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.     

Adjuvant therapy for neuroendocrine small cell carcinoma of the cervix: review of the literature.

Neuroendocrine cell carcinoma of the cervix is a virulent tumor associated with an extremely poor prognosis. Even in clinical Stage I disease, there may be subclinical hematogenous and lymphatic metastases with frequent recurrences. Adjuvant postoperative external pelvic radiotherapy has been reported to offer some degree of local control; however, most patients succumb to distant disease. Following radical abdominal hysterectomy and pelvic lymphadenectomy, with confirmation of the neuroendocrine tumor by electron microscopy and immunohistochemical staining, two patients were given adjuvant systemic chemotherapy with concurrent pelvic radiotherapy, employing regimens with documented activity against small cell carcinoma of the lung of neuroendocrine origin. Despite severe myelotoxicity and persistent neuropathy, both patients are alive without clinical evidence of disease at 28+ and 47+ months.     

Neuroendocrine small cell carcinoma of the uterine cervix showing polypoid growth and complicated by pregnancy

BACKGROUND: Neuroendocrine small cell carcinoma of the uterine cervix is an aggressive disease, and it rarely is complicated by pregnancy. CASE: A polypoid tumor was found in the uterine cervix in a 27-year-old Japanese woman at 27 weeks of gestation. No polyp had been detected at 14 weeks of gestation. The polyp was excised and diagnosed as neuroendocrine small cell carcinoma by histological examination, including Grimelius, neuron-specific enolase, and chromogranin staining. A healthy infant was born by cesarean section at 29 weeks of gestation: this was followed by radical hysterectomy with pelvic lymphadenectomy. After surgery, four cycles of combination chemotherapy with cisplatin and etoposide were administered, and the patient is disease-free as of 13 months after surgery. CONCLUSION: When a polypoid lesion is found, especially when it demonstrates rapid growth, it may be necessary to excise and histologically examine the polyp even during pregnancy.     

A Case of Small Cell Carcinoma of the Uterine Cervix Presenting Cushing's Syndrome

A proportion of small cell carcinoma of the uterine cervix is known to secrete a neuroendocrine substance. However, cases presenting Cushing's syndrome due to ACTH secreted from a cervical small cell carcinoma are extremely rare. Here, we report a case of small cell carcinoma of the uterine cervix that ectopically secreted ACTH and presented Cushing's syndrome. A 42-year-old woman was initially admitted to the endocrine unit for investigation of ectopic ACTH syndrome. Serum cortisol and plasma ACTH levels were elevated with no diurnal variation. After gynecologic examination, her original disease was found to be a stage IIb cervical small cell carcinoma. She underwent a radical hysterectomy and pelvic lymphadenectomy. The entire tumor was excised and post-TNM classification was T2bN1M0. Immunohistochemically, tumor cells stained strongly for ACTH and chromogranin. Electron-microscopic pictures showed typical neurosecretory granules. Although plasma ACTH returned to normal after surgery, liver metastasis appeared during the course of postoperative irradiation. She died 9 months after operation in spite of vigorous systemic chemotherapy.     

子宫颈鳞状细胞癌复发患者血清鳞状细胞癌抗原监测的意义

目的探讨血清鳞状细胞癌抗原（SCCAg）在监测宫颈鳞癌患者复发中的意义。方法对1999-2005年收治的72例宫颈鳞癌复发患者血清SCCAg水平与诊断、预后的关系进行单因素和多因素分析。结果72例复发患者中,术后复发30例、放化疗后复发42例,其中血清SCCAg水平升高者61例（占85％）。此61例患者中,20例在随诊中首先出现血清SCCAg水平升高而临床及影像学检查未发现肿瘤,血清SCCAg水平提前升高的中位时间为3个月,平均4．6个月（1～13个月）。72例复发患者中,45例患者无任何临床症状,仅因血清SCCAg水平升高或常规随诊发现复发;27例患者有症状,其中单侧下肢水肿或疼痛15例,阴道不规则流血7例,出现远处转移相关症状5例。细胞或组织病理学检查诊断复发者33例;临床及影像学检查结合血清SCCAg水平诊断复发者39例,其中29例仅依靠血清SCCAg水平升高及影像学检查即诊断复发。72例复发患者的中位生存时间为11个月,平均生存时间为23个月（2～62个月）,总的3年生存率为25％,5年生存率为19％。单因素分析发现,初治前患者血清SCCAg水平、病理分级、复发部位、复发后治疗方式以及复发时、复发后治疗中、治疗后血清SCCAg水平对患者的3年生存率有明显影响（P〈0．01）;但20例血清SCCAg水平提前出现升高的患者与52例血清SCCAg水平未提前升高的患者相比,3年生存率分别为22％、27％,差异无统计学意义（P=0．5761）。多因素分析发现,复发患者仅病理分级、复发后的治疗方式是独立的预后影响因素（P〈0．05）;而复发部位及各种血清SCCAg状态不是独立的预后影响因素（P〉0．05）。结论血清SCCAg水平监测在宫颈鳞癌复发患者中的诊断及其对预后的判断中有一定的价值。     

Adjuvant combined paclitaxel and carboplatin chemotherapy for glassy cell carcinoma of the uterine cervix: report of three cases with clinicopathological analysis

Glassy cell carcinoma of the uterine cervix (GCC) is a rare form of cervical carcinoma that is characterized by aggressiveness and poor prognosis. We reviewed a variety of clinicopathological features, treatment strategies, and outcomes in three women with GCC. The three patients were successfully treated by radical hysterectomy with pelvic/para-aortic lymphadenectomy. The patients had stage Ib1, stage IIa, and stage Ib2 tumors without lymph node metastases. A 44-year-old woman with stage Ib1 tumor did not undergo adjuvant chemotherapy or radiation therapy. She had recurrent pelvic tumors 12 months after surgery, and died 6 months after the recurrent disease. The histological findings of her cervix, which were different from the other two patients, did not show the marked infiltration of eosinophils. The other two patients with stage Ib2 and IIa tumors underwent adjuvant chemotherapy with paclitaxel and carboplatin, and had disease-free survival for 4.5 and 9 years. We think that all patients with GCC of stage Ib1 or more should undergo adjuvant chemotherapy of paclitaxel and carboplatin or other adjuvant therapies.     

子宫颈小细胞癌八例临床病理分析

目的 研究宫颈小细胞癌的临床病理特征、治疗方法和预后.方法 回顾性分析1999年1月至2005年12月间中国医学科学院中国协和医科大学肿瘤医院妇瘤科收治的8例宫颈小细胞癌患者的临床及病理资料.结果 8例患者均表现为不规则阴道流血或接触性出血.临床分期按1994年国际妇产科联盟分期标准为Ⅰ b1期1例、Ⅰ b2期2例、Ⅱ b期2例、Ⅲb期3例.组织学特点为体积小的圆形或短梭形细胞,形态大小较一致,细胞质少,核深染,染色质细,核仁不明显,核分裂象多见.7例行免疫组化染色,神经元特异性烯醇化酶均为阳性.3例Ⅰ b期和1例Ⅲb期患者行手术治疗,术后辅助化疗(或加放疗),生存时间分别为64、22、14和6个月.2例Ⅱ b期和2例Ⅲb期患者行放、化疗,生存时间分别为25、9、10和5个月.结论 联合光镜和免疫组化法检查可提高宫颈小细胞癌诊断的准确率.治疗应采用综合治疗,尤其应重视化疗的作用.     

Small-cell carcinoma of the uterus and the vagina: experience with ten patients

Background Small cell carcinomas (small-CCs) of the uterine cervix are rare and highly malignant neoplasms. Patients tend to develop distant metastasis early and thus are potential candidates for systemic therapy. We reviewed the experience with small-CCs of the uterus and vagina at two Austrian University hospitals.Material and methods Ten patients (median age, 50 years; range, 18–92) with small-CC of the cervix (n=7), uterine corpus (n=2), and the vagina (n=1) were treated at the two centers between 1988 and 1998. Eight patients underwent radical surgery, 7 of whom also received chemotherapy. Two additional patients underwent primary radiotherapy.Results All Pap smears were suspicious for cervical malignancy. The median survival was 12 months (range, 6–86) and overall 5-year survival was 10%. Five of 8 surgically treated patients had lymph node involvement (62%). Of the 7 patients with small-CC of the cervix only one, who had FIGO stage IIB disease and positive pelvic nodes, survived long-term (86 months) with no evidence of disease. She had received six courses of dose-intensive platinum chemotherapy after radical surgery. All three patients with small-CC of the uterine corpus or vagina developed recurrence within the first year after diagnosis. Of the 7 patients who received chemotherapy, 5 developed progressive or recurrent disease in the paraaortic region (n=2), peritoneum (n=1), liver (n=1), or pelvis (n=1).Conclusion These results confirm the particularly unfavorable prognosis of patients with small-CC of the genital tract. The optimal treatment for these patients most probably including concurrent chemo-radiotherapy remains to be defined.     

A cure from the small cell neuroendocrine carcinoma of the uterine cervix following conventional surgery

The small cell neuroendocrine carcinoma of the uterine cervix is a rare, but very aggressive neoplasm. Previous reports suggested that it had dismall prognosis if treated with conventional surgery and radiotherapy, even in early stage disease. We present the case of neuroendocrine cervical carcinoma that was cured from the disease following conventional surgery only.     

Prognostic significance of histopathological classification in patients with carcinoma of the uterine cervix

In a retrospective study of 724 patients with histologically proven carcinoma of the uterine cervix from 1980 through 1986, the histological classification and clinical stage (FIGO) were investigated for their prognostic value. The clinical stage was very important in relation to prognosis. The histological type of the squamous cell carcinoma (keratinizing, large cell non-keratinizing, small cell non-keratinizing) did not have any value in predicting survival, but small cell non-keratinizing tumor showed a less favorable prognosis than other tumors when surgery was employed. As to survival, there was no difference between adenocarcinoma and squamous cell carcinoma when compared in all patients, but adenocarcinoma had a worse prognosis than squamous cell carcinoma when surgery was employed. The pelvic lymphnode status at operation was correlated with the clinical stage. Adenocarcinoma had more positive nodes than squamous cell carcinoma. There was no significant difference in the frequency of pelvic node involvement among cell types of squamous cell carcinoma. The present histopathological classification of the uterine cervical carcinoma was of little prognostic value in predicting patient outcome.     

子宫颈小细胞癌的临床及病理分析

目的 探讨子宫颈小细胞癌的临床病理特征诊断和治疗。方法 回顾性分析８例子宫颈小细胞癌的临床记录和随访资料。结果 ８例均表现为不同程度的阴道排液增多,病理学特点为大小形态一致的圆形或短梭形小细胞,弥漫性浸润间质,符事宫颈小细胞癌的病理学诊断;２例神经元特异性烯醇化酶免疫组织化学染色阳性,８例中,Ｉｂ期５例,Ⅱｂ期３例,７例接受了广泛子宫切除及盆腔淋巴结清扫描术治疗,１例Ⅱｂ期患者仅接受了放射治疗。２     

Surgery following chemotherapy and radiotherapy for advanced carcinoma of the cervix

Ten patients with advanced squamous carcinoma of the cervix have been treated with both radiotherapy and monthly cyclical chemotherapy. All patients have subsequently undergone a simple hysterectomy and bilateral salpingo-oophorectomy with para-aortic and pelvic node biopsy. Six patients were found to be histologically free of disease, 2 patients had residual cervical disease completely excised, and 2 patients had persistent intra-abdominal disease. Eight patients have survived 24-43 months one of whom has recurrent disease. The addition of chemotherapy to standard radiotherapy appears to have improved the results of treatment, however, in view of the high complication rate (50%) it is considered that surgical assessment of response is not justified and that surgery should only be undertaken where there is good evidence of persistent but operable disease.     

Neuroendocrine tumors of the uterine cervix. Clinicopathologic study of five patients

Four main clinicopathologic features of neuroendocrine tumors (NETs) of the cervix may be stressed: primary diagnosis at an advanced stage, early nodal metastasis even for low disease, early failure of appropriate local treatment (surgery and/or radiation therapy) and aggressive clinical treatment. Five patients with NET of the uterine cervix (small cell carcinoma type) are reported (one stage I, two stages II, one stage III and one stage IV). One patient was treated by surgery combined with radiation therapy, one by surgery combined with chemotherapy and one by surgery with radiation therapy and chemotherapy. Two patients received radiation therapy alone. Three early stage patients are alive with no evidence of disease 8, 26 and 41 months after diagnosis. The two patients with advanced stage died of disease, 3 and 12 months respectively, after diagnosis. Combination chemotherapy (cisplatin and etoposide) is warranted in disseminated NETs. Neoadjuvant or adjuvant chemotherapy should be combined with radiation therapy and surgery even in early stages.     

Intra-arterial Chemotherapy with Cisplatin Followed by Radical Radiotherapy for Locally Advanced Cervical Cancer

Locally advanced cervical cancer has a dismal prognosis, with a high local failure rate and a poor survival rate. To improve the cure rate for advanced carcinoma of the cervix, we initiated a study of intra-arterial (I-A) chemotherapy with cisplatin via the uterine artery prior to definitive radiotherapy. I-A chemotherapy via the internal iliac artery has been used to treat advanced cervical cancer; however, access by way of the uterine artery has not been tested for this purpose. Thirty-four patients with central tumor ≥5 cm in anteroposterior diameter observed on CT scans were treated with I-A chemotherapy. I-A chemotherapy consisted of unilateral catheterization of the uterine artery using 120 mg/m²cisplatin. After assessment of I-A chemotherapy, all but 3 patients were treated with a combination of whole-pelvis external irradiation and intracavitary irradiation. The 3 patients underwent external radiotherapy alone. Twenty-seven of 34 patients treated were evaluable for response to I-A chemotherapy. Eleven patients (41%) experienced a partial response. Seventy-six percent of the 34 patients treated with I-A chemotherapy followed by radiotherapy exhibited a complete response by the end of treatment. Toxicity was well tolerated and no death due to treatment occurred. The 2- and 5-year actuarial survival rates were 64 and 55%, respectively. The crude incidences of pelvic recurrence and distant metastasis observed at a median follow-up of 54 months were both 47%. This study for locally advanced cervical cancer suggests there is benefit to be derived from our I-A chemotherapy followed by radical radiotherapy.     

子宫颈小细胞癌10例临床与预后分析

目的 :研究子宫颈小细胞癌 (SCCC)的临床病理、生物学行为特征及预后 ,探讨其治疗方法。方法 :回顾性分析 10例SCCC患者的临床病理资料及随访记录。结果 :SCCCⅠb期 2例、Ⅱa期 4例、Ⅲb期 4例 ,SCCC早期即可发生盆腔淋巴结转移 ,并很容易转移至肺、肝等器官 ;对 10例患者采用手术 +放疗 +化疗或放疗 +化疗的综合治疗 ,5例分别已存活 37、2 7、16、10、9个月 ,另 5例分别存活 10、10、11、13、14个月后死亡。结论 :SCCC与肺小细胞癌的组织病理学和生物学行为特征相似 ,早期容易发生盆腔淋巴结转移和远处转移 ,对化学治疗比较敏感 ,早期患者应行子宫广泛性切除术 +盆腔淋巴结清扫术 ,术后给予辅助性放疗和化疗 ;晚期患者应采用放疗 +化疗。化疗目的在于预防或治疗远处转移性病变     

A short and intensive single-agent cisplatin regimen for recurrent carcinoma of the uterine cervix

Between May 1991 and September 1993, 36 patients with recurrent carcinoma of the uterine cervix were treated with single-agent cisplatin using an intensive regimen of four weekly cycles of 50 mg m⁻² followed in responders by a further four cycles given every fortnight. The response rate was 47% (95% CI: 27–66%), 56% in those with pelvic recurrence, and 38% in those with metastatic disease. All responses but one were seen within 4 weeks of commencing treatment. Three patients (9%) had a complete response, although in two cases this was of short duration. The treatment was moderately well tolerated and the principle toxicities were myelotoxicity and emesis. The median survival was 32 weeks, and the 18-month survival was 13%.
This regimen gives a response rate similar to that seen with more toxic combination chemotherapy regimens such as BIP (bleomycin, ifosfamide and cisplatin). It has the particular advantages of a short duration of treatment and early response, allowing treatment to be stopped after 4 weeks in non-responders. The response rate in pelvic recurrence was better than that seen in most previous chemotherapy trials, particularly as 78% of the evaluable patients with pelvic recurrence had previously received radical radiotherapy to the pelvis.
Weekly, followed by fortnightly cisplatin, is an appropriate palliative treatment for patients with recurrent carcinoma of the uterine cervix for whom chemotherapy is indicated.     

Role of centralization of surgery in Stage IB carcinoma of the cervix: a review of 498 cases

A review was undertaken of 498 patients with stage IB carcinoma of the cervix managed over a 15-year period in the Regional Gynaecological Oncology Centre, Gateshead. All but 4 were treated by radical hysterectomy, with adjuvant radiotherapy and/or chemotherapy for those with involved pelvic nodes. The overall 5-year survival in those with negative nodes was 91.4% compared with 50.5% in those with positive nodes (P less than 0.05). Of those dying from the disease, 7 patients only (1.4%) developed central recurrence, the remainder experiencing pelvic side-wall or distant recurrence. There was no difference in survival related to patient age. There were three deaths related to surgery and a fistula rate of only 1.2%. Bladder hypotonia and lymphocyst affected a minority of patients in the long term. The data support the case for radical surgery in stage IB carcinoma of the cervix, managed on a centralized referral basis.     

Large cell neuroendocrine carcinoma of the uterine corpus metastatic to brain and lung: case report and review of the literature

Neuroendocrine carcinoma of the uterine corpus is a rare aggressive tumor with a similar unfavorable outcome to that of the cervix. The large cell type is considerably rarer than the small cell neuroendocrine carcinoma of the uterine corpus. We report a case of a 52-year-old woman who presented with a large cell neuroendocrine tumor of the uterine corpus with very aggressive clinical behavior, cerebral and pulmonary metastases six and four months after initial diagnosis and adjuvant radiotherapy, respectively. Despite successful surgical extirpation of the cerebral metastatic lesion she did not respond to chemotherapy and died four months after disease recurrence.     

Primary malignant lymphoma of the cervix. A case report

BACKGROUND: Primary malignant lymphoma of the female genital tract is rare. A review of the literature suggests that 1 in 175 extranodal lymphomas in women is likely to originate in the vagina, uterus or cervix. Often the diagnosis of primary lymphoma is not established until after an operation has been performed. Postsurgical treatment is usually chemotherapy alone or followed by radiotherapy. CASE: A 40-year-old woman presented in January 2001 with uterine bleeding. After the patient underwent total abdominal hysterectomy, primary cervical malignant lymphoma was diagnosed. Six courses of chemotherapy were administered in an adjuvant setting. Twenty-seven months (April 2003) after the diagnosis the patient was alive and without signs of recurrent disease. CONCLUSION: Awareness of this rare clinical entity is important because these tumors can present at any age and may mimic squamous cell carcinoma of the cervix clinically and histologically. Abnormal uterine bleeding is the most common presenting symptom of primary malignant lymphoma of the cervix. Extent of disease, size of primary lesion and type of lymphoma are significant prognostic features. Radical surgery is unnecessary. Standard postsurgical treatment has not yet been established.     

Concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy for women with locally advanced carcinoma of the uterine cervix--final results of a prospective phase II-study

OBJECTIVES: To evaluate the efficacy and toxicity of ifosfamide and cisplatin administered concomitantly with low-dose rate brachyradiotherapy followed by consolidation chemotherapy in the treatment of locally advanced squamous cell carcinoma (LASCC) or adeno/adenosquamous carcinoma of the uterine cervix. METHODS: Sixty-two patients with primary uterine cervical cancer were enrolled between August 1999 and November 2004. The patients had to have FIGO-stage IB2 bulky to IVA disease, biopsy-proven squamous cell or adeno/adenosquamous carcinoma of the uterine cervix. The patients were to receive external radiotherapy (50 Gy in 25 fractions); ifosfamide 2 g/m2 plus cisplatin 75 mg/m2 was applied concomitantly during two low-dose rate brachyradiotherapy applications; the planned dose to point A was 85 Gy in total. After the completion of radiotherapy, i.e. external and concomitant chemobrachyradiotherapy, four cycles of consolidation chemotherapy with the same drug combination were to be administered. RESULTS: The clinical complete response rate according to WHO-classification (assessed after the completion of the whole treatment procedures by gynecologic and radiologic evaluation and cervical biopsy) was 100%. After a median follow-up of 49 months (range 11-74 months), the recurrence-free and overall survival rates were 88.7%, respectively. The most frequent early toxicities were grade 3 and 4 leukopenias occurring in 25% and 11% of the cycles, respectively. Major delayed local complications occurred in 10 patients (16.1%). CONCLUSION: These results indicate that concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy with the same drug combination is a highly efficacious and very promising treatment protocol for patients with locally advanced LASCC or adeno/adenosquamous carcinoma of the uterine cervix.