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Extra-osseous chondrosarcoma. Report of five cases and review of the literature.

In this paper we present five new cases and review sixty-one reported cases of extra-osseous chondrosarcoma. The lesion has a predilection for middle-aged men and for localization in the extremities. The mild and delayed nature of the symptoms contributes to delayed or inadequate treatment and an unusually high over-all recurrence rate of 50 per cent. En bloc resection is the treatment of choice. Amputation should be reserved for large tumors with extensive or intra-articular invasion, osseous erosion, or major neurovascular involvement. Pulmonary lobectomy appears to be effective in treating localized pulmonary metastasis. Chemotherapy and radiotherapy can also provide palliative benefits to patients with widespread metastases. Nearly all (77.8 per cent) of the known disease-related fatalities took place during the first year after operation on the primary tumor. The over-all five-year survival rate most likely is less than 81.2 per cent.

Adolescent↗

[The diagnosis and treatment of bladder cancer metastases].

The study included 27 patients with regional and distant metastases of bladder cancer. Regional and distant metastases were detected in 12 (44.4%) and 15 (55.6%) patients, respectively. Basic treatment consisted in chemotherapy (MVAC scheme) which combined with reaferon immunotherapy. Chemoimmunotherapy in combination with radiotherapy was used in 8 patients to relieve pain caused by the metastases. The response was seen in 37% of patients with regional metastases and 22% of patients with distant ones. The former and the latter were followed up for 15.9 and 9.3 months, respectively.

Adult↗

Photodynamic therapy of orthotopic prostate cancer with benzoporphyrin derivative: local control and distant metastasis.

This is the first report of photodynamic therapy (PDT) in an orthotopic prostate tumor model and shows that PDT combined with surgery (tumor bed sterilization) gave significant local control of the primary tumor and significant reduction in distant metastases. By contrast, either treatment alone (surgery or PDT) gave relatively poorer local control, and PDT gave a significant increase in the mean number of lung metastases. The MatLyLu variant of the Dunning 3327 rat prostate cancer cell line, which has been selected to be metastatic to lymph nodes and lungs, was injected into the ventral lobe of the rat prostate. After 7 days, tumors were either treated by surgical removal of the ventral lobe, PDT with liposomal benzoporphyrin derivative monoacid ring A, or a combination of surgery, followed by PDT of the tumor bed. Results after 21 days showed a reduction in prostate tumor weight in all groups compared with controls, which became highly significant only for the combination group (17% of control mean tumor weight; P < 0.001; 7 of 13 clinical complete responses). The combination treatment also led to a reduction in lymph node metastasis and reductions in both the frequency and mean number of lung metastases compared with other treatment groups. The PDT-alone group, however, had a mean number of lung metastases per animal, which was nine times the control group and 34 times the combination group. These findings suggest that a tumor bed sterilization approach may be promising for locally advanced prostate cancer and suggest that factors other than local control may need to be evaluated when considering PDT for primary prostate cancer.

Adenocarcinoma↗

Pyrimidine nucleoside phosphorylase activity in normal tissues of the uterus and ovary and in benign and malignant lesions of these organs.

BACKGROUND: Pyrimidine nucleoside phosphorylase (PyNPase) is identical to the protein, platelet-derived endothelial cell growth factor (PD-ECGF), which has angiogenic activity. The physiological roles of PyNPase activity in the uterus and ovary are not known. In this study, we measured PyNPase activity in normal tissues of the uterus, ovary, and lymph nodes, and in benign and malignant lesions of these organs, and we considered the clinical implications of PyNPase activity in the uterus and ovary. METHODS: Tissue samples were obtained from 163 patients (whose diseases are listed below) during surgery. PyNPase activity was measured spectrophotometrically, by monitoring the formation of 5-fluorouridine. RESULTS: Mean PyNPase activity in tissues from the lesions of patients with cervical cancer (n = 20), uterine endometrial cancer (n = 26), leiomyoma (n = 23), ovarian cancer (n = 46), ovarian endometriosis (n = 21), and benign epithelial ovarian tumor (n = 27) was significantly greater than that in the corresponding normal tissues. The PyNPase activity in the normal endometrium was significantly higher in the secretory phase than in the proliferative phase. The activity in normal or metastatic lymph nodes was significantly greater than that in normal tissues of the uterus and ovary. Mean PyNPase activity in cancerous cervical tissues was significantly greater than that in cancerous endometrial tissues or cancerous ovarian tissues. There were no significant differences in PyNPase activity in cervical cancer, endometrial cancer, and ovarian cancer tissues according to tumor stage. The enzyme activity appeared to be greater in histopathological G3 grade endometrial cancer than in G1 and G2 endometrial cancer. The enzyme activity in mucinous adenocarcinoma of the ovary was significantly lower than that in serous, endometrioid, and clear cell adenocarcinomas. All patients with cervical squamous cell carcinomas with PyNPase activity greater than 500 nmol/min per mg protein exhibited lymph node metastasis. CONCLUSION: Increased PyNPase activity consistently reflected neoplastic growth, and varying levels of activity were seen in different histologic cell types. This enzyme activity may be involved in cervical squamous cell carcinomas, in normal and metastatic lymph nodes, and in the normal, secretory phase in the endometrium.

Adenocarcinoma, Mucinous↗

An immunohistochemical study of P53 and Ki-67 in gastrointestinal adenoma and adenocarcinoma using tissue microarray.

BACKGROUND: Gastrointestinal carcinogenesis generally follows the adenoma-adenocarcinoma sequence and tumor metastasis determines the survival time of the patients. The expressions of p53 and ki-67 in gastrointestinal adenoma and adenocarcinoma (GIA) were explored and their clinicopathological significance determined. MATERIALS AND METHODS: The expressions of mutant p53 and ki-67 were examined on tissue microarray containing GIA, adjacent mucosa or adenoma and metastases by immunostaining. Their expressions were compared with the clinicopathological parameters of tumors. RESULTS: The expressions of mutant p53 and ki-67 were gradually increased from gastrointestinal mucosa to adenocarcinoma through adenoma (p<0.05). Mutant p53 expression showed a positive association with depth of invasion, local invasion via vessels and lymph node metastasis of GIA (p<0.05). Ki-67 expression was positively correlated with local invasion via vessels and negatively with dedifferentiation and liver metastasis of GIA (p<0.05). The expressions of both markers in metastases of GIA were consistent with their corresponding primary foci (p < 0.05). A positive association between both markers was found in the primary foci of GIA (p<0.05). CONCLUSION: The up-regulated expressions of mutant p53 and ki-67 are involved in the carcinogenesis and progression of GIA. They appear to be objective and effective markers to reflect the development of GIA.

Adenocarcinoma↗

The expression of five different claudins in invasive breast carcinomas: comparison of pT1pN1 and pT1pN0 tumors.

The evaluation of the role of claudins (CLDNs) in breast carcinogenesis has recently begun. We investigated the expression of CLDNs 1, 2, 3, 4, and 7 in pT1pN0 and pT1pN1 invasive ductal breast carcinomas. Tissue arrays of 30-30 pT1pN0 and pT1pN1 invasive ductal breast carcinomas of different grades were constructed, and the expression of CLDN 1, 2, 3, 4, and 7 proteins was analyzed using standard and immunofluorescent immunohistochemistry. The results were evaluated by light and confocal microscopy. Regarding CLDN 1, 4, and 7 expressions, differences were noted between normal and tumor cells and also between tumors of different grades, while no remarkable differences were noted between pT1pN0 and pT1pN1 tumors. CLDNs 1 and 7 were found to be downregulated in tumor cells compared to the normal epithelium, while CLDN 4 expression was decreased in grade 1 tumors. CLDN 7 protein was abundant in normal epithelia, and the staining decreased in grade 3 tumors. There were no differences between normal and neoplastic cells regarding CLDN 2 and 3 expressions. As a preliminary result, our observations suggest that the analyzed CLDNs do not promote tumor metastasis. On the basis of our findings, it seems that CLDN 1, CLDN 4, and CLDN 7 may rather have an important role in tumorigenesis or in cell-to-cell adhesion.

Axilla↗

Malignant fibrous histiocytoma of soft tissue. A population-based epidemiologic and prognostic study of 137 patients.

Epidemiology and prognosis were analyzed in a consecutive, population-based series of 137 patients with malignant fibrous histiocytoma of soft tissue in the extremities and trunk wall, with a complete follow-up of minimum 3 years. All but one patient were treated by surgery in 28 cases combined with adjuvant radiotherapy or chemotherapy. The annual incidence was 0.42/10(5). The ratio men to women was 1.1. The median age was 64 years (range, 22 to 87 years). The thigh was the most common location. The median size was 6 cm. Superficial tumors constituted 43% and were smaller than deep-seated tumors. Eighty-three tumors were storiform-pleomorphic, 53 were myxoid, and one was of inflammatory type. The myxoid tumors were smaller and more often superficial. The cumulative 5-year survival rate for all patients was 0.7, but differed markedly between the histologic types; it was 1.0 in patients with myxoid tumors and 0.5 in patients with storiform-pleomorphic tumors. In the 77 patients with storiform-pleomorphic tumors without metastases at presentation, only tumor size larger than 10 cm and tumor necrosis independently impaired survival. The 23 patients who had none of these risk factors had a 5-year survival rate of 0.8.

Adult↗

A multivariate analysis of the prognosis after surgical treatment of malignant soft-tissue tumors.

Ninety-seven patients who had received their primary and definitive surgical treatment for a soft-tissue sarcoma during the years 1956--1976 were studied with respect to local recurrence, metastasis, and survival. The aim of the treatment was to eradicate the tumor while preserving good function. The influence of host and tumor properties and different diagnostic and surgical procedures on the prognosis was studied by means of nonparametric multivariate analysis. Ninety-four percent of the tumors were located in the extremities. Malignant fibrous histiocytoma was the most common histologic type. A four-grade scale of histologic malignancy was used. Eighty-eight percent of the tumors were Grade III or IV. In 85% of the patients with an extremity lesion, local extirpation was carried out. The overall local recurrence rate was 21.7% and in 76 patients who underwent an adequate surgical procedure it was 6.6%. The overall five-year survival rate was 59%. The survival depended on the local control of the primary tumor, which was related to the adequacy of the surgical procedure and to the histologic grade of malignancy. No patient with a Grade I or II tumor died. The five-year survival rate for patients with Grade III tumors was 68% and for patients with Grade IV tumors 47%.

Adolescent↗

Malignant vascular tumors in young patients.

BACKGROUND: To the authors' knowledge there are few published series of malignant vascular tumors in patients age < or = 21 years. METHODS: The authors retrospectively documented the clinical presentation, pathology, treatment, and outcome of patients age < or = 21 years with malignant vascular tumors treated between 1970-1995 at Memorial Sloan-Kettering Cancer Center. The histologic sections were rereviewed to confirm the diagnosis. RESULTS: Four patients were identified with angiosarcoma and two with malignant hemangioendothelioma. Five patients were female and one was male; the median age at diagnosis was 11.8 years (range, 8 months-21 years). The tumor involved the skin in one patient, soft tissue in one patient, bone in two patients, and internal organs in two patients. One patient had associated diffuse angiomatosis and another had the Klippel-Trenaunay-Weber syndrome. This patient received prior radiation therapy to the primary site with the subsequent development of a vascular sarcoma. None of the patients had distant metastases at diagnosis. Resection was attempted in five patients and completed in four. Chemotherapy alone was given to three patients whereas radiation therapy alone and radiation plus chemotherapy were administered to one patient each. The median follow-up was 4.9 years (range, 1 month-12 years). There were three deaths from progressive disease and two deaths from locoregional recurrences. Reexcision and radiotherapy controlled one local recurrence. Another patient developed recurrence to regional lymph nodes and further dissemination. The primary tumor in all three survivors was excised completely whereas two of the three patients who died of progressive disease underwent an incomplete excision or biopsy alone. CONCLUSIONS: Malignant vascular tumors are rare in the first two decades of life and when they do occur are very aggressive. Complete resection is curative for patients with localized lesions.

Adolescent↗

DNA image cytometry on sections as compared with image cytometry on smears and flow cytometry in melanoma.

DNA measurements of 130 melanomas were carried out by flow cytometry (FCM) and image cytometry (ICM). ICM was applied to cytological preparations of fresh material (cICM) and to sections of formalin-fixed paraffin embedded tissue (sICM). The DNA ploidy, the DNA index of G0/G1 peaks (DI), and the proliferation index (PI) were used to compare all the methods. The following parameters reflecting malignancy were calculated only from ICM histograms: the 5c exceeding rate (5cER) and the malignancy grade (MG). In cases found to be DNA aneuploid by FCM, the PI values (FCM versus cICM) and the DIs (between all methods) showed a high correlation, and the concordance in relation to the DNA ploidy status was 96% (FCM versus cICM) and 94% (FCM versus sICM). However, we ascertained essential differences between FCM and ICM in melanomas classified as DNA diploid by FCM. The concordance in DNA ploidy was only 66% (FCM versus cICM) and 64% (FCM versus sICM). In contrast, cICM and sICM yielded similar results in most cases. With the exception of the near diploid range, ICM is superior to FCM in detecting DNA aneuploidy. In particular, DNA tetraploid stem lines can easily be overlooked by FCM. Therefore, DNA measurements of tumours judged to be DNA diploid by FCM must be verified by ICM. ICM on sections proved to be applicable and yielded reliable results provided that a suitable thickness was used, and the measuring of sectioned and overlapping nuclei was largely avoided by careful focusing in either direction.

Aneuploidy↗

Soft tissue leiomyosarcoma. A population-based epidemiologic and prognostic study of 48 patients, including cellular DNA content.

BACKGROUND: Leiomyosarcoma of soft tissue is a rare tumor. There are different opinions regarding epidemiology and prognosis. METHODS: Epidemiology and prognosis were analyzed in a consecutive, population-based series of 48 patients with subcutaneous and deep-seated leiomyosarcoma in the extremities and trunk wall with a complete follow-up of a minimum of 3 years. Cutaneous tumors were not included. RESULTS: The annual incidence was 0.13/10(5). The ratio of men to women was 1.2, and the median age was 65 years. The thigh was the most common location. Almost half of the tumors were subcutaneous. The median tumor size was 6 cm (range, 1-25 cm). All patients were treated with surgery, and in 19 cases it was combined with adjuvant radiation therapy or chemotherapy. The cumulative 5-year survival rate was 64%. Multivariate analysis indicated that age of 60 years or greater (relative risk [RR] = 8) and intratumoral vascular invasion (RR = 4) were independent risk factors for death resulting from tumor. DNA aneuploidy (RR = 4) and tumor necrosis (RR = 3) were associated with poor prognosis, but did not reach statistic significance. CONCLUSIONS: Advanced age, vascular invasion, and DNA aneuploidy could be used to identify prognostic subgroups.

Adult↗

[Relationship between tissue inhibitors of metalloproteinase and metastasis and prognosis in breast cancer].

OBJECTIVE: To investigate the clinical significance of tissue inhibitors of metalloproteinase (TIMP) -3 and TIMP-4 in human breast cancer. METHODS: The levels of TIMP-3 and TIMP-4 mRNA in paraffin-embedded breast carcinoma specimens from 70 patients with primary invasive breast cancer who had undergone radical mastectomy from January of 1984 to December of 1985 were assessed by in situ hybridization assay. Intratumoral microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression were detected by the standard streptavidin biotin peroxides method. RESULTS: Both TIMP-3 and TIMP-4 mRNA expressions were higher in patients with axillary lymph node metastasis than in those without metastasis (P < 0.01), and patients with higher expression of any of these two genes had a better prognosis than those with lower expression (P < 0.01). We introduced lymph node status, TNM staging, MVD and VEGF expression, plus TIMP-3 and TIMP-4 to the Cox's proportional hazards regression model for significant analysis, and found that the TIMP-3, TNM staging and MVD play an important role in prognosis of this group. CONCLUSIONS: TIMP-3 and TIMP-4 are correlated with metastasis in breast cancer, and TIMP-3 demonstrates an independent prognostic factor for the patients. These results provide a valuable clue for developing new, practical prognosticators in breast cancer patients.

Breast Neoplasms↗

Detection of malignant soft tissue tumors in bone imaging.

A total of 2530 consecutive bone scans were examined to evaluate the number and the type of soft tissue neoplasms detected with bone-seeking phosphonates. Sixty-eight primary or secondary soft tissue neoplasms of 63 patients accumulated 99mTc -methylene diphosphonate and 2 accumulated 99mTc -diphosphonate, and one metastasis was seen as a nonactive 'cold' focus in the urinary bladder. The localization of tumors was: 19 in the lung, 15 in the liver, 11 in the kidney, 10 in the peritoneal cavity or ascites, 5 in the large bowel, 4 in the vascular or lymphatic system, 3 in the connective tissue or muscles, 2 in the ovary, 1 in the urinary bladder, and 1 in the brain. Our results differ in many respects from those reported in the literature. The causes of the differences are discussed.

Abdominal Neoplasms↗