Small cell carcinoma of the bladder. Two cases diagnosed by urinary cytology

BACKGROUND: Primary small cell carcinoma (SCC) of the bladder is a rare but important entity. We report two cases of SCC of the bladder diagnosed by urinary cytology. CASES: A 71-year-old male (case 1) and a 79-year-old female (case 2) presented with asymptomatic gross hematuria. Urinary cytology in case 1 showed the presence of a few undifferentiated malignant small cells and many transitional cell carcinoma (TCC) cells with a bloody and necrotic background. The former cells were small and round, with naked, hyperchromatic nuclei and finely granular chromatin. Pathologic diagnosis after total cystectomy was TCC > SCC > adenocarcinoma, T2M0N0. Urinary cytology of case 2 showed the presence of many undifferentiated malignant small cells and many TCC cells with or without squamous metaplasia. Cytologic features of the former cells were almost the same as those in case 1. Moreover, these cells were neuroendocrine marker positive by immunocytochemistry. Pathologic diagnosis after tumor resection was SCC and TCC > squamous cell carcinoma, T1b. CONCLUSION: The prognosis of primary SCC of the bladder is usually poor. Because our cases were found by urinary cytology at a relatively early stage, both have been well, without any evidence of recurrence, 30 and 25 months after surgery even without adjuvant therapy.     

Establishment and characterization of a new squamous cell carcinoma cell line, TMUU-08, derived from human bladder cancer

Human squamous cell carcinoma (SCC) of the bladder is a rare malignancy that represents less than 5% of bladder tumors. In contrast to non-bilharzial SCC, bilharzial SCC is a distinct pathological disease that is rarely encountered in Japan. The majority of patients with non-bilharzial SCC present with a poorly differentiated, muscle-invasive tumor with no previous episode of urothelial carcinoma (UC). Even in the absence of distant metastases, the prognosis of patients with non-bilharzial SCC of the bladder remains dismal because patients die of localized recurrence. This is in contrast to UC in which distant metastasis accounts for the great majority of recurrence. The 5-year survival rate of the patients treated for non-bilharzial SCC of the bladder was only about 10%. To date, large numbers of reports have examined the establishment of a human bladder cancer cell line with UC. However, few reports exist regarding the establishment of the human bladder cancer cell line with SCC. In the present study, we established a new cell line (TMUU-08) from the metastatic lymph node of a patient with SCC of the bladder. The TMUU-08 cell line of human bladder SCC was characterized. These results indicate that TMUU-08 cells might be useful in basic studies not only in the treatment but also etiology of human bladder SCC.     

Squamous cell carcinoma antigen in genitourinary tumors

We have evaluated the serum levels of squamous cell carcinoma (SCC) antigen in patients with adenocarcinoma of the kidney, adenocarcinoma of the prostate, germ cell tumors of the testis, transitional cell carcinoma of the bladder, and SCC of the penis, urethra, and bladder. Serum SCC antigen levels were elevated in 5 of 11 patients (45%) with metastatic SCC of the penis, and in the 3 patients for whom serial determinations were made, the serum levels correlated correctly with the progression of disease or response to treatment. The antigen was elevated in 1 of 3 patients with SCC of the urethra, and 1 apparent false-positive value was observed in a patient with adenocarcinoma of the prostate. Otherwise, no SCC antigen elevations were noted among 10 patients with metastatic adenocarcinoma of the prostate, 8 with metastatic adenocarcinoma of the kidney, 11 with metastatic transitional cell carcinoma of the bladder, 8 with metastatic nonseminomatous germ cell tumors of the testis, and 2 patients with metastatic SCC of the bladder.     

Long-term Survival From Muscleinvasive Bladder Cancer With Initial Presentation of Symptomatic Cerebellar Lesion: The Role of Selective Surgical Extirpation of the Primary and Metastatic Lesion

A 59-year-old man was diagnosed with urothelial carcinoma involving an isolated cerebellar metastasis after presenting to the emergency department for headache complaints. After selective surgical excision of the symptomatic brain lesion and delayed cystectomy due to intractable hematuria, he survived 11 years without evidence of recurrence or subsequent systemic chemotherapy. He eventually expired after delayed recurrence in the lung, supraclavicular lymph node, and brain. To our knowledge, this is the only case of prolonged survival from urothelial carcinoma after selective surgical extirpation of the primary and metastatic lesion without subsequent systemic chemotherapy.Key words: Bladder cancer, Cystectomy, Metastasis, Urothelial carcinomaUsually, brain metastasis of bladder urothelial carcinoma is associated with widespread systemic disease and/or multiple brain lesions. It is exceedingly rare to have bladder cancer metastasize to the brain without evidence of additional systemic manifestations.¹ As with other forms of distant urothelial carcinoma metastasis, brain metastasis is associated with poor prognosis, with survival often less than 14 months in those with solitary brain lesions.² We report an isolated bladder urothelial carcinoma metastasis to the cerebellum with an 11-year survival fol-lowing extirpative therapy of both the primary lesion and brain metastasis.     

Role of percutaneous pelvic node aspiration cytology in the management of bladder carcinoma

Six of the 23 patients with bladder carcinoma who underwent percutaneous pelvic node aspiration biopsy cytology for staging purposes showed positive findings from nodal chains. Pelvic lymphadenectomy revealed no false-positive or false-negative cytologic results. The fine needle aspiration of opacified pelvic nodes under fluoroscopic control is of great diagnostic value, with a high accuracy in detecting nodal extension of bladder carcinoma and providing a rational basis for proper therapy. Positive aspiration results may be accepted as a basis for therapeutic decisions. Since the metastatic involvement of multiple nodes makes any therapeutic treatment as well as cystectomy completely useless, positive aspirations from more than two nodes may spare patients an unnecessary radical surgery.     

Urine cytology evaluation in cases of uretero-ileal cutaneous diversion

Cytological examination of urine from the ileal conduit in cases of bladder cancer treated by radical surgery can be an important and effective follow-up procedure. A total of 19 patients (18 males and one female) on whom radical cystectomy for cancer was performed were studied. Three urine specimens were examined in each case using routine cytological methods. Three cases of recurrent carcinoma (mainly of papillary type) were diagnosed cytologically before any clinical evidence of disease. the cytological examination of urine at 3-6 month intervals after cystectomy for bladder carcinoma is considered advisable in all cases, since the recurrence rate of transitional cell neoplasms in the upper urinary tract after cystectomy for transitional carcinoma is quite high.     

Expression of p21WAF1/CIP1 in bladder cancer: relation to schistosomiasis

Cell cycle regulation is mediated in part through expression of the cyclin-dependent kinase inhibitor p21WAF1/CIP1. Loss of p21WAF1/CIP1 expression may, therefore, contribute partially to schistosomal carcinogenesis in the urinary bladder. We compared p21WAF1/CIP1 expression in schistosomal and nonschistosomal bladder cancer to explore possible differences in p21WAF1/CIP1 expression between the two subtypes and the possible association between schistosomiasis and loss of p21WAF1/CIP1 expression. Tumor specimens were obtained from 130 patients who underwent transurethral biopsy or cystectomy. p21WAF1/CIP1 was determined by immunodot blot, Western blot, and enzyme immunoassay (EIA). We validated a highly sensitive quantitative EIA assay for determination of p21WAF1/CIP1 in cell lysates. Precision, analytical recovery, and linearity were all excellent. Our results did not show any correlation between p21WAF1/CIP1 expression and most clinicopathologic variables. Lower expression of p21WAF1/CIP1 was evident in squamous cell carcinoma (SCC) and schistosomal subtype than in transitional cell carcinoma and nonschistosomal tumors. Our data suggest a potential role for p21WAF1/CIP1 alteration in schistosomal carcinogenesis.     

FUT4-siRNA增强5-aza-dC对鳞癌细胞增殖和迁移的抑制

岩藻糖基转移酶IV（fucosyltransferase IV,FUT4）是催化蛋白质岩藻糖基化的关键酶．已经证明,FUT4-siRNA能够抑制鳞癌细胞的增殖．5-氮杂-2-脱氧胞苷（5-aza-dC）是临床常用化疗药物,但5-aza-dC是否对鳞癌有治疗作用,以及与FUT4-siRNA联合使用能否加强对鳞癌细胞增殖和迁移的抑制尚不清楚．本研究以鳞癌细胞系A431和SCC12为对象,探讨5-aza-dC及其与FUT4-siRNA联合使用对细胞增殖和迁移的影响．MTT结合流式细胞周期分析显示,5-aza-dC处理A431和SCC12细胞4 d后,细胞增殖被明显抑制,抑制率分别为18%和20% (P<0.05);与对照组比较,加药处理组G1期细胞数量减少,S期细胞数量明显增加．Western印迹结果揭示,A431细胞FUT4表达水平较SCC12细胞高．经5-aza-dC处理后SCC12细胞FUT4表达有所增加,但仍低于A431细胞中的表达．FUT4-siRNA转染结合台盼蓝活细胞记数证明,FUT4-siRNA明显降低细胞FUT4表达,5-aza-dC处理同时转染FUT4-siRNA的A431和SCC12细胞增殖进一步被抑制,抑制率分别为54%和60% (P<0.05)．细胞划痕法显示,5-aza-dC与FUT4-siRNA联合使用,对细胞迁移能力的抑制作用比5-aza-dC单独使用增强．上述结果提示,5-aza-dC通过诱导细胞S期阻滞抑制鳞癌细胞增殖,FUT4-siRNA与5-aza+dC联合使用可加强对细胞增殖和迁移的抑制．     

En Bloc Robot-assisted Laparoscopic Partial Cystectomy,Urachal Resection,and Pelvic Lymphadenectomy for Urachal Adenocarcinoma

Primary adenocarcinomas of the bladder and urachus are extremely rare, accounting for 0.5% to 2.0% of all bladder malignancies. During fetal development, the urachus develops into the median umbilical ligament that stretches from the umbilicus to the bladder. Adenocarcinoma accounts for 90% of all cases of urachal carcinoma. There is no consensus regarding the management of urachal carcinoma. Although the preferred treatment is wide local excision with partial or radical cystectomy, bladder-sparing management is increasing. We report a case of robot-assisted laparoscopic partial cystectomy with en bloc resection of the urachus and bilateral pelvic lymphadenectomy for urachal carcinoma. The robot-assisted laparoscopic approach allowed us to minimize surgical morbidity, postoperative pain, and convalescent time while maintaining the oncologic principle of wide local excision.Key words: Urachal adenocarcinoma, Robotic partial cystectomy, Pelvic lymphadenectomyPrimary adenocarcinomas of the bladder and urachus are extremely rare, accounting for 0.5% to 2.0% of all bladder malignancies.¹ The urachus is a musculofibrous band that extends from the dome of the bladder to the umbilicus. During fetal development, the urachus develops into the median umbilical ligament that stretches from the umbilicus to the bladder. Urachal carcinoma stems from the epithelium of the remnant of this structure, and adenocarcinoma accounts for 90% of all cases.² Historically, patients tend to have a poor prognosis, with 5-year survival rates of 11% to 61%.³ Patients with urachal carcinoma most commonly present with dysuria, hematuria, abdominal pain, or umbilical discharge.There is no consensus regarding the management of urachal carcinoma. Although the preferred treatment is wide local excision with partial or radical cystectomy, ^4–6 bladder-sparing management is increasing because the published reports do not clearly support a survival advantage with more radical extirpation.^7,8We report a case of robot-assisted laparoscopic partial cystectomy with en bloc resection of the urachus and bilateral pelvic lymphadenectomy for urachal carcinoma. The robot-assisted laparoscopic approach allowed us to minimize surgical morbidity, postoperative pain, and convalescent time while maintaining the oncologic principle of wide local excision.     

Signet-ring-cell (colloid) carcinoma of the urinary bladder. Cytologic, histologic and ultrastructural findings in one case

A 65-year-old female presented with a one-and-a-half-year history of intermittent, painless, gross hematuria. She was found to have a large bladder neoplasm. A cytologic diagnosis of signet-ring-cell (colloid) carcinoma was made on a bladder washing and was confirmed histologically by a cystoscopic biopsy. Subsequently, a radical cystectomy was performed. The cytologic findings of this rare pure signet-ring-cell carcinoma of the bladder, not previously described, are presented along with the histologic and ultrastructural findings.     

Carcinoma in situ of the urinary bladder. Clinical presentation, cytologic pattern and stromal changes

The clinical presentation, cytologic pattern and stromal changes in the cystectomy specimen were studied in a group of 26 patients with carcinoma in situ of the urinary bladder who underwent cystectomy. Only cases in which the nuclear area of the carcinoma in situ cells was over 80 sq micron (large-cell type) were included in this study. The results indicate that the cells from large-cell carcinoma in situ of the bladder exfoliate easily, resulting in a cytologic pattern of predominantly single, highly abnormal cancer cells. Due to the increased exfoliation of the affected epithelium, the bladder stroma is focally denuded; therefore, while cytology may be strongly positive for malignancy in these cases, the histologic diagnosis can be falsely negative when only denuded stroma is biopsied. The edematous stroma causes complaints of "cystitis." The neoplastic urothelium may involve contiguously related epithelial surfaces. When the lesion extends into the prostatic ducts, the patient can have "pseudoprostatitis" complaints. Urethral extension may give penile voiding pain. In one female patient, involvement of the vagina and vulva was found. Carcinoma in situ may develop in patients with papillary low-grade bladder carcinoma during follow-up, with a concomitant shift in the cytologic and clinical patterns; this deserves the consideration and attention of the cytologist and the clinician due to its serious clinical implications.     

Neoadjuvant versus adjuvant treatment: which one is better for resectable esophageal squamous cell carcinoma?

ABSTRACT: Esophageal cancer is the eighth most common cancer worldwide, and especially in some areas of China is the fourth most common cause of death and is of squamous cell carcinoma (SCC) histology in >90% of cases. Surgery alone was the mainstay of therapeutic intervention in the past, but high rates of local and systemic failure have prompted investigation into multidisciplinary management. In this review, we discuss the key issues raised by the recent availability of esophageal SCC treatment with the addition of chemotherapy, radiotherapy, and chemoradiotherapy to the surgical management of resectable disease and discuss how clinical trials and meta-analysis inform current clinical practice. None of the randomized trials that compared neoadjuvant radiotherapy or chemotherapy with surgery alone in esophageal SCC has demonstrated an increase in overall survival in those patients treated with neoadjuvant radiotherapy or chemotherapy. Neoadjuvant chemoradiotherapy has been accepted recently for esophageal cancer because such a regimen offers great opportunity for margin negative resection, improved loco-regional control and increased survival. The majority of the available evidence currently reveals that only selected locally advanced esophageal SCC are more likely to benefit from the adjuvant therapy. The focus of future trials should be on identification of the optimum regimen and should aim to minimize treatment toxicities and effect on quality of life, as well as attempt to identify and select those patients most likely to benefit from specific treatment options.     

Fine needle aspiration of urethral recurrence of urothelial carcinoma after radical cystectomy presenting as a perineal mass: a case report

BACKGROUND: Recurrence of urothelial (transitional cell) carcinoma in the urethra after cystectomy for invasive urothelial carcinoma is relatively uncommon. It is also uncommon for the recurring urethral tumor to present as a painful perineal mass. Fine needle aspiration (FNA) can be used to evaluate such perineal lesions and confirm tumor recurrence. CASE: A 5-cm-diameter mass was found in the perineum of a 63-year-old man 1 year after radical cystoprostatectomy for invasive urothelial carcinoma of the urinary bladder. The mass was detected on pelvic computed tomographic scanning. FNA cytology showed numerous urothelial carcinoma cells of high grade displaying squamous cell differentiation mimicking the histopathologic findings of the primary tumor found on cystectomy. Diagnosis of recurrent urothelial carcinoma was rendered. The FNA in this case spared the patient an open biopsy. CONCLUSION: Mass lesions arising in the perineum of patients who underwent cystectomy for urothelial carcinoma should raise the suspicion of urothelial carcinoma recurrence. Evaluation of perineal masses for recurrence of urothelial carcinoma can be made on FNA without the need for open biopsy.     

Downregulation of HIPK2 Increases Resistance of Bladder Cancer Cell to Cisplatin by Regulating Wip1

Cisplatin-based combination chemotherapy regimen is a reasonable alternative to cystectomy in advanced/metastatic bladder cancer, but acquisition of cisplatin resistance is common in patients with bladder cancer. Previous studies showed that loss of homeodomain-interacting protein kinase-2 (HIPK2) contributes to cell proliferation and tumorigenesis. However, the role of HIPK2 in regulating chemoresistance of cancer cell is not fully understood. In the present study, we found that HIPK2 mRNA and protein levels are significantly decreased in cisplatin-resistant bladder cancer cell in vivo and in vitro. Downregulation of HIPK2 increases the cell viability in a dose- and time-dependent manner during cisplatin treatment, whereas overexpression of HIPK2 reduces the cell viability. HIPK2 overexpression partially overcomes cisplatin resistance in RT4-CisR cell. Furthermore, we showed that Wip1 (wild-type p53-induced phosphatase 1) expression is upregulated in RT4-CisR cell compared with RT4 cell, and HIPK2 negatively regulates Wip1 expression in bladder cancer cell. HIPK2 and Wip1 expression is also negatively correlated after cisplatin-based combination chemotherapy in vivo. Finally, we demonstrated that overexpression of HIPK2 sensitizes chemoresistant bladder cancer cell to cisplatin by regulating Wip1 expression.

Conclusions

These data suggest that HIPK2/Wip1 signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of bladder cancer.     

Schistosoma haematobium total antigen induces increased proliferation, migration and invasion, and decreases apoptosis of normal epithelial cells

Schistosome worms are blood-dwelling flukes that cause chronic infection in more than 200 million people and are thought to be responsible for 500,000 deaths annually. During infection with Schistosoma haematobium, eggs are deposited in the mucosa and submucosa of the bladder and lower ureters. Squamous cell carcinoma (SCC) of the bladder is a long-term sequela of chronic infection. The mechanisms underlying the association between S. haematobium and SCC of the bladder are largely unknown, with all reports to date exclusively demonstrating epidemiological evidence linking S. haematobium infection with SCC of the bladder. We hypothesised that the parasite antigens might induce alterations in epithelial cells towards cancer. For this we used Chinese Hamster Ovary (CHO) cells and treated the cells in culture with S. haematobium total antigen (Sh). Our results showed increased proliferation, increased S-phase and decreased apoptosis, as well as down-regulation of tumour suppressor p27 and up-regulation of anti-apoptotic molecule Bcl-2 in Sh-treated cells compared with controls. We also found increased migration and invasion. To our knowledge, this is the first report demonstrating alterations of normal epithelial cells as a direct effect of S. haematobium antigens.     

Primary Kaposi sarcoma of the subcutaneous tissue

Background

Tumor recurrence following radical cystectomy for a low-grade superficial transitional cell carcinoma (TCC) is exceedingly uncommon and has not been reported previously.

Case presentation

We describe a case of a young male presenting with anorexia, weight loss and a large, painful locally destructive pelvic recurrence, ten years after radical cystoprostatectomy. The pathology was consistent with a low-grade urothelial carcinoma. After an unsuccessful treatment with cisplatin-based chemotherapy, the patient underwent a curative intent hemipelvectomy with complete excision of tumor and is disease free at one year follow-up.

Conclusion

A literature review related to this unusual presentation is reported and a surgical solutions over chemotherapy and radiotherapy is proposed.     

Neuroendocrine small cell carcinoma of the cervix associated with endocervical adenocarcinoma: a case report

BACKGROUND: Small-cell carcinoma (SCC) of the cervix is an uncommon member of the neuroendocrine group of cervical carcinomas that is frequently intermixed with a non-SCC component in the form of an adenocarcinoma (ADC) or squamous carcinoma. CASE: Colposcopy revealed a cervical mass in a 41-year-old woman and a Pap smear the presence of some tumor cells from SCC, which was confirmed by subsequent biopsy. The patient received 3 cycles of chemotherapy and then underwent major surgery. The cervical samples showed areas of endocervical ADC adjacent to and intermixed with the SCC. Reviewing the Pap smear, a previously missed malignancy was recognized. On subsequent molecular investigation to assess clonality by microsatellite analysis, the presence of HR-HPV DNA18 on real-time polymerase chain reaction, p16(INK4a) fluorescence in situ hybridization status and the corresponding immunohistochemical expression supported the hypothesis that the two components of the tumor shared the same cell origin. CONCLUSION: SCC of the cervix is a rare but distinct HR-HPV-18-related cervical carcinoma often intermixed with a clonally related non-small cell component consisting of an ADC or squamous carcinoma. The presence of SCC tumor cells in a cervical smear should prompt a search for malignant glandular or squamous tumor cells.     

膀胱副神经节瘤的诊治分析(附1 例病例报告并文献复习)

目的:总结膀胱副神经节瘤的诊治方法及体会,提高膀胱副神经节瘤的诊断和治疗水平。方法:报告1例膀胱嗜铬细胞瘤的临床资料并结合文献复习分析总结膀胱副神经节瘤的诊断治疗方法。结果:患者行腹腔镜下膀胱部分切除术,手术成功,术后顺利出院,随访至今无转移。结论:膀胱副神经节瘤的诊断主要依靠临床表现和实验室检查,血尿、高血压和排尿时典型发作三联征为膀胱副神经节瘤的主要症状,对于瘤体较小的患者要警惕CT检查漏诊的可能性,可行活组织检查进行确诊。腹腔镜下切除是目前治疗膀胱副神经节瘤最有效、创伤最小的方法,但术后要严格随访。     

Synthesis and biological evaluation of new antioxidant and antiproliferative chalcogenobiotin derivatives for bladder carcinoma treatment

Approximately 90% of bladder carcinomas are of the urothelial carcinoma type, which are characterized by high rates of recurrence and predisposition to progress to invasive tumors, representing one of the most costly neoplasms for health systems. Intravesical chemotherapy is a standard for the treatment of non-invasive bladder cancer. However, chemotherapy is usually aggressive and cytotoxic, which increases the death rates caused by cancer. Heterocyclic compounds which exhibit favorable pharmacokinetic and pharmacodynamic properties may enhance drug affinity for a target protein by targeting the treatment. Thus, this work presents the synthesis, characterization, and in vitro biological evaluation of new antioxidant (inhibition of lipid peroxidation, scavenging of free radical DPPH, and thiol peroxidase-like activity) and antiproliferative chalcogenobiotin derivatives and tests them against bladder carcinoma 5637 cells. A prominent response was obtained for the selected compounds, with tellurium biotin derivatives displaying effective antioxidant and antiproliferative activity. The effective compounds also demonstrated no toxicity in in vitro or in vivo studies.     

Pathologic guidelines for orthotopic urinary diversion in women with bladder cancer: a review of the literature

Orthotopic lower urinary tract reconstruction to the native intact urethra following radical cystectomy for bladder cancer was slower to gain clinical acceptance for women than for men. Until the 1990s, little was known about the natural history of urethral involvement by urothelial carcinoma in women with primary bladder cancer. The increasing availability of pathologic data to define the incidence of and risks for urethral involvement in women sparked an increasing interest in orthotopic diversion in female patients. Pathologic guidelines have been suggested to identify women suitable for orthotopic diversion. Preoperative involvement of the bladder neck is a significant risk factor for secondary tumor of the urethra, but is not an absolute contraindication, as long as full-thickness, intraoperative frozen-section analysis demonstrates no tumor involvement of the proximal urethra. Although less common, anterior vaginal wall tumor involvement may be a significant risk factor for urethral tumor involvement. Other pathologic parameters, including tumor multifocality, carcinoma in situ of the bladder, and tumor grade and stage, do not seem to be absolute contraindications. Long-term follow-up is critical for all patients. Women undergoing orthotopic reconstruction, if appropriately selected, should be assured of an oncologically sound operation and good function with their neobladder.