Plasmacytoid Urothelial Carcinoma Research Articles

Plasmacytoid urothelial carcinoma: a rare cause of localized lymphedema

Localized lymphedema of the genital region is arare medical condition. It is named primary lymphedema if caused by acongenital malformation of the lymphatic system. Secondary lymphedemas might be induced by exogenous damage to lymphatic vessels as aresult of surgical interventions, obesity, filariasis, radiotherapy or malignancy. We report acase of localized lymphedema of the genial region for which apreviously unknown urothelial carcinoma turned out to be the underlying cause.

Plasmacytoid urothelial carcinoma of the urinary bladder–A clinicopathological and molecular analysis of 52 cases

Plasmacytoid urothelial carcinoma (UC) is a rare histologic subtype of bladder cancer that is associated with an aggressive clinical behavior. We analyzed the clinicopathologic and molecular features of plasmacytoid UC in 52 patients from a single institute. The patients included 44 men and 8 women, with a mean age of 64 years (range, 41–91 years). All bladder cancers were high-grade UC, and plasmacytoid component accounted for a mean of 47% of bladder tumors (range, 5–100%). Distinct gene mutations were found in most plasmacytoid UCs (n = 49); the most common mutations were TP53 (n = 30), followed by TERT (n = 20), and CDH1 (n = 18). Copy number analysis was performed in 34 patients, and 13 of them showed copy number variations. Expression of HER2 was analyzed in 18 patients by immunohistochemistry, and 3 of them showed HER2 overexpression, which was confirmed by fluorescence in situ hybridization analysis. Thirty-two patients died of disease in a median of 15 months (range, 1–45 months). No individual gene mutations were significantly associated with clinical outcome, but mutations in the mammalian target of rapamycin (mTOR) pathway, including PICK3CA and PIK3R1 mutations, were associated with a significantly shorter survival duration (p < 0.05). Plasmacytoid UC is an aggressive histologic subtype that demonstrates frequent somatic gene mutations and CNVs, which may underlie its oncogenesis and progression. Gene mutations of the mTOR pathway are associated with poor outcome in a subset of patients with plasmacytoid UC.

Abstract 4632: Lineage plasticity as a determinant of antibody-drug conjugate target expression in urothelial bladder cancer

Abstract Bladder cancers display a wide spectrum of morphologies that frequently co-exist within individual tumors. Several histologic variants, including plasmacytoid, neuroendocrine, and micropapillary subtypes, are associated with an increased bladder cancer recurrence risk and cancer-specific mortality. The molecular basis and therapeutic implications of this phenotypical plasticity remain poorly understood. Enfortumab vedotin (EV), an antibody-drug conjugate targeting Nectin-4, has also emerged as a new standard-of-care for metastatic bladder cancer patients, but the association between lineage plasticity as manifested by morphologic heterogeneity in bladder cancer, Nectin-4 expression and ADC response remains poorly defined. Previous DNA-based molecular profiling studies of histologic variants revealed that CDH1 mutations were the pathognomonic molecular alteration in plasmacytoid urothelial carcinoma, but no recurrent driver mutations have been found to be unique to the aberrant histology regions of other mixed histology subtypes. Thus, to explore the molecular basis for the lineage plasticity of bladder cancers with aberrant histology and to define the association between lineage plasticity manifested as morphologic heterogeneity and the expression of Nectin-4, HER2 and other potential ADC targets, we performed RNA-seq of pure urothelial carcinomas (n=118, not otherwise specified, UC-NOS) and bladder tumors with divergent differentiation or histologic subtypes (n=199). Our cohort included a subset of tumors in which RNA-seq was performed on microdissected UC-NOS and variant histology regions of the same tumor. Tumors with neuroendocrine, sarcomatoid and squamous histology had the lowest Nectin-4 expression, whereas histologic subtypes that retained a luminal transcriptional profile such as micropapillary, plasmacytoid and nested histology had higher levels of Nectin-4 expression. In mixed histology tumors, Nectin-4 and/or HER2 expression was often restricted to only one of the two histologic components. Gene Set Enrichment Analysis noted enrichment of distinct oncogenic pathway gene sets in different histologic variants. Preliminary investigation into the mechanism(s) of Nectin-4 regulation using bladder cancer cell lines and patient-derived organoids (PDOs) has identified targetable pathways which when inhibited revert lineage plasticity and induce Nectin-4 expression. In sum, lineage plasticity manifested as heterogenous histomorphologies was associated with heterogeneous Nectin-4 expression in some but not all histologic variants of bladder cancer. Ongoing studies using PDOs from bladder cancer patients with mixed histology will seek to identify molecular pathways whose inhibition leads to increased expression of Nectin-4 or other ADC targets such as HER2 and thus increased sensitivity of ADCs targeting these cell surface proteins. Citation Format: Jiaqian Luo, Sizhi P. Gao, Fengshen Kuo, Gamze Gokturk Ozcan, Merve Basar, Florestan Koll, Jacob E. Tallman, Syed M. Alam, Carissa E. Chu, Ziyu Chen, Eugene J. Pietzak, Gopakumar Iyer, Jonathan E. Rosenberg, David B. Solit, Hikmat Al-Ahmadie. Lineage plasticity as a determinant of antibody-drug conjugate target expression in urothelial bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4632.

Metastatic Pleomorphic Lobular Carcinoma of the Breast to the Urinary Bladder: A Report of 10 Cases and Assessment of TRPS1 in the Differential Diagnosis With Plasmacytoid Urothelial Carcinoma.

Metastatic pleomorphic lobular carcinoma (MPLC) to the bladder is rare and has considerable histologic and immunohistochemical overlap with plasmacytoid urothelial carcinoma (PUC). To distinguish MPLC from PUC morphologically and immunohistochemically, including a newer marker, TRPS1. Ten MPLCs to the bladder were reassessed and stained with estrogen, progesterone, and androgen receptors; GATA3; keratin 5/6; HMWK; GCDFP-15; and TRPS1. Sixteen PUCs constituted controls. We studied 4 transurethral resections of bladder tumors and 6 biopsies from 10 women (median age, 69 years) who had breast cancer on average 15 years prior. Microscopic patterns included single cells and cords of cells (n = 4), nests/sheets of dyscohesive cells (n = 2), or both (n = 4). All tumors had cells with voluminous eosinophilic cytoplasm and eccentric nuclei mimicking PUC, and 7 of 10 tumors had signet ring cells. MPLCs were positive for estrogen (8 of 10), progesterone (3 of 7), and androgen receptors (4 of 10); GCDFP-15 (7 of 10); GATA3 (9 of 10); HMWK (7 of 8); and TRPS1 (7 of 10). No MPLCs stained for keratin 5/6 (n = 9). Of 16 PUCs, 2 showed faint and 2 demonstrated strong TRSP1 staining; 7 of 16 were negative for p63. MPLC to bladder often presents in patients with a remote history of breast cancer, exhibiting significant histologic and immunohistochemical overlap with PUC. Based on prior works and the current study, estrogen receptor (particularly SP-1), mammaglobin, and p63 help differentiate MPLC from PUC. Keratin 5/6 may aid in distinguishing a less frequent basal type PUC because it is typically negative in MPLC. Some PUCs express TRPS1. Caution should be exercised because immunophenotypes of these tumors greatly overlap, and ramifications of misclassification are major.

Plasmacytoid bladder cancer: a rare case report.

The authors report a case of a patient with locally advanced plasmacytoid urothelial carcinoma (PUC) of the bladder. A 71-year-old man with a history of chronic obstructive pulmonary disease presented with gross hematuria. The rectal examination revealed a fixed bladder base. A computed tomography scan showed a pedunculated lesion arising from the anterior and left lateral bladder wall and extended to the perivesical fat. The patient underwent transurethral resection of the tumor. The histologic examination revealed the presence of muscle-invasive PUC of the bladder. The decision of the multidisciplinary consultation meeting was to do palliative chemotherapy. Thus, the patient could not receive systemic chemotherapy and died 6 weeks after transurethral resection of the bladder tumor. A plasmacytoid variant of urothelial carcinoma is a rare subtype of urothelial carcinoma that has a poor prognosis with a high mortality rate. The disease is usually diagnosed at an advanced stage. Given the rarity of plasmacytoid bladder cancer, treatment guidelines are not clear; therefore, more aggressive treatment may be required. PUC of the bladder is characterized by high aggressiveness, an advanced stage at the time of diagnosis, and a poor prognosis.

Impact of surgical margin and extent of lymphadenectomy on oncologic outcomes in plasmacytoid urothelial carcinoma.

Guideline recommendations disagree on template boundaries for pelvic lymph node dissection (PLND) in conventional urothelial carcinoma. Less is known about PLND in variant histology. We aimed to analyze the role of LND in plasmacytoid urothelial carcinoma (PUC). A retrospective review of patients with cTanyNanyM0 PUC who underwent radical cystectomy (RC) with PLND was performed from 2012 to 2022. Lymph node count (LNC) was a surrogate for extent of lymph node dissection and dichotomized based on maximally selected rank statistics. Multivariable cox hazard regression analysis (MVA) for overall survival (OS) corrected for age, perioperative chemotherapy, soft tissue margin status, and stage ≥pT3 and/or pN+ was performed. Disease free survival (DFS) and OS were estimated using Kaplan-Meier (KM) analysis. Sixty-seven patients with median age of 71, who were 79.1% male were included. Neoadjuvant and adjuvant chemotherapy were administered in 61.2% and 19.4% of patients, respectively. At RC, 70.1% were ≥pT3. Median LNC was 22 (IQR 14-27) with 43.3% of patients being pN+. Calculated optimal-LNC cut point for DFS and OS was 19. Grouping by optimal (≥20) vs. suboptimal-LNC (<20), no significant clinicodemographic differences were found. Optimal-LNC provided improved DFS (P = 0.05) and OS (P = 0.02). Optimal-LNC (HR 0.47, 0.24-0.93 CI 95%, P = 0.03) and negative soft tissue margin (HR 0.38, 0.19-0.76 CI 95%, P = 0.01) was associated with improved OS on MVA. Receipt of perioperative chemotherapy did not improve OS (P = 0.46). In PUC, complete surgical extirpation achieving negative soft tissue margins and removing ≥20 lymph should be prioritized if operative intervention is pursued.

Plasmacytoid urothelial carcinoma - A clinicopathological case series of an aggressive variant of urothelial cancer.

Many new morphological variants of urothelial carcinoma of urinary bladder have been described in the literature, plasmacytoid/signet ring cell/diffuse variant being one of the rare amongst these. Till date, no case series has been reported from India, describing this variant. We retrospectively analyzed the clinicopathological data of 14 patients diagnosed at our center with plasmacytoid urothelial carcinoma. Seven cases (50%) were pure forms while the remaining 50% of cases had a concurrent conventional urothelial carcinoma component. Immunohistochemistry was performed to rule out other mimickers of this variant. Treatment-related data were available for seven patients, while follow-up was available for nine cases. Overall, plasmacytoid variant of urothelial carcinoma is considered to be an aggressive tumor with poor prognosis.

The Role of Immunohistochemistry in the Distinction of Invasive Plasmacytoid Urothelial Carcinoma from its Histologic Mimics

The Role of Immunohistochemistry in the Distinction of Invasive Plasmacytoid Urothelial Carcinoma from its Histologic Mimics

Molecular characterization of plasmacytoid urothelial carcinoma and the impact on treatment implications

Bladder cancer researchers and clinicians have increasingly viewed tumor biology through the lens of genomic and molecular alterations, drastically improving our knowledge of the underlying disease biology. This understanding has led to significant advances in treatment options that allow implementation of a personalized approach to cancer treatment. Large-scale genomic studies initially focused on the most common forms of bladder cancer. However, as genomic and molecular technologies become more widespread and are applied to less common variant histologies, we are gaining additional insight into the unique molecular and genomic characteristics driving the biology of variant histologies of bladder cancer. In this review, we summarize the current state of knowledge of molecular alterations underlying the distinct tumor biology of plasmacytoid urothelial carcinoma and how these alterations may impact treatment options.

Pleural fluid metastasis of plasmacytoid urothelial carcinoma in comparison to micropapillary and conventional high-grade urothelial carcinoma: Cytologic and immuonohistochemical findings.

Plasmacytoid urothelial carcinoma (PUC) is a rare but clinically aggressive variant of high-grade urothelial carcinoma (HGUC). Cytological features include single plasmacytoid neoplastic cells with N:C ratio around 0.5, eccentric nuclei, nuclear hyperchromasia, irregular nuclear membrane, and vacuolated cytoplasm. Micropapillary urothelial carcinoma (MPUC) is another clinically aggressive variant of HGUC that shares some overlapping features of PUC. The diagnosis of these two aggressive variants in pleural effusions can be challenging due to features mimicking adenocarcinoma, unusual immunochemistry profile, and confusion with differential diagnoses, especially when pertinent clinical information is unavailable. We present report on one case each of pleural fluid metastasis of PUC and MPUC respectively, and compare the findings with that of a metastatic conventional HGUC originally thought to be metastatic adenocarcinoma. The diagnosis of PUC was confirmed with immunohistochemical studies showing expression for cytokeratin, GATA-3, uroplakin II, and CD138, diminished or loss of E-cadherin membranous expression, negative expression for p63, p53, Epicam-BerEP4, Epicam-MOC31, and p120. The diagnosis of MPUC was confirmed with immunostain profile similar to that of PUC except positive stain for E-cadherin, p120, and p53. The diagnosis of HGUC was confirmed with immunohistochemical studies showing expression for cytokeratin, GATA-3, uroplakin II, p63, Epicam-BerEP4 (focal weak), and Epicam-MOC31. Our cases of metastatic urothelial carcinoma showed features mimicking adenocarcinoma and others, especially the MPUC and HGUC were diagnosed without prior tissue diagnosis of urothelial carcinoma. This report emphasizes the cytohistological and immunohistochemical details of urothelial carcinoma involving effusion fluid and discusses potential pitfalls in diagnosis.

Clinically undetected plasmacytoid urothelial carcinoma of the urinary bladder with non-mass-forming metastases in multiple organs: an autopsy case.

This case report outlines a clinically undetected urinary bladder plasmacytoid urothelial carcinoma (PUC) with multiple metastases detected at autopsy. An 89-year-old man presented with edema in the lower limbs. Pleural fluid cytology revealed discohesive carcinomatous cells, although imaging studies failed to identify the primary site of tumor. The patient died of respiratory failure. Autopsy disclosed a prostate tumor and diffusely thickened urinary bladder and rectum without distinct tumorous lesions. Histologically, the tumor consisted of acinar-type prostate adenocarcinoma with no signs of metastasis. Additionally, small, plasmacytoid tumor cells were observed in the urinary bladder/rectum as isolated or small clustering fashions. These metastasized to the lungs, intestine, generalized lymph nodes in a non-mass-forming manner. Combined with immunohistochemical studies, these tumor cells were diagnosed PUC derived from the urinary bladder. Both clinicians and pathologists should recognize PUC as an aggressive histological variant, which can represent a rapid systemic progression without mass-forming lesions.

Plasmacytoid urothelial carcinoma of the bladder: MRI features and their association with survival.

Plasmacytoid urothelial carcinomas (PUC) of the bladder are rare variants known for diffuse and infiltrative spread, however their magnetic resonance imaging (MRI) features are not well established. We aimed to evaluate MRI features of PUC of the bladder and their association with survival. This retrospective single-center study included 41 patients with pathologically-proven bladder PUC of the bladder that underwent pre-treatment MRI between January 2000 and March 2020. Two radiologists reviewed MRIs independently followed by consensus with a third radiologist. On MRI, tumor extent, size, Vesical Imaging-Reporting and Data System (VI-RADS) scores (≥4, muscle-invasive; 5, extravesical extension [EVE]), pelvic peritoneal spread (PPS), hydronephrosis, pelvic adenopathy and clinicopathological factors of age, gender, pathological stage, and treatment type were extracted. Kaplan-Meier curves and Cox proportional-hazards models were used to evaluate association with survival. Thirty-two men and 9 women (median age 70 years, IQR 64-76) were included. Most were muscle-invasive (n = 30 [73.2%]). On MRI, most tumors were diffuse (n = 28 [68.3%]), >5 cm (n = 30 [73.2%]), VI-RADS 4 to 5 (n = 36 [87.8%]) with features of EVE and (n = 31 [75.6%]) and PPS (n = 25 [61.0%]). Variables associated with survival were: Larger tumors (>5 cm; hazard ratio [HR] = 5.0; 95% confidence interval [CI] 1.6-15.5; P < 0.01), diffuse extent (HR = 4.0; 95% CI 1.4-11.2; P = 0.01), EVE (HR = 4.5; 95% CI 1.5-13.6; P < 0.01), PPS (HR = 3.0; 95% CI 1.2-7.4; P = 0.01), hydronephrosis (HR = 13.7; 95% CI 3.1-60.9; P < 0.01), pathologic stage (≥pT3 vs. pT1; HR = 5.6; 95% CI 1.3-22.0; P = 0.02), and margin positivity (HR = 4.4 [95% CI 1.2-16.4], P = 0.03). PUCs of the bladder are commonly large, diffuse VI-RADS score 4 to 5 tumors with MRI features of EVE and PPS. These features and pathological stage were associated with survival.

A Rare Variant of Urothelial Carcinoma: Plasmacytoid Urothelial Carcinoma

In these case reports, we aimed to show difficulty in diagnosing and treating plasmacytoid urothelial carcinoma due to aggressive behavior of the tumor, lack of standard treatment protocol, and differences from classical bladder cancer pathologic appearance. One of our cases was 71 years old and she had breast cancer at the same time and the other one was 74 years old and he had chronic myeloid leukemia as well. It is essential to be careful when making differential diagnoses whether the tumor is metastatic or primary. As the tissues are being investigated, immunohistochemical tests like CD138 and loss of E-cadherin can be helpful for the diagnosis.

Plasmacytoid urothelial carcinoma; A series of two cases and the approach to diagnosis

Journal of Diagnostic Pathology is a peer reviewed journal published biannually by the College of Pathologists of Sri Lanka. The journal publishes manuscripts dealing with all aspects of pathology. The aim of the journal is to update knowledge and encourage original research in the field of pathology.

Urine Cytology of High-Grade Plasmacytoid Urothelial Carcinoma

Urine Cytology of High-Grade Plasmacytoid Urothelial Carcinoma

Outcomes of poorly differentiated and plasmacytoid variant bladder urothelial carcinoma.

ObjectivesThe aim of this study is to assess the course and management of poorly differentiated bladder urothelial carcinoma (UC), including plasmacytoid UC (PUC), in our local area. Although bladder cancer is relatively common, PUC is a rare and aggressive subtype with a poor prognosis that is still poorly understood.Materials and MethodsA retrospective assessment of all poorly differentiated high‐grade UC over the last 15 years (2005–2020) in the Hunter New England area was completed. In total, 37 patients were included, and PUC variant was compared with the remaining poorly differentiated UC.ResultsOf the included cases, eight were PUC, nine squamous variant, two neuroendocrine, and one sarcomatoid. Overall, 23 cases proceeded to cystectomy, 15 had chemotherapy (six neoadjuvant), and 11 had radiation therapy. In the PUC subgroup, three had metastatic disease at diagnosis (37.5%). Of the three PUC patients who underwent cystectomy, all were upstaged. Two PUC cases had adjuvant chemotherapy, and one case had radiation. Within the follow‐up period, the PUC group had a cause‐specific mortality of 50% with a mean survival in these patients of 202 days, compared with 37.9% cause‐specific mortality with survival of 671.55 days (p = 0.23) in all other undifferentiated UC cases; 5‐year cause‐specific mortality with Kaplan–Meier analysis was estimated at 26% compared with 59%, respectively (p = 0.058).ConclusionPoorly differentiated UC is demonstrated to have a poor prognosis with a high mortality rate, particularly when PUC is present. Given the rarity of these variants, further studies are necessary to explore the impact of current treatment options.

Plasmacytoid urothelial carcinoma (UC) are luminal tumors with similar immune microenvironment as compared to conventional UC.

477 Background:Plasmacytoid urothelial carcinoma (UC) is a rare pathological variant of UC with low chemotherapeutic sensitivity and dismal outcomes. The molecular and immune profiles of such tumors remain poorly investigated. Herein, we investigated the phenotypical features of a cohort of plasmacytoid UC (n = 32) by comparison to a control group of conventional high-grade UC with matched clinicopathological characteristics (n = 30). Methods: Histopathological analysis included the following antibodies: p63, GATA3, CK5/6, CK20 and HER2. In addition, the density of intra-tumor CD8+ lymphocytes, and PD-L1 expression in tumor (TC) and immune cells (IC) were evaluated. Clinical data were collected. Results: Plasmacytoid UC expressed GATA3 (97% vs 86% p = 0.18), CK20 (59% vs 36% p = 0.08) markers and showed a significantly higher rate of HER2 overexpression (2+ and 3+ score: 25% vs 0%, p &lt; 0.01) compared to controls. A significantly lower expression of CK5/6 (22% vs 56%, p &lt; 0.05) and p63 (41% vs 80%, p &lt; 0.05) was observed in plasmacytoid UC compared to controls. The density of tumor-infiltrating CD8+ cells was similar between plasmacytoid and conventional UC (p = 0.5). PD-L1 expression on IC was similar compared to conventional UC (p = 0.3). Overall survival at 5 years was significantly lower among patients with plasmacytoid UC compared to patients with conventional UC (p = 0.02). Conclusions: Together, our study demonstrated that plasmacytoid UC belong to the luminal subtype and display a rather inflamed microenvironment similar to conventional UC. These data support the inclusion of plasmacytoid variant of UC in clinical trials evaluating immune checkpoint inhibitors monotherapy or combination immunotherapeutic strategies.

Natural history, response to systemic therapy, and genomic landscape of plasmacytoid urothelial carcinoma

BackgroundPlasmacytoid urothelial carcinoma (PUC) is a rare, aggressive histologic variant of urothelial cancer characterised by a diffuse growth pattern and CDH1 mutation. We studied the efficacy of preoperative platinum-based chemotherapy in nonmetastatic PUC and immune checkpoint inhibitors (ICIs) in advanced PUC.MethodsCases of nonmetastatic PUC and advanced PUC treated with ICIs at our institution were identified. Outcomes were compared to those of a published cohort of patients with urothelial carcinoma not otherwise specified.ResultsWe identified 81 patients with nonmetastatic PUC. Of the patients with localised disease who underwent neoadjuvant chemotherapy, pathologic complete response and downstaging rates were 12 and 21%, respectively. Pathologic downstaging was not associated with significant improvement in clinical outcomes. Up to 18% of localised disease and 28% of locally advanced cases had unresectable disease at the time of surgery. ICI-treated advanced PUC (N = 21) had progression-free and overall survival of 4.5 and 10.5 months, respectively, and a 38% response rate. FGFR3 and DNA damage response gene alterations were observed in 3 and 15% of cases, respectively.ConclusionsPUC is associated with high disease burden and poor chemosensitivity. Increased awareness and recognition of this disease variant will allow for new treatment strategies.

P-120 Catenin is a Useful Diagnostic Biomarker for Distinguishing Plasmacytoid and Sarcomatoid Variants From Conventional Urothelial Carcinoma.

Plasmacytoid urothelial carcinoma (PC-UC) is an aggressive variant of urothelial carcinoma (UC), characterized by loss of E-cadherin (E-Cad)-mediated intercellular adhesion. Loss of E-Cad by immunohistochemistry can help diagnose PC-UC; however, sensitivity is limited. Expression of other cadherin-catenin adhesion complex members, that is, p-120 catenin (p-120) and β-catenin (B-Cat), which are diagnostically useful for lobular breast carcinoma, remains unknown in UC. To determine the utility of p-120 and B-Cat in conventional and variant UC. E-cadherin, B-Cat, and p-120 immunohistochemistry was performed in 25 conventional UCs and 33 variant UCs, including 22 PC-UCs, 6 sarcomatoid UCs (SUCs), and 5 micropapillary UCs. Membranous staining for all biomarkers was considered normal; however, any cytoplasmic staining or an absence of staining was considered diagnostically abnormal. Next-generation sequencing was performed on 8 PC-UC cases. E-cadherin, B-Cat, and p-120 showed membranous staining in all conventional and micropapillary UCs. In contrast, most PC-UCs were negative for E-Cad (17 of 22; 77%) with an additional 2 of 22 cases (9%) showing cytoplasmic with partial membranous staining. p-120 catenin demonstrated cytoplasmic or negative staining in 21 of 22 cases (95%). Most SUCs showed an absence of E-Cad (5 of 6; 83%) and cytoplasmic or negative p-120 in 5 of 6 cases (83%). Staining for B-Cat was also abnormal in a subset of PC-UCs and SUCs. Five PC-UC cases that harbored CDH1 gene variants were p-120 cytoplasmic positive. p-120 catenin is a useful adjunct biomarker to E-Cad in the clinically important distinction of PC-UC and SUC from conventional UC. In particular, the combination of cytoplasmic p-120 and loss of E-Cad is strongly supportive of PC-UC and SUC.

Plasmacytoid urothelial carcinoma of renal pelvis with positive zinc finger E\u2013box\u2013binding homeobox 1: a case report

BackgroundThe tumor transformation mechanism of a plasmacytoid urothelial carcinoma remains unexplained. We describe the case of a plasmacytoid urothelial carcinoma of the renal pelvis in which the expression of zinc finger E–box–binding homeobox 1 (ZEB1), a key nuclear transcription factor in an epithelial–mesenchymal transition, is involved in tumor transformation.Case presentationThe patient had a left nephrectomy with the clinical diagnosis of left pelvic renal cancer. The resected specimen showed that the tumor surface comprised a noninvasive papillary urothelial carcinoma with the carcinoma in situ, and the invasive area comprised a plasmacytoid urothelial carcinoma characterized by the presence of single dyscohesive malignant cells that resembled plasma cells in a loose myxoid stroma. The noninvasive urothelial carcinoma was positive for cytokeratin and E–cadherin, and negative for vimentin and ZEB1. In contrast, the invasive plasmacytoid urothelial carcinoma was positive for cytokeratin and also vimentin and ZEB1, and negative for E–cadherin. Additionally, this component was immunoreactive for CD138 and CD38 that are immunohistochemical markers for plasma cells.ConclusionWe suggest that ZEB1 is involved in the plasmacytoid transformation by repressing the E–cadherin in a plasmacytoid urothelial carcinoma.