Small cell carcinoma of the cervix

Small cell carcinoma of the cervix is an uncommon aggressive variety of cervical cancer. Between 1982 and 1993, eight cases of this disease were diagnosed at the Queensland Centre for Gynaecological Cancer among 1586 cervical cancers. Treatment results have been poor with one long-term survivor. Literature review suggests that aggressive chemotherapy combined with surgery and/or radiotherapy may improve survival.     

子宫颈小细胞神经内分泌癌的临床病理分析

Objective To analyse the clinico-pathologic characteristics,diagnosis,therapy and prognostic of small cell neuroendocrine carcinoma of the cervix(SCNCC).Methods The clinic-pathological features of 12 patients with SCNCC treated in Tumor Hospital of Guangxi Medical University,admitted during March 2006 to July 2010,were analyzed retrospectively.Results Of 12 patients,the mean age was 38.7 years(rang 28-57 years),6 had stages Ⅰ b1-Ⅱa,6 had stagesⅡb-Ⅳ.Among 8 patients(Ⅰ b1-Ⅲb)underwent surgery,4 of them received neoadjuvant chemotherapy,8 of them received adjuvant chemotherapy and(or)radiotherapy.All had greater than one-half stromal invasion,4 patients had positive pelvic lymph nodes metastases.The positive ratio of the chromogranin(CgA),synaptophysin,neuronspecific enolase(NSE),cytokeratins(CK),CD56 tested by immunohistochemical staining were 8/12,9/10,4/4,4/4,4/4,respectively.Median follow-up period was 3 months(1-22 months).Among 8 patients underwent surgery,2 patients developed lung metastases,1 patient developed liver and lung metastases,1 patient developed liver metastases concurrently with bone metastases,disease-free survival (DFS)were 3 months(Ⅰ b2 with positive lymph nodes),4.6 months(Ⅱ a),7 months(Ⅰ b1),17 months (Ⅰ b2);2 patient died(8.5 and 11.3 months,respectively)after surgery;4 patients are alive and show no evidence of disease.Among 4 patients untreated,1 patients received concurrent chemoradiation and are alive for 10.1 months.Two patient untreated(Ⅲb,Ⅳ)died after 0.6 and 1.3 months final diagnosis,respectively.One patient Was lost follow-up.Conclusions SCNCC is a highly malignant tumor with rare morbility,propensity for distant spread and dismal prognosis.Final diagnosis of SCNCC depends on pathomorphology and immunohistochemical analysis.Combined therapeutic modalities may in favor of survival in some patients.     

子宫颈小细胞神经内分泌癌的临床病理分析

Objective To analyse the clinico-pathologic characteristics,diagnosis,therapy and prognostic of small cell neuroendocrine carcinoma of the cervix(SCNCC).Methods The clinic-pathological features of 12 patients with SCNCC treated in Tumor Hospital of Guangxi Medical University,admitted during March 2006 to July 2010,were analyzed retrospectively.Results Of 12 patients,the mean age was 38.7 years(rang 28-57 years),6 had stages Ⅰ b1-Ⅱa,6 had stagesⅡb-Ⅳ.Among 8 patients(Ⅰ b1-Ⅲb)underwent surgery,4 of them received neoadjuvant chemotherapy,8 of them received adjuvant chemotherapy and(or)radiotherapy.All had greater than one-half stromal invasion,4 patients had positive pelvic lymph nodes metastases.The positive ratio of the chromogranin(CgA),synaptophysin,neuronspecific enolase(NSE),cytokeratins(CK),CD56 tested by immunohistochemical staining were 8/12,9/10,4/4,4/4,4/4,respectively.Median follow-up period was 3 months(1-22 months).Among 8 patients underwent surgery,2 patients developed lung metastases,1 patient developed liver and lung metastases,1 patient developed liver metastases concurrently with bone metastases,disease-free survival (DFS)were 3 months(Ⅰ b2 with positive lymph nodes),4.6 months(Ⅱ a),7 months(Ⅰ b1),17 months (Ⅰ b2);2 patient died(8.5 and 11.3 months,respectively)after surgery;4 patients are alive and show no evidence of disease.Among 4 patients untreated,1 patients received concurrent chemoradiation and are alive for 10.1 months.Two patient untreated(Ⅲb,Ⅳ)died after 0.6 and 1.3 months final diagnosis,respectively.One patient Was lost follow-up.Conclusions SCNCC is a highly malignant tumor with rare morbility,propensity for distant spread and dismal prognosis.Final diagnosis of SCNCC depends on pathomorphology and immunohistochemical analysis.Combined therapeutic modalities may in favor of survival in some patients.     

子宫颈小细胞神经内分泌癌的临床病理分析

目的 分析宫颈小细胞神经内分泌癌(SCNCC)的临床病理特征、诊断、治疗及预后.方法 回顾性分析2006年3月-2010年7月在广西医科大学附属肿瘤医院诊治的12例SCNCC患者的临床病理资料,包括临床特征(患者的年龄、临床分期、肿瘤类型及大小)、病理特征(肿瘤浸润、淋巴结转移、免疫组化检测结果 )、治疗及预后.结果 (1)临床特征:12例患者的平均年龄38.7岁(28～57岁);临床分期:按国际妇产科联盟(FIGO,2009年)标准,Ⅰ b1～Ⅱa期6例,Ⅱb～Ⅳ期6例;肿瘤类型及大小:9例为外生型菜花样肿物,其中7例直径≥4 cm,2例＜4 cm;2例为宫颈糜烂;1例宫颈光滑但颈管增粗.(2)病理特征:8例手术患者(Ⅰ b1～Ⅲb期)中,肿瘤浸润达间质深层(≥1/2宫颈间质)6例,达间质全层2例;盆腔淋巴结转移4例.免疫组化检测显示,嗜铬素A(CgA)、突触素、神经元特异性烯醇化酶(NSE)、细胞角蛋白(CK)、CD56的阳性率分别为8/12、9/10、4/4、4/4、4/4.(3)治疗及预后:8例手术患者中,7例行广泛性子宫切除+双侧(或单侧)附件切除+盆腔(或加腹主动脉旁)淋巴清扫术,1例行广泛性子宫切除+双侧卵巢移位+盆腔淋巴清扫术.其中,4例术前、8例术后接受了辅助治疗(化疗或加放疗).中位随访时间为3个月(1～22个月),8例手术患者中,4例发生转移,其无瘤生存时间分别为3～17个月,其中2例分别于术后8.5、11.3个月死亡;4例患者仍存活,在随访期间,未见明确肿瘤复发和转移表现.未手术的4例患者(Ⅲb～Ⅳ期)中,1例予同步放化疗者确诊后已存活10.1个月,仍在随访中;2例未治疗患者分别于确诊后0.6及1.3个月死亡;1例未治疗患者失访.结论 SCNCC恶性程度高,易发生远处转移,预后差,诊断应联合组织病理学检查及免疫组化法检测,采用以手术为主的综合治疗可改善部分患者的预后.

Abstract：

Objective To analyse the clinico-pathologic characteristics,diagnosis,therapy and prognostic of small cell neuroendocrine carcinoma of the cervix(SCNCC).Methods The clinic-pathological features of 12 patients with SCNCC treated in Tumor Hospital of Guangxi Medical University,admitted during March 2006 to July 2010,were analyzed retrospectively.Results Of 12 patients,the mean age was 38.7 years(rang 28-57 years),6 had stages Ⅰ b1-Ⅱa,6 had stagesⅡb-Ⅳ.Among 8 patients(Ⅰ b1-Ⅲb)underwent surgery,4 of them received neoadjuvant chemotherapy,8 of them received adjuvant chemotherapy and(or)radiotherapy.All had greater than one-half stromal invasion,4 patients had positive pelvic lymph nodes metastases.The positive ratio of the chromogranin(CgA),synaptophysin,neuronspecific enolase(NSE),cytokeratins(CK),CD56 tested by immunohistochemical staining were 8/12,9/10,4/4,4/4,4/4,respectively.Median follow-up period was 3 months(1-22 months).Among 8 patients underwent surgery,2 patients developed lung metastases,1 patient developed liver and lung metastases,1 patient developed liver metastases concurrently with bone metastases,disease-free survival (DFS)were 3 months(Ⅰ b2 with positive lymph nodes),4.6 months(Ⅱ a),7 months(Ⅰ b1),17 months (Ⅰ b2);2 patient died(8.5 and 11.3 months,respectively)after surgery;4 patients are alive and show no evidence of disease.Among 4 patients untreated,1 patients received concurrent chemoradiation and are alive for 10.1 months.Two patient untreated(Ⅲb,Ⅳ)died after 0.6 and 1.3 months final diagnosis,respectively.One patient Was lost follow-up.Conclusions SCNCC is a highly malignant tumor with rare morbility,propensity for distant spread and dismal prognosis.Final diagnosis of SCNCC depends on pathomorphology and immunohistochemical analysis.Combined therapeutic modalities may in favor of survival in some patients.     

Small cell carcinoma of the cervix: a case report

Small cell carcinoma of the uterine cervix accounts for 1–3% of all cervix cancers. It is an aggressive disease with a poor prognosis. To date, no effective treatment protocol has been determined. Surgery, radiotherapy, and chemotherapy have been used either alone or in combination. Recent data suggests that survival in patients with early staged small cell carcinoma of the cervix is better with surgery combined with chemo-radiotherapy. Here, we presented two patients with stage IB1 small cell carcinoma of the uterine cervix. For both patients, definitive surgery was performed with pelvic and para-aortic lymphadenectomy. Subsequently, they were treated with pelvic external radiotherapy and high-dose-rate intracavitary brachytherapy with concurrent cisplatin based chemotherapy. They were alive with no evidence of disease at 91 and 65 months, respectively.     

子宫颈小细胞癌——一种特殊类型宫颈癌

目的 了解子宫颈小细胞癌(SCCC)的临床病理与生物学行为特征,探讨其治疗方法。方法回顾性分析6例SCCC患者的临床病理资料及随访记录。结果Ib期Ⅰ例、Ⅱa期2例、Ⅲb期3例。盆腔淋巴结转移2例,肝等器官转移4例,对6例患者采用手术+放疗+化疗或放疗+化疗的综合治疗,2例分别已存活30、20个月,另4例分别存活10、11、13、14个月后死亡。结论 子宫颈小细胞癌与肺小细胞癌的组织病理学和生物学行为特征相似,早期易发生盆腔淋巴结和远处转移,对化学治疗比较敏感。对早期患者应行广泛性子宫切除术+盆腔淋巴结清扫术,术后给予辅助性放疗和化疗;对晚期患者应采用放疗和化疗。     

Paclitaxel and carboplatin for large cell neuroendocrine carcinoma of the uterine cervix

The prognosis of large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is generally poor despite multimodality of treatments. We report a case of advanced stage cervical LCNEC that showed definite response to paclitaxel/carboplatin, resulting in years of survival. The patient was referred to our institution after undergoing a simple hysterectomy with bilateral salpingo-oophorectomy in her local hospital because of a ruptured metastatic ovarian mass. She declined pelvic radiation treatment, so adjuvant chemotherapy (six cycles of paclitaxel/carboplatin) was given for the residual pelvic nodal diseases. Clinical complete remission was obtained, with a disease-free period of 19 months. Systemic recurrent diseases also showed partial response to the same drug regimen for months with only minimal toxicity. However, she subsequently had progressive diseases in the liver and brain and finally died at 44 months after primary diagnosis and 19 months after recurrent diseases.     

C-kit overexpression in neuroendocrine small cell carcinoma of the uterine cervix

PURPOSE OF INVESTIGATION: Neuroendocrine small cell carcinoma of the uterine cervix (NESCC) grows aggressively, and is resistant to anticancer agents and radiation, having an extremely poor prognosis. The incidence of c-kit proto-oncogene overexpression is high in gastrointestinal stromal tumors (GISTs) and small cell lung cancer, and tyrosine kinase inhibitors have been used effectively to treat GISTs. Few studies have investigated whether c-kit is overexpressed in NESCC. To investigate whether NESCC can be a target for molecular targeted therapy with tyrosine kinase inhibitors, we examined the expression of c-kit in this tumor. METHODS: Twenty-one NESCCs were examined for c-kit expression by immunohistochemical staining using the labeled streptavidin-biotin complex (LSAB) method. The expression of c-kit was regarded as positive (overexpression) and negative when the membrane and cytoplasm of more or less than 25%, respectively, of tumor cells were stained. RESULTS: Nine NESCCs (43%) were c-kit-positive (overexpression). No difference in age or clinical stage was noted. No difference in prognosis was observed between the c-kit-positive and -negative patients. CONCLUSION: The incidence of c-kit overexpression was high in NESCC; therefore, the patients with this tumor may become a future target for molecular-targeted therapy with tyrosine kinase inhibitors.     

Small cell carcinoma of the cervix: a clinical and flow-cytometric study.

The clinical course of 14 patients diagnosed with small cell carcinoma of the cervix (SCC) was reviewed and compared to that of 37 cases of undifferentiated large cell nonkeratonizing carcinoma (LCNK). We observed the following differences between the two: SCC patients had a higher incidence of pelvic wall involvement and distant metastasis; the development of progressive disease was more frequent in SCC than in LCNK patients; median survival time was 9 months in SCC and 40 months in LCNK patients; flow cytometry revealed aneuploidy in all SCC and in 30% of the LCNK patients; the mean DNA index was 2.24 in SCC, significantly higher than in LCNK (1.15). DNA index in cases of SCC was related to survival time. SCC of the cervix is an extremely aggressive tumor, even when compared to other undifferentiated cervical cancers. Aneuploidy is a consistent feature and thus helpful for diagnosis. Due to the wide range of values, the DNA index cannot be used for diagnostic purposes, but it is of prognostic importance in SCC cases.     

Small cell neuroendocrine carcinoma of the cervix with involvement of multiple pelvic nodes--A successfully treated case by multimodal approach

Small cell neuroendocrine carcinoma of the cervix is very rare and is usually associated with dismal prognosis if treated by conventional surgery and radiotherapy even in early stage disease. This tumor is characterized by early lymphatic and hematogenous spread. Only one successfully treated case of small cell neuroendocrine carcinoma of the cervix with dissemination to the pelvic nodes had been reported before in the literature. We are reporting a case of small cell neuroendocrine carcinoma of the cervix with multiple pelvic nodal metastases including the common iliac nodes, which had been successfully treated with a multimodal approach including radical hysterectomy, pelvic/para-aortic lymphadenectomy, and postoperative chemotherapy using cisplatin-etoposide combinations and pelvic irradiation.     

Time course and outcome of central recurrence after radiation therapy for carcinoma of the cervix

We investigated the time course of central disease recurrence (CDR) in 2997 patients treated with radiation for stage I-II squamous cell carcinoma of the cervix. CDR rates were 6.8%, 7.8%, and 9.6%, at 5, 10, and 20 years, respectively. The risk of CDR was independently correlated with tumor size (P < 0.0001) but not with FIGO stage. The hazard rate peaked in the first year of follow-up and then fell steeply; after 3 years, the hazard rate was approximately constant at 0.2-0.4% per year. Although after 3 years the risk of CDR was low, it continued to be slightly greater for patients with tumors > or =5 cm than for those with smaller tumors (P= 0.001). Patients who had CDR < 36 months after treatment were less likely to be candidates for salvage therapy and had a poorer post-recurrence survival rate than those with recurrence > or =36 months after treatment (4.5% versus 42.1%, P < 0.0001). The higher rate of CDR in the first 3 years and the poor survival after early recurrence suggest that most early CDRs are true relapses. The relatively stable annual actuarial risk between 3 and 25 years and the better survival rate after late CDR suggest that most "recurrences" after 3 years are actually new neoplasms.     

Large cell neuroendocrine carcinoma of the cervix: prognostic factors and survival advantage with platinum chemotherapy

Objective

Large cell neuroendocrine carcinoma of the cervix (LCNEC) is a rare cervical neoplasm associated with poor survival. Our objective was to identify treatments associated with improved survival.

Methods

Relevant data were abstracted from an English literature MEDLINE search, SEER database, and a patient treated at our institution. Multivariate analysis was performed by generating Cox proportional hazard ratios.

Results

We identified 62 patients with LCNEC: 49 cases from the English literature, 12 patients in the SEER database and our patient. Out of the 62 women, median age was 37 (range, 21-75). FIGO stage was as follows: 58% had stage I disease, 16% had stage II, 2% had stage III, 8% had stage IV disease and 16% had no stage documented. Of all patients, 73% underwent primary surgery, 4.7% underwent primary radiation, 4.7% underwent chemotherapy, 8% had chemoradiation, and 9.6% had no primary treatment. Of all patients, 58% died of disease, 26% had no evidence of disease, 3% were alive with disease, and 13% had no survival data. The overall median survival was 16.5 months (0.5-151 months). Median overall survival for stage I, II, III, and IV cancers was 19, 17, 3, and 1.5 months, respectively. In a multivariate analysis, earlier stage (p < 0.00001) and the addition of chemotherapy (p = 0.04) were associated with improved survival. Both platinum agents (p = 0.034) and platinum and etoposide together (p = 0.027) were associated with improved survival.

Conclusions

Perioperative chemotherapy, in particular platinum with or without etoposide, improves survival in the rare LCNEC.     

Late recurrence in carcinoma of the cervix

The incidence of late recurrence of cancer of the cervix (more than 10 years after primary therapy) was low, namely, 0.76 per cent (16 of 2,107 patients treated). Although these 16 patients were accepted as having bona fide recurrences, some of them may have had new cancers or even radiation-induced cancers. Radiation was the initial therapy for every patient who had recurrence. The sites of recurrence varied, and multiple regions and organs, particularly within the pelvis, were often involved. Treatment was individualized and included radical surgery, radiation (intracavitary radium and external-beam therapy), and chemotherapy with 5-fluorouracil. To date 3 patients have survived for 4½ years or longer after treatment of the recurrence. In all 3, the treatment of the recurrence was surgical.