The prognosis of adenosquamous carcinomas of the uterine cervix.

OBJECTIVES: Firstly, to identify a cohort of women with invasive adenosquamous carcinomas of the uterine cervix, including mucin-producing squamous cell carcinomas. Secondly, to compare the biological characteristics and behaviour of a cohort of adenosquamous carcinomas with a cohort of non-mucin-producing squamous cell carcinomas. DESIGN: Histological review, retrospective survival analysis. SETTING: Regional multidisciplinary gynaecological oncology service. SUBJECTS: 161 cases of stage 1B and above invasive cervical carcinoma presenting between 1 January 1980 and 31 July 1987. Thirty nine women with adenosquamous carcinomas were compared with 103 women with non-mucin-producing squamous cell tumours. RESULTS: Inclusion of routine stains for mucin in the assessment of histological material resulted in the reclassification of 38 (24%) of the cases, including the identification of 31 mucin-producing squamous cell carcinomas. The survival with adenosquamous tumours was significantly worse than with squamous cell cancers (P = 0.006), 5-year survival rates being 52% and 75% respectively. Multivariate analysis showed that this effect was explained by differences in clinical stage, pelvic lymph node metastasis and vascular invasion by tumour. CONCLUSIONS: The application of routine mucin stains to cervical tumours identifies a group of previously unrecognized adenosquamous cancers. Tumours so identified are likely to pursue a more aggressive clinical course associated with a poorer survival when compared to non-mucin-producing squamous carcinomas.     

Endometrial extension of adenosquamous carcinoma of the uterine cervix

Endometrial in situ extension of cervical cancer is extremely uncommon. Previous reports only present the cases of squamous cell carcinoma or related category. This report presented adenosquamous carcinoma of the uterine cervix that showed a paradoxical extension of each component in a 72-year-old patient. Main tumor in the cervix was revealed to be adenosquamous carcinoma. The glandular component extended to the vagina, while the squamous component grew into the entire uterine cavity and replaced the glandular epithelium. We presented the first case of adenosquamous carcinoma of the uterine cervix with vaginal and endometrial extension. Furthermore, the endometrium was replaced with squamous component, while the vagina was invaded by glandular component. The observed paradoxical extension of the present case was extremely rare.     

Clinicopathologic study of adenosquamous carcinoma of the uterine cervix

The 22 adenosquamous carcinoma cases were studied clinicopathologically. The tumor provides many difficulties such as: rapid spreading properties, delayed detection as advanced carcinoma because of the presence of endophytic growth, frequent prevalence of vessel permeation, and radioresistance. Adenosquamous carcinoma was categorized histochemically and histomorphologically into two types--adenosquamous carcinoma (AC) and mucoepidermoid carcinoma, with a comparison being given. As a result, adenosquamous carcinoma (AC) was found inferior to mucoepidermoid carcinoma in radiosensitivity and prognosis, so that categorization into the two types has been considered to be clinically meaningful.     

KIT activation in uterine cervix adenosquamous carcinomas by KIT/SCF autocrine/paracrine stimulation loops

ObjectivesUterine adenosquamous carcinoma (ASC) is an uncommon, yet, one of the most aggressive cervical cancer subtype. The successful treatment of some tumors, such as gastrointestinal stromal tumors (GISTs), by anti-KIT inhibitors fosters the study of this receptor tyrosine kinase in other malignancies. In the present study, we intended to molecularly characterize KIT in ASC.MethodsIn a series of 30 cases, we studied KIT (CD117), KIT phosphorylated / activated form, as well as KIT ligand, stem cell factor (SCF), by immunohistochemistry. We further screened for KIT hotspot mutations (exon 9, 11, 13 and 17) by PCR-SSCP and for KIT gene amplification by Quantitative real-time PCR in CD117 positive cases.ResultsWe observed CD117 expression in ～ 13% of cases, with ～ 7% co-expressing SCF, which resulted in KIT phosphorylation/activation. No KIT activating mutations or gene amplification were found, despite the presence of 4q aneuploidy in one case.ConclusionsThis is the first study assessing KIT activation and molecular alterations in a large series of rare ASC. Our findings showed the absence of KIT molecular alterations and suggested the presence of KIT activation in a small proportion of cases through KIT/SCF co-expression.     

Poor prognosis in patients with adenosquamous cell carcinoma of the cervix

From 1 July 1974 to 31 December 1982, 127 patients with primary carcinoma of the cervix were assessed to determine the prognosis of patients with adenosquamous cell carcinoma. Of all patients, 34 are dead of disease for an overall corrected survival rate of 73.2%. The survival of 20 patients with adenosquamous cell carcinoma is 20%. Seventy-five percent of the adenosquamous cell patients had stage IB lesions. When patients with adenosquamous cell carcinoma were compared with patients with squamous cell carcinoma or adenocarcinoma, there was a statistically significant decrease in survival. Patients with adenosquamous cell carcinoma were relatively young with a mean age of 41.1 years. A normal appearing cervix was noted in 30% of all patients with adenosquamous cell carcinoma. The majority of adenosquamous cell patients (87.5%) dead from cancer had distant metastases. This report emphasizes that, independent of stage, adenosquamous cell cervical carcinoma is an extremely aggressive neoplasm and carries a poor prognosis.     

Mucin production in carcinomas of the uterine cervix

The histological types of the cervical carcinoma effect the incidence, prognosis and the treatment methods. One hundred and eighty-seven cases selected randomly among the cervical carcinoma were stained with mucicarmen, alcian blue, PAS, and PAS with diastase to identify the presence of intracellular mucin. One hundred and seventy-two squamous carcinoma were examined and 27.3% (47 cases) of them were shown to contain some degree intracellular mucin (nine cases which were originally diagnosed squamous carcinoma after the application of mucin stains to the tumors, reclassified as adenosquamous carcinoma because of demonstrated widespread intracellular mucus). Of the 14 adenocarcinomas, 13 were mucin positive. Mucin-positive tumors (independent of histological type) had metastasized to the lymph nodes in 23 of 60 cases (38.3%), in contrast to mucin-negative tumors which had metastasized in 24 of 127 cases (18.9%). The application of mucin stains can assist in the classification of poorly differentiated lesions as well as help in the planning of management and in the prognosis.     

Human papillomavirus deoxyribonucleic acid in adenocarcinoma and adenosquamous carcinoma of the uterine cervix

This report describes the detection of human papillomavirus type 16 or 18 deoxyribonucleic acid (DNA) in nine of 15 invasive tumors of the cervix, including three squamous carcinomas, four adenosquamous carcinomas, one glassy cell carcinoma, and one adenocarcinoma. The viral DNA was identified by Southern blotting and DNA hybridization. Human papillomaviruses may play an etiologic role in the development of at least some adenocarcinomas and adenosquamous carcinomas as well as most squamous tumors of the cervix.     

Reducing the burden of glandular carcinomas of the uterine cervix

Widespread use of the Papanicolaou test for the screening of cervical cancers has lead to a significant decline in overall incidence and mortality rates over the past 3 decades. When different histologic types of cervical cancers are considered and trends are reexamined, it becomes apparent that observed declines are reflective of squamous cell carcinomas predominantly; the rates for adenocarcinomas continue to rise. This rise in incidence may be due to the greater difficulty in screening for glandular precursor lesions that often arise high within the endocervical canal. Reducing the incidence and mortality rates that are associated with adenocarcinomas can be accomplished by using improved screening techniques and large-scale implementation of cervical cancer vaccines that target the predominant oncogenic human papillomavirus types that are associated with adenocarcinoma.     

Locally advanced adenocarcinoma and adenosquamous carcinomas of the cervix compared to squamous cell carcinomas of the cervix in Gynecologic Oncology Group trials of cisplatin-based chemoradiation

Objective

Conflicting results have been reported for adeno- and adenosquamous carcinomas of the cervix with respect to their response to therapy and prognosis. The current study sought to evaluate impact of adeno- and adenosquamous histology in the randomized trials of primary cisplatin-based chemoradiation for locally advanced cervical cancer.

Methods

Patients with adeno- and adenosquamous cervical carcinomas were retrospectively studied and compared to squamous cell carcinomas in GOG trials of chemoradiation.

Results

Among 1671 enrolled in clinical trials of chemoradiation, 182 adeno- and adenosquamous carcinomas were identified (10.9%). A higher percentage of adeno- and adenosquamous carcinomas were stage IB₂ (27.5% versus 20.0%) and fewer had stage IIIB (21.4% versus 28.6%). The mean tumor size was larger for squamous than adeno- and adenosquamous. Adeno- and adenosquamous carcinomas were more often poorly differentiated (46.2% versus 26.8%). When treated with radiation therapy alone, the 70 patients with adeno- and adenosquamous carcinoma of the cervix showed a statistically poorer overall survival (p = 0.0499) compared to the 647 patients with squamous cell carcinoma of the cervix. However, when treated with radiation therapy with concurrent cisplatin-based chemotherapy, the 112 patients with adeno- and adenosquamous carcinomas had a similar overall survival (p = 0.459) compared the 842 patients with squamous cell carcinoma. Adverse effects to treatment were similar across histologies.

Conclusion

Adeno- and adenosquamous carcinomas of the cervix are associated with worse overall survival when treated with radiation alone but with similar progression-free and overall survival compared to squamous cell carcinomas of the cervix when treated with cisplatin based chemoradiation.     

Prognosis and treatment of primary adenocarcinoma and adenosquamous cell carcinoma of the uterine cervix.

PURPOSE: To evaluate a cohort of women with primary invasive carcinomas of the uterine cervix, and to compare the biological characteristics and behavior of a cohort of adenosquamous carcinomas with a cohort of adenocarcinomas and squamous cell carcinomas. METHODS: One hundred and fourteen cases of primary invasive cervical carcinoma presenting between 1 January 1987 and 31 December 1997 were studied. Sixteen (14%) women with adenosquamous cell carcinomas and eight (7%) adenocarcinomas were compared with 90 (79%) women with squamous cell carcinomas. Patients with Stage Ib and IIa were treated by radical hysterectomy and pelvic lymph node dissection. All patients with stage IIb and over were treated by radiation. Patients with bulky, large, barrel-shaped lesions were selected for treatment by a combination of radiation and extrapelvic hysterectomy. RESULTS: The corrected survival rate for stage Ib patients with adenosquamous cell carcinoma was only 27.2%, compared with a 92.2% corrected survival rate for squamous cell, and a 100% corrected survival rate for adenocarcinoma. CONCLUSION: There is a higher proportion of adenosquamous cell and adenocarcinoma of the cervix than generally appreciated. The epidemiological risk factors associated with adenosquamous carcinomas of the cervix are more similar to those of squamous cell carcinomas than of adenocarcinomas. The survival difference between two groups is explained by effects of clinical stage, nodal spread, and vascular space involvement.     

Human papillomavirus type 18 DNA sequences in adenocarcinoma and adenosquamous carcinoma of the uterine cervix

Human papillomavirus (HPV) DNA sequences were detected by Southern blot hybridization and polymerase chain reaction (PCR) in 10 out of 19 patients (52.7%) with adenocarcinoma [15] and adenosquamous [4] carcinoma of the uterine cervix. HPV 18 DNA was detected in 8 of these 19 patients (42.1%), HPV 16 DNA in 1 patient (5.3%) and HPV type X (unknown) in another (5.3%). Of the 10 HPV positive samples HPV 18 was found in 6 out of 6 pure adenocarcinomas (100%), and in 2 of 4 (50%) adenosquamous carcinomas. HPV 16 and HPV X were each detected in 1 out of 4 (25%) adenosquamous carcinomas. The physical state of the viral DNA was investigated in 5 of the 10 HPV-positive cases. All the specimens from these 5 cases showed HPV to be integrated into the host genome, except for one adenosquamous specimen, which showed both episomal and integrated forms of HPV 16. Six of 8 HPV 18 DNA positive specimens were from cases of pure adenocarcinoma and it was found by PCR that five of these 6 specimens retained fragments of E6/E7, LCR/E7 and early sequence of E1 fragment (sequence: 1188–1373) but deleted most part of E1.     

Reproducibility of classification in non-squamous cell carcinomas of the uterine cervix

OBJECTIVE: Reproducibility of histopathologic classification systems is of major importance for their utility in daily practice and in research. The reproducibility of histologic classification of non-squamous carcinomas (non-SCC) of the uterine cervix was evaluated, using population-based material from two 5-year periods in Norway. METHODS: Histologic slides from 388 tumors were reviewed by three experienced pathologists and analyzed for inter- and intraobserver agreement on histological subtypes and grade. RESULTS: Kappa values of inter- and intraobserver agreement were moderate to substantial for all major adenocarcinoma subgroups (endocervical, endometrioid, clear cell, or serous carcinoma), and fair to poor for mixed carcinomas and adenocarcinomas not otherwise specified (NOS). Interobserver agreement on villoglandular and adenosquamous carcinomas was poor, and the distinction of adenocarcinoma in situ from well-differentiated carcinoma proved difficult. Reproducibility of the high-risk subgroups of small cell and undifferentiated carcinomas was acceptable from a statistical point of view (kappa values >0.50). However, the authors agreed upon the diagnosis of small cell carcinomas and undifferentiated carcinomas only in 2/3 of these high-risk diagnoses. Patients with high-risk diagnoses showed significantly lower overall survival than patients with non-high-risk diagnoses (P < 0.001). This inferior survival was independent of whether the reviewers had agreed on the high-risk diagnosis or not. CONCLUSION: Clinicians should be aware of the potential inconsistencies of histopathologic diagnoses. No histopathological classification system will ever be perfectly reproducible. Future histopathologic classification of the uterine cervix should emphasize the distinction between groups of particularly low or high prognostic risks.     

Clinical analysis of patients operated for adenocarcinoma and adenosquamous carcinoma of uterine cervix]

OBJECTIVES: The aim of our study was clinical analysis of patients with operated adenocarcinoma and adenosquamous carcinoma of uterine cervix. STUDY DESIGN: The mean age, number of pregnancies and labours, the incidence of adenocarcinoma and carcinoma adenosquamous in the stage Ib and IIa, and also in 2 following decades (1972-81 and 1982-91), the influence of positive lymph nodes on the survival have been estimated. MATERIALS AND METHODS: Between 1972 and 1991 at the 2nd Department of Obstetrics and Gynecology, Medical University of Gdańsk, 499 radical hysterectomies were performed in the patients with cervical cancer stage Ia, Ib and IIa. In this group there were 41 (8.2%) patients selected with adenocarcinoma and 16 (3.2%) with carcinoma adenosquamous. In the group of 18 pregnant women (3.6% of the whole group) there was diagnosed 1 case of adenocarcinoma and 1 case of carcinoma adenosquamous. The incidence of both-adenocarcinoma and carcinoma adenosquamous amounted to 11.4%. RESULTS: The number of pregnancies and labours was similar to other histological types. Nulliparas made up respectively 10.5% adenocarcinoma and 6.25% carcinoma adenosquamous. The incidence of adenocarcinoma stage Ib has been found to be more than twice higher than the incidence of adenocarcinoma stage IIa (9.0% and 3.8% respectively). The percentage of carcinoma adenosquamous in those two clinical stages was similar. The three times decrease in the incidence of adenocarcinoma, and the four times increase in the incidence of carcinoma adenosquamous has been found in the years 1982-91 in comparison to 1972-81. It was also stated that an adenouse type, comparing to other histological types, most often occurs without any clinical symptoms--in 23.1% a course of the disease was asymptomatic. As for an adenosqamous type the figures were lower--12.5%. In the patients with adenocarcinoma the incidence of positive pelvic nodes in the stage Ib-IIa was 34%. The incidence of positive lymph nodes in the patients with carcinoma adenosqamous and adenocarcinoma was lower and similar--25% and 23.7% respectively. The analysis of the 5-year survival showed 69.8% in patients with adenocarcinoma stage Ib-IIa and 66.3% in patients with carcinoma adenosquamous the (same stages). The difference is not statistically significant (p = 0.8).     

A matched study of surgically treated stage IB adenosquamous carcinoma and adenocarcinoma of the uterine cervix

Thirty-eight patients with surgically treated stage IB adenosquamous carcinoma of the uterine cervix (AS) have been matched with patients with other histologic subtypes of adenocarcinoma (A) for stage, lesion size, node status, grade of adenocarcinoma and age at diagnosis. An additional six patients with AS were unable to be matched. Overall 5-year survival and disease-free survival for the matched AS and A were not significantly different, 83 vs. 90%, and 78 vs. 81% nor were the number of recurrences, 8/38 AS vs. 6/38 A, but the mean time to recurrence was significantly shorter in the AS group: 11 vs. 32 months ( P = 0.003). A subgroup of AS with a high risk of a poor outcome can be identified based on either lesion size ≥ 4 cm, depth of invasion ≥ 10 mm or plevic lymph node metastasis. These patients may be suitable candidates for adjuvant therapy before or after surgical treatment.     

Influence of metastases on the prognosis of adenocarcinoma of uterine cervix.

95 cases of adenocarcinoma of the uterine cervix were analysed for the influence of metastasis on the prognosis. When there was penetration of cervical stroma, < 10 mm or > 10 mm, spread of the tumour to the uterine corpus, metastasis in the ovaries and no detection of metastasis in patients the differences in survival rates were not statistically significant. Local spread of adenocarcinoma to the uterine corpus, penetration of cervical stroma > 10 mm and metastasis to ovaries may not adversely influence the patients survival.     

Two cases of coincident carcinomas of the head and neck and the uterine cervix

BACKGROUND: Human papillomavirus (HPV) is an independent risk factor for select head and neck carcinomas and most uterine cervix carcinomas. We report two patients with synchronous diagnoses of cervical cancer and HPV-related head and neck cancer. CASE: One patient was a 53-year-old woman with regionally metastatic tonsillar carcinoma treated surgically and with adjuvant radiation. Abnormal vaginal bleeding developed. Gynecologic examination showed advanced cervical carcinoma. The other patient was a 78-year-old woman surgically treated for carcinoma of the left anterior nose. Five months later, symptoms of recurrent nasal carcinoma and concurrent vaginal bleeding developed. Gynecologic examination showed advanced cervical carcinoma. CONCLUSIONS: These cases of coincident tumors demonstrate possible systemic susceptibility to the carcinogenic effects of HPV. The common association of HPV with both uterine cervix cancers and select head and neck cancers should prompt early evaluation of gynecologic or upper aerodigestive tract symptoms for patients with known HPV-related cancers.