[Treatment of squamous intraepithelial lesion of type CIN2 et CIN3 with laser CO2 vaporization: retrospective study of 52 cases]. / Prise en charge des lésions malpighiennes intra-épithéliales de type CIN2 et CIN3 par vaporisation au laser: étude rétrospective sur 52 cas.

OBJECTIVES: This study was carried out over an 8-year period in order to evaluate the long-term effectiveness of laser CO2 vaporization in the treatment of squamous intraepithelial lesion of type CIN2 and CIN3. MATERIALS AND METHODS: A retrospective study of 52 cases of cervical lesions of type CIN2 and CIN3 treated in first intention by laser CO2 vaporization was carried out at the hospital Jeanne-de-Flandre in CHRU of Lille from 1996 to 2003. This treatment was performed on only high-grade exo-cervical lesions, of small size (<2cm2), after a complete colposcopic examination. RESULTS: Fifty-two patients were treated by first-intention laser vaporization only. Mean age was 29.4 years and 51.9% were nulliparous. At the first cyto-colposcopic control, there were 17 persistent lesions (32.7%). Among the 35 patients without persistent lesion, 29 achieved cure (absence of recurrence), 4 presented a recurrence and 2 were lost to follow-up. CONCLUSION: The current data of the literature concerning the treatment by laser CO2 vaporization authorize application of this method for certain high-grade exocervical lesions after a complete colposcopic examination. This type of treatment remains less aggressive than a surgical treatment. The high rate of residual lesions in particular in the event of CIN3 can be due to an incomplete destruction of the lesion. Patients should thus be advised that monitoring is an integral part of the treatment. Laser vaporization could be limited to CIN1 and CIN2 lesions.

[Phyllodes tumor of the breast: analysis of 8 patients]. / Tumeurs phyllodes du sein: à propose de 8 patientes.

INTRODUCTION: Phyllodes tumors of breast are rare and usually benign. These are histologically fibro-epithelial tumors similar to fibroadenomas. Histological confirmation on the operative specimen is required to establish the diagnosis and histological pronostic of phyllode tumors. MATERIALS AND METHODS: We reviewed 8 cases of phyllodes tumors and the literature to report the circumstances of occurrence of these tumors, and their specific clinical diagnosis, therapeutic, prognostic features. RESULTS: 62.5% of patients were nulliparous. The mean age at diagnosis was 33.4 years. Mean tumor size was 3.75 cm. Tumours predominated on the right side (87.5%) and upper-outer quadrant (62.5%). Imaging findings were helpful for diagnosis. Aspiration cytology demonstrated the phyllode tumor in 43% of patients. Wide tumorectomy was performed in seven patients. One patient underwent mastectomy and radiotherapy and chemotherapy. The recurrence rate (37.5%) justifies wide margin excision. There were no deaths in our series. DISCUSSION: and conclusion. These results together with those reported in the literature show that the loco-regional and general spread depends on margin surgery.

[Extensive Hirschsprung's disease associated with intestinal malrotation]. / Maladie de Hirschsprung à forme iléocolique associée à une malrotation intestinale.

Hirschsprung's disease (HD) involves the entire colon in less than 5% of cases, and the association of extensive HD with intestinal malrotation is very rare. This association of symptoms may delay both diagnosis and treatment. An infant presented with an intermittent occlusive syndrome that began neonatally. Intestinal malrotation was diagnosed radiologically, and treated surgically when the child was 2 months old. However, a chronic occlusion persisted. Biopsies of the rectum and the appendix demonstrated an absence of neurons in intestinal plexi. When the child was 17 months old, ileostomy and surgical excision of the segment affected by HD (the colon and terminal ileum) were performed. An ileoanal anastomosis was performed at the age of 29 months, with favorable outcome. The persistence of symptoms of intestinal occlusion after attempted treatment of intestinal malrotation must therefore suggest the possibility of associated HD in a young child.

Congenital idiopathic intestinal pseudo-obstruction and hydrocephalus with stenosis of the aqueduct of sylvius.

We present the first report of an association between hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS) and a specific form of congenital idiopathic intestinal pseudo-obstruction (CIIP) in an infant. Diagnosis of HSAS was suspected during the neonatal period because of a severely dilated ventricular system associated with bilateral adducted thumbs, and was confirmed by demonstration of a mutation in the gene encoding L1 cell adhesion molecule (L1CAM). L1CAM mutations cause a variable clinical spectrum. This gene is located at Xq28 and encodes a transmembrane glycoprotein involved in neurite outgrowth and neuronal migration. Hirschprung disease has been reported to involve an L1CAM mutation that manifests as a quantitative defect in the migration of neural crest cells in distal segments of the gut. We report an association that suggests that alterations of L1CAM may cause another type of intestinal pseudo-obstruction distension with a qualitative defect in differentiated Cajal's cells in the anterior part of the gut. This observation suggests that L1CAM has a role in the developmental regulation of multiple systems. Further clinical descriptions of gastroenterological and neuropathological data are required to extend our understanding of the mechanisms underlying L1CAM functions.

[Histological diagnosis after Pap smears detecting cancer or high-grade lesion of the cervix]. / Correspondance histologique des frottis cervico--utérins détectant un cancer ou une lésion de haut grade.

OBJECTIVE: The aim of the study is to analyze the histological-cytological correlations for Pap smears having detected cancer or high-grade squamous intra-epithelial lesion (HSIL) of the cervix. PATIENTS AND METHOD: The study about 311 women is retrospective. The average age is 36.4 years. Group 1 (histological diagnosis of high-grade or invasive lesion) includes 244 women (77.5%). Group 2 (histological diagnosis other than high-grade or invasive lesion) includes 37 women (11.9%) with a presumed diagnosis of HSIL. Group 3 (absence of histological follow-up) includes 30 women (9.6%) with a presumed diagnosis of HSIL. RESULTS: In group 1, the presumed cytological diagnosis is HSIL in 229 cases, squamous carcinoma in 11 cases and adenocarcinoma in two cases. In this group, the average delay between the Pap smear and the first histology is equal to two months. It is longer than 6 months in seven cases. The diagnosis of cancer or high-grade lesion is confirmed histologically on a first biopsy of the cervix in 196 cases, a second or a third biopsy in 10 cases, an endocervical curettage in six cases and a surgical specimen in 32 cases. In the group 2, the histological diagnosis is normal-benign in 14 cases (presumed cytological false positives) and condyloma-CIN 1 in 23 cases (presumed overevaluations). DISCUSSION AND CONCLUSION: Results highlight benefits of interactive exchanges between clinicians and pathologists, and the necessity of review of discordant cases by several pathologists in due time, with written comments and coding of the conclusions of the review. Histological follow-up is late or not done in some women.

[Intractable diarrhoea revealing a neuroblastoma hypersecreting the vasoactive intestinal peptide]. / Diarrhée profuse révélatrice d'un neuroblastome hypersécrétant le vasoactive intestinal peptide.

In children, the watery diarrhoea-hypokalemia-achlorhydria (WDHA) syndrome is uncommon and usually due to a neuroblastic tumour hypersecreting the vasoactive intestinal peptide (VIP). We report a case of WDHA syndrome secondary to hypersecretion of VIP that revealed a neuroblastoma in a 13-month-old girl. A secretory diarrhoea, characterised by the persistence of diarrhoea despite the cessation of oral feeding, led to the search of a neuroblastic tumour in the patient. The serum concentration of VIP decreased to normal values soon after the surgical excision of the tumour.

Mesenchymal hamartomas of the liver may be associated with increased serum alpha foetoprotein concentrations and mimic hepatoblastomas.

A mesenchymal hamartoma (MH) of the liver in a seven-month-old girl was associated with slightly elevated alpha fetoprotein (AFP) concentrations (320 microg/L, normal < 25 after six months of age). Hepatocytes were abundant at the periphery of the tumour at histopathological examination. These were slightly atypical and expressed AFP immunohistochemically. In two other girls, aged 14 months and two months respectively, with MH and increased serum AFP concentrations (320 microg/L and 7500 microg/L, respectively), hepatoblastomas were misdiagnosed preoperatively. MH of the liver with increased serum AFP concentrations may thus mimic hepatoblastoma radiologically if cysts are lacking, and foetal hepatoblastoma pathologically if a biopsy samples only the peripheral hepatocellular component of the MH.

Value of human papillomavirus testing after conization by loop electrosurgical excision for high-grade squamous intraepithelial lesions.

OBJECTIVE: The aim of the study was to evaluate human papillomavirus (HPV) testing during the follow-up of patients after conization by loop electrosurgical excision for high-grade squamous intraepithelial lesion. METHODS: A prospective study was conducted on 205 patients who underwent conization for high-grade squamous intraepithelial lesion (CIN 2 or 3). Loop electrosurgical excision procedure (LEEP) was used in all cases. High-risk HPV testing was realized by the Hybrid Capture II system before and 3 months after conization. RESULTS: Of the 205 patients, 193 (94.1%) were positive for the HPV test before conization. Seventy-one were HPV positive after conization (34.6%). The margins were positive in 36.1%. Residual disease was observed in 27 cases (13.2%). Four patients (2%) developed a recurrence after a mean follow-up of 18.1 months (+/-12). There was no correlation between pretreatment HPV testing and the residual disease or recurrence. Patients with positive margins were significantly more likely to have residual disease than those with negative margins (P < 0.0001). Residual disease was more likely to occur when the posttreatment HPV test was positive (P < 10(-7)). All recurrences were observed in patients with a positive posttreatment HPV test (P < 0.05). Residual disease and recurrence were correctly predicted with a sensitivity of 81 and 100%, respectively, and a negative predictive value of 96 and 100%. CONCLUSION: Posttreatment HPV testing could be useful in the follow-up of patients after conization. In case of negative posttreatment HPV testing, the frequency of follow-up could be reduced, particularly in those patients with free margins.

[Cytological history of 148 women presenting with invasive cervical cancer]. / Histoire du suivi cytologique de 148 femmes atteintes d'un cancer invasif du col utérin.

OBJECTIVES: The aim of this study was to analyse the cytological history of women presenting with invasive cervical cancer. MATERIAL AND METHODS: Retrospective study of 148 patients treated for invasive cervical cancer in three hospitals of the North Pas de Calais in France. RESULTS: The average age of patients was 49 (26-86). Squamous carcinomas represented 81% of cases (120/148), adenocarcinomas 17% (25/148) and adenosquamous carcinomas 2% (3/148). 36.5% of patients (54/148) had never had a Pap smear. 34.5% (51/148) had had an occasional Pap smear (the last one dated of more than three years). 8.1% (12/148) were lost for follow up after a positive Pap smear. 3.4% (5/148) were treated for cervical dysplasia less than three years before the diagnosis of the cervical cancer. 17.5% (26/148) had had a Pap smear reported as negative less than three years before the diagnosis of the cervical cancer. In this last group, squamous carcinomas represented 57.7% of cases (15/26), adenocarcinomas 38.5% (10/26) and adenosquamous carcinomas 3.8% (1/26). 18 Pap smears of 26 reported as negative less than three years before the diagnosis of the cancer were reviewed. These Pap smears came from 11 patients presenting with squamous carcinoma and seven other presenting with adenocarcinoma. After review, 15 Pap smears were reported as false negatives and two as true negatives. The review was not possible in one case. CONCLUSION: In this study, the failures of cervical cancer screening were essentially attributed to the lack or the insufficiency of screening and the existence of false negatives of the cytology.

Phytosterols have an unfavourable effect on bacterial activity and no evident protective effect on colon carcinogenesis.

The effects of physiological dietary phytosterol supplements on intestinal microflora activity and faecal sterols and their capacity to protect rats fed a normal or high saturated fatty-acid diet against tumour development were studied. A group of 80 female Wistar rats were fed an 8% lipid diet for 4 weeks (adaptation period) and then randomly assigned in a factorial experimental design study to diets containing 8% or 24% hydrogenated coconut oil, with or without a 24-mg/day/rat phytosterol supplement. They were instilled intrarectally with saline or methyl-nitroso-urea (MNU). Faecal sterol output was analysed for one week each month. Pathological analysis was done at the end of the 30-week experiment. Animals treated with MNU and given phytosterol supplements had tumour frequencies (8/20) similar to those not fed phytosterols (11/20). The fat-supplemented diet had no significant influence. Colonic glands were found in area of lymphoid follicles in all the groups, but were more frequent in rats on high-fat diets (P < 0.01). The coprostanol and the cholesterol excretion of the phytosterol-supplemented rats was significantly enhanced. Therefore phytosterols have an unfavourable effect on bacterial activity. These data confirm the capacity of phytosterols to decrease cholesterol absorption, but indicate that a large excess of phytosterol must be avoided until further research on its effects on carcinogenesis has been done.

Mucin gene transcripts in benign and borderline mucinous tumours of the ovary: an in situ hybridization study.

Mucinous tumours of the ovary are characterized by mucin-secreting cells exhibiting a variable endocervical, intestinal, gastric or pancreatobiliary phenotype as ascertained by microscopy, electron microscopy, histochemistry or immunohistochemistry. The molecular mechanisms underlying the tumourigenesis process are not well understood. The mucin glycoproteins expressed by ovarian mucinous tumours have not been fully characterized, but mucins are known to be implicated in tumour progression in various epithelial neoplasms. The purpose of this study was to evaluate the expression of mucin genes (MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6) in ovarian mucinous tumour cells, to relate MUC gene expression to the histological diagnosis, and to compare the expression patterns with those observed in normal tissues. The expression of mucin genes was evaluated by in situ hybridization in 21 mucinous tumours (11 adenomas and ten borderline tumours). Heterogeneity of expression correlated with morphological heterogeneity. Intense expression of the MUC5AC gene, suggesting a gastric surface cell phenotype, was demonstrated in 18/21 tumours (86%). Goblet cells expressing the MUC2 gene and columnar cells expressing the MUC3 gene were consistent with an intestinal phenotype, which was observed in 15 tumours (71%) including nine adenomas and six borderline tumours. Major expression of MUC4 and MUC5B consistent with an endocervical phenotype was observed in seven benign (64%) and three borderline (30%) tumours. In all, the MUC profiles suggested gastrointestinal-type cells in 13 cases (62%), gastric-type cells in five cases (24%), and intestinal-type cells in two cases (one benign, one borderline) (9%); the results were inconclusive in one borderline tumour (5%). It is concluded that gastric and, to a lesser degree, intestinal differentiation are early and almost constant events in ovarian mucinous tumourigenesis.

[A proposal for a method of reporting cervico-uterine smears]. / Proposition de méthode de réponse des frottis cervico-utérins.

A method for reporting Papsmears is proposed. Paperwork is limited to choosing a few codes on a working list prepared according to the Bethesda system and the ADICAP coding system. The method is easy to use. It reduces the work load of time for cytologists and secretaries. It allows harmonization and structurization of the look and the filling of reports for Papsmears. It may be easily adapted for vaginal smears. It leads to a report complete and adapted to the Bethesda system. It gives the possibility of adding comments and additional codes. It avoids most mistakes about öbligatory codes. It makes easier to perform statistical evaluation and to initiate a quality control program.

Positive margins after conization and risk of persistent lesion.

OBJECTIVE: The aim of this study was to investigate a method to reduce the frequency of uterine reoperation with no persistent lesion and to identify factors predictive of persistent or recurrent lesions. MATERIALS AND METHODS: Of 505 conizations performed by the same surgeon, 71 had positive margins (average patient age = 35.7 +/- 7.7 years). The patients underwent either immediate reoperation or monitoring with a Pap smear and colposcopy. RESULTS: Histologic assessment of the cervical cone after conization showed positive margins in 14.1% of cases [endocervical and exocervical margins affected in 50 of 505 (9.9%) and 21 of 505 (4.2%) cases, respectively]. Of 59 of these patients (83.1%) who underwent follow-up monitoring over an average of 35.2 months (range: 2.6-180. 8), 12 patients (average age: 40.8 +/- 6.4 years) underwent immediate hysterectomy and 47 (average age 34.0 +/- 7.4 years) benefited from monitoring first [secondary discovery of 19 persistent lesions within 6 months and 9 recurrences within 18 months on average (range: 8.8-48 months)]. Of the 9 patients with recurrent lesions, 7 underwent reintervention and 2 monitoring. Of the 19 patients with persistent lesions, 18 underwent reintervention and 1 monitoring. Normal histology was observed in 29.4% of patients undergoing secondary reoperation for an abnormal smear compared with 66.7% of patients undergoing immediate reoperation (P = 0.04). Severity of lesion and age of patients could not be used to predict the incidence of a persistent or recurring lesion. Seventy-nine percent of conizations had positive endocervical margins in patients with a recurring or persistent lesion compared with 48% in patients with normal follow-up (P = 0.03). CONCLUSION: Cytology and colposcopy follow-up in cases of positive conization margins may help to establish justification for the choice of reoperation, thereby limiting morbidity following repeated surgery.

[Detection of human papillomavirus DNA by molecular hybridization in tube: interest in cervical neoplasia]. / Détection de l'ADN des papillomavirus humains par hybridation moléculaire en tube: intérêt dans les dysplasies cervicales.

The presence of human papillomavirus (HPV) DNA in 79 cervical specimens obtained from 70 patients was studied by using a molecular hybridization technique performed in tube. The results were compared to those of the cytological and histological studies. The molecular hybridization technique in tube (Hybrid Capture I) detects two groups of HPV types. One group is highly associated with the development of cancer (types 16, 18, 31, 33, 35, 45, 51, 52, 56) whereas the second group (types 6, 11, 42, 43, 44) is not. Among 42 patients with cervical lesions before any treatment, high risk DNA of HPV was found in 50% of those with low grade cytology and 90% with high grade cytology. In total, 32 out of the 42 patients (76%) who presented histological lesions, were actually infected by HPV. Samples were obtained before and after treatment from 9 patients. Seven out of 9 presented high grade cervical intraepithelial neoplasia (CIN) and 2 other patients had low grade CIN. HPV DNA was not detected in any of the patients after treatment. Detection of HPV DNA by molecular hybridization in tube is simple, sensitive, standardized, inexpensive and is well adapted to screening programs. It can be used in complement of the cytological diagnosis, in the surveillance of equivocal cytological abnormalities, and in the follow-up of treated patients.

[Why we prefer the thin layer technique to conventional Pap smears. A double-blind study of 473 specimens]. / Pourquoi nous préférons la technique en couche mince aux frottis cervico-utérins conventionnels. Etude en double aveugle de 473 prélèvements.

The study evaluated the feasibility of a thinlayer technique on a routine basis for cervical smears and compared 473 ThinPrep preparations to the matched conventional Papsmears. The interpretation was double-blind and performed according to the Bethesda system. A consensus was established in discordant cases. The technique was easily mastered by gynecologists and technicians. Main advantages of the thinlayer technique were: a low number (1%) of unsatisfactory samples; a constant quality; homogeneity of cell distribution; the disappearance of problems of interpretation due to fixation or smear artifacts, red cells, polymorphs; a more precise interpretation, a firmer diagnosis; less visual fatigue; a shorter time of interpretation; the possibility of preparing more slides and performing special techniques on the same specimen. Main disadvantages were a higher cost and a necessary period of learning for cytologists.

Deletion mapping of the tumor suppressor locus involved in colorectal cancer on chromosome band 8p21.

Several somatic genetic alterations have been described in colorectal carcinoma (CRC). Recurrent chromosomal deletions have suggested the presence of tumor suppressor genes (TSG) specifically involved in colorectal carcinogenesis. For one of them, two non-overlapping regions have been proposed on the short arm of chromosome 8, encompassing the LPL and NEFL genes. The short arm of chromosome 8 has been extensively studied in colorectal cancer and in other cancer types. Both regions have been reported as candidate loci for a TSG. In order to delineate a reliable region of deletional overlap on chromosome arm 8p in CRC, a series of 365 CRC samples was selected for the absence of microsatellite instability (RER, replication error); tumor and normal matched DNAs were studied for 54 microsatellite polymorphisms distributed on 8p using multiplex-PCR amplification. After purification of tumor nuclei by flow cytometry based on either the abnormal DNA index or the presence of a high expression of cytokeratin, complete allelic losses on 8p were observed in 48% of cases. Measurement of the DNA index showed that 88% of RER tumors were hyperploid. Complete allelic losses of only part of the short arm were observed on 26 occasions. These data allowed us to define a 1 cM interval of common deletion, flanked by the loci D8S1771 and NEFL, where a putative TSG may be localized.

[Serous papillary cystadenocarcinoma of the recto-vaginal septum: a rare primary localization]. / Cystadénocarcinome séreux papillaire de la closion recto-vaginale: une localisation primitive exceptionnelle.

A primary serous papillary cystadenocarcinoma of the rectovaginal septum was diagnosed in a 35-year-old woman. There were invasive microfoci in peritoneum and lymph node micrometastasis as well as a small superficial non invasive tumor focus in the left ovary. Diagnosis was based on morphological, immunohistochemical and ultrastructural features of tumor tissue. The patient had surgery and post-operative chemotherapy. Progression of peritoneal disease was found six months after surgery. In this very rare location of serous carcinoma, tumor might have developed from peritoneal inclusions in the rectovaginal septum.

Virilizing ovarian dermoid cyst with peripheral steroid cells. A case study with immunohistochemical study of steroidogenesis.

A case of virilizing ovarian dermoid cyst with peripheral steroid cells and virilization is reported in a 62-year-old woman. The level of testosterone dropped to normal after oophorectomy. The cyst wall was bordered by a discontinuous band of steroid cells focally accompanied by smooth muscle cells. Immunohistochemically, the steroid cells were enzymatically active and displayed a profile similar to the internal theca cells of ovarian follicles. These steroid cells were most probably modified stromal cells associated with smooth muscle metaplasia of the ovarian stroma.