Micropapillary urothelial carcinoma of the urinary bladder: A clinicopathological analysis of 24 cases

Objectives: To stratify patients with micropapillary urothelial carcinoma of the urinary bladder based on the percentage of micropapillary component and to correlate tumor volume with other clinicopathological features. Methods: Cases of micropapillary urothelial carcinoma of the urinary bladder from 2002 to 2009 were identified. Only patients with available follow‐up information were included in the analysis. Tumor volumes were stratified based on the percentage of micropapillary component (<50%, >50% and 100%). Results: Overall, 24 cases were analyzed. Mean patient age was 71 years (range 55–86 years), with a male to female ratio of 3:1. Six cases (6/24; 25%) were composed entirely of micropapillary component. A total of 12 cases (12/24; 50%) showed >50% micropapillary component. Six cases (6/24; 25%) showed <50% micropapillary component. A higher percentage of micropapillary urothelial carcinoma component was significantly associated with male sex, regional lymph node metastasis and pathological stage (P‐values = 0.0005, 0.01 and 0.03, respectively). The percentage of the micropapillary component was, however, unrelated to patients' survival. Conclusions: The present study confirms that micropapillary urothelial bladder carcinoma is typically aggressive and presents with advanced stage disease in most cases. A quantification of the micropapillary component is to be recommended. An accurate diagnosis of this entity in relatively small biopsies or transurethral resection of bladder tumor specimens is especially critical to define the best treatment plan.     

A case of micropapillary bladder carcinoma

A case of urothelial carcinoma containing micropapillary variant in the urinary bladder is reported. The micropapillary bladder carcinoma isa rare variant of urothelial carcinoma and has an aggressive clinical course. A 45-year-old man complained of hematuria in October, 2009. He visited a hospital and was diagnosed with a bladder tumor. Transurethral resection of the bladder tumor was performed at the hospital. The transurethral resection demonstrated poorly differentiated adenocarcinoma invading the bladder muscle layer. Then he consulted our hospital. Our pathologist diagnosed the case as micropapillary variant of urothelial carcinoma in the urinary bladder. Accordingly, radical cystectomy and pelvic lymph nodes dissection were performed. After the operation, he received three courses of gemcitabine and cisplatin as adjuvant chemotherapy. The patient remains free of tumor recurrence and metastasis for 28 months after the cystectomy.     

Micropapillary carcinoma of the urinary bladder: a case report and review of the literature

Micropapillary carcinoma is an uncommon variant of urothelial carcinoma with high metastatic potential. The presence of micropapillary carcinoma component in bladder biopsies should alert urologists to its aggressive behaviour. We report the case of a 70-year-old man who presented with macroscopic hematuria lasting 2 weeks. Magnetic resonance imaging revealed a bladder tumour in the dome area extended to perivascular adipose. The transurethral biopsy showed a high-grade micropapillary carcinoma with muscle invasion. Radical cystectomy with lymph node dissection was then performed. The pathological examination revealed a high-grade purely micropapillary carcinoma invading the perivesical adipose. No tumour recurrence or metastasis were reported at the 6-month follow-up.     

Clinical Stage T1 micropapillary urothelial carcinoma presenting with metastasis to the pancreas

Micropapillary carcinoma of the bladder is an extremely aggressive variant of urothelial carcinoma. Radical cystectomy is the standard treatment for all patients, including those with nonmuscle-invasive disease. We present a patient diagnosed with clinical Stage T1 micropapillary carcinoma of the bladder who was found to have a 2-cm metastasis to the head of the pancreas. To our knowledge, this case represents the first report of a solitary metastatic urothelial carcinoma to the pancreas.     

Variant histologies in bladder cancer: Does the centre have an impact in detection accuracy?

ObjectiveTo compare the accuracy in detecting variant histologies (VH) at transurethral resection of bladder (TURB) and radical cystectomy (RC) specimen among tertiary referral centres, in order to investigate potential reasons of discrepancies from the pathological point of view.Patients and MethodsClinical and histopathological data of TURB specimen and subsequent cystectomy specimen of 3,445 RC candidate patients have been retrospectively collected from 24 tertiary referral centres between 1980 and 2021. VH considered in the analysis were pure squamous cell carcinoma, urothelial carcinoma with squamous differentiation, pure adenocarcinoma, urothelial carcinoma with glandular differentiation, micropapillary bladder cancer (BCa), neuroendocrine BCa, and other variants. The degree of agreement between TURB and RC concerning the identification of VH was expressed as concordance, classified according to Cohen's kappa coefficient.ResultsA VH was reported in 17% of TURB specimens, 45% of which were not confirmed in RC. The lowest concordance rate was reported for micropapillary BCa with 11 out of 18 (61%) centres reporting no agreement, whereas neuroendocrine BCa achieved the highest concordance rate with only 3 centres (17%) reporting no agreement. Our results shows that even among centres with the advantage of a referent uropathologist the micropapillary variant is characterized by scarce accuracy between TURB and RC. Differences in TURB specimen acquisition by the urologist and in sampling methods among different centres are the main limitations of the study.ConclusionsAccuracy of TURB in detecting VH is poor for certain VH, in particular for micropapillary BCa, with evident variation among centres. Novel diagnostic tools are required to better identify these VH and drive patients toward a personalized treatment.     

Local recurrence of micropapillary bladder tumor after radical cystectomy : successful treatment with radiation therapy : a case report

A 75-year-old man consulted a physician because of gross hematuria and right flank pain. Since a bladder tumor and right hydronephrosis were found, the patient was referred to our hospital. The clinical diagnosis was cT3bN0M0 and radical cystectomy was done. The pathological diagnosis was micropapillary variant of urothelial carcinoma, pT3bN0M0. The local recurrence appeared in the interior of the pelvis by computed tomography after the operation. A complete response was obtained by radiotherapy.     

The impact of variant histology on the outcome of bladder cancer treated with curative intent

Patient risk stratification is essential for optimal management of patients with bladder cancer. Risk status determines the application and timing of therapeutic interventions such as repeat transurethral resection, intravesical chemo- and immunotherapy, systemic chemotherapy, and radical cystectomy. One key factor in such risk stratification appears to be the presence of variant histologic patterns in the bladder tumor. More than 90% of tumors are conventional urothelial carcinoma, and the rest consist of urothelial carcinoma with aberrant differentiation (squamous/glandular differentiation, small cell carcinoma, sarcomatoid carcinoma, and micropapillary carcinoma) or nonurothelial carcinoma (squamous cell carcinoma and adenocarcinoma). In this review, we focus on the implications of aberrant differentiation on the management of patients with bladder cancer. All of the variant histologies portend a worse prognosis than pure urothelial carcinoma. Although radical cystectomy remains the mainstay of treatment in all forms of bladder cancer, we highlight the use of neoadjuvant chemotherapy in patients with subtypes responsive to such therapy.     

Plasmacytoid and micropapillary urothelial carcinoma: rare forms of urothelial carcinoma

Plasmacytoid urothelial carcinomas (PUC) along with micropapillary urothelial carcinoma (MPC), small cell cancer, and nested-typed tumors are among the rare variations of urothelial carcinomas. The molecular characterization of PUC and MPC is currently the focus of our research on bladder cancer which we are conducting in cooperation with the Institute of Pathology in Erlangen. PUCs account for approximately 0.9% of all urothelial carcinomas. The diagnosis of these rare variants has acquired increasing importance since this may have prognostic and possibly therapeutic consequences for the patients. By analysis of 32 PUCs we were able to demonstrate the most comprehensive results available to date on the underlying molecular and clinical characteristics of these variants. Micropapillary cancers have already been described in multiple organs. Micropapillary breast cancer represent an individual entity with characteristic genomic aberrations and corresponding clinical and pathological features     

MICROPAPILLARY BLADDER CARCINOMA: A CLINICOPATHOLOGICAL STUDY OF 20 CASES

PURPOSE: Micropapillary bladder carcinoma is rare, with only 18 cases reported to date. We report 20 additional cases with long-term followup. MATERIALS AND METHODS: A total of 680 patients with an initial diagnosis of bladder carcinoma in western Sweden in 1987 and 1989 were prospectively registered. The clinical records of all 816 patients with bladder cancer treated at Sahlgrenska University Hospital with external beam irradiation between 1962 and 1989 were reviewed. The histopathological material was reviewed and immuno-histochemical analyses were performed on 20 cases identified with micropapillary bladder carcinoma. RESULTS: The incidence of micropapillary bladder carcinoma was 0.7%. Mean patient age at diagnosis was 69 years (range 45 to 82) and the male-to-female ratio was 2.3:1. All but 5 patients had stage T3a disease or higher. There was no difference in stage or prognosis between the 5 prospectively identified patients and those treated with external beam irradiation. Only 2 patients had micropapillary bladder carcinoma as the only pattern, while 1 had 10% and the remainder had 20 to 95% micropapillary bladder carcinoma. Transitional cell carcinoma was noted in 17 patients and 5 had areas of gland forming adenocarcinoma. Carcinoma in situ was noted in 13 patients and 15 had lymphatic invasion. Only 5 patients survived 5 years, 1 of whom died of bladder cancer after 7 years. Radiation and chemotherapy did not seem to be effective. CONCLUSIONS: The light microscopic appearance, which is strikingly similar to ovarian papillary serous carcinoma, and immunohistochemical staining pattern lend some support to the theory that micropapillary bladder carcinoma is a variant of adenocarcinoma. Since even the focal presence of micropapillary bladder carcinoma is associated with a poor prognosis, recognition of this entity is important. Due to its rarity, the optimal treatment of micropapillary bladder carcinoma needs to be determined in a multicenter study.     

乳腺浸润性微乳头状癌与浸润性导管癌的临床病理对照研究

目的 探讨浸润性微乳头状癌(invasive micropapillary carcinoma,IMPC)和浸润性导管癌(invasive ductal carcinoma,IDC)的差异,分析乳腺浸润性微乳头状癌的临床病理及免疫组化特点.方法 回顾性分析2004年10月至2007年11月51例浸润性微乳头状癌患者临床病理资料.选取同期临床病理资料完整的102例浸润性导管癌患者做对照.结果 浸润性微乳头状癌和浸润性导管癌的乳头侵犯、淋巴管侵犯、淋巴结转移率、淋巴结转移水平、软组织侵犯、雌激素受体(estrogen receptor,ER)、孕激素受体(progestin receptor,PR)、三阴(ER,PR,HER2均为阴性)表达差异有统计学意义(P＜0.05).而闭经状态、发病侧别、淋巴结转移个数、人类表皮生长因子受体2(human epidermal growth factor receptor-2,HER2)表达及局部复发和远处器官转移差异无统计学意义.浸润性微乳头状癌组中位随访时间46个月(16～ 75个月),3年生存率和无病生存率分别为90.2％和84.3％.结论 浸润性微乳头状癌是一种呈现侵袭性生长方式的少见乳腺癌类型,具有嗜淋巴特性和易发结外软组织侵犯的特点.乳腺浸润性微乳头状癌高表达激素受体,三阴乳腺癌比例较少.     

In situ adenocarcinoma of the bladder.

In situ adenocarcinoma of the bladder has not been well studied. Only one other case not associated with infiltrating adenocarcinoma has been reported in the literature. We identified 19 biopsies of in situ adenocarcinoma of the bladder without concurrent infiltrating adenocarcinoma or villous adenoma from the surgical pathology files of the Johns Hopkins Hospital between May 1984 and July 2000. The majority of patients (89%) were seen in consultation. The mean age at diagnosis was 70.4 years (range 48-88 years) and 79% were male. None of the patients developed a pure infiltrating adenocarcinoma; however, two patients had invasive urothelial carcinoma with focal glandular differentiation on prior or subsequent specimens. Two cases were pure in situ adenocarcinoma and 10 were seen with carcinoma in situ and/or papillary transitional cell cancer without invasion. Most patients (74%) had invasive carcinoma on either concurrent or subsequent specimens (five small cell and nine transitional cell [four micropapillary]). The majority (84%) of in situ adenocarcinomas were papillary, often seen in combination with either cribriform or flat architecture. In most cases the in situ adenocarcinoma was the predominant component when it was present with another in situ urothelial carcinoma. Seventy-nine percent of in situ adenocarcinomas showed >5 mitoses/10 HPF and 42% showed >10 mitoses/10 HPF. Moderate to severe nuclear pleomorphism was seen in 84% of cases. All cases showed apoptosis, and only one case showed focal necrosis. Seven patients were treated with cystectomy within 2-12 months. Of the other 12 patients, 10 were followed for a mean of 19.3 months (range 1-62 months). Ten (52%) patients were treated with bacille Calmette-Guérin, of whom four had no residual tumor on subsequent biopsy or cystectomy specimens. Three patients developed metastatic disease. In situ adenocarcinoma is a rare lesion that has a high incidence of association with small cell and micropapillary transitional cell carcinomas. When identified, in situ adenocarcinoma may indicate subsequent development of specific types of prognostically poor invasive carcinomas.     

Presence of a micropapillary pattern in mucinous carcinomas of the breast and its impact on the clinical behavior

Infiltrating micropapillary carcinomas (IMPC) of breast are highly angioinvasive tumors with poor prognosis. This study is based on the observation that a similar micropapillary pattern is also observed in mucinous carcinomas of breast. About 102 mucinous carcinomas were evaluated for the presence and impact of this micropapillary pattern on the clinical behavior. Of these, 68 were mucinous carcinomas with a micropapillary pattern (MUMPC), 20 had MUMPC mixed with an infiltrating duct carcinoma component, two were solid variants of papillary carcinoma with mucin (SVPCMU), five had collision of the MUMPC and SVPCMU patterns and seven were mucinous carcinomas with signet ring cells (MUS). The factors negatively affecting overall survival (OAS) and disease-free survival (DFS) included the histological type of mucinous carcinoma, nodal metastases, an irregular tumor border, <50% mucin and an IMPC type of local recurrence or metastases. In the multivariate analysis, the histologic type of mucinous carcinoma and an irregular tumor border were most significant for OAS and DFS. Thus, 86% of mucinous carcinomas in this study were mucinous variants of the angioinvasive infiltrating micropapillary carcinomas. These tumors can produce IMPC type of metastases and thus should be treated aggressively.     

Invasive micropapillary carcinoma of the ampulla of Vater with extensive lymph node metastasis: Report of a case

Invasive micropapillary carcinoma is characterized by extensive lymph node metastasis and a poor prognosis. This histological variant was first described in breast cancer, with a few subsequent reports of it in the ampullo-pancreato-biliary region. We report a case of invasive micropapillary carcinoma of the papilla of Vater. A 53-year-old man was admitted to our hospital with signs of obstructive jaundice. Detailed investigations revealed a tumor in the periampullary region, and pancreatoduodenectomy was performed for cancer of the ampulla of Vater. Microscopic examination of the resected specimen revealed a tumor composed mainly of carcinoma cells arranged in micropapillary structures, with extensive regional lymph node metastasis. The patient had an uneventful postoperative course and was followed up in the outpatient clinic. Tumor recurrence with progressive ascites and hydronephrosis was found 8 months after surgery, and the patient died of the disease 20 months after surgery.     

Overexpression of p27kip1 in urinary bladder urothelial carcinoma

OBJECTIVES: Cyclins and cyclin-dependent kinase (CDK) complexes have important regulatory roles during cell cycle progression and can be used as prognostic markers in various kinds of malignant tumors. This study investigated the expression of proliferative cell nuclear antigen (PCNA), p53, Rb, p27(kip1), and cyclin D1 by immunostains in bladder tumors, especially urothelial papilloma, papillary urothelial neoplasm of low malignant potential, and low and high grade urothelial carcinoma, to see if their expression is associated with classification or grading of the urinary bladder urothelial carcinoma. METHOD: Nuclear expression of PCNA, p53, Rb, p27(kip1), and cyclin D1 was determined immunohistochemically in a series of 89 urinary bladder tumor specimens, including 13 papilloma, 15 urothelial neoplasm of low malignant potential, 17 low grade urothelial carcinoma, and 44 high grade urothelial carcinoma. The results of immunoreactivity were analyzed with respect to the associations with tumor grade. RESULTS: Eighty-two percent (38/45) of the p27(kip1) positive tumors were urothelial carcinoma, and the percentage of the p27(kip1) positivity was higher with increasing grade of the urothelial carcinoma (P = 0.011). A tendency of higher percentage of positive p53 immunoreactivity was noted in the urothelial carcinoma (P = 0.053). There was no significant difference in cyclinD1, Rb and PCNA expression between benign, low malignant potential and urothelial carcinoma. CONCLUSION: We first noted an overexpression of p27(kip1) in urinary bladder urothelial carcinoma. The result indicates that some urothelial carcinomas may tolerate this inhibitor of cell cycle progression.     

A comparison of cytology and fluorescence in situ hybridization for the detection of urothelial carcinoma

PURPOSE: We determine the relative sensitivities of cytology and fluorescence in situ hybridization (FISH) for the detection of urothelial carcinoma. MATERIALS AND METHODS: A mixture of fluorescent labeled probes to the centromeres of chromosomes 3, 7 and 17, and band 9p21 (P16/CDKN2A gene) was used to assess urinary cells for chromosomal abnormalities indicative of malignancy. A total of 280 urine specimens from 265 patients, including 150 with a history of urothelial carcinoma and 115 without a history of urothelial carcinoma, were analyzed. FISH analysis was performed without prior knowledge of clinical findings, that is biopsy, cystoscopy and cytology results. A positive result was defined as 5 or more urinary cells with gains of 2 or more chromosomes. RESULTS: A total of 75 biopsies showed urothelial carcinoma at FISH analysis among the 265 patients. The sensitivity of urine cytology for pTa (36 cases), pTis (18) and pT1-pT4 (15) tumors was 47%, 78% and 60%, respectively, for an overall sensitivity of 58%. The sensitivity of FISH for pTa (37 cases), pTis (17) and pT1-pT4 (19) tumors was 65%, 100% and 95%, respectively, for an overall sensitivity of 81%. FISH was significantly more sensitive than cytology for pTis (p = 0.046), pT1-pT4 (p = 0.025), grade 3 (p = 0.003) and all tumors (p = 0.001). The specificity of cytology and FISH among patients without cystoscopic evidence of urothelial carcinoma and no history of urothelial carcinoma was 98% and 96%, respectively (p = 0.564). CONCLUSIONS: The sensitivity of FISH for the detection of urothelial carcinoma is superior to that of cytology, and the specificity of FISH and cytology for urothelial carcinoma are not significantly different. Further prospective studies are required but FISH has the potential to improve significantly the management of urothelial carcinoma.     

Urothelial carcinoma (clear cell variant) diagnosed with useful immunohistochemistry stain

The case is reported of urothelial carcinoma (clear cell variant) that was diagnosed with useful immunohistochemistry stain. A 70-year-old man, who had undergone left radical nephrectomy for renal cell carcinoma in August 2003 and partial lobectomy for pulmonary metastasis in May 2005, complained of hematuria in June 2005. On evaluation, a papillary pedunculated tumor was detected in the left wall of the urinary bladder. A transurethral resection of the bladder tumor (TUR-Bt) was performed in July 2005. The pathological diagnosis was difficult due to diffuse clear cell appearance. Immunohistochemistry stain showed urothelial carcinoma, not metastasis of the renal cell carcinoma. Finally it was diagnosed as urothelial carcinoma clear cell variant. Urothelial carcinoma has many variants that show a variety of appearances and characteristics. These should be well known before medical therapy is initiated.     

Serous borderline tumors of the ovary: a long-term follow-up study of 137 cases,including 18 with a micropapillary pattern and 20 with microinvasion

The natural history of serous borderline tumors (SBTs) of the ovary varies considerably. A group of investigators have proposed that a small subset of SBTs with a micropapillary architecture and an allegedly higher incidence of invasive peritoneal implants should be designated "micropapillary serous carcinomas." Based on the overall favorable prognosis of the nonmicropapillary SBTs, these investigators have recommended abandoning the borderline category of serous tumors, restricting them to benign (benign and typical SBTs) and malignant types; other investigators, however, are in favor of retaining the original grouping, designating borderline tumors with a micropapillary pattern as such instead of designating them carcinomas. We have reviewed the clinicopathologic records of 137 patients with ovarian SBTs and obtained follow-up information on 106 of them ranging from 1 to 18 years (mean 7 years). Of the 21 patients with stage I tumors who had conservative surgical treatment, only two (9.5%) were subsequently found to have tumor in the contralateral ovary. Both were successfully managed by reoperation alone. Forty-five stage I patients had procedures that included bilateral oophorectomy, and two of them (4.4%) had a pelvic recurrence, which was fatal in one patient (whose tumor had been understaged) and occurred on multiple occasions in the other patient, finally transforming into invasive carcinoma; that patient survived. Of the 45 stage II-IV patients, only the six (13%) with invasive implants had an unfavorable outcome: three died of tumor (from 7 to 9.3 years), and the other three were alive with progressive disease from 5 to 10 years. Solid epithelial nests or small papillae surrounded by clefts and micropapillary architecture were found more often in invasive than in noninvasive implants. However, the only feature specifically associated with a poor outcome was obvious destructive invasion of the underlying tissue. Among the 137 SBTs, we identified 18 cases of serous borderline tumors with a micropapillary pattern (SBT-MP) (so-called "micropapillary carcinoma") and 20 cases of SBT with microinvasion (SBT-Minv) (three of which were also micropapillary). We compared the two groups of tumors with the remaining 102 cases of typical SBTs (which lacked micropapillary pattern and microinvasion). Of the 17 patients with SBT-MP and follow-up data, only the one patient with invasive implants had an unfavorable outcome; similarly, of the two patients with SBT-Minv and an unfavorable outcome, one had invasive implants and the other had been incompletely staged. SBTs have a very favorable prognosis, but complete surgical staging and prolonged follow-up are advised because pelvic recurrence and occasionally transformation to invasive carcinoma may occur. Designation of SBTs as "atypical proliferative tumors" is not recommended because it discourages complete surgical staging and follow-up. Advanced stage tumors with noninvasive implants are common, characteristically behave in a benign fashion, and can be safely treated conservatively. The rare SBTs associated with invasive implants are almost always fatal. SBT-MP and SBT-Minv are much closer in their biologic behavior to SBTs than to serous carcinomas. The micropapillary pattern alone does not imply an unfavorable prognosis; only micropapillary tumors associated with invasive implants behave aggressively.     

NIFT-P: Are they indolent tumors? Results of a multi-institutional study

Background

Encapsulated follicular variant of papillary thyroid carcinoma has recently been reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features on the basis of its highly indolent behavior, as proposed by an international group of experienced thyroid pathologists.

Micropapillary bladder cancer: Current treatment patterns and review of the literature

ObjectivesNo guidelines exist for the management of micropapillary bladder cancer (MPBC) and most reports of this variant of urothelial carcinoma are case series comprising small numbers of patients. We sought to determine current practice patterns for MPBC using a survey sent to the Society of Urologic Oncology (SUO) and to present those results in the setting of a comprehensive review of the existing literature.Materials and methodsA survey developed by the Translational Science Working Group of the Bladder Cancer Advocacy Network–sponsored Think Tank meeting was distributed to members of the SUO. The results from 118 respondents were analyzed and presented with a literature review.ResultsMost survey respondents were urologists, with 80% considering bladder cancer their primary area of interest. Although 78% of the respondents reported a dedicated genitourinary pathologist at their institution, there were discrepant opinions on how a pathologic diagnosis of MPBC is determined as well as variability on the proportion of MPBC that is clinically significant. Among them, 78% treat MPBC differently than conventional urothelial carcinoma, with 81% reporting that they would treat cT1 MPBC with upfront radical cystectomy. However, the respondents had split opinions regarding the sensitivity of MPBC to cisplatin-based chemotherapy, which affected utilization of neoadjuvant chemotherapy in muscle-invasive disease.ConclusionsThe management of MPBC is diverse among members of the SUO. Although most favors early cystectomy for cT1 MPBC, there is no consensus on the use of neoadjuvant chemotherapy for muscle-invasive MPBC.