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Biomedical subjects

Philippe Vielh

Publications and source records attributed to Philippe Vielh.

33 records · Page 2Linked to original sources

Clinical and histopathological characterization of cutaneous melanomas in the melanoblastoma-bearing Libechov minipig model.

Spontaneous animal tumors appear to be highly suitable models to study human oncology and cancer therapy. The aim of this study was to characterize the clinical and histological features of hereditary melanocytic lesions found in the French herd of melanoblastoma-bearing Libechov minipigs (MeLiM) and their Duroc crossbreeds. Clinically, we discriminated between three types of melanocytic skin lesions, which offer a lesion continuum from lentigo to metastatic melanomas. More than 70% of these lesions appear on piglets before they are 3 months old and preferentially on homogeneous black coat piglets. The incidence of melanoma reaches 50% in MeLiM. Most of the highly invasive melanomas regressed spontaneously in the first year of the piglet's life and the regression was followed by hair, skin and iris depigmentation. A histopathological study was conducted according to the human melanoma classification. Except for lentigo maligna, we observed the three main types of human melanoma in swine [superficial spreading melanoma (SSM), nodular or unclassified melanoma] with an excess of SSM (59-67%). The histological events leading to total spontaneous regression are chronologically described. The genetic predisposition, the high incidence of melanoma, the clinical and histopathological features similar to the human disease and the high rate of spontaneous regression offer an opportunity to use this model for studying genetic events controlling melanoma development and regression and the biological mechanisms involved in oncogenesis and anti-cancerous self-defense.

Animals↗

Solid tumor DNA content analysis.

Flow cytometric DNA content analysis provides a rapid and reliable analysis of DNA ploidy and the proliferative fraction of tumor specimens. Both archival and fresh specimens are suitable for this technique. This information can be used in conjunction with traditional prognostic factors in the biological assessment of certain carcinomas. Among these tumors are early stages of breast, colon, lung, and bladder carcinomas.

Carcinoma↗

ThinPrep-processed fine-needle samples of breast are effective material for RNA- and DNA-based molecular diagnosis: application to p53 mutation analysis.

BACKGROUND: Fine-needle sampling is the least invasive method of in vivo breast carcinoma sampling and can provide material for breast carcinoma diagnosis. The aim of the current study was to assess the accuracy of molecular diagnosis techniques using fine-needle sample (FNS) material stored in PreservCyt (Cytyc Corp., Boxborough, MA). METHODS: The p53 tumor suppressor gene was chosen as a model because it can be used for DNA, RNA, and protein analysis. Molecular analysis was performed using a yeast functional assay and DNA sequencing. p53 accumulation was evaluated by immunocytochemistry. RESULTS: DNA and protein analysis indicated that samples stored for periods of several months, either at room temperature, 4 degrees C, or -20 degrees C, can be processed reliably. For RNA-based diagnosis, samples were still intact after 5 months of storage in PreservCyt at 4 degrees C. In addition, using FNS material that was stored for 16 months at 4 degrees C, the authors detected p53 mutations with either the functional assay for separating alleles in yeast (an RNA-based functional assay) or direct cDNA sequencing. CONCLUSIONS: Fine-needle samples stored in PreservCyt at 4 degrees C are very good material for molecular diagnosis techniques. In addition, it is feasible to adopt a strategy of storing excess FNS material to create cellular banks that will be invaluable for future gene studies.

Biopsy, Needle↗

Cross sectional study of conventional cervical smear, monolayer cytology, and human papillomavirus DNA testing for cervical cancer screening.

OBJECTIVES: To compare the sensitivity, specificity, and interobserver reliability of conventional cervical smear tests, monolayer cytology, and human papillomavirus testing for screening for cervical cancer. DESIGN: Cross sectional study in which the three techniques were performed simultaneously with a reference standard (colposcopy and histology). SETTING: Public university and private practices in France, with complete independence from the suppliers. PARTICIPANTS: 828 women referred for colposcopy because of previously detected cytological abnormalities and 1757 women attending for routine smears. MAIN OUTCOME MEASURES: Clinical readings and optimised interpretation (two blind readings followed, if necessary, by consensus). Sensitivity, specificity, and weighted kappa computed for various thresholds of abnormalities. RESULTS: Conventional cervical smear tests were more often satisfactory (91% v 87%) according to the Bethesda system, more reliable (weighted kappa 0.70 v 0.57), and had consistently better sensitivity and specificity than monolayer cytology. These findings applied to clinical readings and optimised interpretations, low and high grade lesions, and populations with low and high incidence of abnormalities. Human papillomavirus testing associated with monolayer cytology, whether systematic or for atypical cells of undetermined significance, performed no better than conventional smear tests. CONCLUSIONS: Monolayer cytology is less reliable and more likely to give false positive and false negative results than conventional cervical smear tests for screening for cervical cancer.

Colposcopy↗

Fine-needle aspiration of leiomyosarcoma: a correlative cytohistopathological study of 96 tumors in 68 patients.

To better define the cytological features of various leiomyosarcoma (LMS) variants, we reviewed the fine-needle aspiration material and the corresponding histologic sections of 96 tumors in 68 patients. Histological variants of LMS were as follows: 80 (83.3%) were of the classical/usual, seven (7.3%) were epithelioid, and nine (9.4%) were myxoid. Review of original cytology reports showed that 23 (24%) tumors were diagnosed as LMS and 69 (71.8%) as other types of malignancies. Two (2.1%) cases were reported as suspicious and two (2.1%) were unsatisfactory. The classical variants of LMS were characterized cytologically by various proportions of spindle-shaped, cohesive, small- or large-sized cells arranged in parallel alignment. Large spindle, round, binucleated, giant cells with intracytoplasmic granulations were frequently seen. Blunt-ended nuclei, intranuclear inclusions and mitotic figures were occasionally seen, as well as stromal fragments. The epithelioid tumors were composed of an admixture of small and large, spindle-shaped and round cells, also arranged in parallel alignment. Tumor cells with granular cytoplasm, blunt-ended nuclei, intranuclear inclusions, mitotic figures, fibrous or myxoid stroma were not observed. The myxoid tumors disclosed large amounts of background myxoid matrix containing large spindle-shaped and giant cells. Entities such as leiomyoma, malignant peripheral nerve sheath tumor, monophasic synovial sarcoma, and malignant fibrous histiocytoma should be considered in the differential diagnosis of LMS of the classical type. Epithelioid leiomyoma may share similar cytological features with epithelioid LMS. The cytological features of the myxoid variant of LMS can be easily confused with other types of benign and malignant mesenchymal tumors depicting degenerative myxoid changes and/or a myxoid matrix component.

Adolescent↗

Cytohistologic correlations in angiosarcoma including classic and epithelioid variants: Institut Curie's experience.

To characterize the cytological features of angiosarcomas, we reviewed the fine-needle aspiration material and corresponding histologic sections of 29 tumors in 23 patients. Histologically, 24 tumors were of the classic type, and 5 were epithelioid angiosarcomas. The original corresponding cytologic diagnoses were as follows: angiosarcoma, 17 cases; sarcoma not otherwise specified, 8 cases; and rhabdomyosarcoma, 1 case. Three samples were cell-poor and were considered suspicious of malignancy. The review of cytology samples showed that smears were cell-rich in 17 tumors and cell-poor in 12 tumors. A hemorrhagic background was present in 9 cases. Tumor cells were polymorphous, including spindle-shaped, round to oval, and polygonal epithelioid cells and giant cells in different proportions. Erythrophagocytosis was seen in 12 tumors. Smears of classic angiosarcomas were polymorphous and lacking specific characteristics, whereas smears of epithelioid tumors were morphologically similar and composed of round to oval and polygonal, epithelial cells frequently arranged in clusters, and showing erythrophagocytosis. The wide spectrum of cellular components of angiosarcomas accounts for the difficulty in establishing accurate tumor typing, particularly with cell-poor samples and low-grade classic angiosarcoma. Entities to consider in the differential diagnosis are carcinoma, epithelioid sarcoma, pleomorphic rhabdomyosarcoma, and malignant melanoma.

Adolescent↗

Comparative fine-needle aspiration and pathologic study of malignant fibrous histiocytoma: cytodiagnostic features of 95 tumors in 71 patients.

To determine diagnostic cytomorphologic features of malignant fibrous histiocytoma (MFH) on fine-needle aspiration (FNA) materials, we reviewed the cytologic material and corresponding histologic slides of 95 tumors in 71 patients. Forty-four (46%) tumors were primary, 38 (40%) were recurrent, and 13 (14%) were metastatic. Histological variants of MFH were as follows: 52 (54.7%, 43 patients) were of the storiform/pleomorphic, seven (7.4%, five patients) were giant cells, four (4.2%, four patients) were inflammatory, and 31 (33.7%, 19 patients) were myxoid type. Review of original cytology reports showed that only 23 (24.2%) tumors were diagnosed as MFH and 68 (71.6%) as other types of malignancies. Four (4.2%) cases were reported as unsatisfactory/suspicious. Our findings showed that spindle-shaped, round, giant cells, osteoclastic-like giant, and inflammatory cells were the most consistent features that allow identification of the storiform/pleomorphic, giant cell, and inflammatory variants of MFH. The myxoid tumors had marked myxoid background matrix with spindle-shaped cells and, less frequently, round and giant cells. Pleomorphic leiomyosarcoma and dedifferentiated liposarcoma should be considered in the differential diagnosis of stroriphorm/pleomorphic, giant cells, and inflammatory variants of MFH. However, myxoid MFH may resemble their leiomyosarcoma and liposarcoma counterparts.

Adolescent↗

A Fluorospot assay to detect single T lymphocytes simultaneously producing multiple cytokines.

Various subpopulations of T lymphocytes-i.e. Type 1, Type 2, Tr1 T cells-play a major role in the homeostasis of the immune system and in the pathogenesis of many inflammatory and auto-immune diseases. At present, in the absence of specific surface markers, these T cells can only be reliably distinguished on the basis of their cytokine production profile. The Elispot assay detects cytokine-producing cells, but in most cases can detect only one secreted cytokine, which represents a major limitation of this technique. We have developed a Fluorospot assay to detect single cells that simultaneously produce multiple cytokines. The Fluorospot assay permits the detection of regulatory T cells with an immunosuppressive activity, identified by their coexpression of IL-10 and IFNgamma. Polarized type 1 and type 2 specific tetanus toxoid T cells are also directly detected using a dual color Fluorospot. This technique will therefore be useful for detailed analysis of T lymphocytes in various disease states in which an imbalance of T cell subpopulations is suspected, but will also provide a better characterization of polarized specific immune responses.

Cell Polarity↗

Efficiency of the hybrid capture 2 HPV DNA test in cervical cancer screening. A study by the French Society of Clinical Cytology.

The aim of this study was to determine the efficiency of the Hybrid Capture 2 (HC2; Digene, Gaithersburg, MD) human papillomavirus (HPV) assay for the detection of cervical neoplasia. Of the 1,785 patients recruited, 462 (25.88%) were referred for colposcopy owing to previously detected cytologic abnormalities, and 1,323 (74.12%) were voluntary candidates for screening. For all patients, a Papanicolaou smear and a monolayer smear (ThinPrep, Cytyc, Boxborough, MA) were done. HPV DNA was detected on the residual liquid-based material. False-positive results were observed in 111 cases and comprised 34 cross-reactions (1.90%) and 77 false-positive cases (4.31%) owing to a contiguous strong chemiluminescence signal. Interestingly, all these samples had a relative light units value of 1 to 3 and were contiguous to a sample with a very high HPV DNA load. The final results showed that high-risk and low-risk HPV DNA were detected in 480 samples (26.89%) and 135 samples (7.56%), respectively. Although HC2 can be considered a reliable and sensitive test for HPV DNA detection, we do not advocate its use for large-scale screening for cervical neoplasia.

Adult↗

Incidence and prognostic significance of complete axillary downstaging after primary chemotherapy in breast cancer patients with T1 to T3 tumors and cytologically proven axillary metastatic lymph nodes.

PURPOSE: To determine the incidence and prognostic significance of eradication of cytologically proven axillary lymph node metastases in breast cancer patients treated with primary chemotherapy. PATIENTS AND METHODS: Between January 1985 and December 1994, 152 breast cancer patients with invasive T1 to T3 tumors and axillary metastases cytologically proven by fine-needle sampling underwent primary chemotherapy followed by lumpectomy or mastectomy, level I and II axillary lymph node dissection, and irradiation. We studied pathologic complete responses (pCRs) of axillary nodes and breast tumors, as well as predictors of distant metastases. RESULTS: Thirty-five patients (23%) had axillary pCRs, and 20 patients (13.2%) had pCRs of primary breast tumors. Scarff-Bloom-Richardson grade 3 tumors (P =.04) and a clinical response to chemotherapy > or = 50% (P =.003) were associated with negative axillary status at dissection. An initial tumor size < or = 3 cm (63 patients) was associated with pCR of the primary tumor (P =.02) but not with complete histologic clearance of axillary lymph nodes. The median length of follow-up was 75 months. In the univariate analysis, age greater than 40 years (P =.003), absence of residual nodal disease (P =.01), and pCR of the tumor (P =.05) were associated with better distant disease-free survival. Five-year distant disease-free survival rates were 73.5% +/- 14.9% among patients with no involved nodes at the time of surgery and 48.7% +/- 9.2% among patients with residual nodal disease. In the multivariate Cox regression analysis, parameters associated with poor distant disease-free survival were age < or = 40 years (P =.002), persistence of nodal involvement (P =.03), and S-phase fraction greater than 4% (P =.02). CONCLUSION: Our results suggest that axillary status is a better prognostic factor than response of the primary tumor to primary chemotherapy.

Adult↗

Quantitative FISH analysis on interphase nuclei may improve diagnosis of DNA diploid breast cancers.

The detection of DNA aneuploid cells using flow cytometry is an indication for the presence of tumor cells, but when DNA diploid cells are found in 25-33% of the cases, the diagnostic and prognostic significance of DNA ploidy is more limited. We analyzed interphase nuclei after in situ hybridization and using image cytometry on 50 breast tumors with diploid DNA content to investigate whether early chromosome rearrangements were detectable and if their occurrence was clinically significant. Imbalances between the two arms of chromosome 1 were found in 55% of the cases and values ranged from 1.5-3.0. Comparison with histological data showed that Grade I tumors mainly have imbalances (67%) and that Grade III tumors were mainly without the imbalance (67%), whereas Grade II tumors were intermediate (50% imbalance). These data suggest that the diagnosis of DNA diploid cases may be improved by using interphase FISH. In addition, the data also indicates that early breast tumors may have different genetic origins, which is important in the comprehension of tumor malignancy in early stages, especially for preinvasive lesions.

Adult↗

Cytohistologic correlations in 56 synovial sarcomas in 36 patients: the Institut Curie experience.

Synovial sarcoma (SS) is a high-grade malignant soft tissue tumor that manifests different phenotypic subtypes that may render their cytologic evaluation challenging. Although several cytologic studies of SS have been published, correlative studies of cytologic and corresponding histologic features are limited. To better define the cytological features of various SS forms, we reviewed the cytologic and the corresponding histologic material of 56 tumors from 36 patients. Classical patterns were defined as dispersed or small clusters of cells with bland chromatin, inconspicuous nucleoli, oval to spindle-shaped cytoplasm and branching tumor tissue fragments, vessel stalks, acinar structures in scant mucin background, seen in all 53 (94.7%) cellular cases. Epithelial, squamous, round cells, mast cells, necrosis, comma-like nuclei, marked nuclear atypia, secretory mucin, and rosette-like structures were also occasionally observed. Comparing the histological subtype we noted that epithelial cells and secretory mucin were restricted to biphasic SS, round cells to poorly differentiated SS, and comma-like nuclei to monophasic fibrous SS. We conclude that the classical pattern is highly suggestive of SS of all three monophasic, biphasic, or poorly differentiated subtypes. These characteristics, along with molecular genetic studies, may improve the cytologic diagnosis of SS.

Adolescent↗

Cytohistologic correlations of 24 malignant peripheral nerve sheath tumor (MPNST) in 17 patients: the Institut Curie experience.

Cytomorphological patterns of malignant peripheral nerve sheath tumor (MPNST) are insufficiently documented in the literature. Cytological and histological specimens in 24 tumors in 17 patients were correlated. The review of the original cytology reports showed that four (16.6%) tumors were correctly diagnosed, eight (33.3%) were diagnosed as sarcoma not otherwise specified, four (16.7%) as fibrosarcoma, three (12.5%) as synovial sarcoma, three (12.5%) as leiomyosarcoma, and one (4.2%) case each as malignant fibrous histiocytoma and rhabdomyosarcoma. At the review tumors were histologically reclassified as well-differentiated MPNST in 11 (45.9%) cases, anaplastic MPNST in 11 (45.9%) cases, and epithelioid MPNST and malignant Triton tumor in one (4.2%) case each. Cytologically, well-differentiated MPNST were composed of polymorphous oval to round cells, small spindle-shaped cells with wavy and comma-like naked nuclei, and a fibrillary, delicate stroma. Anaplastic MPNST, moreover, were composed of anaplastic giant and polymorphous cells. The malignant Triton tumor was composed of oval to round rhabdomyoblastic cells with eccentric nuclei and the epithelioid MPNST of polymorphous and round, epithelial-like cells. The cytological diagnosis of MPNST may be difficult, especially in anaplastic tumors. The correlation between the cytological features and the clinical information--origin of the tumor from a nerve trunk, a preexisting neurofibroma, patients with known history of neurofibromatosis 1--could be indicative of an MPNST diagnosis.

Adult↗

Cost of screening for cancerous and precancerous lesions of the cervix.

This paper is part of the cost-effectiveness study of cervical cancer screening conducted by the French Society of Clinical Cytology (SFCC). It describes the evaluation of costs of conventional smear tests, thin-layer smear tests (ThinPrep 2000 system), and viral typing by the HCS test. For 100,000 examinations per year, the average cost of a conventional smear test is 11.53 dollars in a private anatomo-pathology clinic. The cost of the thin-layer test for the same number of examinations and in the same type of clinic is 13.93 dollars. For 20,000 annual tests, the average cost of human papillomavirus (HPV) is 23.43 dollars in the public sector and 23.48 dollars in the private one. The higher price of the thin-layer method is only justifiable if this screening technique outperforms the conventional method. Furthermore, the high cost of the HPV test means that its integration into a population-based screening program must be carefully defined.

Cost-Benefit Analysis↗