[Headache, fever and behavior problems. Lymphoma].
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Biomedical subjects
Publications and source records attributed to A Verhest.
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Cytogenetic analysis of a metastatic biphasic synovial sarcoma showed two structural abnormalities: t(X;7)(q11 or 12;q32) and t(7;14)(q22;q11.2). This is the first report of a synovial sarcoma without the involvement of either Xp11 or 18q11.
Cytogenetic study of five biphasic and five monophasic synovial sarcomas revealed the specific abnormality t(X;18) (p11;q11) in eight cases and t(X;15;18) (p11;q15;q11) and t(X;7) (q11-12;q32) in one case each. Additional, secondary aberrations were present in eight of these tumors. By combining our data with information on previously published cytogenetically abnormal synovial sarcomas, we were able to evaluate 32 tumor samples from 29 patients. The modal chromosome number was pseudodiploid or near diploid in 26 of the 32 tumors. A t(X;18) was present in 21 of 29 cases (72%). Complex translocations involving chromosomes X and 18 and another autosome were present in five cases, and one displayed a t(5;18). There was no visible rearrangement of chromosome bands Xp11 or 18q11 in only 2 of the 32 synovial sarcomas. Half of the primary tumors (6 of 12) had the X;18-translocation as the sole abnormality. Of the remaining 20 specimens from recurrent or metastatic tumors (in three cases two tumors could be analyzed), only one had t(X;18) as the sole change. The secondary aberrations in cases exhibiting clonal evolution were also generally more extensive in the metastatic and recurrent than in the primary sarcomas (five additional aberrations per case, compared with two). Chromosomes 1 and 12 were the chromosomes most frequently (one fourth of the cases) involved in additional structural changes, but with several different breakpoints. No differences were identified between the karyotypic profiles of monophasic and biphasic synovial sarcomas.
We studied 55 renal tissue samples from 16 patients corresponding to normal (19 samples, group 1), low-grade (18 samples, group 2), and high-grade (18 samples, group 3) tumoral tissues. For this purpose, we used digital cell image analysis (the SAMBA 200 processor) to describe the morphonuclear patterns of Feulgen-stained nuclei from the 3 above-mentioned groups. Our results show that nuclear DNA ploidy is positively correlated with histopathological differentiation, which is also positively correlated with an increase in nuclear DNA heterogeneity. Morphometric and textural parameters computed on such Feulgen-stained nuclei make it possible to describe the typical morphonuclear patterns of normal, low-grade, and high-grade neoplastic renal tissues. Using multiparametric, i.e. principal-component and canonical analyses, we set up preliminary morphonuclear data banks that we used to assess the diagnosis of 6 ungraded samples. We expect that this kind of morphonuclear data banks might be helpful, on one hand, to select specific morphonuclear parameters related to patient survival, and on the other hand to establish the cytological diagnosis of deep fine-needle aspiration material, sonographically assisted, on suspicious kidneys. Such hypotheses are now under further study.
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Morphonuclear assessments were performed using the SAMBA 2005 cell image processor on cell nuclei in fine needle aspirates and corresponding imprint smears from 17 not-otherwise-specified (NOS) breast carcinomas to study the influence of cell sampling on the morphonuclear measurements. Fourteen parameters related to densitometric (nuclear DNA content), morphometric (nuclear area) and textural (chromatin organization and distribution) characteristics were computed for each nucleus. The results demonstrated that such morphonuclear features evolved significantly and positively with respect to conventional histopathologic grading. The method of cell sampling significantly influenced the results, but without altering the general conclusions regarding evolution of the morphonuclear features.
Fifty-eight Feulgen-stained imprint smears from freshly resected colorectal tissue were analyzed by means of a SAMBA 200 cell image processor to establish a quantitative grading of their evolution from normal to malignant mucosa on the basis of 15 morphonuclear parameters relative to morphometry (nuclear size), densitometry (DNA content), and texture (chromatin pattern). The colorectal samples belonged to six groups: normal mucosa from patients without (Group 1) or with (Group 2) colorectal cancer, adenomas (Group 3), and cancers corresponding to the three stages of the Dukes' classification (Groups 4 to 6). Results indicated that analysis of the morphonuclear parameters computed on 250 to 300 nuclei/cases objectively and quantitatively showed the adenoma-cancer sequence. This need for only a small number of nuclei to assess a highly efficient analysis created a preoperative investigative tool using cytologic smears during endoscopy. The authors also made preliminary data banks for objective and reproducible grading of unknown cases by comparisons (discriminant analyses) with their contents. This approach must be validated prospectively on a large series of cases to furnish a system for colorectal malignancy diagnosis.
The relationship between several morphonuclear parameters related to nuclear densitometry (DNA content and ploidy), and the chromatin pattern of Feulgen-stained nuclei is confronted to the histopathological grading of 39 prostatic samples obtained from surgical adenomatous or transurethral resection. We use a SAMBA 200 cell image processor with software allowing for the setting up of preliminary data banks that enable carrying out an objective and reproducible grading of unknown cases obtained from core biopsies of fine-needle aspirations. The present approach must be validated prospectively on a large series of cases in order to create an expert system for diagnosing such fine-needle aspirations from prostate.
We analyzed the relationship between several morphonuclear parameters related to nuclear size, densitometry (deoxyribonucleic acid content and ploidy) and the chromatin pattern versus the histopathological grading of 46 bladder cancer samples graded according to the World Health Organization classification. We used a SAMBA 200 cell image processor with software allowing for the discrimination of 15 different parameters on Feulgen-stained imprint smears. In addition, we set up preliminary data banks that enable objective and reproducible grading of unknown cases. This approach must be validated in a large series of cases to create an expert system for bladder malignancy diagnosis.
The M13 bacteriophage probe, which makes possible the establishment of DNA fingerprints, was used to study a phenotypically normal woman with a 46XY karyotype and her twin brother. Identical fingerprints and positive hybridization with a series of Y-specific probes were obtained on blood samples from the siblings. DNA from a skin biopsy of the woman yielded a clearly different pattern and displayed no Y-specific hybridization, indicating that she is a spontaneous chimera. This study illustrates the use of DNA fingerprinting as a powerful and simple aid to the diagnosis of natural chimerism.
A case of a ruptured metastatic aneurysm of choriocarcinoma is reported. The fourteen other cases of the literature are summarized. The pathological significance of this rare presentation of metastatic disease is discussed. The treatment of choice is defined as excision followed by chemotherapy and whole brain irradiation. The prognosis remains poor.
After modified radical mastectomy, 490 primary breast cancer patients were followed for a median of 75 months. Bloom grade was measured in 340 patients and ER status in 341. Follow-up of these patients has yielded the following results: (a) The value of traditional indices has been reaffirmed. (Cox's multivariate analysis identified, in order of decreasing importance, the number of invaded lymph nodes, the initial tumor size and the histological grade. Other variables were found to be of lesser importance and were correlated with the three main indices.) (b) The value of ER status disappeared after more than 3 years of follow-up. (c) ER positive patients fared better after recurrence. This was interpreted as being a consequence of their responsiveness to hormonal treatment.
This article reports the surprising history of a patient presenting a von Recklinghausen neurofibromatosis. Ten years after a full program of radio- and chemotherapy for a so-called invasive uterine leiomyosarcoma, the diagnosis of intestinal neurofibromatosis is finally established and the patient is surgically cured. The authors discuss the difficulties of the histologic diagnosis and the aid of the recent techniques of immunohistochemical markers. The second part of the article provides the actual clinical classification of the different types of neurofibromatosis with their diagnostic approach. It also offers a review of the literature concerning the intestinal location of the disease and the potential risks of cancer formation.
Forty-one Feulgen-stained cervical imprint smears were analyzed by means of the SAMBA 200 cell image processor in order to quantitatively score human papillomavirus (HPV) 16-18-induced morphonuclear modifications as assessed by morphometric, densitometric, and textural parameters. Molecular hybridization technology using 16 and 18 type specific genetic probes made it possible to divide our series into three groups: Group 1, containing noninfected smears; Group 2, containing "suspicious", i.e., borderline positive, smears; and Group 3, those related to infected patients. Our results show that nuclei from infected smears are much more hyperchromatic and bigger than those arising from noninfected smears. This quantitative description of HPV 16-18-induced chromatin modifications enabled us to create preliminary data banks which could lead to an objective and reproducible grading of unknown cases. This approach is now being prospectively assessed on a large series of cases because the value of the current study is limited until the data bank is tested against unknown specimens with a broader spectrum of HPV infection.
A continuous series of 649 patients, treated by modified radical mastectomy for primary breast carcinoma, is analyzed after a median follow-up of 92 months. 'True isolated' locoregional recurrences (LR), defined as LR not preceded or followed by distant metastases within 6 weeks, appeared with a cumulative actuarial incidence rate of 6%, 14% and 19% after 1, 5 and 7 years respectively, whereas the respective figures for distant metastases (M1) were 10%, 37% and 48%. The main initial parameters, predicting both the LR-free and the M1-free interval, are presented by statistical analyses in the following order of importance: number of invaded lymph nodes in the axilla, tumor size (T) and histological grading of differentiation. The same factors also predicted the imminence of M1 once LR had occurred, as well as survival after LR. A higher incidence of M1 after LR was also correlated with estrogen-receptor negative tumors and with those LR occurring within one year after mastectomy. LR occurred at the chest wall (65%), in the sub-clavicular fossa (16%) and the axilla (6%); the remaining 13% occurred in two of the sites. There was a trend towards longer survival after chest wall recurrence than after LR recurrence at another site. Axillothoracic irradiations postmastectomy gave a lower rate of LR in 227 patients than did a regimen of 12 months adjuvant chemotherapy with irradiation restricted to the internal mammary lymph nodes in 120 subsequent patients: 17 vs 25% at 5 years (P = 0.03 when adjusted by initial nodal involvement and T-size). Total excision of LR (repeated if new LR occurred) gave better rates of local ultimate control and survival than other kinds of treatments, with or without adjuvant local or systemic therapy. LR is not always a sign of imminent generalized disease. Actuarial 5-year survival after LR is 26.2% overall whereas, if only 'true isolated' LR are considered, the survival is 37%.
A pilot study analyzed the relationship between several morphonuclear parameters and the Bloom-Richardson score for 37 invasive, not-otherwise-specified (NOS) ductal breast carcinomas. The SAM-BA 200 cell image processor and its software were used to measure the nuclear features on Feulgen-stained imprint smears. Two parameters representing the numbers of large and dense chromatin clots and two parameters describing the heterogeneity of the chromatin among nuclei in a specimen evolved in a continuous manner parallel with the Bloom-Richardson score from stages NOS-4 to NOS-8. The systematic measurement of these four parameters on a large series of breast cancers may be able to define an objective and reproducible "scale" of differentiation that could be a helpful tool for pathologists and clinicians.
Intestinal neurofibromatosis without other manifestations of von Recklinghausen's neurofibromatosis was found in a multigeneration family. Neurofibromas were strictly limited to the intestine. Onset of symptoms was delayed until adulthood and some gene carriers remained asymptomatic into their middle or late adult years. One other family with intestinal neurofibromatosis has been described in 1966. No symptomatic male is yet known, although an asymptomatic male in our family is an obligate gene carrier. The gene for intestinal neurofibromatosis may be incompletely penetrant and its expression varies even in symptomatic patients. No male-to-male transmission has been recorded to rule out X linkage. Intestinal neurofibromatosis presents as a distinctive dominant phenotype with an increased risk of intestinal problems including bleeding, intussusception and obstruction.
A translocation was found in members of a family with intestinal neurofibromatosis, a rare dominant disorder phenotypically distinct from von Recklinghausen neurofibromatosis. The translocation was reciprocal between chromosomes 12 and 14. Four of 5 family members carrying the gene for intestinal neurofibromatosis had the translocation. This may be due to change alone or linkage of the gene for intestinal neurofibromatosis to one of the translocation breakpoints in chromosome bands 12q13 and 14q13.