Small Cell Carcinoma Of The Cervix Research Articles

2100 Local therapy for small cell carcinoma of the cervix

2100 Local therapy for small cell carcinoma of the cervix

Prognostic factors of early stage cervical cancer treated by radical hysterectomy.

This study was performed to identify pathologic and clinical features that best correlate with lymph node metastasis and disease free survival among patients with Stage I and II cervical cancer treated by radical hysterectomy. Three hundred-seventy patients with complete clinical information and pathologic material, including cone and cervical biopsies, were selected for analysis. Of these patients, 301 with clinical stages I and II disease were the subject of this paper. The results of patients with microinvasive carcinoma of the cervix, as defined by the Society of Gynecologic Oncologists (depth of invasion < or = 3 mm and no lymph node vascular space invasion), were reported previously and excluded from this analysis. Patients with small cell carcinoma of the cervix were found to have a very poor prognosis (disease free 5-year survival of 36%) and were also excluded from this analysis (Sevin BU, Nadji M, Metkoch MW, Lu Y, Averette HE. Unpublished data, 1995). Variables studied were patient age, weight, race, marital status, and economic status; tumor size; depth of invasion; lymph node-vascular space involvement; cell type; tumor grade; lymph node metastasis; and number of lymph nodes removed. The influence of these variables on survival was examined by univariate analysis with use of Cox's regression model and the log rank test for comparison of survival curves. Factors that predict disease free survival, ranked by degree of significance, were depth of invasion, tumor size, lymph node-vascular space invasion, number of positive nodes, tumor volume, clinical stage, and tumor extension to the vagina or surgical margins. Radical hysterectomy and bilateral lymphadenectomy is standard therapy for patients with Stage IB and IIA carcinoma of the cervix. A variety of surgically defined risk factors predict 5-year disease free survival, and many of these factors are related. Identification of independent risk factors requires a multivariate analysis of data.

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.

Small Cell Carcinoma of the Cervix Treated with Concurrent Radiotherapy, Cisplatin, and Etoposide

A multimodality regimen of four cycles of cisplatin and etoposide with concurrent locoregional radiotherapy (XRT) has been, since May 1988, the standard therapy for women with small cell carcinoma of the cervix (SCCC). Prophylactic cranial irradiation was to be used in all but primary progressors. All 11 patients (median age 47; 4 with pure SCCC and 7 with mixed histology) seen by us were treated with this regimen. Only 1 patient progressed while on treatment. The 3-year overall and failure-free survivals were 28%. Four patients remain alive in first remission; the remaining 7 died (2 from toxicity, 5 from cancer). Although not statistically significant due to the small numbers, it appeared that the chance of long-term survival depended both on the amount of the cancer as indicated by the FIGO stage and size of the primary and also the performance status. The toxicity was significant with 70% experiencing severe neutropenia and 40% being admitted for control of emesis. This regimen is only appropriate for those women in whom all of the apparent tumor can be encompassed within a radiation field and who, in addition, have a performance status of 0 or 1. For the remainder it does not offer any chance of lung-term survival and its toxicity renders it antipalliative.

Small Cell Carcinoma of the Cervix

Background Small cell carcinoma of the cervix is a rare and aggressive tumor. Most gynecologic oncology centers have little experience with this tumor, and only small series have been published. Methods Twenty-six patients with small cell carcinoma of the uterine cervix were treated at the Norwegian Radium Hospital. Clinical data, immunohistochemical characteristics, and infection with human papillomavirus were studied. Results Twelve tumors were of oat cell type and 14 of intermediate cell type. Twelve tumors were associated with other forms of carcinoma: squamous cell carcinoma (6 tumors), adenocarcinoma (5 tumors), and adenocarcinoma in situ (1 tumor). Neuroendocrine differentiation was expressed in 79% of the tumors. Human papillomavirus (HPV)-18 was detected in 40% of the tumors and HPV-16 in 28%. Fifteen patients had Stage I disease, 7 had Stage II, 2 had Stage III, and 3 had Stage IV. Fourteen patients with Stage I and II disease underwent radical hysterectomy with pelvic lymph node dissection. In four, the operation was preceded by intracavitary radiation treatment. The patients with Stage II, III, and IV disease were treated with a combination of intracavitary radium, external beam radiation therapy, and chemotherapy. The 5-year survival rate was 14%. Four patients are alive, one with recurrent disease 50 months after diagnosis. Three patients free of disease have been followed up 26, 54, and 101 months, respectively. Conclusions Small cell carcinoma of the cervix is an aggressive tumor with a propensity for rapid recurrence; it is associated with high mortality.

Small cell carcinoma of the cervix. A clinicopathologic study of 26 patients.

Small cell carcinoma of the cervix is a rare and aggressive tumor. Most gynecologic oncology centers have little experience with this tumor, and only small series have been published. Twenty-six patients with small cell carcinoma of the uterine cervix were treated at the Norwegian Radium Hospital. Clinical data, immunohistochemical characteristics, and infection with human papillomavirus were studied. Twelve tumors were of oat cell type and 14 of intermediate cell type. Twelve tumors were associated with other forms of carcinoma: squamous cell carcinoma (6 tumors), adenocarcinoma (5 tumors), and adenocarcinoma in situ (1 tumor). Neuroendocrine differentiation was expressed in 79% of the tumors. Human papillomavirus (HPV)-18 was detected in 40% of the tumors and HPV-16 in 28%. Fifteen patients had Stage I disease, 7 had Stage II, 2 had Stage III, and 3 had Stage IV. Fourteen patients with Stage I and II disease underwent radical hysterectomy with pelvic lymph node dissection. In four, the operation was preceded by intracavitary radiation treatment. The patients with Stage II, III, and IV disease were treated with a combination of intracavitary radium, external beam radiation therapy, and chemotherapy. The 5-year survival rate was 14%. Four patients are alive, one with recurrent disease 50 months after diagnosis. Three patients free of disease have been followed up 26, 54, and 101 months, respectively. Small cell carcinoma of the cervix is an aggressive tumor with a propensity for rapid recurrence; it is associated with high mortality.

Effect of medical audit on prescription of palliative radiotherapy.

Cadherins are tissue-specific cell adhesion molecules that function as tumor suppressors. Analysis of cadherin expression is useful for differentiation of tumor histogenesis, and because they serve as markers of tumor behavior and prognosis. Since the pattern of cadherin expression is not well characterized for small cell carcinoma of the cervix, we examined cases of these tumors for expression of cadherins, and two other oncoproteins p53 and BCL2. Four cases of small cell neuroendocrine carcinomas were identified from the Gynecologic Oncology Service with diagnoses confirmed by immunohistochemistry for neuroendocrine markers. Archival paraffin blocks were studied by heat-enhanced immunohistochemistry using commercially available antibodies specific for E-cadherin, P-cadherin, and N-cadherin, p53, and BCL2. Sections were examined for specific membrane staining of cadherins, nuclear staining of p53, and cytoplasmic staining of BCL2. E-cadherin was expressed in three of four cases, P-cadherin in one of four, and N-cadherin in none of four cases. P53 was expressed in one of four cases and BCL2 in one of four cases. The four cases showed three different patterns of immunohistochemical staining for the five oncoproteins. Specifically, two cases expressed E-cadherin only; one case lacked all three cadherins, was negative for BCL2, and was only positive for p53; and one case expressed E- and P-cadherin and BCL2. Prior studies of other neuroendocrine and small cell tumors of other organs showed E-cadherin expressed in 98% (42 /43), N-cadherin in 65% (28/43), and P-cadherin in 40% (17/43) of cases. Additionally, one case of vaginal small cell carcinoma showed expression of all three cadherins. The only significant difference between cervical primaries and other primary sites is that N-cadherin was not detected in our four cases vs. 65% expression in other sites (<i>P</i> &lt; 0.001). We conclude that cadherin and oncoprotein profiles in small cell carcinoma of the cervix are different in the four cases analyzed. Additional cases need to be studied to determine the specificity and frequency of these oncoprotein profiles for small cell carcinoma of the cervix. These may possibly represent different oncogenic pathways in development of small cell cancer of the cervix. Also, our results suggest that N-cadherin may be a tumor suppressor gene in these tumors.

Detection of human papillomavirus DNA in invasive cervical cancers by the polymerase chain reaction and its clinical significance.

In order to detect human papillomavirus (HPV) DNA in invasive cervical cancers, three different polymerase chain reactions to amplify different subgenomic fragments of HPV DNA were carried out on DNA extracted from 93 formalin-fixed and paraffin-embedded tumor tissues. This study detected HPV DNA in 54 cases (58.1%), which broke down to HPV 16 in 39 (41.9%) cases, HPV 18 in six (6.4%), HPV 52 in three, HPV 33 in one and unclassified HPV type in the remainder. Histopathologically, squamous cell carcinomas frequently contained HPV 16, whereas, HPV 18 was present in adenocarcinoma, adenosquamous cell carcinoma and small cell carcinoma of the cervix. Clinicopathological study revealed that HPV 16 and 18 DNA found were more frequently than other HPV subtypes in premenopausal patients. Moreover, HPV 18 DNA-positive cancers had a relatively high recurrence rate. These results indicate that cervical cancers might be clinically influenced by the difference in subtypes of the infecting HPV.

Treatment of small cell carcinoma of the cervix with cisplatin, doxorubicin, and etoposide

Between July 1986 and February 1991, 10 patients with small cell carcinoma of the cervix were prospectively treated with combination chemotherapy using cisplatin (50 mg/m 2) and doxorubicin (50 mg/m 2) on Day 1 and etoposide (75 mg/m 2) on Days 1–3. All patients underwent an extensive pretreatment metastatic survey and had histologic confirmation of small cell carcinoma prior to entry in the study. Seven patients had stage Ib, 1 stage IIa, and 2 stage IIb. Nine patients received chemotherapy at primary presentation and 1 was treated for recurrent disease. In 6 cases, chemotherapy was given and then followed by radiation therapy. Three patients received chemotherapy following radical hysterectomy and 1 was treated for persistent disease after radiation therapy. Patients received a median of four courses of chemotherapy (range 2–6). Neutropenia was the dose-limiting toxicity with 9 of 10 patients requiring a dose reduction. There was no instance of neutropenic sepsis or other major toxicity. Seven patients had measurable disease at the start of therapy. Three of these patients had a complete clinical response, 1 had a partial response, 2 had stable disease, and 1 had progressive disease (response rate = 57%). The median survival was 28 months. At the time of this report, 4 of 6 patients with stage Ib cancers given primary treatment on this regimen remained free of disease (with 28 months the median follow-up). Our pilot study indicates that this chemotherapy regimen has activity in small cell carcinoma of the cervix and should be further evaluated as an adjuvant to surgery or radiation in patients with early stage disease.

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.

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.

Simultaneous small cell carcinoma of the cervix and adenocarcinoma of the ovary

Simultaneous small cell carcinoma of the cervix and adenocarcinoma of the ovary

Small cell carcinoma of the cervix with inappropriate antidiuretic hormone secretion. Case report

Small cell carcinoma of the cervix with inappropriate antidiuretic hormone secretion. Case report

Treatment of small-cell carcinoma of the cervix with weekly combination chemotherapy

Three patients with small-cell carcinoma of the cervix entered a pilot study of combination chemotherapy with agents that are not cross-resistant. Two patients had local disease and the third had extensive metastatic disease of the liver. The regimen consisted of weekly chemotherapy for 16 weeks with cisplatin, vincristine, methotrexate, doxorubicin, cyclophosphamide and etoposide followed by radiotherapy and/or surgery. The two patients with local disease achieved a pathological complete response, with no evidence of disease at 24 months and 15 months from diagnosis. The third patient achieved a partial response and is alive at 13 months with progressive disease. Side-effects were tolerable.

An immunohistochemical study of neuroendocrine cells in gynecologic tumors

Various gynecologic tumors with argyrophilia were studied immunohistochemically for chromogranin using two antibodies, antichromogranin and antineuroendocrine. Of seven small cell carcinomas of the cervix, four were immunoreactive with antichromogranin and seven with antineuorendocrine. Argyrophil cells of six cervical adenocarcinomas were all immunoractive with both antibodies. Type I argyrophil cells of 20 endometrial carcinomas were likewise stained positively. However, of the 30 endometrial carcinomas with type II argyrophil cells, 19 showed positive immunoreactivity for chromogranin and 22 for neuroendocrine. Of the ovarian tumors tested, argyrophil cells of 11 mucinous tumors, three carcinoid tumors, and the pancreatic tissue of a malignant mixed germ cell tumor were all chromogranin- and neuroendocrine-immunoreactive. Type I argyrophil cells of five endometrioid carcinomas of the ovary were also immunoreactive with both antibodies. Of the 13 endometrioid carcinomas with type II argyrophil cells, only four showed positive immunoreactivity for chromogranin and only five for neuroendocrine. In conclusion, both antichromogranin and antineuroendocrine detect the specific neuroendocrine markers in close association with argyrophilia in gynecologic tumors, the latter being more sensitive for small cell carcinoma of the cervix, and for type II argyrophil cells in adenocarcinoma of the endometrium and endometrioid carcinoma of the ovary.

Malignant Peripheral Primitive Neuroectodermal Tumor of the Uterus

Peripheral primitive neuroectodermal tumor (PPNET) is rare, occurring most often in young adults. Approximately 50 cases have been reported, with only four cases involving the female genital tract. We report the fifth patient. The term PPNET should be used only for tumors with neuroectodermal elements exclusively that occur at sites outside the central and sympathetic nervous system. The pathologic differential diagnoses include rhabdomyosarcoma, immature malignant teratoma, small cell carcinoma of the cervix, and ganglioneuroma. Therapy for this tumor has varied, and no effective regimen has been established.

The pathologic spectrum of small cell carcinoma of the cervix.

Small cell carcinoma of the cervix is a term used to describe several entities including cervical carcinoid, "oat cell" carcinoma, reserve cell carcinoma, and poorly differentiated nonkeratinizing squamous cell carcinoma. The light microscopic, ultrastructural, and clinical features of seven small cell cervical carcinomas are presented in this report. Five tumors in our report were diagnosed as small cell anaplastic or oat cell carcinoma by light microscopy. This diagnosis was associated with a poor prognosis, and four of these patients were dead of disease within 24 months. The ultrastructural features of these tumors were similar, but neurosecretory granules were demonstrable in only three of the five cases. Evidence of glandular differentiation was present in one of the five cases, and dual differentiation, i.e., neuroendocrine and squamous, was noted in another. The similarities between pulmonary small cell carcinoma and these cervical lesions are discussed and the literature is reviewed. Also included in the study is a well-differentiated neuroendocrine lesion, a carcinoid that behaved in an aggressive fashion. The final case was a carcinoma putatively derived from reserve cells. The features that help make the diagnosis of reserve cell carcinoma and that distinguish this lesion from other small cell carcinomas are presented.

Immunohistochemical demonstration of peptide hormones in cervical adenocarcinomas with argyrophil cells.

Thirty patients with cervical adenocarcinoma were analyzed clinicopathologically with special reference to argyrophil cells. In contrast to argyrophil small cell carcinoma of the cervix, four adenocarcinomas with argyrophil cells were not more aggressive than the remaining 26 usual ones. One or two peptide hormones were demonstrated in three out of four tumors with argyrophil cells which were examined by immunohistochemistry. Somatostatin- and gastrin-containing cells were found in one tumor, but were located differently from each other. Either gastrin- or adrenocorticotropic hormone (ACTH)-containing cells were detected in two other tumors. They all corresponded to argyrophil cells, but were less numerous.

Cushing's syndrome with small cell carcinoma of the uterine cervix

A 28 year old white woman was found to have a cervical tumor in the 25th week of pregnancy. Pathologic examination revealed a nonkeratinizing small cell carcinoma. After delivery by cesarean section, pelvic lymph node exploration was carried out, and all 15 nodes were free of tumor. Her condition was staged as II-A, and she was treated with local radiation. Metastatic disease became manifest almost a year later and was histologically similar to her primary disease. A Cushingoid appearance was noticed and plasma cortisol levels were elevated. Twenty-four hour urinary 17-hydroxycorticosteroid (17-OHCS) and 17-ketosteroid (17-KS) levels were elevated and failed to suppress with dexamethasone. Plasma adrenocorticotropin (ACTH) level was elevated. Electron microscopic examination of the tumor tissue revealed neurosecretory granules. Immunoperoxidase stains for ACTH were positive. The patient's course was one of progressive decline and eventual death. A literature review revealed two other cases in which carcinoma of the uterine cervix was considered to be the source of ectopic ACTH. Some small cell carcinomas of the cervix may arise from cells of the APUD series. Small cell carcinoma of the uterine cervix may behave differently from the more commonly encountered keratinizing and large cell nonkeratinizing carcinomas of the cervix and may not respond as well to standard therapy. Ectopic hormone production, production of abnormal peptides or of vasoactive amines may be more common in small cell carcinoma of the cervix than is currently recognized, and these products may be clinically useful as tumor markers.

Small cell nonkeratinizing carcinoma of the cervix associated with acth production

The case of a 40-year-old woman with primary small cell carcinoma of the cervix is reported. She developed widespread metastates and florid Cushing's syndrome. Serum ACTH levels were greatly elevated and no site of production other than the tumor could be demonstrated at autopsy. The tumor cells demonstrated features characteristic of cells of the APUD series. Such cells have been demonstrated in normal cervical epithelium; it is likely that they may become malignant, giving rise to tumors with a potential to secrete polypeptide hormones. This case suggests that endocrine active "Apudomas" may arise from the uterine cervix. Certainly, patients with small cell carcinoma of the cervix should be investigated with appropriate serum assays for polypeptide hormones.