Biological agents of bioterrorism - preparedness is vital.

Bioterrorist threats and attacks are still an issue of concern in the world. Biological agents are divided into three categories. The highest priority agents classified in category A pose a massive risk to public health and national security. The society should be prepared for this risk. Health professionals in the Czech Republic should be aware of the diseases caused by category A agents, which are not common in the country. In this context, the project of the Ministry of the Interior of the Czech Republic “Decontamination of the injured persons” has been implemented at the Faculty of Health Sciences, Palacký University, Olomouc. The article provides an overview of selected serious infectious risks and information on the project the aim of which is to create certified methodical procedures and guidelines on situations related to bioterrorism.

Peritumoral stromal remodeling, pattern of invasion and expression of c-met/HGF in advanced squamous cell carcinoma of the cervix uteri, FIGO stages III and IV.

OBJECTIVE: Different patterns of invasion (PIs) have prognostic impact in several types of cancer and are associated with different grades of peritumoral stromal remodeling, characterized by the desmoplastic stromal response (DSR). One key regulator influencing cellular motility and peritumoral stromal response is c-met/HGF. This study evaluates the association between different PI, peritumoral DSR and its correlation to the expression of c-met/HGF in squamous cell carcinomas of the uterine cervix (CX). STUDY DESIGN: 131 advanced stage CX (FIGO III/IV) were re-evaluated histologically regarding PI, using a two-level scoring system. The tumor grows in solid cords/trabeculae in finger-like PI and in very small groups or single cells in spray-like PI. DSR was categorized as none/weak and moderate/strong. The tumors were stained with antibodies against c-met and HGF. The staining of >30% of tumor cells was defined as overexpression. The PI was correlated to the prognostic outcome, different categories of DSR and expression status of c-met and HGF. RESULTS: 66.4% of the tumors showed a finger-like, and 33.6% a spray-like PI. The spray-like PI showed a reduced two-year overall survival when compared to the finger-like PI (14.0% vs. 29.1%, respectively; p=0.012), and was associated with moderate/strong DSR. The majority of the tumors showed overexpression of c-met (85.4%) and HGF (74.8%). There was no correlation between the expression status of c-met/HGF and the FIGO stage, peritumoral DSR or the prognostic outcome. CONCLUSIONS: Spray-like PI is of prognostic impact in cervical carcinoma FIGO III/IV and is associated with strong peritumoral stromal remodeling. There is no prognostic impact of the immunohistochemical expression of c-met/HGF in advanced stage cervical carcinomas.

[Carcinosarcomas (malignant mixed Mullerian tumors) of the uterus. Morphology, pathogenetic aspects and prognostic factors]. / Karzinosarkome (maligne Müller-Mischtumoren) des Uterus. Morphologie, molekulare Pathogenese und morphologische Prognosefaktoren.

Malignant mixed Mullerian tumors (MMMT; carcinosarcomas) are rare epithelial-mesenchymal tumors. With an overall survival rate of 30%-40% the prognosis is much worse compared to high grade endometrioid or serous/clear cell carcinomas. Depending on the histology of the mensenchymal components a distinction is made between homologous and heterologous MMMT. Clinical, morphologic and molecular data suggest that MMMTs are really metaplastic carcinomas in which the mesenchymal part retains epithelial features. The strongest prognostic factor is tumor stage followed by lymph node metastases, deep myometrial infiltration, involvement of the cervix and tumor size. The distinction between homologous and heterologous MMMT is prognostically insignificant. Due to unreliable clinical staging and a high rate of occult lymph node metastases, the pathological-anatomical work-up is of great importance. Clinical and pathologic staging should be performed as in endometrial carcinoma. The main differential diagnoses include uterine sarcomas, adenosarcoma and benign metaplastic change within the endometrium.

Tumor size is of prognostic value in surgically treated FIGO stage II cervical cancer.

OBJECTIVES: Tumor size is a well recognized prognostic factor in early stage cervical carcinoma (CX). However, limited knowledge exists about the value of tumor size in surgically treated CX with extrauterine extension. METHODS: 245 cases of local advanced CX (FIGO stage IIA and IIB) who received upfront surgery were evaluated regarding tumor size, regarding the prediction of pelvic lymph node involvement and recurrence free and overall survival during a median follow-up time of 54 months (95% CI 45.4-62.6 months). Tumors larger than 4 cm were defined as bulky stage disease. RESULTS: Bulky disease was seen in 46.1% (113/245). 60.2% of these patients showed pelvic lymph node involvement, compared to 42.4% (56/132) in non-bulky tumors (p=0.006; odds ratio: 2.2 [95% CI: 1.3-3.6]). Patients with bulky tumors showed an increase of recurrent disease (40.2% vs. 28.0%; p=0.045). The relative risk for recurrent disease was 1.97 (95% CI: 1.3-3.0). The 5-year overall survival rate was significantly lower (67.7% [95% CI: 58.2-74.8] vs. 49.5% [95% CI: 36.8-59.1]; p=0.0015). In multivariate analysis, tumor stage, pelvic lymph node involvement and maximal tumor size were independent prognostic factors. CONCLUSIONS: The results suggest that tumor size, defining bulky disease as tumors larger than 4 cm, is of prognostic impact also in FIGO stage II cervical carcinomas. A revised FIGO/TNM classification system similar to the subgrouping of stage IB CX is recommended for stage II using a cut-off value of 4 cm as discriminator: stage IIA1 and stage IIB1 for tumors with 4 cm (i.e. bulky disease).

Pattern of invasion is of prognostic value in surgically treated cervical cancer patients.

OBJECTIVES: Different patterns of invasion (representing different grades of tumor cell dissociation) are associated with prognostic outcome in cancer. We evaluated the prognostic value of different patterns of invasion (PI) in cervical carcinomas (CX). METHODS: Six hundred eleven surgically treated CX (FIGO IB to IIB) were re-evaluated histologically regarding the PI, using a three-level scoring system. Closed PI was defined as cohesive growth with well-delineated (pushing) borders. In finger-like PI the tumor grows in solid cords/trabecles. Highly dissociative growth in small groups or single cells was defined as spray-like PI. Types of PI were correlated to tumor stage, histo-morphologic factors and prognostic outcome. RESULTS: Sixty percent of the tumors showed a spray-like PI, 30% a finger-like PI and only 7.4% were of the closed type. Spray-like PI showed a significant correlation with advanced stage disease, lymphovascular space involvement, poorly differentiated tumors and pelvic lymph node metastases. Spray-like PI was accompanied by a reduced 5-year overall survival when compared to the finger-like and closed PI (68.7% vs. 80.9% vs. 88.5%; P=0.0004). The prognostic impact of the PI disappeared in node-positive patients (P=0.06) but persisted in patients without pelvic lymph node disease (P=0.03). In multivariate analysis, using COX regression model, the PI represented as independent prognostic factor. CONCLUSIONS: Spray-like PI (i.e., highest degree of tumor cell dissociation) is associated with advanced tumor stages, increased rate of recurrency and a reduced overall survival. In separate analysis of patients with and without lymph node metastases, the impact of PI persisted only in node-negative cases as a prognostic factor.

Clinicopathologic characteristics and subsequent pregnancy outcome in 139 complete hydatidiform moles.

OBJECTIVE: The most common form of gestational trophoblastic disease is the complete hydatidiform mole (CHM). The study reports our experience of clinicopathologic characteristics and subsequent pregnancy outcome of patients with CHM. STUDY DESIGN: One hundred fifty-one subsequent cases with initial diagnosis of CHM were re-evaluated histopathologically. Clinical characteristics, the need for chemotherapy and subsequent pregnancy outcome were evaluated. RESULTS: Twelve out of 151 cases were re-evaluated as hydropic abortion, as partial hydatidiform moles or were insufficient for morphologic examination and therefore excluded from further analysis. The leading clinical symptoms of the remaining 139 cases were irregular vaginal bleeding (67%) and uterine enlargement (41%). Twenty-six patients (19%) required chemotherapy because of gestational trophoblastic neoplasia (GTN; low-risk: 23 out of 26). All patients were cured successfully. The subsequent pregnancy rate was 15% (21/139). Five patients suffered from abortions, 12 women delivered a healthy offspring. Four women presented with recurrent CHM with a spontaneous normalization of HCG levels after D&C. CONCLUSIONS: The clinical and morphologic diagnosis of CHM is a challenge, and diagnosis as well as treatment should be multidisciplinary and centralised. One fifth of CHM are at risk of a GTN, but the cure rate is 100% with adequate management. Pregnancy outcome following CHM is complicated by an increased risk of abortion.

Prognostic value of trophoblastic proliferation in complete hydatidiform moles in predicting persistent disease.

The clinical outcome of patients with complete hydatidiform moles (CHM) is variable. The correlation between trophoblastic proliferation and development of persistent disease was evaluated. A hundred and fifty-one cases with the initial diagnosis of CHM were re-evaluated histopathologically. The need for chemotherapy and occurrence of metastatic disease was correlated with the histologic grade using a three-level score. Twelve out of 151 cases were re-evaluated as hydropic abortion, partial moles, or were insufficient for morphologic examination, representing a diagnostic agreement of 92%. A total of 63.4% of the CHM presented with low trophoblastic proliferation with focal areas of slight hyperplasia (grade 1), and 23.7% with moderate proliferation with slight anaplasia and medium-sized sheets of free trophoblast in between the villies (grade 2). In all, 12.9% of the cases showed marked hyperplasia with marked anaplasia and involvement of nearly all villies, as well as a large amount of intervillous trophoblastic sheets (grade 3). Twenty-six of the CHM (19%) required chemotherapy. Grade 3, on histology, showed a positive correlation with the necessity of chemotherapy (p=0.04), but not with the occurrence of metastatic disease. Histomorphology might predict the risk of persistent disease, indicating the necessity for closer a follow-up, but further studies are required.

Expression of COX-2 and HER-2/neu and estrogen and progesterone receptor in primary squamous cell carcinomas of the endometrium.

PURPOSE: Primary endometrial squamous cell carcinoma (ESCC) are rare but aggressive malignancies. To evaluate therapeutically relevant molecules, ESCC were investigated immunohistochemically. MATERIAL AND METHODS: Eight ESCC were stained with antibodies against estrogen and progesterone receptors, HER-2/neu, and COX-2 followed by semiquantitative evaluation of the staining results. RESULTS: Seven out of eight ESCC were negative for estrogen receptor as well as for HER-2/neu. Four tumors showed positivity for progesterone receptor. All ESCC displayed COX-2 overexpression. CONCLUSIONS: Primary ESCC are probably not under hormonal control of estrogens and lack HER-2/neu expression. Thus, anti-hormonal or antibody therapy with herceptine is not indicated. The use of COX-2 inhibitors might be a therapeutic alternative in ESCC that requires further investigation.

Risk of progression in complex and atypical endometrial hyperplasia: clinicopathologic analysis in cases with and without progestogen treatment.

In most cases, the endometrioid adenocarcinoma of the endometrium is preceded by hyperplasia with different risk of progression into carcinoma. The original histologic slides from 560 consecutive cases with complex and atypical hyperplasia were re-examined to assess the interobserver-correlation. The hyperplasias were analyzed separately for their likelihood of progression to carcinoma in patients with and without progestogen hormonal therapy. In all cases, a fractional re-curreting was performed to establish the state of the disease. The leading symptom was vaginal bleeding in 65.5% of the cases in the postmenopausal period. Eighty-six percent of the patients presented with obesity (BMI > 30 kg/m(2)), 23% had had an exogeneous use of estrogens. Twenty-two cases were reclassified as simple hyperplasia and excluded from further analysis. The interobserver-correlation was 91% for complex, 92% for atypical hyperplasia, and 89% for endometrioid carcinoma, representing an overall correlation of 90%. Two percent of the cases with complex hyperplasia (8/390) progressed into carcinoma and 10.5% into atypical hyperplasia. Fifty-two percent of the atypical hyperplasias (58/112) progressed into carcinomas. In the case of progestogen treatment (n = 208; P < 0.0001) 61.5% showed remission confirmed by re-curetting, compared with 20.3% of the cases without hormonal treatment (n = 182; P < 0.0001). Endometrial hyperplasia without atypia is likely to respond to hormonal treatment. Especially in postmenopausal situation, atypical hyperplasia should be treated with total hysterectomy.

p53 in surgically treated and pathologically staged cervical cancer: correlation with local tumor progression, but not with lymphatic spread.

There is only limited information about the prognostic value of p53 immunostaining in cervical cancer. The purpose of this study was to assess the clinical significance of p53 and prognosis in operatively treated cervical carcinoma. A hundred and fourteen primary surgically treated cervical carcinomas (CX) were obtained from the so called Wertheim Archive in the Department of Obstetrics and Gynecology at the University of Leipzig. These included 105 squamous cell cancer (SCC) and nine adenocarcinomas (AC). No cases received neoadjuvant therapy. For immunohistochemical analysis, the cases were tested with the monoclonal antibody DO-7 (DAKO Diagnostics, Denmark). Two hundred tumor cell nuclei were counted for positive nuclear immunostaining, regardless of staining intensity. Cases were stated as positive when a minimum of 10% nuclei showed positive staining. Fresh frozen tissue was available from 21 CX for p53-mutation analysis (exons 4-9) using PCR-based amplification and SSCP-analysis. Of the squamous cell cancers (SCC), 63.8% showed positive nuclear p53-immunostaining; adenocarcinomas (AC) were completely negative (P = 0.0000, Chi2-test). Stage-by-stage analysis revealed no differences in p53-expression. However, combining pT1b- and pT2-cases, the difference in positive immunostaining reached statistical significance (44.4% vs. 71.7%; P = 0.007). There were no differences in p53-reactivity regarding the presence of pelvic lymph node metastases, tumor grading, relapse-free survival and tumor recurrence. In addition, only 5% of CX with positive p53-immunostaining showed genomic alterations in mutational analysis. p53-immunoreactivity showed significant correlation with local tumor progression but not with lymphatic spread, lacking any prognostic impact in surgically treated cervical cancer. There is no correlation of p53-immunostaining with the occurrence of p53-gene mutations in cervical cancer.

[Pathologic-anatomic description and basic morphological information for management of dysplasias and carcinomas of the cervix uteri]. / Pathologisch-anatomische Aufarbeitung und morphologische Basisinformationen für das Management von Dysplasien und Karzinomen der Cervix uteri.

Histopathology is the bedrock and cornerstone in the management of malignant tumors. Careful macroscopic description with selection of representative tissue for histologic examination is required for quality assurance and quality improvement and for assessing prognostic factors in cervical cancer specimens. The pathology report in cervical cancer (CX) should include three-dimensional tumor measurement, the exact measurement of depth of infiltration of the cervical wall, tumor grading, the presence of lymphatic space as well as blood vessel involvement. The statement for resection margins should include the vaginal, parametrane, rectal and vesical direction. All resected lymph node should be counted, measured and processed completely in step sections. If lymph node metastases are diagnosed, the report should include the size and count of metastatic nodes in relation to resected nodes. Pelvic and para-aortal nodes should be reported separately. Lymph nodes in the parametrane tissue represent regional nodes; and metastatic involvement should be stated as pN1 and not as pT2b. The tumor typing and staging should be conform with WHO-classification of malignant tumors and the TNM-classification system. The last one should be used in all cases which were surgically treated. Konizations and LOOP-excision specimens should be processed completely in step sections. The pathology report must include the severity of CIN-lesion, changes caused by HPV-infection, according to colposcopic localisation.

[Histopathological prognostic factors in primary surgically treated cervix carcinoma]. / Histopathologische Prognosefaktoren beim primär operativ therapierten Zervixkarzinom.

OBJECTIVE: Standardised morphologic evaluation of radical hysterectomy specimens in primary surgically treated cervical cancer improves the selection of cases for adjuvant therapy and the precision for prognosis and may be helpful in quality control of oncologic surgery. MATERIAL AND METHODS: Following standardised macroscopic evaluation [29] the original histologic slides of all surgically treated patients with cervical cancer were searched for tumor type, histologically proven pelvic lymph node metastases (PLM), lympho-vascular space involvement (LVSI), tumor differentiation (grading), peritumoral inflammatory response, pattern of cervical wall involvement and relative depth of invasion. The results were compared with follow up. RESULTS: The frequency of patients up to 35th year of age was 28.8% and increased between 1979 and 1993 of about 10% (p > 0.05). Younger women represented more pT1 b1-tumors (55.6% vs. 47%), but without statistic significance. Contrary to advanced tumor stage and the presence of PLM, adenocarcinomatous histology (5.1% of all cases) was not associated with poor prognosis. Patients with pT1b-tumors of more than 4 cm largest extension (pT1 b2) showed a twice-fold frequency of PLM and pelvic recurrences. Five-year survival rate (5-Y-SR) decreased (82.7% vs. 64.9%) and more patients died of cancer (p = 0.005, each). Diffuse infiltration pattern was accompanied with higher rate of tumor recurrency and a shortening of 5-Y-SR compared with pushing borders at the front of infiltration, 38% versus 13.7% and 45.4% versus 75.2%, respectively. Similar was seen in poorly differentiated tumors (G3), compared with well differentiated (G1) carcinomas (recurrency: 15.1% vs. 27.5%, 5-Y-SR 75.7% vs. 59.3%; p < 0.05). Cases with the presence of LVSI, absence of peritumoral inflammatory response and deep cervical infiltration (> 66%) were accompanied with poor prognostic outcome. CONCLUSIONS: In patients with primary surgically treated cervical cancer prognostic risk evaluation can be made by standardised histopathologic handling of hysterectomy specimens. Cases with early cervical cancer and high tumor load (pT1 b2), advanced staged disease (pT2 b), histologically proven PLM, LVSI, poor tumor differentiation (G3), absence of peritumoral inflammatory response and deep cervical wall infiltration are associated with poor prognostic outcome. Patients with these morphologic patterns, which can be established by clinical examination and diagnostic biopsy, represent the clientel for adjuvant or neoadjuvant therapy.

[Cancer register for cervix carcinoma--useful and necessary?]. / Krebsregister beim Zervixkarzinom--sinnvoll und notwendig?

During the last two decades, cancer research has shifted from using cell lines and animal models to using methods and models that use human tissues from defined tumors. DNA and RNA can be analysed from fresh tissue from samples obtained at surgery, biopsy, cytologies or necropsy as well as from paraffin-embedded material. Archival material has several advantages: not only it is from individuals for whom disease process has been documented, but also data may available about the outcome as well as the response to treatment. Material available from well-controlled clinical trails would enable a wide range of hypotheses to be tested. Laser microdissection allows to sample cellular material from histopathologic well documented areas of the tumor, including special differentiated areas. It is necessary to establish tumor registries, especially in gynecologic oncology to get material from well described tumors for molecular profiling, the molecular analysis of clonality in tumors and malignant progression. At the Leipzig University a cervical tumor registry has been established in March 1979. Until the end of December of the year 2000 1,030 cases of surgically treated cervical cancer from stage pT1b1 up to pT2b including paraffin blocks and original histologic slides were collected. First evaluation up to the end of 1996 (n = 919) has shown, that 27.2% of the patients represented with histological proven pelvic lymph node metastases. The majority of cases were staged pT1b1 (52.1%), followed by stage pT2b (23.9%), pT1b2 (9.7%) and pT2a (9.5%). In 44 cases stage was not documented. In about 95.2% datas about the follow up of the patients were available. In conclusion, tumor registries are helpful in establishing and controlling uniform criteria for the accurate determination of prognostic factors and exact histopathologic evaluation can ideally be combined with new tools in molecular pathology, i.e. histopathology meets genomics.

[Epidemiology and pathogenesis of cervical cancer]. / Epidemiologie und formale Pathogenese des Zervixkarzinoms.

The majority of the estimated incidence of 471,000 new cases for invasive cervical cancer (CX) and 215,000 cancer deaths occurs in the developing countries. For Germany the CX accounts at 8th position of all cancers in women in 1997 with 5,800 newly diagnosed cases. But, every fourth woman between 25th- and 35th-year of life has been affected by CX. This counts at the upper third of the incidence in the European Union (EU). The estimated loss of live-years for women affected by CX is about nine years. The lethality for all stages of invasive cervical cancer is about 30%. For the last two decades stagnation of the reduction of mortality by CX has been reported for EU and the USA, especially affecting woman up to 35th-year of life. The percentage of this age group of all primary operative treated CX at the Leipzig University Hospital between 1979 and 1999 was 26.2%, with a mean age of 43.4 +/- 11.1 years. Improved screening for CX in the western countries and a change in environmental factors have been caused an increase of cervical precancerous (CIN-) lesions. The frequency of CIN-lesions has been estimated to be 100-times higher than the incidence of invasive cancer (21.1) in Germany. The pathogenesis of CX is multistage and CIN I and II represent highly regressive lesions, whereas CIN III requires therapeutic intervention, caused by high progression rate. The Bethesda-classification of low und high grade squamous intraepithelial lesions (SIL) cannot be recommended for biopsies or conisation specimens. Dsyplastic lesions of endocervical columnar epithelium should not be graded, the only general accepted lesion represents the adenocarcinoma in situ (ACIS). Both, CIN and ACIS represents proliferative active lesions, caused by infection with HPV. But the detection of morphologic alterations, associated with HPV, like koilocytes, are inverse correlated with the grade of the CIN-lesion.

Prospective evaluation of the argon laser treatment of trachomatous trichiasis.

PURPOSE: To evaluate the effectiveness of argon laser photocoagulation for the treatment of trachomatous trichiasis. METHODS: This report presents a prospective, non-masked study of 22 patients (36 eyelids) with trachomatous trichiasis treated with the argon laser. Each abnormal lash was treated with a beam of 50- to 200-micron spot size, for 0.2 seconds, and 1 to 1.2 watts power. In 30 lids (83.3%) infiltration anesthesia was used and in 6 lids (16.7%) no anesthesia was used. RESULTS: Successful treatment with no evidence of recurrence was achieved in 55.5% of lids after one laser session. The remaining 44.5% of the lids required two or three sessions. The final success rate of the method was 88.9%. No complications were observed. The mean follow-up time was 10.6 months. CONCLUSION: Argon laser photocoagulation is an effective and safe method for the treatment of trachomatous trichiasis.

Tumor-associated proteolytic factors uPA and PAI-1 in endometrial carcinoma.

The levels of plasminogen activator urokinase (uPA) and of its inhibitor (PAI-1) were measured by use of ELISA in the cytosol of tissue homogenates obtained from endometrial carcinomas and the marginal, tumor-free endometrium of postmenopausal patients (n = 64). Significantly higher median levels of uPA and PAI-1 were found in malignant endometrium (uPA 1.89 ng/mg, PAI-1 3.04 ng/mg) compared to tumor-free endometrium (uPA 0.84 ng/mg, PAI-1 1.01 ng/mg). Concerning uPA, no significant differences were found in dependence on histomorphological prognostic factors (staging, grading), but the median level of PAI-1 was significantly higher in G2/G3 carcinomas compared to G1 tumors (5.08 ng/mg vs 2.19 ng/mg). Because of the good prognosis of operated patients with endometrial carcinomas, the prognostic value of uPA and PAI-1 can only be decided by a larger number of patients and a long observation time.

[Surfactant administration and laterally independent positive pressure ventilation in acute lung failure and atelectasis after septic abortion. Case report]. / Surfactantgabe und seitengetrennte Uberdruckbeatmung bei akutem Lungenversage und Atelektase nach septischem Abort. Kasuistik.

We report the case of a 35 years old female patient suffering from Staphylococcus aureus induced abortion in the 7th/8th week of gestation. Sepsis with acute respiratory failure (ARDS) developed, which could be treated successfully. Pneumonia, caused by Pseudomonas aeruginosa, induced a recurrence of ARDS, complicated by a persistent incomplete atelectasis of the left lung. Independent ventilation of both lungs with increased pressure on the left side combined with bronchoscopy guided instillation of 1 g of bovine surfactant (Alveofact), caused improvement of arterial oxygenation and radiological signs, signalling airation of collapsed lung areas.

Primitive neuroectodermal tumor of the cervix uteri. A case report.

Primitive neuroectodermal tumors (PNET) of the female genital tract are rare and more common in the ovary, but uncommon in the cervix uteri. A 26-year-old woman presented with suspect cervical smears. The conization specimen showed a small cell non-keratinised squamous cell carcinoma with involved margins. The patient underwent radical abdominal hysterectomy and pelvic lymphonodectomy. The microscopic examination showed a densely cellular tumor of small neuroendocrine cells with scanty cytoplasm and rosettes. Immunohistochemically, the cells were slightly positive for NSE and negative for S 100, GFAP, neurofilaments, squamous cell cytokeratin 1, vimentin, desmin and leukocyte common antigen. The diagnosis of PNET, stage pT1b1,N0, M0 was made. The patient underwent adjuvant pelvic radiation. Three years later, pulmonary metastases occured. Radiation therapy of the thorax and six courses of combination chemotherapy (5-FU and cis-platinium) could not prevent tumor progression. The patient died 4.2 years after diagnosis. The autopsy showed widespread lymphatic metastases and hepatic, pulmonal and skeletal metastases and a peritoneal carcinosis. The tumors are resistent to radio- and chemotherapy, and the prognosis is generally poor. Up to 15% foci of squamous or glandular differentiation occur in or adjacent to these tumors. So the authors favor the histogenesis from a pluripotent endocervical stem cell. The neuroendocrine component of mixed tumors improve the prognosis. Therefore, it is necessary to recognize this component.