Adenoid basal carcinoma of the cervix uteri: a case report

We report a rare case of adenoid basal carcinoma of the uterine cervix, unexpectedly found in a uterus resected for the treatment of cervical intraepithelial neoplasia (CIN) 3. The patient was a 47-year-old Japanese female. She received a total abdominal hysterectomy under a diagnosis of CIN 3 of the cervix. Grossly, there were no significant findings in the surgical specimens. Microscopically, in seven of the 12 blocks of the cervix examined, scattered small nests of uniform small cells, which extended 4 mm below the epithelial surface, with dark nuclei and scant cytoplasm were observed. Peripheral palisading as well as the formation of gland-like or acinar structures were noted. The latter were positive for mucicarmine. Stromal reaction was not obvious. There were also foci of squamous differentiation in some portions of the small nests. Occasional mitoses as well as large atypical cells were also seen in this area. Immunohistochemically, the foci of squamous differentiation were positive for carcinoembryonic antigen. The epithelial surface in other portions showed CIN 3 with crypt extension. Distinction between adenoid basal carcinoma of the cervix and other diseases, such as adenoid cystic carcinoma and squamous cell carcinoma with basaloid features, is important for clinical management because the clinical behavior of adenoid basal carcinoma is less malignant.     

Carcinomas of Bartholin''s gland. Histogenesis and the etiological role of human papillomavirus

In this study, we examine 10 primary carcinomas of Bartholin's gland, including seven squamous carcinomas, two adenoid cystic carcinomas, and one adenocarcinoma, as well as four non-neoplastic Bartholin's gland. Six of seven squamous cell carcinomas contained human papillomavirus (HPV) type 16 DNA detectable by the polymerase chain reaction; one of these demonstrated HPV type 16 by in situ hybridization. The two adenoid cystic carcinomas, the adenocarcinoma, and the non-neoplastic Bartholin's gland epithelium showed no evidence of HPV DNA by polymerase chain reaction or in situ hybridization. A panel of eight antibodies (Cam 5.2, B72.3, CEA, EMA, MCA, Lewis X, ER, and PR) demonstrate that the squamous, transition zone, duct, acinar, and myoepithelial cells or Bartholin's gland are antigenically distinct, and are similar to those reported in analogous areas of the uterine cervix. Squamous carcinoma and adenocarcinomas of Bartholin's gland are antigenically similar, and seem to arise from the transition zone of the Bartholin's gland duct. The origin of adenoid cystic carcinomas is more difficult to determine; it is distinct from squamous and adenocarcinomas and seems more likely to arise from myoepithelial cells. We conclude that adenocarcinoma and squamous cell carcinoma of Bartholin's gland arise in the transition zone of Bartholin's gland, which is similar to the transition zone of the uterine cervix. We also show that HPV is associated with Bartholin's gland carcinoma and may play a role in the genesis of malignancy.     

Adenoid basal epitheliomas of the uterine cervix: a reevaluation of distinctive cervical basaloid lesions currently classified as adenoid basal carcinoma and adenoid basal hyperplasia

A series of 12 adenoid basal carcinomas and three adenoid basal hyperplasias of the cervix were analyzed. The ages of the patients with adenoid basal carcinoma ranged from 30 to 91 years with a mean of 71 years. Pap smear results for 11 of 12 (92%) were abnormal. Almost all patients were asymptomatic. None had a gross cervical tumor. All tumors had typical histologic features of adenoid basal carcinoma, with various degrees of squamous differentiation. Depth of tumor invasion ranged from 2 mm to 10 mm (mean, 4.3 mm; median, 3.7 mm), exceeding 3 mm in six tumors (50%). Tumor volume was >500 mm3 in four tumors (33%). An associated neoplastic squamous lesion was present in 92% of patients, including high-grade cervical intraepithelial neoplasia in 10 cases and microinvasive squamous cell carcinoma in one. Treatment was predominantly surgical, usually after some form of cervical conization; conization alone was performed in three patients. Lymph nodes were removed in five patients; none of 104 nodes had metastases. No recurrence of tumor developed in any patient. Nine patients were alive without disease after 4 to 82 months (mean, 30 months), and three died without disease after 24, 63, and 87 months. The three patients with adenoid basal hyperplasia also were asymptomatic and did not have a gross cervical lesion. Pap smear results for two patients were abnormal. The adenoid basal hyperplasias were incidental, very superficial lesions that resembled small adenoid basal carcinomas. Generally, they were attached to the squamous or endocervical mucosal epithelium; all were less than 0.5 mm in depth. Treatment was hysterectomy in one patient and conization in two. Follow-up was short but uneventful. Our findings, together with those previously reported, indicate (1) adenoid basal carcinoma with typical histologic features is not a malignant neoplasm in that it typically presents in asymptomatic women, usually is discovered after an abnormal Pap smear result due to cervical intraepithelial neoplasia, does not produce a grossly visible lesion, has never metastasized to regional lymph nodes or elsewhere, and has never itself caused death; (2) rare, histologically atypical tumors with distinctly malignant features should not be regarded as adenoid basal carcinoma; and (3) adenoid basal hyperplasia probably is a small adenoid basal carcinoma. We propose the term "adenoid basal epithelioma" to replace adenoid basal carcinoma and adenoid basal hyperplasia, because it better describes the clinicopathologic features of these distinctive lesions and their excellent prognosis and may reduce the likelihood of unnecessarily aggressive treatment.     

Fine needle aspiration of basal cell adenocarcinoma of the parotid gland. Report of a case with assessment of DNA ploidy in aspirates and tissue sections by image analysis

BACKGROUND: Basal cell adenocarcinoma of the parotid gland is a low grade malignant neoplasm. It has cytologic features of basal cell adenoma and a histologically infiltrative growth pattern of malignant tumors with perineural and vascular invasion. CASE: Fine needle aspiration biopsy findings of basal cell adenocarcinoma of the parotid gland in a 77-year-old male were supplemented by DNA ploidy analysis. CONCLUSION: No single cytologic feature was found to unequivocally distinguish this lesion from basal cell adenoma and/or solid variant of adenoid cystic carcinoma. Therefore, for diagnostic purposes, we grouped all three lesions under the term basal cell tumor. Evaluation of DNA content of tumor cells revealed diploid histograms in both cytologic material and paraffin-embedded tissue. Infiltrative tumor nests, the histologic basis for differentiating basal cell adenocarcinoma from adenoma, showed the same diploid pattern. Though DNA quantitation may not discriminate basal cell adenoma from basal cell adenocarcinoma, it may prove useful in separating them from adenoid cystic carcinoma, which is considered to be a tumor with high malignant potential.     

Radiotherapy of humero-scapular periarthritis using ultra-hard photons. Evaluation by MRI findings

OBJECTIVE: To determine the clinical implications of atypical glandular cells of uncertain significance (AGCUS) in cervical cytologic smears. STUDY DESIGN: Retrospective analysis. RESULTS: Eighty-eight of 32,181 (0.27%) cervical smears obtained during the study period contained AGCUS. Of the 47 women with AGCUS, 16 had intraepithelial or invasive neoplasms (34%; 95% confidence interval, 21-49%), including 9 low or high grade squamous intraepithelial lesions, 1 adenocarcinoma in situ of the cervix, 3 adenocarcinomas of the cervix, 2 adenocarcinomas of the endometrium and 1 adenoid basal cell carcinoma of the cervix. CONCLUSION: The high prevalence of cervical and endometrial neoplasia among women with the isolated finding of AGCUS on cervical cytologic smears warrants a thorough diagnostic evaluation.     

Identification and biosynthesis of fibrinogen in human uterine cervix carcinoma cells

Fibrinogen has been detected in ME-180 human uterine cervix carcinoma cells, and synthesis of fibrinogen by ME-180 cells has been measured using [35S] L-methionine incorporation. Expression of mRNA for the B beta-chain of the fibrinogen in ME-180 cells has been identified by PCR-assisted mRNA amplification. The A alpha-, B beta-, and gamma-chains of fibrinogen synthesized by ME-180 cells were chemically and immunologically identical to those of plasma fibrinogen. These findings suggest that fibrinogen is present and synthesized in ME-180 human uterine cervix carcinoma cells, and that fibrinogen plays a role in these malignant tumor cells.     

Small-cell neuroendocrine carcinoma of the uterine cervix associated with micro-invasive squamous cell carcinoma and adenocarcinoma in situ

A case of small-cell neuroendocrine carcinoma of the uterine cervix associated with squamous cell carcinoma and adenocarcinoma in situ is reported. The tumor consisted mainly of uniform small cells with a population of intermediate cells that resembled carcinoid tumor cells. Foci of micro-invasive squamous cell carcinoma and adenocarcinoma in situ were recognized separately, adjacent to the main tumor. Both Grimelius stain and immunostaining of serotonin were positive for small-cell and intermediate-cell carcinoma. Neurosecretory granules were demonstrated by electron microscopy. Microacini with positive mucin staining and microvilli-like structures suggested glandular or exocrine differentiation of the tumor. Three distinctive types of differentiation, neuroendocrine, exocrine and squamous characteristics, were expressed in the tumor.     

Metastatic adenocarcinoma to the uterine cervix from gastric cancer. A clinicopathologic analysis of 16 cases

BACKGROUND: Metastatic adenocarcinoma to the uterine cervix from gastric cancer is rare, and the clinicopathologic features of this metastasis are unclear. METHODS: A clinicopathologic review of 16 patients with metastatic adenocarcinoma to the uterine cervix from gastric cancer was performed. RESULTS: The ages of the patients ranged from 29 to 57 years, and 81.3% of the patients were premenopausal. Nine of the patients had undergone gastrectomy previously. In 11 patients the histologic type of the gastric cancer was poorly differentiated adenocarcinoma and, in 5 patients, signet ring cell carcinoma. The cervical metastasis was diagnosed 11-121 months (mean, 57.5 months) after the diagnosis of the gastric cancer in 10 of the patients. In six patients, the cervical metastasis was discovered synchronously or before the diagnosis of the gastric cancer. The colposcopic findings were normal in 57.1%, but 56.3% had abnormal cervical smears. In all patients, tumor cells were present in the dilated lymphatics of the cervix. Metastases to the uterine body and bilateral ovaries were common, and half of the patients had metastases to the paraaortic lymph nodes. Extirpation of the cervix was performed in six patients. The prognosis was poor, regardless of the treatment method. CONCLUSIONS: The route of metastasis to the cervix is surmised to be retrograde lymphatic, and this extension is often slow. Periodic gynecologic examinations should be performed indefinitely for premenopausal female patients with advanced gastric cancer.     

Specific respiratory manifestations associated with hemorrhagic rectocolitis. Analysis of a case and review of the literature

In a 59-year-old woman suffering from the syndrome of inappropriate antidiuretic hormone secretion, a small cell carcinoma of the uterine cervix was detected. The tumor was immunoreactive for antidiuretic hormone as well as for neuron specific enolase, chromogranin A, and Leu-7, but not vimentin. Electron microscopic examination of the tumor revealed neurosecretory granules. To our knowledge, this is only the second report of the syndrome of inappropriate antidiuretic hormone secretion with small cell carcinoma of the uterine cervix and the first one confirmed immunohistopathologically.     

Angiogenesis in squamous cell carcinoma in situ and microinvasive carcinoma of the uterine cervix

OBJECTIVE: To evaluate angiogenesis in squamous cell carcinoma in situ (CIS) and microinvasive squamous cell carcinoma of the uterine cervix and to investigate the relations among angiogenesis, stromal inflammation, and depth of invasion. METHODS: Three groups of women were studied: 22 controls who had undergone hysterectomy for benign conditions; 18 with squamous cell CIS of the cervix who underwent cone biopsy, hysterectomy, or both; and 14 with microinvasive squamous cell carcinoma who underwent conization of the cervix and subsequent surgical management according to depth of invasion. All specimens were stained immunohistochemically for factor VIII-related antigen. Areas below the basement membrane with the highest angiogenic density were selected. The degree of stromal inflammatory reaction was assessed. Statistical analyses included Kruskal-Wallis, analyses of variance and covariance, Scheffe and Bonferroni-Dunn post hoc procedures, and Pearson correlation analysis. P < .05 was considered statistically significant. RESULTS: Microvessel counts per high-power field (x 400) of microinvasive squamous cell carcinoma of the cervix differed significantly from those of controls and squamous cell CIS (median 34.5 per high-power field, range 9-76 versus median 17, range 7-47, and median 19, range 8-39, respectively; P < .005). Microvessel counts per high-power field in squamous cell CIS did not differ significantly from those of controls (P = .91). Among patients with microinvasive squamous cell carcinoma of the cervix, no significant correlation was found between microvessel counts per high-power field and the depth of invasion (r = 0.19, P = .51). Stromal inflammatory reaction (graded 0-3) differed significantly among controls, squamous cell CIS, and microinvasive carcinoma (mean 0.40, 0.83, and 1.64, respectively; P < .005). CONCLUSIONS: Microinvasive squamous cell carcinoma of the uterine cervix is angiogenic, but depth of invasion is not associated with increased angiogenicity. Squamous cell CIS is not angiogenic.     

Experience and results of application of remote afterloading system (RALS) optimization program for intracavitary treatment of squamous cell carcinoma of the uterine cervix

An optimization program for a remote after-loading system (RALS) for intracavitary treatment of cancer of the uterine cervix was established in 1982 by Tabushi and his co-workers. This system has been used in our hospital since 1986, using MODULEX. Seventy-three cases of untreated squamous cell carcinoma of the uterine cervix have been treated under RALS, 29 under conventional RALS and 44 under the RALS optimization program. The cumulative 5-year survival rates were obtained for the groups treated under each system by the Kaplan-Meier method. The 5-year survival rate of stage II cases treated under the RALS optimization program was 68.2%, and that of stage III cases 58.5%. On the other hand, that of stage II cases treated under conventional RALS was 56.3%, and that of stage III cases 44.9%. There was no significant difference between these two groups. Local control rates for stage II and III cases were higher than 5 year-survival rates. Among complications, the frequency of grade 2 radiation colitis was 15.9% with the RALS optimization program cases, and that of grade 2 radiation cystitis was 4.5%. We consider the RALS optimization program to be a clinically useful method for the intracavitary treatment of squamous cell carcinoma of the uterine cervix.     

Method for determining optimal intracavitary radiotherapy conditions for carcinoma of the uterine cervix with tumor infiltration of the vaginal wall

Stage III carcinoma of the uterine cervix is occasionally accompanied by tumor infiltration of the vaginal wall. Currently, the vaginal wall has to be irradiated in the same manner as the uterine cervix. The authors have developed a system for determining the optimal irradiation conditions for treating the two regions, uterine cervix and vaginal wall, at the same time. A comparison of two methods is shown in simulation, and then a clinical case is reported. The first method consists of two treatment plans, one for the uterine cervix without tumor infiltration of the vaginal wall, and the other for the vaginal wall without carcinoma of the uterine cervix. The second, newly developed method considers the two regions together. Irradiation times of ovoid sources obtained with the second method are 15-25% less than those of the first method. Isodose curves obtained with the two methods are very different, and thus the uterine cervix and vaginal wall must be considered together in order to determine irradiation conditions.     

Differential expression of Mr 70,000 heat shock protein in normal, premalignant, and malignant human uterine cervix

Transformed cells differ from normal cells in their pattern of heat shock protein expression. Here, we report differential expression of a Mr 70,000 heat shock protein (HSP70) in squamous cell carcinomas of the uterine cervix compared to normal or premalignant uterine cervix. Expression of HSP70 was measured using a mouse mAb against HSP70 by an ELISA. A significant increase in the level of expression of HSP70 was observed in fresh tumor cells as compared to normal or dysplastic ones (P < 0.001). The induction of HSP70 in tumor cells subjected to hyperthermia was less than that in normal or premalignant cells. Strong cytoplasmic and nuclear immunostaining was observed in cancerous tissues using anti-HSP70 mAb, biotinylated rabbit antimouse immunoglobulins, avidin combined in vitro with biotinylated horseradish peroxidase, and diaminobenzidine tetrachloride. HSP70 immunostaining was not detected in normal or dysplastic tissue sections. The results were confirmed by immunoprecipitation using anti-HSP70 mAb. These results are the first demonstration of overexpression of HSP70 in squamous cell carcinomas of the uterine cervix as compared to that in dysplastic or normal uterine cervix cells. We conclude that tumor cells differ from normal cells in their pattern of HSP70 expression, and increased levels of HSP70 correlate with an increase in tumor size.     

Cystoscopic staging of carcinoma uterine cervix, revisited

Of the 378 cases of stage 3 carcinoma uterine cervix, only 10 showed vesical invasion, while 19 of 24 cases of stage 4 disease had vesical invasion. Results of this procedure did not alter the management of the disease in any of these cases. From the whole series it was concluded that cysto-urethroscopy is an unnecessary, cost ineffective, invasive procedure which has no role in either diagnosis or in planning the definitive treatment of carcinoma uterine cervix.     

The importance of the results of pretreatment pelvic lymphographies in the prognosis of carcinomas of the uterine cervix. A critical evaluation of the proposal to classify these tumors according to the TNM system (author's transl)

Between 1966 and 1969, 494 patients with carcinoma of the uterine cervix stages I a to IV were admitted in our hospital for primary treatment. In 420 of these patients with carcinoma of the cervix stage I b to IV, complete results of bilateral pretreatment pelvic lymphography are available. The correlation between the results of the lymphographies, the choice of the operative treatment and the cure rates in these 420 cases are reported. All the correlations between the results of the pretreatment lymphography and the prognosis are described. A positive lymphography was in our series of high prognostic value. A plea is therefore made to include the results of the pretreatment lymphography into the classification of carcinoma of the cervix. Classification of the carcinoma of the cervix into the TNM categories is desirable. Our series is reported in these TNM categories. The advantages of such classification are described. The morbid entity of carcinoma of the cervix becomes more transparent to the observer and the choice of operative therapy becomes easier. The prognosis is more clearly established. The proposals of the TNM committee of the UICC for the classification of carcinoma of the cervix according to the TNM categories and the staging according to these categories are discussed critically.     

Papillary squamous cell carcinoma of the uterine cervix: report of a case with HPV 16 DNA and brief review

Papillary squamous cell carcinoma (PSCC) of the uterine cervix is a rare variant of squamous cell carcinoma (SCC). It is characterized by a papillary architecture and markedly atypical epithelium. Invasion and metastasis have been reported. We report a case of PSCC in a 72-year-old woman who subsequently tested positive for HPV 16. To our knowledge, this is the first report of HPV typing in a case of PSCC. Our finding of a high-risk HPV type in PSCC may help explain why PSCC has been reported to have a clinical course similar to that of nonpapillary SCC.     

Factors regulating SCC antigen expression in squamous cell carcinoma of the uterine cervix

Expression of squamous cell carcinoma (SCC) antigen emerged concurrently with squamous formation of the uterine cervix and increased during the neoplastic transformation of the cervical squamous epithelium. SCC antigen expression differed considerably among the histomorphologic cell types of cervical carcinoma. Large cell nonkeratinizing carcinoma contained high levels of the antigen. In contrast, no appreciable expression of SCC antigen was observed in small cell nonkeratinizing carcinoma. The pattern of SCC antigen expression closely coincided with EGF receptor (EGF-R) expression in cervical squamous neoplasia. This suggests that the expression of SCC and EGF-R in cervical carcinoma is related to the differentiation or dedifferentiation processes of the tumor cells. SCC production by CaSki cervical epidermoid carcinoma cells was stimulated by EGF. It seems likely that an autocrine system, in which EGF serves as the signal, may exist in cervical squamous carcinoma. 17beta-estradiol and L-triiodothyronine were found to upregulate EGF-R expression, proliferative potential and SCC production in the CaSki cervical carcinoma cells.     

Adenoid cystic carcinoma of the submandibular gland with symptomatic ovarian metastases

We report the clinical and pathologic features of an adenoid cystic carcinoma of the submandibular gland that metastasized to the ovaries 10 years after initial presentation. A 30-year-old woman underwent excision of a right submandibular adenoid cystic carcinoma followed by regional external beam radiation therapy. Three years later, she underwent extended hepatic resection and localized radiotherapy to the hepatic region for metastatic disease. The patient was without evidence of disease for 7 years when she developed pelvic pain and a pelvic mass was found. A solid and cystic 10-cm left ovarian mass and a single metastatic tumor nodule involving the right ovary were excised via the laparoscope. Histologically, the tumor was identical to the patient's initial salivary gland neoplasm. The neoplastic cells were CAM 5.2 positive, S100 positive, muscle-specific actin positive, and smooth muscle actin positive. Ultrastructurally, characteristic pseudocysts (pseudolumina) with abundant basal lamina and true glandular lumina lined by short microvilli were present. Other than a single anecdotal account of a parotid gland adenoid cystic carcinoma, this case represents the first documented report of an adenoid cystic carcinoma of salivary gland origin that was associated with symptomatic ovarian metastases. This case demonstrates that the ovary is a potential site for metastatic disease many years following the diagnosis and treatment for a primary neoplasm however uncommon or remote the site of origin. Since metastatic adenoid cystic carcinoma can rarely present as an ovarian mass, a clinical history of this neoplasm should be heavily weighed in the differential diagnosis of any unusual ovarian tumor with a predominant cribriform, trabecular, or tubular pattern.     

Pseudocystic metastases of carcinoma of the uterine cervix mimicking polycystic liver disease

Pseudocystic liver metastases are rare and mainly described in neuroendocrine or ovarian tumors. We report the case of a 46-year-old woman who presented with multiple hepatic metastases mimicking polycystic liver disease. Carcinoma of the uterine cervix had been diagnosed 9 years earlier, and initially treated by radiumtherapy and surgery. Although histological post mortem examination of the pseudocystic liver metastases was not characteristic, they were related to the uterine cervix carcinoma for the following reasons: no other primary tumor was discovered, especially carcinoid or ovarian tumors: immunostains were positive for epithelial cells and negative for the neuroendocrine panel: the cystic cerebellum metastasis had a typical histologic aspect. Uterine cervical carcinoma must thus be included in the list of tumors which may form cystic hepatic metastases.     

Effects of incubation temperature on the energetics of embryonic development and hatchling morphology in the Brisbane river turtle Emydura signata

AIMS: To investigate the malignant potential of lichen sclerosus, a study using the cell proliferation marker Ki67 comparing lichen sclerosus with and without associated squamous cell carcinoma was performed. METHODS AND RESULTS: Formalin-fixed, paraffin-embedded slides of 13 cases of lichen sclerosus with associated carcinoma, and 31 cases without associated carcinoma, including 16 random cases, seven with epidermal thickening and eight with epidermal thinning, were examined by the immunoperoxidase technique for Ki67, a cell proliferation marker. Ki67 reactivity was mostly seen in the basal and parabasal cells in both groups of lichen sclerosus and this pattern was similar to normal skin, squamous cell hyperplasia and analogous to that of one form of squamous cell carcinoma. There was a mean of 50 Ki67 positive cells per 100 basal cells in lichen sclerosus with associated squamous cell carcinoma; however, in squamous cell hyperplasia adjacent to carcinoma this rose to 90 Ki67 positive cells per 100 basal cells. In lichen sclerosus without associated carcinoma, the random cases had a count of 53 per 100 basal cells, those with epidermal thickening 53 and those with thinning 42. Non-genital normal skin had a count of 71 per 100 basal cells. CONCLUSION: The lack of qualitative differences of Ki67 expression in normal skin, in lichen sclerosus with and without carcinoma, in squamous cell hyperplasia and in one form of squamous cell carcinoma indicates that these conditions share a common localized pattern of cell proliferation and does not support or deny the malignant potential of lichen sclerosus. The higher Ki67 count in squamous cell hyperplasia adjacent to carcinoma could indicate premalignancy or a reaction to the carcinoma. In patients without carcinoma, the higher Ki67 count in thickened lichen sclerosus compared to thinned suggests that some or all of the cases of thickened lichen sclerosus were lichen sclerosus with squamous cell hyperplasia or that lichen simplex chronicus superimposed on lichen sclerosus has a higher Ki67 expression or that the distinction between squamous cell hyperplasia and lichen simplex chronicus is only one of terminology.