Uterine leiomyosarcoma metastatic to thyroid shown by 18F-FDG PET/CT imaging.

About one third of focal thyroid uptakes in a fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) study are malignant, the most frequent histological type being papillary carcinoma. Metastases to the thyroid account for approximately 7.5% of thyroid malignancies and come mainly from kidney, lung, head and neck, and breast cancers. We report the case of a 64-year-old woman presenting a fast growing thyroid nodule whose primitive or metastatic origin was not obvious, for which 18F-FDG PET/CT helped in the diagnostic process and in the later management of the patient. Histopathologic findings finally revealed a metastasis of uterine leiomyosarcoma.

Can c-myc amplification reliably discriminate postradiation from primary angiosarcoma of the breast?

PURPOSE: Breast angiosarcomas are rare vascular malignancies that arise secondary to irradiation or de novo as primary tumours. The aim of this study is to know whether c-myc amplification can reliably discriminate these two entities. MATERIEL AND METHODS: Forty-seven patients treated for breast angiosarcomas were studied. Thirty-two patients were diagnosed with postradiation angiosarcomas after breast cancer treatment and 15 patients with primary angiosarcomas. Interphase fluorescence in situ hybridization (FISH) was performed by hybridization of probes covering C-MYC (chromosome 8q24.21) and CEP8 on tissue sections. RESULTS: Amplification (5- to 20-fold) of the c-myc oncogene was found in all breast radiation-induced angiosarcomas (32 tumours) but in none of the 15 primary angiosarcomas except one (7%). CONCLUSION: This study reinforces that there are true pathogenetic differences between the two types of breast angiosarcomas which are morphologically indistinguishable. These data point the pathways preferentially involved in the pathogenesis of post radiation angiosarcomas of the breast and may provide the basis for an additional targeted therapy.

Effect of adjuvant chemotherapy on survival in FNCLCC grade 3 soft tissue sarcomas: a multivariate analysis of the French Sarcoma Group Database.

BACKGROUND: The predictive value of grade for benefit from adjuvant chemotherapy (AC) in soft tissue sarcoma (STS) patients has never been explored. PATIENTS AND METHODS: From 1980 to 1999, 1513 adult patients with non-metastatic STS were included prospectively in the French Sarcoma Group database. Grade was assessed according to the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system after central review. RESULTS: AC was delivered to 13 grade 1 patients (3%), 145 grade 2 patients (35%) and 262 grade 3 patients (62%). Young age, non-well-differentiated liposarcoma histology, deep location, bone and/or neurovascular invasion and grade 2 or 3 were significantly associated with a higher likelihood to receive AC. Median follow-up was 9 years. On multivariate analysis, AC was significantly associated with improved metastasis-free survival (MFS) [5-year MFS: 58% versus 49%, hazard ratio (HR) 0.7 (95% confidence interval (CI) 0.6-0.9), P = 0.01] and overall survival (OS) [5-year OS: 58% versus 45%, HR 0.6 (95% CI 0.5-0.8), P = 0.0002] in grade 3 patients. This was not observed in grade 2 patients [5-year MFS: 76% versus 73%, HR 0.8 (95% CI 0.5-1.2), P = 0.27; 5-year OS: 75% versus 65%, HR 0.8 (95% CI 0.6-1.1), P = 0.15]. CONCLUSION: This large cohort-based analysis with long-term follow-up indicates that patients with FNCLCC grade 3 disease may benefit from AC.

Soft tissue sarcomas of the trunk wall (STS-TW): a study of 343 patients from the French Sarcoma Group (FSG) database.

BACKGROUND: Soft tissue sarcomas of the trunk wall (STS-TW) are usually studied together with soft tissue sarcomas of other locations. We report a study on STS-TW forming part of the French Sarcoma Group database. PATIENTS AND METHODS: Three hundred and forty-three adults were included. We carried out univariate and multivariate analysis for overall survival (OS), metastasis-free survival (MFS) and local recurrence-free survival (LRFS). RESULTS: Tumor locations were as follows: thoracic wall, 82.5%; abdominal wall, 12.3% and pelvic wall, 5.2%. Median tumor size was 6.0 cm. The most frequent tumor types were unclassified sarcoma (27.7%) and myogenic sarcoma (19.2%). A total of 44.6% of cases were grade 3. In all, 21.9% of patients had a previous medical history of radiotherapy (PHR). Median follow-up was 7.6 years. The 5-year OS, MFS and LRFS rates were 60.4%, 68.9% and 58.4%, respectively. Multivariate analysis retained PHR and grade for predicting LRFS and PHR, size and grade as prognostic factors of MFS. Factors influencing OS were age, size, PHR, depth, grade and surgical margins. The predictive factors of incomplete response were PHR, size and T3. CONCLUSIONS: Our results suggest similar classical prognostic factors as compared with sarcomas of other locations. However, a separate analysis of STS-TW revealed a significant poor prognosis subgroup of patients with PHR.

Leiomyosarcoma of the great saphenous vein.

Peripheral vascular leiomyosarcomas are rare. A case of leiomyosarcoma of the great saphenous vein diagnosed pre-surgically by MRI and fine-needle aspiration is presented. Characteristics of the tumour and imaging features are discussed.

Cytology vs molecular analysis for the detection of head and neck squamous cell carcinoma in oesopharyngeal brush samples: a prospective study in 56 patients.

Oesopharyngeal brush (OPB) sampling with cytological analysis can yield exfoliated cells from asymptomatic tumours of the upper aero-digestive tract and the oesophagus. In this study, we compared cytological evaluation and molecular analysis for the detection of exfoliated cancer cells sampled with an OPB. A total of 56 patients with a known unique head and neck squamous cell carcinoma (HNSCC) and five healthy controls were enrolled prospectively. Exfoliated cells from these 61 patients were collected with an OPB before initial endoscopy. p53 mutations and UT 5085 microsatellite instability (MI) were analysed in the HNSCC tumour, lymphocytes and the corresponding OPB DNA samples. p53 mutations and UT5085 MI were detected in 31 out of 56 and 14 out of 56 HNSCC, respectively, but not in any of the five controls. Direct sequencing of p53 was able to detect mutations in OPB DNA in only two out of 29 patients harbouring a p53-mutated primary tumour. Microsatellite instability was detected in OPB DNA of 11 out of 13 informative (bandshift detected in tumour) patients, whereas cytological analysis detected abnormal cells in only six of the same 13 patients (P=0.03). In informative patients, all positive OPB samples at cytological analysis were also positive at molecular analysis of UT5085, and both analyses confirmed the two negative samples. Molecular analysis of OPB from eight uninformative patients and from five healthy controls were all negative. OPB sampling with MI-based molecular analysis could be efficient for early detection of recurrent HNSCC. This result prompts us to use other microsatellite markers in order to maximise the percentage of informative patients.

[HER2 gene amplification assay: is CISH an alternative to FISH?]. / Recherche de l'amplification du gène HER2: la CISH est-elle une alternative à la technique FISH?

The HER2 proto-oncogene encodes a transmembrane protein, which is considered to function as a growth factor receptor. Overexpression of this protein found by immunohistochemistry in about 20% of infiltrating breast carcinomas, has a predictive value of response to treatment by trastuzumab, an anti-HER2 humanized monoclonal antibody. Search for HER2 gene amplification is necessary to adapt the immunohistochemical technique quality and also in the cases of delicate analysis or weak overexpression. It is usually carried out by Fluorescence In Situ Hybridization (FISH). A more recent hybridization technique, named CISH because of its chromogenic revelation is an alternative method, which gives highly correlated results with FISH. We present details of this technique, which may be more familiar for the pathologists than FISH, because reading analysis is similar to that of immunohistochemical staining.

Comparison of enzyme immunoassay and immunohistochemical measurements of estrogen and progesterone receptors in breast cancer patients.

Before replacing enzyme immunoassay of estrogen and progesterone receptors by immunohistochemistry, results of both methods were compared on 437 samples obtained from breast cancer patients (342 primary breast carcinomas, 16 local recurrences, 49 biopsies, and 30 tumor specimens obtained after neoadjuvant treatment). Immunohistochemistry (IHC) results were first assessed semiquantitatively on the basis of the estimated proportion of positive tumor cells, and then quantitatively using the "quick score." Semiquantitative IHC hormone receptors results (positive > or = 10%) correlated well with enzyme immunoassay status (positive >15 fmol/mg protein) in 358 surgical samples (342 primary tumors and 16 recurrences), with overall concordance rates of 89.9% and 82.1%, respectively. Among the 100 discordant cases, a large intraductal carcinoma component was observed in 7 of 36 cases for estrogen receptor (ER) and 15 of 64 for progesterone receptor (PR). Thirty-five discordant cases also were observed near the cut-off values. Hormone receptor levels by enzyme immunoassay correlated strongly with the quantitative IHC "quick score." Whatever the method, hormone receptor status was associated with histologic grade (SBR) and tumor size, whereas age correlated strongly with ER positivity. Similar results were obtained for biopsy specimens and posttreatment samples. This comparison improved the reliability of the IHC technique, which is currently routinely used for ER and PR determination in the authors' institution.

Detection of the synovial sarcoma translocation t(X;18) (SYT;SSX) in paraffin-embedded tissues using reverse transcriptase-polymerase chain reaction: a reliable and powerful diagnostic tool for pathologists. A molecular analysis of 221 mesenchymal tumors fixed in different fixatives.

Synovial sarcoma (SS) is a relatively rare sarcoma, which may be confused with several other mesenchymal and nonmesenchymal lesions. It bears the t(X;18) (SYT;SSX) translocation, which seems to be specific for this tumor type and can be detected in paraffin-embedded tissue, using reverse transcriptase-polymerase chain reaction (RT-PCR). However, the specificity and sensitivity of this detection method have rarely been examined in a large series. Using RT-PCR, we examined 250 mesenchymal and nonmesenchymal, benign and malignant, paraffin-embedded lesions for the SS t(X;18) (SYT-SSX) translocation. PCR products were obtained from 221 tumors (88.5%). There were 135 non-SS tumors, 22 biphasic, and 64 monophasic spindle/round cell SS, of which 10 were cytogenetically confirmed as t(X;18)-positive. SYT-SSX gene fusion transcripts were detected in the SS tumor category only (100% specificity), including 100% of the biphasic SS and 86% of monophasic spindle/round cell SS. Nine tumors originally diagnosed as SS were t(X;18) (SYT-SSX)-negative. Following reassessment, only 3 of these tumors showed clinicopathologic, immunohistochemical, and/or ultrastructural features consistent with that diagnosis, thus raising the overall detection sensitivity to 96%. With regard to the potential adverse effect of the fixatives used, PCR products were obtained in 100%, 91.5%, 90.5%, and 0% of tumors fixed with AFA, buffered formalin, Holland Bouin, and conventional Bouin's fluid, respectively. This study shows that the detection of the SS t(X;18) (SYT-SSX) in paraffin-embedded tissue is feasible with a 100% specificity and an overall 96% sensitivity, provided non-Bouin's fluid fixation is used.

Prognostic factors in localized primary synovial sarcoma: a multicenter study of 128 adult patients.

PURPOSE: To identify most significant and therapeutically relevant prognostic factors in adults with localized primary synovial sarcomas (SS) and to confirm the usefulness of the French Federation of Cancer Centers (FNCLCC) grading system, the prognostic impact of which has been already proven in soft tissue sarcomas. PATIENTS AND METHODS: Data on 128 patients with nonmetastatic SS collected from a cooperative database by the FNCLCC Sarcoma Group between 1980 and 1994 were studied retrospectively. Immunohistochemistry was performed at diagnosis in 77 cases (61%). The tumors were classified as biphasic (n = 45), monophasic fibrous (n = 72), and poorly differentiated (n = 10) subtypes. Histologic grade was determined according to the FNCLCC method, and vascular invasion was assessed in every case. RESULTS: The 5-year disease-specific survival (DSS) rate for this series of patients with localized SS was 62.9% (+/- 9.6% [SD]) with a median follow-up time of 37 months (range, 8 to 141 months). In multivariate analysis, the adverse risk factors associated with decreased DSS were International Union Against Cancer/American Joint Committee on Cancer stage III/IVA disease, male sex, and truncal tumor locations. For metastasis-free survival (MFS), disease stage III/IVA, tumor necrosis, and monophasic subtypes were the major factors associated with a less favorable prognosis. Separately, when not using disease stage, tumor necrosis, and mitotic activity, histologic grade became the most significant prognostic factor for both DSS and MFS. In addition, larger tumors and older patients become associated with a significantly worse prognosis. Independent adverse risk factors for local recurrence-free survival included histologic grade 3 and truncal tumor location. CONCLUSION: These data confirm that not all SS present the same severe outcome. High-risk patients identified on the basis of these parameters may qualify for an aggressive treatment approach.

Somatic genetic alterations (LOH) in benign, borderline and invasive ovarian tumours: intratumoral molecular heterogeneity.

Loss of heterozygosity (LOH) affects a number of chromosome regions in ovarian cancer, pointing to the possible involvement of tumour-suppressor genes in ovarian tumorigenesis. We performed comparative analysis of allelic loss at 6 frequently affected chromosome regions in a panel of 53 benign, borderline and malignant ovarian tumours. Precursor lesions could provide evidence that an accumulation of genetic events is required for normal ovarian epithelium to generate malignant tumours. LOH on chromosome 1p was relatively common in benign, borderline and malignant tumours, while at 11p and 7q it was observed not only in invasive but also in borderline tumours. Moreover, 17q and 18q were affected mainly in advanced malignant tumours and revealed a high frequency of clonal intratumoral heterogeneity. We encountered different spectra of genetic alterations in primary tumours and their metastasis, which may be the results of intratumoral heterogeneity leading to dissemination in only some sub-clones.

[Intraoperative cytology of breast lesions]. / La cytologie extemporanée en pathologie mammaire.

Evaluation of intraoperative cytology and frozen sections for breast lesions is essential to single-stage and cost effective management. The aim of this study is to evaluate the diagnostic accuracy and the potential role of intraoperative cytology. The results of the study undertaken at the René Huguenin Center and the data of the literature suggest that intraoperative cytology may be helpful in some cases, especially as an adjunct to frozen sections. If frozen sections could be avoided any time clear features of benignity or malignancy are offered by both clinical data and macroscopic and cytologic examination, this approach does have limitations. Intraoperative cytology should not be used as an alternative to frozen sections except, in a few cases, when technical conditions required for them are not available or suitable. It can also constitute a good way for continuous education of our cytotechnologists.

Analysis of alterations adjacent to invasive vulvar carcinoma and their relationship with the associated carcinoma: a study of 67 cases.

A retrospective analysis of histological lesions adjacent to 67 invasive vulvar squamous cell carcinomas (SCC) was undertaken to analyse their nature, as well as their relationship to SCC. Patient age, clinical presentation and histological type of carcinoma, ISSVD classification of its adjacent lesions, disease-free and overall survival were reviewed. Severe undifferentiated vulvar intra-epithelial neoplasia (VIN3) was found in 19.4% of cases and vulvar lichen sclerosus (VLS) in 76.1% of cases. All VLS, except 2 cases, were associated with squamous cell hyperplasia (SCH), and a concomitant differentiated VIN was found in 76.6% of cases. Undifferentiated VIN3 was never associated with VLS. VLS was significantly associated with a keratinizing, well-differentiated SCC (98% of cases), while undifferentiated VIN3, was linked preferentially to 2 other types of SCC: in 77% of cases, a moderately-differentiated SCC with the same histological features as the so-called basaloid carcinoma and, in 23% of cases, a well-differentiated SCC with a variable extent of koilocytic atypia, similar to the so-called warty carcinoma. Carcinoma of the fourchette was more often associated with undifferentiated VIN3. Disease-free and overall survival were significantly better for carcinoma associated with undifferentiated VIN3 (p < 0.01 and p < 0.05, respectively). These findings suggest invasive vulvar SCC occurs on 2 distinct types of vulvar lesions: differentiated VIN and/or SCH associated with VLS and undifferentiated VIN3. Furthermore, the histological type of the carcinoma seems to differ according to adjacent lesions.

Angiosarcoma arising in a solitary schwannoma (neurilemoma) of the sciatic nerve.

Angiosarcomas rarely develop within a peripheral nerve or a peripheral nerve sheath tumor. We describe an epithelioid angiosarcoma that arose in a benign schwannoma (neurilemoma) of the right thigh in a 65-year-old man who did not have von Recklinghausen's disease. Histologically, the resected tumor was a high-grade undifferentiated sarcoma that was predominantly arranged in solid sheets or nests and composed of epithelioid cells. The endothelial origin of the tumor was suggested by Factor VIII R-ag, Ulex europaeus-I, CD34, CD31, BNH9, and vimentin immunoreactivity, along with the ultrastructural evidence of occasional Weibel-Palade bodies. In this location, epithelioid angiosarcoma should be distinguished from malignant transformation of a schwannoma with epithelioid changes. This observation stresses the importance of immunohistochemical and ultrastructural analysis in the differential diagnosis of vascular tumors with features of epithelioid sarcoma.

[An unusual way of manifesting acute granulocytic leukemia: granulocytic sarcoma of the breast. Apropos of a case with trisomy 22]. / Un mode inhabituel de révélation des leucémies aiguës granuleuses: le sarcome granulocytaire du sein. A propos d'un cas porteur d'une trisomie 22.

A case of granulocytic breast sarcoma in a 19 year-old-girl is reported. Surgical excision of the tumor was followed by radiotherapy of the breast and lymph nodes. Then 3 months later acute M2 myelocytic leukemia was diagnosed, complete remission being attained using rubidazone-cytarabine and maintained by monthly reinduction courses. Trisomy of chromosome 22 was present in leukemic cells and disappeared during remission. Its pathogenic significance is briefly discussed.