[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.

Sublocalisation of the X breakpoint in the translocation (X; 18)(p11.2; q11.2) primary change in synovial sarcomas.

A specific translocation between chromosomes X and 18 was identified in synovial sarcomas. From a girl with synovial sarcoma, we isolated two clones with t(X; 18)(p11.2; q11.2) and which had lost the normal X chromosome. Southern blot analysis of DNA from the tumor, the patient and her parents demonstrated that the normal X chromosome, lost in the tumor, was the paternal one. A somatic hybrid cell line was established by fusing tumor cells (after passages on athymic mice) to an HPRT deficient hamster cell line. By cytogenetic, in situ hybridization and molecular analysis, it was found to contain the derivative (X) chromosome in the absence of the der (18) chromosome. To determine the position of the breakpoint on the X chromosome, Southern blots of DNA from this hybrid were hybridized to [32P]-labelled X chromosome probes. DXS146 and DXS255 were retained in the hybrid cell line whereas GAPDP1, the ARAF1 and TIMP proto-oncogenes were not present, indicating that the breakpoint lies proximal to GAPD1, ARAF1 and TIMP and distal to DXS255 and DXS146. Results obtained from other authors are compared. Further studies will be necessary to determine the extent of variation of the breakpoint in different tumors.

[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.

Infrequent mutation of the p53 gene in fibrous tumors of infancy and childhood.

Mutations in the p53 tumor suppressor gene occur in > 50% of human malignancies, but are exceedingly rare in benign tumors. The malignant potential of fibrous tumors of children may be unpredictable at microscopic examination. We therefore sought to determine whether malignant fibrous tumors could be distinguished from their benign counterparts by the presence of mutations in p53. We screened 27 fibrous tumor samples from 20 young patients. Tumors were classified as benign, borderline, or malignant by conventional microscopic criteria. RNA extracted from each specimen was used as the template for reverse transcription followed by polymerase chain reaction (PCR) amplification, with six pairs of primers covering the whole coding region of the p53 gene. All PCR products were screened for the presence of mutations using single-strand conformation polymorphism analysis. In addition, PCR products encompassing exons 5-9, the sites of the most frequent mutations in human tumors, were sequenced directly. Both methods detected a single point mutation in a highly malignant tumor (malignant fibrous histiocytoma). The mutation was a silent one at codon 36 (CCG-CCA, Pro-Pro). We conclude that p53 mutations are infrequent in childhood fibrous tumors, consistent with previous observations of low malignant potential (< 10%) and better prognosis in this tumor group. Therefore, screening for p53 mutations is not a useful prognostic indicator in fibrous tumors with borderline pattern at microscopic examination.

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.

Latent Epstein-Barr virus infection demonstrated in low-grade leiomyosarcomas of adults with acquired immunodeficiency syndrome, but not in adjacent Kaposi's lesion or smooth muscle tumors in immunocompetent patients.

BACKGROUND: Incidence of smooth muscle tumors is increased in patients with human immunodeficiency virus infection and organ transplant recipients. Smooth muscle tumors in immunocompromised patients often occur in unusual locations and exhibit evidence of latent infection by clonal, presumably tumorigenic, Epstein-Barr virus (EBV). OBJECTIVE: To investigate the presence of EBV latent infection in smooth muscle tumors in patients with acquired immunodeficiency syndrome and in immunocompetent patients. DESIGN: Twenty-two extrauterine, extraintestinal smooth muscle and myofibroblastic tumors were reviewed pathologically, and clinical charts were screened. Tumors were malignant (15 patients), benign (6 patients), and borderline (1 patient). Tissue specimens were investigated for latent EBV infection by latent membrane protein immunocytochemistry and EBV-encoded RNA in situ hybridization. SETTING: University Hospital of the University of Nancy, France. PATIENTS: Patients were 18 adults and four children. Two adults had acquired immunodeficiency syndrome. Both had low-grade leiomyosarcomas located in adrenal gland. Moreover, in patient 1, leiomyosarcoma was multifocal in pericardium and lymph node; in lymph node, muscle tumor was adjacent to nodal and skin Kaposi's lesions. RESULTS: In both patients with acquired immunodeficiency syndrome and leiomyosarcoma, latent infection by EBV could be demonstrated in tumor cells, contrasting with absence of detectable EBV infection in adjacent non-neoplastic tissues and nearby Kaposi's lesions. Latent infection by EBV could not be demonstrated in smooth muscle and myofibroblastic tumors in immunocompetent patients. CONCLUSIONS: Latent EBV infection is associated with smooth muscle cell tumors in immunocompromised patients, but not in immunocompetent patients.

[Histological and immunohistochemical diagnosis of bone marrow metastases of neuroblastomas]. / Diagnostic histologique et immunohistochimique des métastases ostéomédullaires des neuroblastomes.

A retrospective, morphological and immunochemical study was performed on 60 bone marrow biopsies (BOM) and 12 tumor specimens surgically excised, from 9 patients with neuroblastoma (NB). Immunochemistry concerned "neuron-specific enolase" (NSE), chromogranin A (CGA) and synaptophysin (SP). The results of immunochemical stains and the study of reticulin network on the argentic stain were compared to the results of morphological evaluation on the routine stain. NSE, CGA and SP staining of tumor cells (part or all of them) was obtained from all surgical specimens. 17/75 BOM (20%) were discarded because of poor material. NB cells were observed in 24 BOM from 3 patients. Tumor cells formed large strands (1 patient) or nests (2 patients) associated with segregated cells. Diagnosis of metastatic BM involvement was negative or doubtful for 6 BOM (3 obtained at the same time, 2 patients), in which NB cells were clearly demonstrated by immunochemical staining of NSE and/or CGA. Reticulin and/or collagen myelofibrosis was present in 32/35 BOM from the 3 patients metastatic in bone marrow (BM+) even if NB cells could not be demonstrated in these samples.

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.

[Localization of a tumor suppressor gene distal to D22S270 in colorectal cancers]. / Localisation d'un gène suppresseur de tumeur distal à D22S270 dans les cancers colorectaux.

Recurrent allelic losses on chromosome 22q have been reported in colorectal cancer, distal to the NF2 gene, suggesting that another tumor suppressor gene might be involved. We report here the typing of 256 sporadic colorectal tumors and 18 colonic cancer cell lines using a set of chromosome 22 polymorphisms, ranging from 20 to 45. A panel of somatic cell hybrids, that allows to distinguish 11 bins in the 22q13 region, was used to localize 19 of the 45 selected markers and the putative tumor suppressor gene BZRP. Allelic-loss was observed in 43% of tumors. The minimal region of deletion that could be determined, telomeric to locus D22S270, refines significantly the position of the gene. The localization of the BZRP gene in this region led to a systematic screening for somatic point mutation. Direct sequencing of its coding sequence in 36 tumors hemizygous for chromosome 22 allowed the identification of three polymorphisms but failed to detect somatic mutation.

Brain tissue heterotopia in the nasopharynx. Contribution of MRI to assessment of extension.

The authors report two cases of brain tissue heterotopia in the nasopharynx, without other malformations and, in one of the cases, with a persistent craniopharyngeal canal opening onto the heterotopia. This exceptional malformation is very similar to brain heterotopia in the nose, or "nasal glioma", which is more frequent and less diversified at histology. The malformation is revealed by obstruction of the pharynx with respiratory distress immediately after birth or during the first weeks of life. Total surgical excision provides cure without sequelae. The diagnosis is based on histology. MRI is essential to the diagnostic and pretherapeutic evaluation, notably to avoid missing an ectopic hypophysis, but it is insufficient to diagnose a sphenoidal meningoencephalocele.

[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.

[Gelatinous transformation of the bone marrow. Apropos of 3 cases]. / Transformation gélatineuse de la moelle osseuse. A propos de trois observations.

Gelatinous transformation of the bone marrow is a rare histological lesion usually associated with cachexia. The authors report three new cases, two in anorexia nervosa and the third in Hodgkin disease. A review of the literature underlines association with marrow cell necrosis and provides the most frequent etiologies. Pathogenesis of gelatinous transformation remains unclear and her prognostic depends on etiology.

[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.

[Neuromuscular hamartoma]. / Hamartome neuromusculaire.

Neuromuscular hamartoma is a pseudotumour characterized by the presence of striated muscle fibers in a nerve trunk. The reported case was located in the left sciatic nerve in a 4-year-old girl with equinism and spasticity. A first surgical procedure, with muscle biopsy, did not permit diagnosis of hamartoma. It was followed by the occurrence of a firm mass at the same location. Partial excision was performed; the mass revealed to be fibrous. Further aggravation of functional symptoms lead to leg amputation and correct diagnosis. Discussion is focused on the unique features of this rare disorder, for which therapeutic attempts might be avoided, whereas diagnosis proved to be sometimes difficult.

[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.

[Bifocal lesion of striated muscle (hamartoma or focal myositis) in the course of Proteus syndrome]. / Lésion musculaire striée bifocale (hamartome ou myosite focale) au cours d'un syndrome de Protée.

We report a case of bifocal recurrent lesion developed in muscles of the left thigh in a 5 year-old-girl with Proteus syndrome (rare congenital hamartomatous disorder). We discuss the diagnosis of focal myositis versus hamartoma. The clinical and morphological features favour the second hypothesis.

[Myofibromatosis in children. Histopathologic and ultrastructural study of a localized form with a spontaneously regressive course]. / La myofibromatose infantile. Etude histopathologique et ultrastructurale d'une form localisée à évolution spontanément régressive.

Report of a case of the localized form of infantile myofibromatosis, in a three-month-old boy with a brachial mass and osteolytic lesion of the adjacent humerus at radiographic examination. Diagnosis is made on the histopathological features of the lesion at biopsy. Ultrastructurally, the tumor cells have myofibroblastic differentiations. Evolution is regressive without any treatment. The anatomical, clinical, pathological, ultrastructural and evolutive features are discussed.

[Importance of the study of the expression of MIB-1 (Ki-67) for the diagnosis of endocervical glandular lesions]. / Intérêt de l'étude de l'expression de MIB-1 (Ki-67) pour le diagnostic des lésions glandulaires endocervicales.

The morphological criteria for the diagnosis of endocervical atypia and dysplasia are variably defined. Diagnosis is difficult. MIB-1 (Ki-67) cell proliferation-associated antigen was detected retrospectively by immunohistochemistry in 230 cervical cone specimens. The percentage of MIB-1 positive cells was 1 to 25% (median 2%) and limited to small hot spots in normal and subnormal glands (140 cases). It was 1 to 30% (median 4%) in endometrioid metaplasia and microglandular hyperplasia (55 cases); 30 to 60 (median 40%) and limited to 1-3 glands in atypia (24 cases); 45 to 60% (median 50%) and diffusely distributed in dysplasia (5 cases). In situ (3 cases) and invasive (3 cases) adenocarcinomas were characterized by a high% (> 60) of MIB-1 positive cells.

[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.

[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.