Squamous carcinoma of the uterine cervix with CIN 3-like growth pattern: An under-diagnosed lesion

Abstract. Al-Nafussi AI, Monaghan H. Squamous carcinoma of the uterine cervix with CIN 3-like growth pattern: An under-diagnosed lesion.
Invasive squamous carcinomas of the cervix have traditionally been classified into keratinizing, non-keratinizing, verrucous, warty (condylomatous), papillary transitional (squamo-transitional), and lymphoepithelioma-like carcinomas. The majority of these tumors are easily recognized. We present for the first time the pathological appearances of six cases of invasive squamous carcinoma with growth pattern simulating tangentially cut CIN 3 involving endocervical glandular crypts/clefts. In all cases initial diagnosis on biopsy and/or loop excision was thought to be CIN 3, perhaps with suspicion of early invasion. On further excision and/or on clinical grounds the tumors were frankly invasive. We propose the use of the term squamous carcinoma with CIN 3-like growth pattern for such lesions. This is in order to avoid misinterpretation as CIN 3 with subsequent inappropriate management of patients with this type of tumor.     

Angiogenesis in the uterine cervix

Abstract. Abulafia O, Sherer DM. Angiogenesis in the uterine cervix.
Our objective was to present current data pertaining to angiogenesis of the uterine cervix. We conducted a computerized search to identify relevant studies published in the English language literature. MEDLINE, Current Contents and Index Medicus were searched utilizing the terms: angiogenesis, uterine cervix, intraepithelial neoplasia, squamous cell carcinoma, and adenocarcinoma, from 1966 through June 1999. In contrast to the cyclic phases of the menstrual cycle of the ovary and endometrium in which angiogenesis plays a significant physiologic role, angiogenesis in the uterine cervix is involved primarily in neoplastic processes. These include intraepithelial disease, human papilloma-related disease, and microinvasive and invasive squamous cell and adenocarcinoma of the cervix. In invasive squamous cell and adenocarcinoma of the uterine cervix, angiogenesis appears to be a prognostic indicator for overall survival and disease-free survival. Initial trial studies with anti-angiogenic (angio-inhibitor) therapy such as TNP-470 have been reported and concurrent antitumor activity observed in a limited number of patients with advanced (inoperable or metastatic) disease.     

Signet-ring cells in squamous cell carcinoma of the cervix and in non-neoplastic ectocervical epithelium

Two cases of cervical carcinoma and two cases of normal ectocervical epithelium with a squamous signet-ring cell component are presented. In one carcinoma the vacuolization was so prominent that it partially obliterated the epithelial pattern of the tumor. Paraffin specimens were studied with a panel of histo- and immunohistochemical stains and by electron microscopy. The vacuoles of the squamous signet-ring cells did not contain glycogen, mucopolysaccharides or masses of intermediate filaments. The findings are discussed in relation to possible human papillomavirus and Chlamydia trachomatis infection. The true nature and possible clinicopathologic implications of the squamous carcinoma with signet-ring cells remain to be established, but the phenomenon may cause diagnostic difficulties, especially in biopsy specimens.     

Simultaneous squamous carcinoma involving the fallopian tube and the uterine cervix

INTRODUCTION: Primary fallopian tube carcinoma are extremely rare and are most commonly of serous or endometrioid type. Primary squamous cell carcinomas are exceptional with only three cases reported in the English literature. MATERIALS AND METHODS: We present the case of a 43-year-old woman operated for cervical carcinoma. RESULTS: Histologic examination, showed a squamous cell carcinoma of cervix with post operative discovery of a concomitant microinvasive squamous carcinoma of fallopian tube developing on high grade dysplasia and in situ carcinoma lesions. CONCLUSION: Clinico-pathological features of fallopian tube carcinoma, in general, and squamous carcinoma, in particular, will be discussed.     

Phase II study of vindesine in disseminated squamous cell carcinoma of the uterine cervix: an EORTC Gynecological cancer Cooperative Group study

Abstract. Vermorken JB, Landoni F, Pecorelli S, Piccart MJ, van derBurg MEL, ten Bokkel Huinink WW, George M, Greggi S, Rotmensz N. Phase II study of vindesine in disseminated squamous cell carcinoma of the uterine cervix: an EORTC Gynecological Cancer Cooperative Group study. Int J Gynecol Cancer 1991; 1 : 248–252.
Twenty-nine patients with disseminated squamous cell carcinoma of the uterine cervix were treated with a 3 mg/m² weekly i.v. bolus schedule of vindesine for 6 weeks (thereafter every 2 weeks). Twenty-seven patients were evaluable for response, 19 of whom had received prior chemotherapy (14 also vincristine). Five of the 27 patients (19%) showed a partial response, all being part of the 22 patients with only distant metastases. No objective response were observed among five patients who also had loco-regional recurrent disease. The median duration of response was 21 (11–58) weeks. Dose-limiting toxic effects were leukopenia and peripheral neuropathy. Vindesine warrants further study in combination chemotherapy protocols for cervical cancer.     

Large cell neuroendocrine carcinoma of the uterine cervix: a report of a case and review of the literature

Introduction Large cell neuroendocrine carcinoma is a rare aggressive cervical neoplasm, considerably rarer than the well-recognized small cell neuroendocrine carcinoma of the cervix. Cervical large cell neuroendocrine carcinomas are distinctive cervical carcinomas that are frequently misdiagnosed and have an unfavorable outcome, similar to that of small cell carcinoma. Case report We report a 45-year-old woman with large cell neuroendocrine uterine cervical carcinoma.     

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

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

Radiotherapeutic management in carcinoma of the uterine cervix: current status

Despite refinement in the delivery of external radiation and brachytherapy, there has been little improvement in the survival rate of patients with invasive cancer of the uterine cervix in recent years. With advancing stage disease, there is an increase in both local failure and distant metastases. Although recent efforts to improve local control for late stage disease have been encouraging, research efforts should be directed to the identification of new active drugs for radiation sensitization and systemic therapy. Also, due to early detection, therapeutic investigations should focus on the high-risk subsets of patients with early stage disease.     

Unusual form of superficial spreading microinvasive squamous cell carcinoma of uterine cervix involving the endometrium of uterus

Microinvasive squamous cell carcinoma of the uterine cervix is a recognized entity and is defined as carcinoma with invasion of less than 5 mm penetration of the stroma and seldom metastasized. Our patient was a 70-year-old, multiparous woman who had a microinvasive, cervical, squamous cell carcinoma. The tumor had spread superficially into the entire endometrial cavity up to the fundus, totally replacing the columnar epithelium. This is an extremely rare phenomenon, with fewer than 20 cases reported so far in the literature.     

Squamous cell carcinoma of the uterine cervix in association with stage 0 chronic lymphocytic leukemia/small lymphocytic lymphoma

BACKGROUND: There have been many cases of multiple malignant neoplasms involving the female genital tract reported, but involvement by epithelial and hematologic malignancy is extremely rare. CASE: A 52-year-old woman, who was followed for stage 0 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), had developed invasive squamous cell carcinoma of the uterine cervix. Microscopic examination of the hysterectomy specimen disclosed invasive squamous cell carcinoma in the cervix and monotonous populations of small lymphoid cells with proliferation centers, which are consistent with CLL/SLL, in the cervix as well as parametrium. Thirty months after the initial diagnosis of CLL/SLL, the patient died with systemic dissemination of squamous cell carcinoma, but the CLL/SLL remained a local disease. CONCLUSION: The clinical course of squamous cell carcinoma in this case appeared to be aggressive, but it was unclear whether the outcome was associated with an altered immune status due to the presence of concurrent CLL/SLL.     

Comparison of gene expression in squamous cell carcinoma and adenocarcinoma of the uterine cervix

OBJECTIVES: Microarray expression analysis of cervical tumors has revealed differential expression of genes that may be useful as markers or targets for treatment. We question the application of array findings across the major categories of cervical cancer. We sought to identify differences between normal squamous epithelium (NSQ) and glandular epithelium (NGL) of the uterine cervix and their malignant variants: squamous cell cancer (SCC) and adenocarcinoma (ACA). METHODS: Eight genes were selected: 12-lipoxygenase (12-LOX), keratin 4, trypsinogen 2 (TRY2), Rh glycoprotein C (RhGC), collagen type V alpha 2, integrin alpha 5, integrin alpha 6, and c-myc. Ten cases each of SCC and ACA of the cervix were selected from our tumor bank. NSQ and NGL epithelia were obtained from consecutive patients undergoing surgery for benign disease. RNA extraction, cDNA synthesis, and DNA amplification of all samples were performed according to an established protocol. Electrophoresis of the multiplexed polymerase chain reaction (PCR) products was performed under standard conditions, followed by digital image capture. A ratio of target to control gene (beta-actin) was obtained for each sample. Analysis of variance was applied to the mean ratios for each tissue to establish significant differences. Individual pairwise comparisons were made by Student t tests and verified with the Tukey-Kramer test. RESULTS: Clinically valid comparisons are NSQ to NGL, NSQ to SCC, NGL to ACA, and SCC to ACA. Various expression patterns were observed between the epithelia and their malignant phenotypes. Significant differences in gene expression were observed between benign squamous and glandular epithelium in four of the eight genes and between malignant squamous and glandular epithelium in three of the eight genes. Significant differences in gene expression between benign and malignant tissues were demonstrated in four of the eight genes. CONCLUSIONS: We have defined significant differential expression changes between the two principal cervical tumor types. Differences in genes are demonstrated and must be considered if array technology is applied to the study of the biologic behavior of these tumors as well as their screening and management. The observed differential expression should be a compelling argument to perform type-specific expression analysis for other tumors with histological variants.     

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.     

An unusual endometrioid adenofibroma of the uterine cervix: a histologic and immunohistochemical study

An unusual adenofibroma of the uterine cervix is reported. The cervix was bulkily enlarged but did not have a polypoid appearance. The neoplastic epithelium was in continuity with the covering epithelium of the cervix and consisted predominantly of endometrioid cells which proliferated to form numerous glandular structures of irregular size and shape. The glandular component resembled an endometrial hyperplasia, and was set in an abundant fibrous stroma which was moderately cellular and hyalinized. Both the epithelial and mesenchymal cells lacked cytologic atypia. Despite its benign appearance, the tumor occupied almost all the uterine cervix and extended into the upper vaginal wall. The epithelial cells showed diffuse positive staining for CA19-9 and were focally positive for carcinoembryonic antigen. The presence of dense periglandular fibrosis distinguished the present case from a minimal deviation adenocarcinoma of endometrioid type.     

Coexistent squamous cell carcinoma and adenoid basal carcinoma in the uterine cervix and infection with human papillomavirus (HPV 31)

ObjectiveAdenoid basal carcinoma (ABC) is an uncommon neoplasm of the uterine cervix. ABC can be accompanied by carcinoma in situ or invasive carcinoma. Most cases are discovered accidentally during radical hysterectomy. ABC is associated with a high risk of human papillomavirus infection (HPV), most often HPV 16 infection.Case reportWe present a rare case of an 86-year-old Taiwanese married woman who suffered from bloody vaginal discharge and occasional lower abdominal pain and received cervical biopsy. The pathological report revealed squamous cell carcinoma (SCC) of the uterine cervix. After radical hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymph node dissection, the final pathological report revealed SCC coexisting with ABC, and both of the components were infected by HPV 31. After receiving radiotherapy, she maintained outpatient department follow-up.ConclusionA literature review revealed that this was a rare case of combined ABC–SCC associated with HPV 31 infection. In this case, the ABC component did not affect the tumor stage because it was confined to the cervix. However, we must avoid overestimating the clinical stage because the ABC component is thought to be a benign lesion.     

Prognostic factors of the uterine cervix adenocarcinoma

Background: Prognosis factors for adenocarcinoma of the uterine cervix after primary treatment are poorly established. Methods: A retrospective study of 45 cases of adenocarcinoma of the cervix with a follow-up of 96 months on average was performed. The primary treatment consisted in combined radical surgery and radiotherapy for stage I-II patients while patients with advanced disease were treated by radiotherapy. In case of poor prognosis factors, they were given chemotherapy. Survival rates were established and prognosis factors influencing survival and recurrences were studied. Results: Fifteen women remained alive without evolutive disease. FIGO stage and pelvic node involvement were the most important parameters influencing overall survival. Local failures (27%, average period of 30 months) were unpredictable and led to a dramatic outcome. Histological grade and pelvic node status were significant predictive factors for metastatic recurrence (40%, average period of 29 months). Conclusions: Local recurrence and metastatic dissemination of cervical adenocarcinoma after primary treatment prove to be rapidly fatal although life expectancy can be prolonged with adjuvant treatment of the recurrence. In the event of aggressive tumors with high histological grade and pelvic node involvement, an attempt to assess adjuvant systemic chemotherapy could be useful.     

Small-cell carcinoma of the uterine cervix: a clinicopathologic study of 11 cases

We report the clinical profiles and immunohistochemical features of small-cell carcinoma of the uterine cervix. Eleven cases that we have encountered at the Department of Gynecology, Kitasato University Hospital, between 1971 and 2003 are presented. Of 1370 invasive carcinomas of the uterine cervix, the incidence of small-cell carcinoma was 0.8%. Patient ages ranged between 32 and 65 years, with a mean age of 46.3 years. The clinical stages at diagnosis were Ib in four patients, IIb in three, IIIb in three, and IVb in one. All patients presented with abnormal vaginal bleeding. Two patients who are alive with no evidence of disease for 12 years and 3 years 6 months, while eight patients died of primary carcinoma between 4 and 25 months after treatment. Histopathologic findings showed solid nests with marked peripheral palisading pattern and rosette formation. Small tumor cells with scant cytoplasm demonstrated a very high nuclear/cytoplasm ratio and indistinct cell borders. The nuclei were round to oval and demonstrated increased but fine granular chromatin. Nucleoli were indistinct in all cases. Immunohistochemical findings were positive in 81.8% each for neuron-specific enolase and protein gene product 9.5, 72.7% for synaptophysin, 63.6% for chromogranin A, and 54.5% for neural cell adhesion molecule. All specimens were positive for at least one of the above. In conclusion, small-cell carcinoma of the uterine cervix revealed poor prognosis. Making an accurate diagnosis of small-cell carcinoma before performing treatment is of great significance but often difficult. Immunohistochemical analysis using several kinds of neuroendocrine markers is helpful in establishing the correct diagnosis in addition to focusing on characteristic histo- and cytopathologic features.     

Surgical treatment for neuroendocrine carcinoma of the uterine cervix.

OBJECTIVE: To identify the best operative approach for neuroendocrine cervical carcinoma (NECC). METHODS: The records of surgically treated patients with stages IB to IIB NECC were reviewed. RESULTS: Of 10 patients who met the study criteria for NECC and underwent radical hysterectomy, 4 had pT1bN0, 4 had pT1bN1, 1 had pT2aN0, and 1 had pT2bN1 disease. Those with pT1bN1 or pT2bN1 disease received postoperative adjuvant radiotherapy and/or chemotherapy, and recurrence occurred in 7 patients (70%). Among these 7 patients, 5 (71%) had a primary NECC tumor with deep stromal invasion and 5 (71%) had extrauterine disease (parametrium and/or lymph node). The recurrences in 6 patients (86%) were located outside the pelvis (lung, liver, or brain). Stromal invasion was 6 mm or less in the 3 patients who did not experience disease recurrence. CONCLUSIONS: Pelvic control by radical hysterectomy may not be beneficial for patients with NECC except for those with an early invasive lesion.