CD56 reactivity in small cell carcinoma of the uterine cervix.

Small cell carcinoma (SCC) of the uterine cervix, like its pulmonary counterpart, is a rare but distinctive neoplasm that should be separated from nonendocrine carcinomas because of its highly aggressive clinical course and response to chemotherapy and irradiation. CD56 (neural cell adhesion molecule) has recently been shown to be the best marker for the diagnosis of pulmonary SCC. In this study, we assessed the sensitivity and specificity of CD56 in the diagnosis of SCC of the uterine cervix compared with those of chromogranin and synaptophysin. Twenty-two (88%) of 25 SCCs of the uterine cervix labeled with CD56 in a predominantly membranous and diffuse pattern, whereas 16 of 25 (64%) stained with synaptophysin in a predominantly diffuse pattern and 8 of 25 (32%) showed predominantly focal immunoreactivity for chromogranin. In contrast, 3 of 21 (14%) moderately to poorly differentiated squamous cell carcinomas and 1 of 16 (6%) moderately differentiated adenocarcinomas showed focal immunoreactivity for CD56. Although not specific, CD56 seems to be the most sensitive marker for the diagnosis of SCC of the uterine cervix. Moreover, its diffuse reactivity reduces the possibility of obtaining negative results in small biopsy samples.     

C-kit overexpression in neuroendocrine small cell carcinoma of the uterine cervix

PURPOSE OF INVESTIGATION: Neuroendocrine small cell carcinoma of the uterine cervix (NESCC) grows aggressively, and is resistant to anticancer agents and radiation, having an extremely poor prognosis. The incidence of c-kit proto-oncogene overexpression is high in gastrointestinal stromal tumors (GISTs) and small cell lung cancer, and tyrosine kinase inhibitors have been used effectively to treat GISTs. Few studies have investigated whether c-kit is overexpressed in NESCC. To investigate whether NESCC can be a target for molecular targeted therapy with tyrosine kinase inhibitors, we examined the expression of c-kit in this tumor. METHODS: Twenty-one NESCCs were examined for c-kit expression by immunohistochemical staining using the labeled streptavidin-biotin complex (LSAB) method. The expression of c-kit was regarded as positive (overexpression) and negative when the membrane and cytoplasm of more or less than 25%, respectively, of tumor cells were stained. RESULTS: Nine NESCCs (43%) were c-kit-positive (overexpression). No difference in age or clinical stage was noted. No difference in prognosis was observed between the c-kit-positive and -negative patients. CONCLUSION: The incidence of c-kit overexpression was high in NESCC; therefore, the patients with this tumor may become a future target for molecular-targeted therapy with tyrosine kinase inhibitors.     

Pigmented squamous cell carcinoma of the uterine cervix.

A 57-year-old female presented with an abnormal Pap smear. Colposcopic examination of the cervix revealed white mucosa with erosion and several areas of black pigmentation. After a colposcopically directed biopsy and loop conization, radical hysterectomy and bilateral salpingo-oophorectomy with pelvic and paraaortic lymphadenectomy were performed. Pathological examination disclosed an invasive squamous cell carcinoma admixed with many dendritic melanocytes. Melanin granules were present within the melanocytes and tumor cells. Although similar tumors have been reported in other sites, this is the first report to our knowledge of a pigmented squamous cell carcinoma of the uterine cervix.     

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.     

Cellular immunity in squamous cell carcinoma of the uterine cervix.

The thymus-dependent immunity of 42 patients with SCCC was evaluated by: delayed cutaneous reactions to ubiquitous antigens, DNCB sensitization, and lymphocyte response to PHA. In addition, T and B lymphocytes were detected in peripheral blood and in tumor sections, by adherence to E and HEAC. Depressed CMI was more intense in patients with disseminated disease, although a premature impairment of CMI was observed in some patients with initial-stage tumors. The absolute number of peripheral T lymphocytes showed association with both cutaneous reactions and PHA response. However, there appeared to be no significant correlation between the stage of the tumor and the pattern of adherence of E or HEAC to the biopsies.     

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.     

Microinvasive carcinoma of the uterine cervix.

MICA is the transition stage from intraepithelial growth to clinical invasive cancer. The early invasive growth must be accepted as an indication that the lesion is significant; it may be self-healing but it is objective evidence of progression and invasion remains the most significant indication of malignancy. The subjective changes of CIS, nuclear enlargement, pleomorphism of nuclei, altered nuclear-cytoplasmic ratio, etc., are transcended and the recognition and diagnosis of MICA should be facilitated for the pathologist. Treatment which tends to be conservative is more widely accepted, but the disease can be lethal and the most serious complication appears to be, like CIS, vaginal recurrence.     

Coexistent squamous cell carcinoma and adenocarcinoma of the uterine cervix

The clinical and pathological features of 20 patients with coexistent squamous cell carcinoma and adenocarcinoma of the uterine cervix have been analyzed. Various combinations of in situ and invasive carcinomas were found. Located adjacent to each other and at times intermingling, these lesions probably originated from the subcolumnar reserve cells of the transformation zone. They are early lesions and may be precursors of adenosquamous and mucoepidermoid carcinomas of the cervix. The diagnosis of these double carcinomas depends upon being aware that the two entities may coexist in the same cervix. Treatment is conventional, and the prognosis is not worsened by the presence of the two types of neoplasms.     

The treatment of microinvasive squamous cell carcinoma of the uterine cervix.

Between 1947 and 1971 254 cases of microinvasive carcinoma of the uterine cervix were treated in this institution. Cervical cytology was used to detect the cervical abnormality and the diagnosis of microinvasion was established by cone biopsy. During this time period microinvasion was defined as the breakthrough of the basement membrane and the penetration of neoplastic epithelium into the stroma to a depth of no greater than 5 mm, and excluded those cases which had lymph or blood vessel involvement, a dentritic or staghorn pattern, many epithelial cells in clusters in the stroma, or the presence of confluence. Of the 254 cases, 250 were followed for 5 years or more. Treatment methods for microinvasive cervical cancer over this time period included surgery alone, radiotherapy alone, or a combined approach using both surgery and radiotherapy. None of the 125 cases treated by surgery alone have died of cervical cancer. It is concluded that microinvasive carcinoma, as defined in this study, can be cured by conservative surgical means.     

Early squamous cell carcinoma of the uterine cervix. I. Definition and histology

Different names and histopathologic definitions concerning early squamous cell carcinoma of the uterine cervix cause divergent opinions on the treatment of this lesion. From a prognostic and therapeutic viewpoint, it is advisable to distinguish two microscopic forms of this early cancer: early stromal invasion and microcarcinoma. While in early stromal invasion, only isolated, variably shaped projections with early signs of infiltration occur, in microcarcinoma, one already finds true confluent carcinomatous masses. The extent of the neoplastic stromal infiltration in microcarcinoma is limited. Tumor length and width amount at most to 10 mm and depth to 5 mm. The tridimensional definition of the size of the tumor requires a very careful histologic workup and diagnosis. Only then can microscopic diagnosis of early stromal invasion and microcarcinoma be reliably made and a definite separation from carcinoma in situ on one side and from advanced carcinoma on the other side be guaranteed.     

Hepatic resection for metastatic squamous cell carcinoma from the uterine cervix.

A solitary hepatic tumor was diagnosed 3.5 years after a 67-year-old woman had undergone radical hysterectomy and postoperative irradiation for stage Ib squamous cell carcinoma of the cervix. Hepatic resection confirmed squamous cell carcinoma that had metastasized from the uterine cervix. One year and 10 months following hepatic resection, this patient is doing well with no evidence of any recurrence. This is a report of successful hepatic resection for metastatic carcinoma from the uterine cervix.     

Adenoid cystic carcinoma of uterine cervix.

A 68-year-old postmenopausal patient with adenoid cystic carcinoma of the cervic is described. Thirty-two other cases were collected from the literature, and a clinicopathologic analysis for the whole group is presented. The study indicates that a) adenoid cystic carcinoma usually occurs in postmenopausal patients in the commonest presenting problems; c) vaginal cytology was abnormal in most cases in which it was reported; d) the lesion usually forms a mass and infiltrates parametrial and paracervical tissues; e) the tumor is frequently associated with squamous cell carcinoma (in situ or invasive) or other types of cancer; f) local recurrence after radical surgery and /or irradiation, as well as pelvic and widespread metastases, can occur; and g) the histogenesis of this type of tumor is unclear. The various possibilities are discussed.     

Lymphoid cell distribution as prognostic factor in carcinoma of the uterine cervix.

Pretreatment assessment of blood lymphoid cells was performed in 44 patients with carcinoma of the cervix and in 19 healthy controls. White blood cells were determined by routine differential counting, and T-lymphocyte subsets and monocytes were quantitated using monoclonal antibodies. Increase in monocyte numbers, as determined by the 1D5 antibody, was seen in the cancer patients, especially in the group with advanced disease. No change in T-lymphocyte subpopulations could be found. During the 5-year follow-up period, 17 patients had a recurrence or died of cancer. The best prognostic information was obtained from conventional clinical parameters, e.g. stage, tumor size and lymph node status. Increased numbers of granulocytes and monocytes were found in advanced stage disease but had no independent prognostic influence. In pelvic lymph node biopsies taken from patients undergoing Wertheim-Meigs operation the T-helper/T-suppressor ratio was higher and the monocyte number lower than in peripheral blood. No correlation could be detected between node cell distribution and the prognosis. It is concluded that immunological testing, as performed in this study, elicits very little new prognostic information.     

Glandular cell properties of cell line (HKUS) derived from small cell non-keratinizing squamous cell carcinoma of the uterine cervix

HKUS cell line was established by culturing a uterine cervical small cell non-keratinizing squamous cell carcinoma from a 70-year-old woman. The cells were spindle-like and roundish in shape and in an epithelial cell arrangement. No contact inhibition was observed, and the cells proliferated in multi-layer fashion. Proliferation was quick and more than 250 passages were observed within 4 years after establishment. The chromosome number mode was found in the diploid range, and the chromosomes of stem cells showed a structure abnormality of 45, X, -X. Most HKUS cells had characteristics of glandular cells, and adenocarcinoma was formed when the cells were transplanted into the subepidermis of nude mouse. Some HKUS cells had characteristics of squamous epithelial cells. The HKUS line is regarded as a primitive carcinoma cell line that can differentiate into squamous cell carcinoma and adenocarcinoma.     

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.