Search

BACKGROUND. Cutaneous vascular proliferations that occur in the field of prior radiotherapy include angiosarcoma and small, cutaneous lesions with a pseudosarcomatous pattern that previously were reported as atypical vascular lesions or benign lymphangiomatous papules. METHODS. The objective of this study was to investigate the clinicopathologic features and outcomes of 56 radiation-induced vascular proliferations that occurred in 36 patients who received previous treatment for breast carcinoma. Data from all patients were retrieved from the files of the French Sarcoma Group. Immunostaining with D2.40 antibody was performed in 24 lesions. RESULTS. All patients (median age, 52 years) had received external radiotherapy. Small papules developed within the field of prior radiotherapy (median latency interval, 66 months). Microscopically, the lesions were relatively well circumscribed, and they were located mostly in the superficial/middermis. They were composed of dilated or irregular-jagged vascular channels that were lined by a single layer of bland endothelial cells, and they demonstrated either a predominately lymphangioendothelioma-like or lymphangioma/lymphangioma circumscriptum-like growth pattern. Micropapillary tufts were common findings. Ten lesions showed additional cytologic and/or architectural atypia. Twenty of 24 lesions showed D2.40 positivity. Follow-up information was available for 31 patients (median follow-up, 48 months): Five women developed new cutaneous lesions, and 1 woman had spontaneous regression of her lesions. None of the patients developed cutaneous angiosarcoma. Five patients were lost to follow-up. CONCLUSIONS. Although vascular proliferations in irradiated skin may mimic angiosarcoma morphologically, the large majority of these lesions showed a benign clinical outcome. Despite relatively limited follow-up, the current results indicate the benign nature of these vascular proliferations. Cancer 2007. © 2007 American Cancer Society.

BACKGROUND. Clear cell sarcoma (CCS) is a rare tumor with a very poor prognosis that occurs predominantly in the distal extremities of young adults. Most patients bear the t(12;22) reciprocal translocation, which involves the EWS and ATF1 genes. The diagnosis of CCS usually is easy but may be challenging in unusual sites, and the detection of EWS-ATF1 fusion transcripts is helpful to rule out a metastatic melanoma. METHODS. Forty-four patients with CCS and 14 conventional melanomas were examined for the presence of EWS-ATF1 transcripts by using real-time polymerase chain reaction (PCR) analysis on paraffin embedded tissues, including frozen samples for 9 CCS samples and 9 melanoma samples. Prior to molecular analysis, the diagnosis of CCS was considered certain in 35 patients and as probable in 9 patients on the basis of location, histologic features, and immunohistochemical profile. Treatment modalities and follow-up were available for 41 patients with CCS. RESULTS. EWS-ATF1 fusion transcripts were detected in 38 paraffin embedded CCS tissues (86% of all samples; 93% of interpretable samples), 3 samples (7%) were negative, and 3 samples (7%) were considered uninterpretable. Fusion transcripts were detected in 7 of 9 samples for which the diagnosis of CCS was considered probable. EWS-ATF1 transcripts were not detected in the 14 samples of melanoma. Results from frozen tissues were concordant with those from all corresponding paraffin embedded samples. Twenty-eight of 41 patients (68%) experienced lymph node and/or distant metastasis, and the 5 year-survival rate was 44%. Mitotic index and histologic grade were predictive of survival and distant metastasis. CONCLUSIONS. The results of this study showed that the molecular detection of EWS-ATF1 fusion transcript by real-time PCR on paraffin embedded tissues is a sensitive and specific method for the diagnosis of CCS. It is an efficient tool for the diagnosis of unusual tumors, especially with regard to its distinction from melanoma. The current results also confirmed the poor prognosis for patients with this tumor type. Mitotic index and grade were predictive factors for survival and distant metastasis. Cancer 2006. © American Cancer Society.

Identification of the alveolar subtype of rhabdomyosarcoma (ARMS) is important, because the poor prognosis associated with this subtype necessitates a modified therapeutic regimen. At present, ARMS diagnoses are made on the basis of histologic findings and the extent of myogenin immunopositivity. Nonetheless, the absence of an alveolar pattern in the solid variant, the low degree of differentiation in certain embryonal rhabdomyosarcomas (ERMS), and the increasing use of microbiopsy samples make the diagnosis of ARMS somewhat difficult. Two specific translocations have been found in ARMS, and fusion transcripts can be detected by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of paraffin-embedded tissue (PET).To assess the value of myogenin staining and molecular testing in the diagnosis of rhabdomyosarcoma, the authors examined 109 rhabdomyosarcoma samples (45 ARMS samples and 64 ERMS samples). Real-time RT-PCR analysis of PET was performed in all 109 rhabdomyosarcomas, and RT-PCR analysis of frozen material was performed in 24 cases.PAX fusion transcripts were present in 44 cases (39 ARMS and 5 ERMS) and absent in 52 cases (2 ARMS and 50 ERMS). In 13 cases (4 ARMS and 9 ERMS), the results were not interpretable. Results were concordant between paired frozen and fixed tumor samples. All 35 interpretable ERMS samples that contained50% myogenin-positive cells failed to yield detectable PAX fusion transcripts. Of the 61 interpretable tumor samples (41 ARMS and 20 ERMS) that contained50% myogenin-positive cells, 44 (39 ARMS and 5 ERMS) yielded detectable PAX fusion transcripts.The current study demonstrates that molecular detection of PAX fusion transcripts via real-time RT-PCR analysis of PET is a sensitive and specific method for the diagnosis of ARMS and that immunohistochemical analysis of myogenin expression can be used to select cases for such molecular testing. Although RT-PCR analysis appears not to possess diagnostic value in tumors with50% tumor cell immunopositivity, it is strongly recommended for the diagnosis of tumors containing50% myogenin-positive cells.

BACKGROUND Heterologous carcinosarcomas of the urinary bladder are rare neoplasms, the histogenesis of which is still disputed. METHODS The clinicopathologic, immunohistochemical, and ultrastructural features of eight cases were analyzed. RESULTS The patients, 5 males and 3 females, had a median age of 70 years. Gross hematuria, dysuria, and urinary tract infections were the main presenting symptoms. Tumors were solitary in all cases and located in the right wall in six cases. Tumor size ranged from 2 to 12 cm (median, 5 cm). Four patients died of disease 2, 6, 17, and 42 months postoperatively, respectively. Microscopically, the tumors consisted mostly of a varied mixture of high grade transitional cell carcinoma with chondrosarcoma, osteosarcoma, rhabdomyosarcoma, and undifferentiated spindle cell (leiomyosarcoma-like) components with occasional transitional features between one component and another. All tumors but one invaded the muscularis propria or the perivesical fatty tissue. Immunohistochemically, keratin expression was observed focally in the sarcoma component as well as the carcinoma component. Reactivity for vimentin, desmin, muscle specific actin, and S-100 protein was observed in poorly differentiated areas in addition to the expected positivity of each histologic subtype of sarcoma. Ultrastructurally, one tumor showed evidence of both epithelial and chondrosarcomatous differentiation, whereas three contained rhabdomyosarcomatous elements. CONCLUSIONS On the basis of the current series and a review of 55 reports from the literature, primary heterologous carcinosarcoma of the urinary bladder proved to be a highly malignant type of neoplasm occurring predominantly in elderly males that was most often in an advanced stage at presentation and rapidly became lethal. Histogenetically, some heterologous carcinosarcomas should be regarded as a variant of sarcomatoid carcinoma (metaplastic carcinoma) that shows prominent heterologous differentiation. Cancer 1998;82:1535-49. © 1998 American Cancer Society.

BACKGROUND. Malignant mixed mesodermal tumors (malignant mixed Mullerian tumors [MMMT]) occur rarely in extragenital sites. METHODS. The authors analyzed the clinical, pathologic, and immunohistochemical features of three cases of primary MMMT of the female peritoneum. RESULTS. The neoplasms occurred in 60-, 64- and 84-year-old women and arose from pelvic peritoneum. Two patients died with disseminated disease 8 and 24 months postoperatively. The third died of cardiac failure 12 months postoperatively with questionable metastatic disease. Microscopically, two tumors were of the heterologous type, containing foci of rhabdomyosarcomatous (case 1) and chondrosarcomatous (case 3) differentiation. Immunohistochemically, coexpression of keratin and vimentin was observed focally in both carcinomatous and sarcomatous components in all three neoplasms, whereas coexpression of low molecular weight cytokeratin, vimentin and actin was observed focally in case 2. Rhabdomyosarcomatous areas were positive with desmin and actin, and chondrosarcomatous areas for S-100 protein. Both epithelial and mesenchymal components were positive for alpha-1 antichymotrypsin in all cases. CONCLUSIONS. On the basis of the present cases and a review of 15 reports from the literature, primary MMMT of the female peritoneum proved to be a rare but highly malignant neoplasm occurring in elderly postmenopausal women. Of 15 patients with available follow-up, 12 died with disease, mostly within 1 year, regardless of the initial tumor stage, histology (homologous versus heterologous MMMT) or treatments attempted. The tumor developed within pelvic peritoneum in half the cases. Histogenetically, peritoneal MMMT are thought to represent "metaplastic" carcinomas originating from the secondary Mullerian system

BACKGROUND The t(X;18) translocation is a specific marker of synovial sarcomas (SS). Detection of SYT-SSX transcripts by polymerase chain reaction (PCR) was tested on preselected specimens of well-established histologic types, but to our knowledge, the diagnostic utility of molecular assays on a series of potential SS in comparison with conventional tools has never been reported. METHODS Two hundred four consecutive cases of potential SS submitted for a second opinion were studied prospectively. On the basis of clinical context, histologic aspect, and immunohistochemical profile, the tumors were divided into three categories: 1) diagnosis of SS certain, when the only possible diagnosis was SS; 2) diagnosis of SS probable, when SS was the first diagnosis contemplated, but a differential diagnostic issue was raised by other tumors; 3) diagnosis of SS possible, when the diagnosis of SS was not the first diagnosis considered. Detection of SYT-SSX transcripts was performed using real-time PCR from fixed, embedded tissue as a systematic test. RESULTS Sufficient RNA samples were recovered for PCR from 177 specimens (87%). One hundred four specimens (51%) were positive for SYT-SSX transcripts. Tumor sites of SS included the extremities (n = 57), lung (n = 13), trunk wall (n = 12), head and neck (n = 6), and other sites (n = 16). There were 61 monophasic, 22 poorly differentiated, 17 biphasic, and 4 predominantly epithelial SS. For 58 tumor specimens (29%), diagnosis of SS was certain before molecular testing; 49 (84.5%) of these 58 contained SYT-SSX transcripts. For 39 tumor specimens (19%), diagnosis of SS was probable; 29 (74.4%) of these 39 contained SYT-SSX transcripts. For 107 tumor specimens (52%), diagnosis of SS was only possible and strongly challenged by another histologic type. The issue consisted mainly of making the distinction between an SS and a poorly differentiated spindle cell sarcoma (n = 49), a poorly differentiated round cell sarcoma (n = 34), a carcinoma (n = 11), a myoepithelioma (n = 8), or an epithelioid fibrosarcoma (n = 5).Twenty-six tumor specimens (24.3%) contained SYT-SSX transcripts—10, 7, 5, 3, and 1 in the spindle cell tumor, round cell tumor, carcinomalike tumor, myoepitheliomalike tumor, and epithelioid-fibrosarcoma-like tumor categories, respectively. CONCLUSIONS Molecular testing was not required if the diagnosis of SS was certain or probable on the basis of clinical, histologic, and immunohistochemical evaluation. However, it proved to be very helpful or necessary when the diagnosis of SS was only possible and was challenged by other tumor types, mainly other spindle cell sarcomas, round cell sarcomas, carcinomas, myoepitheliomas, and epithelioid fibrosarcomas. Cancer 2003;98:2700–7. © 2003 American Cancer Society.

BACKGROUND CD9 has been implicated in cell adhesion, motility, and proliferation, and numerous studies have demonstrated its prognostic value in different solid tumors. The objective of this study was to determine the relation of CD9 expression to tumor grade and tumor stage of urothelial carcinoma of the bladder and to define the value of CD9 in predicting the behavior of superficial papillary tumors (SPTs) (pathologic Ta [pTa] and pT1). METHODS Three hundred twenty patients (118 patients with pTa tumors, 111 patients with pT1 tumors, and 91 patients with pT2 tumors) were examined for CD9 expression using immunohistochemistry applied on formalin fixed, paraffin embedded tissue. Patients were stratified into 3 categories, depending on CD9 expression: positive (> 50% positive cells), reduced (5–50% positive cells), or negative (< 5% positive cells). RESULTS Loss of CD9 expression was found to be associated significantly with high-grade and high-stage urothelial tumors (P < 0.0001). A reduced/negative (altered) CD9 expression was associated with SPT progression, but not with recurrence (P < 0.001). Patients who had pTa or pT1 tumors with altered CD9 expression had a relative risk of 5.59 (P = 0.005; 95% confidence interval [95% CI], 1.69–18.48) for progression compared with patients who had tumors with positive CD9 expression. Kaplan–Meier curves showed that a lack of CD9 expression was associated significantly with progression free survival (P < 0.001; log-rank test), but not with recurrence. In patients with SPTs, multivariate Cox proportional hazards regression analysis revealed that negative CD9 expression was an independent prognostic marker for the prediction of tumor progression (P = 0.007; 95% CI, 0.11–0.70). CONCLUSIONS In patients with urothelial bladder carcinoma, CD9 expression was associated significantly with tumor stage and grade, and a loss of CD9 expression was an independent prognostic factor for predicting progression in patients with SPTs. Thus, CD9 immunoexpression is a potential new predictor of tumor behavior in patients with SPTs of the urinary bladder. Cancer 2003. © 2003 American Cancer Society. DOI 10.1002/cncr.11698

BACKGROUND Histologic grade is said to be the most important prognostic factor in adult soft tissue sarcomas (STS), but most grading systems have been tested in the overall sarcoma group and the predictive value of histologic grade needs to be assessed specifically for each of the histologic categories. METHODS From 1980 to 1994, 1240 nonmetastatic patients were entered in the French STS database. The following parameters were studied: patient's age and gender, previous history, tumor location, size and depth, neurovascular or bone involvement (NBI), histologic type and subtype, and grade (the French Federation of Cancer Centers [FNCLCC] system). Median follow-up for the survivors was 88 months; only 5% of patients were lost to follow-up. The authors performed univariate and multivariate analyses for metastasis-free survival for the overall sarcoma group and for every main histologic type. RESULTS In order of importance, parameters were respectively retained as independent predictors of metastasis as follows: grade, tumor size, NBI and tumor depth for the overall group, grade and NBI for malignant fibrous histiocytomas (n = 349), tumor size, histologic subtype and grade for liposarcomas (n = 188), NBI, grade and tumor size for leiomyosarcomas (n = 148), grade and NBI for synovial sarcomas (n = 125), grade for unclassified sarcomas (n = 140), and sarcomas of other types (n = 158). No parameter was significant for malignant schwannomas (n = 72) or for rhabdomyosarcomas (n = 60). CONCLUSION In this study, histologic grade appeared as an independent predictor of metastasis development in the main histologic types of adult STS, with the exception of malignant schwannomas and rhabdomyosarcomas. Cancer 2001;91:1914–26. © 2001 American Cancer Society.