Sertoli-Leydig cell tumours are rare sex stromal tumours with an incidence of < 0.5% of all ovarian tumours. Most frequently this tumour occurs in young women with a history of amenorrhoea, hirsutism and lowered pitch. Here, we report on a woman with IRS, postmenopausal virilization and increased testosterone levels due to a Sertoli-Leydig cell tumour. This is the first case to suggest an association between IRS and Sertoli-Leydig cell tumours. Furthermore, we highlight the difficulties in detecting this ovarian tumour with sonography.

Previous studies including various tumor types have shown different associations between tumor tissue levels of plasminogen activator inhibitor 2 (PAI‐2) and patient survival. High tumor tissue concentrations of PAI‐2 have been associated with good prognosis in patients with breast cancer, small cell lung cancer and ovarian cancer, but with poor histologic differentiation and poor prognosis in patients with colorectal cancer. On the other hand, high tumor tissue concentrations of urokinase plasminogen activator (uPA), uPA receptor (R) and PAI‐1 have more consistently been associated with poor histologic differentiation and poor prognosis. Our study quantified PAI‐2 and uPAR using specific enzyme‐linked immunosorbent assays in homogenates of 274 samples of endometrial cancer tissue. The prognostic power of each factor was analyzed in the subgroup of patients with early stage disease, i.e., International Federation of Gynecology and Oncology (FIGO) surgical stage I–II (n = 188). This group had a median follow‐up time of 6.8 years (range 0.7–9.9), and 23 progressions were observed. The 80th percentile for PAI‐2 and uPAR was used to dichotomize the material, and the results were analyzed for associations with clinical data including progression‐free survival. The results were also compared with DNA ploidy status, S‐phase fraction, uPA and PAI‐1, which we reported in a previous study (Fredstorp Lidebring et al., Eur J Cancer 2001; in press). A high PAI‐2 level was associated with shorter progression‐free survival in univariate analysis and was an independent prognostic factor in bivariate analyses, which included PAI‐1, uPA and DNA ploidy status. In contrast, a high level of uPAR had no association with prognosis in early stage endometrial cancer. The combination of high PAI‐2 and PAI‐1 levels in tumors revealed a small group of stage I–II patients with an accumulative progression rate of 50%. © 2001 Wiley‐Liss, Inc.

Primary adenocarcinoma of the vulva is rare, and cloagocenic adenocarcinoma of the vulva is extremely rare. Here we report a vulvar tumor characterized by columnar cells with prominent brush border and the presence of goblet cells and endocrine cells, presenting the tubulovillous pattern and mucin histochemistry of enteric adenocarcinoma. Electron microscopy verified a colon-like pattern. We suggest that cloacogenic carcinoma of the vulva arises from embryonic tissue, normally present in the vulvar introital area. In our case, a wide local excision was sufficient for radical cure.

Tissue samples were obtained from normal (n = 92), hyperplastic (n = 22) and malignant (n = 35) endometria. Urokinase and tissue plasminogen activators (u-PA, t-PA) were assayed in acetate detergent buffer extracts and their mRNAs quantitated in autoradiograms of Northern blots. The tissue content of u-PA was significantly higher in adenocarcinomas compared to normal and hyperplastic endometria. Tumors with poor differentiation and extensive myometrial invasion had the highest levels. The content of t-PA was increased in hyperplastic endometria but not in adenocarcinomas. The tissue content of t-PA was inversely related to clinical stage and loss of differentiation in malignant tumors. In contrast to the protein data, u-PA mRNA was not higher and t-PA mRNA was much lower in malignant compared to benign tumors. Thus, high tumor tissue content of u-PA does not result from transcriptional regulation, and reduction of t-PA mRNA may indicate down-regulation of transcription or possibly reduced mRNA stability. Furthermore, the discrepancy between protein and mRNA for both activators probably indicates up-regulation of the translation process since decreased degradation of activator proteins is a less likely explanation.

In women with recurrent cervical cancer after radical surgery, lymph node metastasis is detectable histologically at the time of surgery in only about 50% of cases. The present study was designed to determine whether the detection of human papilloma virus (HPV) DNA in lymph nodes extirpated at operation, as an indication of micrometastasis, is predictive of recurrence. Using polymerase chain reaction (PCR), a total of 140 lymph nodes from 31 patients with HPV 16 DNA positive primary cervical tumours were tested for the presence of an HPV 16 LCR/E6 gene fragment. HPV 16 DNA was detected in extirpated lymph nodes in 75% (6/8) of patients with recurrence (and who died within 5 years after surgery) and in 70% (16/23) of recurrence-free patients. In only four of the patients with recurrence (three of whom had HPV 16 DNA positive lymph nodes) was metastasis detectable histologically at surgery. HPV DNA positive lymph nodes were found in 91% (10/11) of patients with histologically detectable metastasis at surgery and in 60% (12/20) of patients without metastasis. It is concluded that the presence of HPV DNA in extirpated lymph nodes at cervical cancer operation does not appear to be predictive of tumour recurrence.

A human ovarian mesodermal mixed heterologous carcinoma, with a high content of cellular retinol-binding protein (CRBP), was used to study the effects of retinoid and hormonal treatment on tumour CRBP content, tumour growth rate, differentiation and turnover of CRBP. Tumour growth in general was accompanied by an increase in the CRBP concentration of the xenografted tumours. This was related to the appearance of more mature epithelial cells, showing CRBP immunoreactivity. The increase in CRBP concentration was more pronounced in retinyl palmitate-treated tumours than in tumour tissue from etretinate- (an aromatic retinoid) treated mice and controls, suggesting that CRBP synthesis is under the influence of its ligand. Various hormonal treatments had no influence on the CRBP concentration in these tumour cells. The CRBP turnover was similar to that of the bulk of cellular proteins.

The measurement and localisation of cellular retinol-binding protein (CRBP), in samples of normal oral mucosa, larynx papilloma and malignant lymphoma of the oropharynx, was performed with a radioimmunoassay and immunolocalisation techniques. As compared with CRBP concentration in normal mucosa, those in laryngeal papilloma were significantly higher, but those of malignant lymphoma were similar. CRBP concentrations were highest in maturing keratinocytes within the prickle cell layers of normal mucosa and in laryngeal papillomas, as estimated on the basis of immunoreactivity to CRBP. The retinyl palmitate concentrations in extracts of oral mucosa correlated to the retinol concentrations, both in plasma and mucosal extracts, but not to the CRBP content in mucosal extracts. The immunolocalisation of a cellular retinoic acid-binding protein (CRABP) like antigen in normal oral mucosa showed much the same picture with strongest staining of the maturing keratinocytes of the prickle cell layers.

Two xenografted tumor lines, established from squamous cell carcinomas of the head and neck, were studied with respect to the growth parameters of the Gompertz function and changes in growth rate, cell cycle phase distribution, and histologic pattern during the course of growth. The tumors were transplanted subcutaneously in the back. Both tumor lines exhibited growth curves compatible with Gompertzian growth. The parameters of the Gompertz function differed significantly between the tumor lines. Tumor volume doubling time also varied during the course of growth. Flow cytometric analysis of cell cycle phase distribution showed an initial decrease in the fraction of cells in S-phase, parallel with an increase in the fraction of cells in GO/1-phase. As much as 50% of the cells were mouse-derived in tumors less than 100 mm3 in volume, after which the proportion of mouse-derived cells decreased to below 10%. This variation correlated with changes in the histopathologic picture.

The concentration of cellular retinol-binding protein (CRBP) was determined by radioimmunoassay in biopsies of normal mucosa and squamous-cell carcinomas of cervix uteri from 30 women. The tumour tissues contained significantly higher concentrations of CRBP (median = 120 micrograms/g protein) than normal mucosa (median = 32 micrograms/g protein). The distribution of CRBP in normal mucosa and squamous-cell carcinomas from cervix uteri and from oral cavity was evaluated by immunohistochemical techniques. In tissue sections of normal epithelium from the cervix uteri and the oral cavity, the maturing keratinocytes in the prickle-cell layers were moderately or strongly stained when antiserum against CRBP was used, while the proliferating cells in the basal-cell layer were stained only lightly if at all. Squamous-cell carcinomas of the cervix uteri and the oral cavity presented much the same picture. The observed difference in CRBP concentration between squamous-cell carcinomas and normal squamous-cell mucosa may therefore be more quantitative than qualitative.

A 78-year-old man had profuse bloody diarrhea of sudden onset following a traffic accident associated with mild hypothermia. Rectoscopy performed one day later showed severe acute inflammatory changes, and biopsy revealed acute necrotizing colitis. Treatment was conservative. At control colonoscopy 3 weeks later the mucosa was mainly normal.

A case of malignant abdominal hemangiopericytoma in a 74-year-old man is presented. The tumor was surgically removed. A large local recurrence and a minor abdominal metastasis were excised 5 years later. The patient is well and apparently tumor-free 6 months post-operatively. Other methods of treatment are discussed.

Human tumours heterotransplanted to nude mice vary both with respect to take rate and the rate of tumour line establishment, according to their histological type and between primary and recurrent tumours. The acceptance rate of squamous cell carcinomas of the head and neck is also thought to vary, according to their degree of differentiation and their site of origin. This provided the basis of the present analysis of different tumour characteristics predicting growth of squamous cell carcinomas of the head and neck. Eighty-five attempted heterotransplantations were analysed with respect to T-stage, site of origin, degree of differentiation, and a histopathological malignancy grading score based upon four tumour variables and four tumour-host variables. Of the 85 attempted transplantations, first passage was successful in 24 cases (28%), of which sixteen (19% of 85) resulted in established tumour lines. The frequency of established tumour lines was higher among T4 and poorly differentiated tumours (33% and 22%, respectively), than among less advanced or more differentiated tumours. Tumour size was a more crucial factor than degree of differentiation, and tumours of the oral cavity grew less readily than those from other sites. The take rate was strongly correlated to malignancy grading scores, increasing as they increased. The most predictive information was provided by tumour-host variables, of which vascular invasion and lack of lymphocytic response were the most important in this respect.

A 57-year-old man with a history of right-sided renal colic had a stricture of the right ureter which was suspected to be caused by a tumour or retroperitoneal periureteric fibrosis. Peroperative frozen section examination revealed tumour-forming amyloidosis of the ureter. The right kidney therefore could be salvaged by an end-to-end ureter anastomosis. Although primary amyloidosis of the ureter is rare, it should be included in the differential diagnosis of ureteric strictures.

Nude athymic rats of Rowett genetic background were injected subcutaneously with cells from a poorly differentiated human pulmonary adenocarcinoma, following propagation in nude mice. The tumour cells were obtained by thoracentesis and by pleural biopsy during thoracoscopy. So far, we have heterotransplanted 13 different malignant human tumours including malignant mesothelioma, pulmonary adenocarcinoma, malignant melanoma and malignant lymphoma. Subcutaneous tumour growth was seen in all inoculated animals, with an exponential tumour growth pattern and with tumour volume doubling times of approximately 8 days. After two initial passages in nude athymic mice of BALB/c genetic background, the human tumour so far has undergone 9 passages in athymic rats, i. e. collection of tumour material by biopsy from the preceding tumour‐bearing rat generation, processing and inoculation of tumour brei with subsequent tumour growth have been repeated 8 times. Four‐ to 8‐week‐old rats of both sexes were used throughout and tumour growth was controlled by palpation twice a week. Routine histopathological sections were prepared from the tumour at various passages to assess similarity to the original tumour in the patient. The growth pattern of the xenografts remained similar at all passages just as the remarkable similarity of the heterotransplanted tumours to the original adenocarcinoma was retained at all passages. No spontaneous regressions of heterotransplanted tumours could be demonstrated. Electron microscopical analysis revealed numerous blunt microvilli and lumina partly filled with conglomerates of mucigen granules and small glycocayceal bodies associated with external superficial microvilli. Scantiness of dark secretory granules together with free and membrane‐bound polyribosomes were seen in the cytoplasm. We believe that the nude athymic rat is a valuable research tool and that the permanently transplantable human tumour reported here could be of value in delineating further the mechanisms for tumour take, growth and control.