voided urine specimens collected from patients with histopathologic diagnoses of LGPUC. Their cytomorphological features were compared with those from patients with benign conditions and high-grade papillary urothelial carcinoma (HGPUC). A total of 115 voided urine specimens were evaluated, including 30 benign, 41 LGPUC, and 44 HGPUC cases. In LGPUC, 18 cases (44%) were diagnosed as atypical, a proportion significantly higher than that observed in benign cases (4 cases, 13%), while the remaining 23 cases (56%) were diagnosed as negative. LGPUC urine samples tended to have higher cellularity than benign cases, but the difference was not statistically significant. Three cytological features, namely nuclear enlargement, higher nuclear-to-cytoplasmic (N/C) ratio, and presence of small cell clusters, were statistically more prevalent in LGPUC compared to benign cases, although the changes were relatively subtle. In contrast, cytomorphological distinction between LGPUC and HGPUC was evident, as high cellularity, nuclear enlargement, hyperchromasia, high N/C ratio, irregular nuclear membrane, and apoptosis were significantly more prevalent in HGPUC cases. Several cytomorphologic features in voided urine samples were more prevalent in cases with LGPUC, albeit not observed in all instances. Since these alterations were relatively subtle, meticulous attention to these cytomorphologic details is crucial to suggest the possibility of LGPUC.

A case report of MiNEN: concomitant primary small-cell neuroendocrine carcinoma and high-grade papillary urothelial carcinoma of the urinary badder. Composite or Collision Tumor?

Bladder cancer is the tenth most diagnosed cancer worldwide, and urothelial carcinoma is the most common histologic type. On the contrary, small primary cell neuroendocrine carcinoma of the bladder is sporadic and accounts for less than 1% of all bladder tumors. These malignancies can be observed in mixed neuroendocrine/non-neuroendocrine neoplasms (MiNENs), which have been studied more in the gastrointestinal tract and lungs but scarcely in this organ due to their low incidence. There are concerns about the pathogenic connection between these two tumors, and the limited evidence accounts for the lack of consensus regarding prognosis and treatment for these patients; therefore, they may need a multimodal approach. Here, we describe the case of a 63-year-old woman who presented with gross hematuria, weight loss, and hypogastric discomfort for the past five months. An intravesical mass was found, and transurethral resection was performed. The Histopathology revealed a high-grade papillary urothelial carcinoma with an invasive component through muscularis propria of the bladder, so she was taken to radical cystectomy with extended pelvic lymphadenectomy. The final pathology report revealed an accompanying primary small cell neuroendocrine carcinoma intermingled with the urothelial one. She received postoperative adjuvant chemotherapy and finally died six months after surgery.

Ventral corporal reinforcement using a pericardium allograft (Tutoplast®) in a patient undergoing urethrectomy procedure with an inflatable penile prosthesis in place: A case report

AbstractBackgroundErectile dysfunction is a common consequence following radical cystectomy (RC), with inflatable penile prostheses (IPPs) placement considered as the gold standard for refractory cases. Urethral recurrence post‐RC necessitates urethrectomy, which poses challenges for patients with an IPP in place. The thinning of the ventral tunica albuginea during urethrectomy may increase the risk of corporal disruption and IPP cylinder aneurysm, affecting device functionality. This case report introduces a novel surgical technique using Tutoplast, a human‐derived pericardium allograft, for corporal reinforcement during urethrectomy in the presence of an in‐situ IPP.MethodsA 74‐year‐old male, with a history of robotic‐assisted RC and IPP presented with recurrent bleeding per urethra. Imaging revealed urethral masses. The patient underwent total urethrectomy which resulted in significant thinning of the ventral tunica albuginea. To prevent device aneurysm or mechanical failure, a Tutoplast graft was used intraoperatively to reinforce the thinned tunica. Patient was followed up six months postoperatively.ResultsFinal pathology showed urethral high‐grade papillary urothelial carcinoma. Postoperatively, the patient exhibited smooth recovery, with normal IPP functionality up to the 6‐month follow‐up period. While Tutoplast has been used in other settings, its application in preventing IPP malfunction posturethrectomy is a unique contribution.ConclusionCorporal reinforcement using Tutoplast during urethrectomy in patients with an existing IPP presents a simple and cost‐effective solution to mitigate the risks of corporal disruption and IPP cylinder aneurysms. The positive outcomes demonstrated in this case report warrant further studies on larger patient populations and longer follow‐up periods to assess the long‐term outcomes of this technique.

A histopathological and epidemiological study of urothelial carcinoma at a tertiary care centre in Peshawar, Pakistan

Bladder cancer is the ninth leading cause of death worldwide and 14th leading cause of death in Pakistan. The objective of this study was to determine the frequency of urothelial carcinoma in various age groups, its gender distribution, and grades. A total of 131 cases of urothelial carcinoma, received at Department of Pathology, Peshawar Medical College, Peshawar, between January 2017 to December 2022, were included in the study; of them 107 (81.6%) were males while 24 (18.3%) were females with a mean age of 62±13 years. The most common histological subtype was papillary urothelial carcinoma in 117(89.3%) cases, followed by Squamous and Glandular in 5(3.8%) cases. Majority of the urothelial carcinoma with high grade showed a statistically significant relation with muscle invasion (n=38, 50.66%). Males were four times more likely to have urothelial carcinoma while older age groups were more likely to have high grade urothelial carcinoma. Keywords: Carcinoma, Urinary bladder, Cancer, Neoplasm, Urothelial.

Abstract A018: A case of Buschke-Löwenstein tumor with superimposed infection and associated urothelial carcinoma

Abstract The Giant Condyloma Acuminata (GCA), the Buschke-Löwenstein tumor, is a rare and challenging pathology with a less than 0.1% prevalence. This disease is often considered a transitional phase between condyloma acuminatum and squamous cell carcinoma, potentially representing a variant of verrucous carcinoma. Despite its initially benign histological presentation, GCA can evolve into expansive papillomatous proliferations that deeply invade underlying tissues. Studies indicate that GCA may transform into invasive squamous cell carcinoma in 8.5-23.8% of cases. The strong correlation between GCA and human papillomavirus (HPV) infections, particularly subtypes 6 and 11, underscores the role of viral factors in developing this condition. The presented case involves a 57-year-old male with pre-existing medical conditions, including hypertension and diabetes mellitus, who sought emergency care due to escalating suprapubic and penile discomfort. A biopsy of the genital warts identified condyloma acuminatum with an overlying bacterial infection of Proteus mirabilis. Concurrently, pathology identified anogenital squamous cell carcinoma. Notably, the patient had no associated sexually transmitted infections and no prior immunocompromised status. Imaging studies revealed a multilobulated soft tissue mass in the pelvis with prostatic invasion and enlarged lymph nodes. Further investigations, including a transurethral resection of bladder tumor (TURBT), revealed multiple tumor deposits in the bladder, penile lesion, and suprapubic papule. Pathological examinations indicated non-invasive and invasive papillary urothelial carcinoma as well as invasive squamous cell carcinoma in different locations. The tumor was staged as pathologic IIIB T2N3M0, and a collaborative decision between Urology and Oncology teams led to the initiation of neoadjuvant chemotherapy with TIP (cisplatin, ifosfamide, and paclitaxel). The patient underwent the initial chemotherapy cycle with subsequent cycles scheduled every three weeks. Management options for GCA include radiotherapy, cryosurgery, CO2 laser surgery, systemic chemotherapy, and radical surgical excision. While radiotherapy has shown successful outcomes, concerns about anaplastic transformations and post-treatment condylomas make its utilization contentious. The absence of unequivocal guidelines for radiotherapy dosage and fractionation has led to considerations of alternative modalities, but the primary approach remains radical surgical excision. The risk of recurrence remains high due to potential tumor cell spillage during surgery. In conclusion, this case report highlights an advanced manifestation of the Buschke-Löwenstein tumor coexisting with multiple HPV infections. The complexity of GCA and the lack of consensus on optimal therapeutic strategies emphasize the need for timely diagnosis and intervention to ensure favorable prognoses. Various treatment paradigms exist in medical literature, but their efficacy varies, reflecting the ongoing challenges in managing this rare and clinically intricate condition. Citation Format: Aliya M. Khan, Sophia Navajas, Mehmet Hepgur, Samuel A. Kareff. A case of Buschke-Löwenstein tumor with superimposed infection and associated urothelial carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A018.

Case Report: Urothelial urethral carcinoma in HIV patient underwent total urethrectomy and perineal urethrostomy

Introduction HIV affects over 38 million people worldwide, affecting the immune system and leading to symptoms like fever, lymphadenopathy, and sore throat. High viral loads can lead to opportunistic infections and tumors. The life expectancy of HIV patients has increased due to high-efficiency combination anti-retroviral therapy. Urothelial carcinoma, a malignant development, damages the urinary canal lining. The connection between HIV and urinary cancers is unclear, the aims of this study to report a case of urethral urothelial Carcinoma in HIV patient who underwent total urethrectomy and perineal urethrostomy. Case presentation A 34-year-old male patient with a papilliferous lump on the glans penis for over six months was admitted to the hospital. Preoperative screening revealed HIV and a urethral mass was found. A partial urethrectomy was performed, revealing high grade papillary urothelial Carcinoma. Five months after surgery, the patient developed a recurrent lump, requiring a total urethrectomy, TUR (transurethral resection) of the mass in the prostatic urethra, and perineal urethrostomy. Conclusion Primary carcinoma of the urethra in HIV patient is an extremely rare case. To date, there is no consensus on the primary urethral carcinoma therapy. The treatment of primary urethral carcinoma is tailored specifically to the patient based on the location, histology, and stage of the carcinoma.

Outcome Analysis of a Series of Mixed-Grade, Non-muscle Invasive, Papillary Carcinomas of the Bladder.

Introduction. Papillary urothelial carcinomas are currently graded as either low- or high-grade tumors based on World Health Organization (WHO) 2022 guidelines for genitourinary tumors. However, a minority of tumors are mixed-grade tumors, composed predominantly of low-grade cancer with a minor high-grade component. In the 2022 WHO these cancers are recognized as having outcomes comparable to low-grade cancers, although data to date has been limited. Methods. The pathology records of a large academic institution were searched for mixed-grade, non-muscle invasive papillary carcinomas of the bladder and ureter in order to characterize prognosis of these cancers. Results. Of 136 cancers, the majority (n = 104, 76.5%) were solitary, mixed-grade tumors, while 21 (15.4%) had a concurrent low-grade cancer and 11 (8.1%) had multiple mixed-grade tumors at the time of diagnosis. At follow-up (median 48.3 months, range = 1.3 months-18.1 years), 71 cancers recurred (52.2%): 52 (38.2%) as low- or mixed-grade cancers and 18 (13.2%) as high-grade cancers. There were no instances of stage-progression to >pT2. Conclusions. The clinical outcome of mixed-grade carcinomas was similar to what has been reported for low-grade carcinomas. Based on our results, and prior congruent studies of mixed-grade lesions, these lesions may be regarded as a distinct sub-category with a better prognosis than high-grade tumors.

Spatial Distribution of Macrophage and Lymphocyte Subtypes within Tumor Microenvironment to Predict Recurrence of Non-Muscle-Invasive Papillary Urothelial Carcinoma after BCG Immunotherapy.

Non-muscle-invasive papillary urothelial carcinoma (NMIPUC) of the urinary bladder is the most common type of bladder cancer. Intravesical Bacille Calmette-Guerin (BCG) immunotherapy is applied in patients with a high risk of recurrence and progression of NMIPUC to muscle-invasive disease. However, the tumor relapses in about 30% of patients despite the treatment, raising the need for better risk stratification. We explored the potential of spatial distributions of immune cell subtypes (CD20, CD11c, CD163, ICOS, and CD8) within the tumor microenvironment to predict NMIPUC recurrence following BCG immunotherapy. Based on analyses of digital whole-slide images, we assessed the densities of the immune cells in the epithelial-stromal interface zone compartments and their distribution, represented by an epithelial-stromal interface density ratio (IDR). While the densities of any cell type did not predict recurrence, a higher IDR of CD11c (HR: 0.0012, p-value = 0.0002), CD8 (HR: 0.0379, p-value = 0.005), and ICOS (HR: 0.0768, p-value = 0.0388) was associated with longer recurrence-free survival (RFS) based on the univariate Cox regression. The history of positive repeated TUR (re-TUR) (HR: 4.93, p-value = 0.0001) and T1 tumor stage (HR: 2.04, p-value = 0.0159) were associated with shorter RFS, while G3 tumor grade according to the 1973 WHO classification showed borderline significance (HR: 1.83, p-value = 0.0522). In a multivariate analysis, the two models with a concordance index exceeding 0.7 included the CD11c IDR in combination with either a history of positive re-TUR or tumor stage. We conclude that the CD11c IDR is the most informative predictor of NMIPUC recurrence after BCG immunotherapy. Our findings highlight the importance of assessment of the spatial distribution of immune cells in the tumor microenvironment.