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DNA-content in endometrial carcinoma of tamoxifen-treated breast cancer patients.

DNA measurements and histopathologic evaluation were performed in 17 patients treated with adjuvant tamoxifen for early breast cancer and who developed endometrial carcinoma during or after the tamoxifen therapy. The tumors were exclusively characterized by euploid DNA content except for two cases, one mixed mesodermal sarcoma, a highly malignant and rare tumor, and one adenocarcinoma. Although the use of adjuvant tamoxifen therapy most likely enhances the risk of developing endometrial carcinoma, the beneficial effects of adjuvant breast cancer treatment is of well-known clinical importance. The hazards of giving long-term tamoxifen seem to be low since the endometrial tumors were associated with low-grade malignancy and euploid DNA pattern.

Journal Article↗

Malignant mixed müllerian tumor of the extraovarian secondary müllerian system. Report of two cases and review of the English literature.

OBJECTIVE: To report two cases of malignant mixed müllerian tumor of the extraovarian secondary müllerian system and to identify cases reported in the English literature. DESIGN: Two cases are described and discussed along with cases reported previously in the English literature. SETTING: The University of Cincinnati Medical Center. PATIENTS: (1) A 62-year-old woman with a bilateral ovarian poorly differentiated endometrioid adenocarcinoma with multiple peritoneal metastasis and a malignant mixed müllerian tumor with heterologous elements arising from the pelvic peritoneum. (2) An 83-year-old woman with a malignant mixed müllerian tumor with heterologous elements arising from the cecal peritoneum. RESULTS: Seventeen previously reported cases were identified in the English literature. CONCLUSIONS: The malignant mixed müllerian tumor of the extraovarian secondary müllerian system is a rare disease with only 17 cases reported to date to our knowledge. The prognosis is poor. Of 12 patients with follow-up information available, 10 died within 1 year and 2 within 2 years after diagnosis. The histogenesis of the tumor remains unclear; however, data exist that support transformation of epithelial neoplastic cells into sarcomatous cells (metaplastic theory) and origin from a single totipotential cell. It is possible that both situations may occur.

Adenocarcinoma↗

[Radiotherapy in the treatment of uterine sarcomas].

OBJECTIVE: To study radiotherapy in the treatment of uterine sarcomas and response to radiation in primary or recurrent uterine sarcomas. METHODS: A total of 102 uterine sarcomas treated in the Cancer Hospital from May 1960 to June 1999. A retrospective review of 45 patients receiving surgery alone, 29 patients for postoperative radiotherapy, 4 radiotherapy alone, 24 recurrent sarcomas receiving radiotherapy. RESULTS: The 5-year overall survival for 45 patients treated with surgery alone and 29 patients managed by postoperative radiotherapy were 56.7% and 58.6% respectively (P > 0.05). The addition of radiotherapy significantly reduced the local recurrence rate from 42.2% to 20.7% (P < 0.05). The tumor was disappeared completely by treatment of radiotherapy alone in 3 patients of primary uterine cervix sarcomas. 1 patient was free of disease at 36 months. Other 2 patients died 9 and 11 months later because of distant metastases. The complete and partial response rate of radiotherapy was 50.0% for recurrent tumors. The radiotherapeutic sensibility of endometrial stromal sarcomas, mixed mesodermal sarcomas and leiomyosarcomas was downward tendency in turn. CONCLUSIONS: The postoperation adjuvant radiotherapy reduced the pelvic recurrent significantly. Radiotherapy should be used in the treatment of uterine sarcomas as an important part of combination therapy.

Female↗

A comparison of acridine orange and Feulgen cytochemistry of human tumor cell nuclei.

Specimens of cells derived from tumors of the human female genital tract plus normal cells as standards have been divided into aliquots and stained according to acridine orange or pararosanilin:Feulgen procedures. Acridine orange-stained cells were slit-scanned for 535 nm nuclear fluorescence; Feulgen-stained cells were comb-scanned for 580 nm nuclear absorbance. For each specimen examined, the tumor cell:normal cell ratio of mean nuclear fluorescence following acridine orange staining was greater than the tumor cell:normal cell ratio of mean nuclear absorbance following Feulgen staining. The tumor cell:normal cell ratio of mean nuclear fluorescence ranged from 2.3 for a nonkeratinizing squamous cell carcinoma to 3.9 for a keratinizing squamous cell carcinoma. The tumor cell:normal cell ratio of mean nuclear absorbance ranged from 1.4 for a mixed mesodermal sarcoma to 2.3 for a small cell squamous cell carcinoma. These results indicate that the elevated nuclear fluorescence intensity from acridine orange-stained tumor cells cannot be explained solely on the basis of elevated Feulgen:DNA content. An alternative hypothesis, consistent with these results, is that DNA is the principal binding substrate for intranuclear acridine orange and that the DNA of certain tumor cells is more accessible to acridine orange than is the DNA of normal cells.

Acridines↗

Fine-needle aspiration of inguinal lymph nodes in gynecologic practice.

Palpable inguinal lymph nodes are a common finding in gynecologic patients. Assessment of such nodes is especially important in the clinical staging of pelvic cancers. To determine the accuracy, safety, and usefulness of fine-needle aspiration in this setting, we retrospectively reviewed pathologic and clinical data from 62 consecutive aspirates of inguinal lymph nodes in 48 gynecologic patients, of whom 42 had cancer. Aspirates from 37 patients yielded diagnostic material. Aspirated tumor cells consistently reflected the primary tumor histology. Tumors included carcinomas of the vulva, vagina, and cervix, and carcinomas and mixed mesodermal cancers of the corpus and ovary. Node excision and clinical observations provided adequate follow-up for 19 positive and 15 negative aspirates, and identified no false positives and two false negatives. The role of fine-needle aspiration varied with the tumor type and stage. It provided the first microscopic diagnosis of cancer in six patients and the first diagnosis of metastasis in six others. Decisions concerning surgery, radiation ports, and chemotherapy frequently depended on the results of fine-needle aspiration. There were no complications from the procedure. Fine-needle aspiration is an accurate, safe, and useful method for assessing clinically suspicious inguinal nodes.

Biopsy, Needle↗

Radiotherapy in the treatment of uterine sarcomas. A retrospective analysis of 54 cases.

BACKGROUND: In the general population, uterine sarcoma (US) is an uncommon tumor, which accounts for approximately 1-3% of all uterine neoplasms. Its biological behavior is characterized by hematogenous metastases and local recurrent growth including the pelvis and peritoneal cavity. In the management of US, surgery is the primary form of treatment. Up to now the role of adjuvant radiotherapy has not been clearly established. PATIENTS AND METHODS: We report about 54 patients with US treated from 1954 to 1994 by surgical resection alone (22) or a combination of surgery and irradiation (32) and evaluate the influence of histology, stage and different treatment options on survival. RESULTS AND CONCLUSIONS: Our data indicate an increased disease-free survival for patients treated with adjuvant radiotherapy, especially if poor prognostic factors are present (advanced tumor stage, histopathological grade II or III of leiomyosarcoma and mixed mesodermal sarcoma). Postoperative irradiation using doses between 50 and 60 Gy is recommended, in selected cases brachytherapy should be added. Prospective multicentric trials including a statistically evaluable number of patients are necessary to further clarify the role of multimodality treatment programs for US.

Disease-Free Survival↗

[The stromal and myogenic sarcomas of the uterus (author's transl)].

Stromal sarcomas of the uterus generally originate as homologous tumors from endometrial stromal cells with fixed potentialities. They may be composed of one type of cell or of several types, or rarely they may consist only of endometrial granulocytes. From the same source but with a more favorable prognosis is endolymphatic stromatosis, which arises primarily in the myometrium but does not diffusely invade it, as the stromal sarcoma does. By contrast, heterologous malignant mesenchymal mixed tumors of the endometrium originate from Müllerian epithelium derived fro the mesoderm, and are therefore pluripotential. In this group we find rhabdomyosarcomas and chondroblastomas which have a very poor prognosis. The myogenic sarcomas are three times more common, and arise from smooth muscle cells of the myometrium or its blood vessels. The degree of nuclear pleomorphism may vary considerably, from normal to giant cell types, and may differentiate also as clear-cell myoblasts. They portend a somewhat more favorable prognosis than the stromal sarcomas.

Endometrium↗

Mixed mesodermal sarcoma of the ovary. Treatment with combination radiation therapy and chemotherapy.

Twenty patients with mixed mesodermal sarcoma of the ovary treated at the M. D. Anderson Hospital and Tumor Institute in Houston, Texas are reviewed. This report focuses on 12 patients treated post-operatively with combination radiation therapy and chemotherapy with vincristine, dactinomycin, and cyclophosphamide (VAC). There were 4 patients achieving complete tumor control, including one who is alive without disease beyond 5 years and 3 who died of unrelated causes without disease at autopsy. One other patient had a significant disease-free interval of 18 months. Compared to previous reports, combination radiation and VAC chemotherapy appears effective in this disease. Due to the observed myelosuppression and gastrointestinal and neurologic toxicities, however, treatment modifications have been recommended.

Adult↗

Cisplatin therapy for disseminated mixed mesodermal sarcoma of the uterus.

Eighteen patients with metastatic mixed mesodermal sarcoma of the uterus received cisplatin therapy at the University of Texas (UT) M.D. Anderson Hospital and Tumor Institute at Houston. The dose of cisplatin varied from 75 mg/m2 to 100 mg/m2. Previous therapy included surgery in 11 patients, radiotherapy in two patients, and surgery plus radiotherapy in four patients. One patient had no prior therapy. Seven patients had also received prior chemotherapy with doxorubicin. Of 12 patients with measurable disease, one (8%) had a complete response and four (33%) had a partial response for an overall response rate of 42%. The median progression-free survival of patients treated with cisplatin as first- and second-line therapy was 4.5 and 5.5 months, respectively. Cisplatin demonstrated moderate activity with mild toxicity in this group of patients with metastatic mixed mesodermal uterine sarcomas. Further studies including cisplatin-containing combination regimens seem to be warranted.

Aged↗

Three-dimensional culture of a mixed mullerian tumor of the ovary: expression of in vivo characteristics.

The Rotating-Wall Vessel (RWV) is a novel in vitro cell culture system used to successfully culture a cell line derived from a heterologous mixed mullerian tumor cell of the ovary. Although the original tumor was comprised of both epithelial and mesodermal components, long-term culture in conventional flasks established a cell line from this tumor with homogeneous epitheliallike growth characteristics (1). Cells from Passage 36 were seeded into a Rotating-Wall Vessel containing Cytodex-3 microcarrier beads. Scanning electron micrographs of tumor cells cultured for 32 d in the RWV showed the presence of heterogeneous cell populations organized into three-dimensional tissuelike architecture. Immunocytochemical analysis confirmed the cellular heterogeneity, as demonstrated by expression of both epithelial and mesenchymal antigens. Reverse transcription polymerase chain reaction amplification demonstrated the presence of mRNA for cellular oncogenes HER-2/neu, H-ras, K-ras, and tumor suppressor p53. Thus, there are two advantages to propagation of tissue in the RWV culture system:(a) tissue diversification representing populations present in the original tumor, and (b) the three-dimensional freedom to organize tissues morphologically akin to those observed in vivo. These data indicate that the RWV culture system is suitable for generating large quantities of ovarian tumor cells in vitro that are amenable to immunocytochemical, oncogenic, morphologic characteristics demonstrated in vivo.

Bioreactors↗

A mixed tumor of the omentum majus in an adult with discussion related to hepatoblastoma.

A mixed tumor of the omentum majus found at autopsy of a 28-year-old man with a huge liver tumor is described. The primary tumor was identified in the omentum majus by macroscopic, histologic and electron-=microscopic observations. The tumor was finally diagnosed as a mixed tumor which resembled a hepatoblastoma consisting of immature and embryonal types of epithelial component and of mesodermal tumor including hemangioma, osteoid and myxomatous tissues in the primary lesion. Widespread multiple metastases of the epithelial component mainly to the liver, and partially in the lungs, diaphragm and lymph nodes were noted. The levels of alpha-fetoprotein and carcinoembryonic antigen were within normal limits, but the epithelial component showed a resemblance to primitive hepatocytes. This tumor was discussed related to hepatoblastoma in an adult, with the features compatible with description of the same tumors reported previously in the literature.

Adult↗

Cytogenetic, morphologic and oncogene analysis of a cell line derived from a heterologous mixed mullerian tumor of the ovary.

A cell line was established from a mixed mullerian tumor of the ovary and designated LN1. Histopathologic analysis of the fresh tumor specimen demonstrated a highly aneuploid heterologous tumor comprised of undifferentiated mesodermal components with carcinomatous cells present as a smaller population. Long-term in vitro culture resulted in the establishment of a cell line that exhibits an epithelial-like morphology and expresses epithelial antigens cytokeratin, epithelial membrane antigen, and carcinoma antigen TAG-72. These cells also express mesenchymal intermediate filaments, vimentin, and desmin. Karyotypic analysis revealed a basic triploid pattern with multiple chromosomal abnormalities, most notably an isochromosome of the short arm of five present in three copies. Analysis of oncogene expression revealed that LN1 cells constitutively express mRNA for c-ras, c-erbB2, and p53. The expression of mRNA for cellular oncogenes correlated with the presence of corresponding oncoproteins, p21H-ras, p21K-ras, and p185erB2 and mutant p53 protein. In summary, coexpression of epithelial and mesenchymal antigens by LN1 cells lends support to the hypothesis that epithelial and mesenchymal elements comprising mixed mullerian tumors of the ovary are derived from a common stem cell precursor. Furthermore, this cell line represents a functional in vitro model to evaluate the biologic activities of these unusual and highly aggressive ovarian malignancies.

DNA, Neoplasm↗

Uterine sarcoma.

Thirty-four cases of uterine sarcoma were studied with regard to their pathologic characteristics and response to treatment. Pathologic features did not always correlate with subsequent course. Combined therapy seems to enhance two-year survival in endometrial stromal sarcoma (ESS), although some patients may have low-grade tumors and hence represent a more favorable group. Adjuvant irradiation may improve local control rates in some mixed mesodermal sarcomas (MMS), but does not add appreciably to survival. It is of doubtful benefit in the leiomyosarcoma (LMS) group. When irradiation is employed, preoperative therapy is preferred except in the highly malignant mixed mesodermal sarcomas where prompt surgery seems indicated first. Supplemental brachytherapy may also be employed.

Adult↗

Expression of WT1 in pediatric small cell tumors: report of two cases with a possible mesothelial origin.

The WT1 gene is normally expressed in fetal kidney and mesothelium, and its expression has been suggested as a marker for Wilms tumor and mesothelioma. We examined WT1 expression levels by reverse-transcriptase polymerase chain reaction (RT-PCR) in 38 childhood small-cell tumors including Wilms tumor, embryonal and alveolar rhabdomyosarcoma, Ewing sarcoma, lymphoma, desmoplastic small round-cell tumor (DSRCT), synovial sarcoma, extrarenal rhabdoid tumor, and two tumors that were atypical for this group of tumors. WT1 expression was only detected in Wilms tumor, rhabdoid tumor, and in these two cases of uncertain histogenesis. Both arose in the peritoneal cavity and by immunohistochemistry were diffusely positive for vimentin, keratin, and desmin. Tonofilaments were identified by electron microscopy in one of the cases. RT-PCR failed to detect the t(11;22) translocation associated with DSRCT in either case. Our results suggest that WT1 expression is an unusual feature of childhood non-Wilms tumors and, in the right setting, it may indicate a mesothelial origin. The expression of WT1 may play a role in mesodermal cells acquiring epithelial characteristics, a concept supported by the mixed epithelial and mesenchymal phenotype of these two cases.

Biomarkers, Tumor↗

Benign tumors and tumor-like lesions of the adult kidney. Part II: Benign mesenchymal and mixed neoplasms, and tumor-like lesions.

In this review article the benign tumors and tumor-like lesions of the adult kidney are discussed. The incidence of benign renal tumors is low, especially when compared to renal cell carcinomas, as most are detected incidentally or at autopsy. Some of these tumors, as their names imply, are unique to the kidney, e.g., renal adenoma, metanephric adenoma, renal oncocytoma, nephrogenic adenofibroma, mesoblastic nephroma, capsuloma, juxtaglomerular cell tumor, renomedullary interstitial cell tumor (medullary fibroma), cystic nephroma, cystic partially differentiated nephroblastoma, and cystic hamartoma of the renal pelvis, while others, such as angiomyolipoma, leiomyoma, hemangioma, lipoma, etc., are not unique to the kidney and show similar morphologic features in the other sites they affect. Of the tumor-like lesions, xanthogranulomatous pyelonephritis, malakoplakia, and renal cysts are the most common. The other entities, such as fibroepithelial polyp, are rare, most having been the topic of case reports. In Part I of this paper the benign epithelial tumors of the kidney were previously discussed. This paper (Part II) is devoted to the benign mesenchymal tumors, mixed mesenchymal and epithelial tumors, and the tumor-like lesions.

Adenoma↗

A ureteral small cell carcinoma mixed with malignant mesodermal and ectodermal elements: a clinicopathological, morphological and immunohistochemical study.

A 60-year-old male with a small cell carcinoma of the right lower ureter is presented. The tumor mainly comprised a small cell carcinoma but also included a full variety of histological types such as transitional cell carcinoma, squamous cell carcinoma, adenocarcinoma, leiomyosarcoma and chondrosarcoma. Immunohistochemical staining was positive for neuron specific enolase and cluster 1 small cell lung cancer antigen/N-CAM in the small cell carcinoma and S-100 in the chondrosarcoma component. The patient underwent a right nephroureterectomy, and received prophylactic radiation of the pelvic and para-aortic lymph node regions and cisplatin and etoposide combination chemotherapy. Eight months after the chemotherapy, a transitional cell carcinoma was found in the bladder neck, and a cystectomy with urethrectomy performed. To our knowledge, this is the second report of a small cell carcinoma originating from the ureter.

Biomarkers↗

Ovarian teratomas associated with the insertion of an imprinted transgene.

Ovarian teratomas are tumors that arise from female germ cells and are often a mixture of immature embryonal carcinoma cells and mature embryonic cells. Tissues derived from all three primary embryonic lineages (ectoderm, mesoderm, and endoderm) are typically found in the mature elements of a teratoma. In the case of the transgenic mouse line TG.KD, created with an imprinted transgene construct, malignant ovarian teratomas of a mixed germ cell tumor morphology occur in 15-20% of hemizygous female carriers of the transgene. The tumors frequently metastasize and can result in death of the mouse. Genetic analysis indicates that the tumors are associated with the transgenes integration site. Inbred FVB/N and female mice of other transgenic lines, also created in the inbred FVB/N strain with the same DNA construct as TG.KD, do not develop teratomas. In addition to teratomas, the integration of the transgene on Chromosome (Chr) 8 is associated with a perinatal lethality in homozygous transgenic carriers. The hemizygous genotypes of the teratomas suggest that they arise from early germ cells, prior to the completion of meiosis I.

Animals↗

Endometrial stromal sarcoma: review of Mayo Clinic experience, 1945-1980.

Uterine sarcomas are uncommon malignancies. We retrospectively examined 24 cases of "high grade" endometrial stromal sarcomas (ESS). The histologic diagnosis was made if there was a high grade sarcoma with a high mitotic index and nuclear anaplasia. Heterologous elements could be present, if focal only. Leiomyosarcomas, mixed mesodermal sarcomas, and carcinosarcomas were excluded. Mitotic index was expressed as the number of mitoses per 10 high-power fields in active areas. Tumor grade was based on nuclear anaplasia. ESS were 5.7% of all uterine sarcomas. Median age was 58.2 years; median duration of symptoms was 67.5 days. Abnormal bleeding was the presenting complaint in 91.7%. Uterine enlargement was seen in 33%; protrusion through the cervical os was seen in 9 cases. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed in 95.8%. Twenty patients had myometrial involvement; 5 patients had serosal spread and extrauterine disease; residual disease was seen in 3 patients. Adjuvant radiation was not beneficial. Ten patients had recurrences: 60% in the pelvis, 50% each with subcomponent of abdominal or distant disease. Overall survival was 3.4 years and was significantly associated with extent of disease, size of the primary tumor, and grade.

Adult↗