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Uterine sarcoma in the south of Israel: study of 36 cases.

BACKGROUND: Uterine sarcomas are rare, charaterized by rapid clinical progression and poor prognosis, and their management has been a challenge. The purpose of this study was to investigate the clinical and histologic findings, treatment, and outcome of patients with uterine sarcoma in the south of Israel. METHODS: Data from the files of 36 patients with uterine sarcoma who were managed at the Soroka Medical Center between January 1961 and December 1994 were evaluated. RESULTS: The 5-year survival rate was 32% overall; 63% for 9 patients with endometrial stromal sarcoma (ESS). 30% for 14 patients with mixed mesodermal sarcoma (MMS) and 18% for 13 patients with leiomyosarcoma (LMS): 41% for 22 patients with Stage I and 19% for 14 patients with Stages II, III, and IV. Only the difference in the 5-year survival rate between ESS and LMS was statistically significant (P < 0.05). Eleven patients (30.6%) were treated with surgery alone, 4 (11.1%) with surgery followed by pelvic radiotherapy, 11 (30.6%) with surgery followed by chemotherapy, 8 (22.2%) with surgery followed by pelvic radiotherapy and chemotherapy, one (2.8%) with chemotherapy alone, and one (2.8%) had no treatment. CONCLUSIONS: Uterine sarcomas are aggressive tumors with a poor prognosis. The treatment is surgery generally followed by adjuvant pelvic radiotherapy and/or systemic chemotherapy.

Adult↗

[Adenosarcoma of the uterus].

A case of a 67-year old woman with adenosarcoma of the uterus is reported. Adenosarcoma is a mixed mesodermal tumour with a low malignant potential. It is characterised by a benign glandular and a malignant stromal component. Adenosarcomas are usually treated by hysterectomy with bilateral salpingo-oophorectomy. Patients with myometrial invasion have an increased risk of recurrence. It may be appropriate, to consider adjuvant chemotherapy or radiation treatment for these patients.

Aged↗

A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas.

Various drug combinations including Adriamycin have been tested in soft tissue sarcomas, but optimal treatment remains unclear. We have evaluated Adriamycin with and without dimethyl-triazeno-imidazole-carboxamide (DTIC) in the treatment of Stage III or IV and recurrent sarcomas of the uterus. Two hundred and forty cases of these rare tumors were evaluable. Of 146 evaluable patients with measurable disease, 13/80 (16.3%) of Adriamycin-treated patients and 16/66 (24.2%) of patients receiving the combination showed an objective response (P greater than 0.05). Lung metastases responded more frequently (P equal to 0.04) to combination therapy, but there was no survival advantage. For patients with nonmeasurable disease the progression-free interval was similar (10.0 months for Adriamycin and 8.0 months for the combination). Leiomyosarcomas had a significantly longer survival than other cell types (12.1 versus 6.0 months, P less than 0.001) but there was no advantage for either regimen. There was a suggestion that heterologous mixed mesodermal sarcomas were more responsive to the combination (27.3 versus 8.7%). The addition of DTIC produced significantly more hematologic and gastrointestinal toxicity. Other Adriamycin combinations should be evaluated in uterine sarcomas.

Adult↗

A left pleural effusion with a calcified tumoral mass and left hemithoracic uptake on bone scan.

Diffuse malignant pleural mesothelioma is a rare primary tumor of the pleura with three principal histological types, epithelial; mesenchymal and mixed epithelial and mesenchymal. We report here a case of a mesenchymal mesothelioma with foci of osteosarcomatous degeneration revealed by dense calcifications associated with the pleural effusion on the computed tomography (CT) of the thorax. The bone scan revealed extraosseous uptake corresponding to the left pleura.

Aged↗

Growth control of cultured microglia.

Microglia, the resident macrophages of the brain, typically react to injuries or chronic diseases with proliferation and expression of differentiated features, such as production of cytokines associated with inflammatory events. Regulation and control of microglial cytokine expression, therefore, is a major focus of scientific interest. It has been shown that GMCSF and Il-3 are potent mitogens for microglia. Moreover, Il-3 and other cytokines are products of microglia. It is shown here that interleukin-1 (Il-1) as well as tumor necrosis factor (TNF alpha) increased microglial proliferation in mixed astrocyte-microglial cultures but had no mitogenic effects on isolated microglia. Lipopolysaccharide (LPS), the bacterial endotoxin, irreversibly inhibited microglial cell division in both mixed astrocyte-microglial cultures and in isolated microglial cultures. By contrast, the corticosteroids hydrocortisone and aldosterone and the synthetic glucocorticoid dexamethasone reversibly inhibited microglial proliferation. They also antagonized the stimulatory effects of Il-3 and granulocyte macrophage colony-stimulating factor (GMCSF). Estradiol and progesterone had no significant effects on mixed cultures but inhibited microglial proliferation in isolated cultures. Conditioned media from mixed cultures, isolated cultures, from the WEHI-2B cell line, or from fresh (serum-supplemented) media stimulated microglial proliferation to various extents. In summary, cytokine-mediated microglial proliferation can be down-regulated by a variety of steroid hormones. Along with their unimpaired access to brain cells in general, corticosteroids likely maintain an inhibitory tonus on microglial proliferation. It is hypothesized that this inhibition is overcome locally and temporally in brain injury and repair.

Acid Anhydride Hydrolases↗

Selected miscellaneous ovarian lesions: small cell carcinomas, mesothelial lesions, mesenchymal and mixed neoplasms, and non-neoplastic lesions.

This contribution will cover a variety of uncommon tumors and tumor-like lesions of the ovary that can be associated with a myriad of diagnostic problems for the pathologist. A few of these lesions are not specific to the ovary and may be more common in the uterus or even extraovarian sites, but the mere knowledge that they also occasionally occur in, or involve, the ovary will facilitate their recognition by the pathologist. In contrast, the entity considered first, the highly malignant small cell carcinoma of hypercalcemic type, is an enigmatic tumor unique to the ovary.

Carcinoma, Small Cell↗

Carcinosarcoma, endometrial intraepithelial carcinoma and endometriosis after tamoxifen therapy in breast cancer.

The fourth case of heterologous mesodermal tumour of the uterine corpus, that developed, years following tamoxifen therapy for breast cancer in a postmenopausal woman with no previous pelvic irradiation, is presented with coincidental endometriosis and endometrial intraepithelial carcinoma. This coincidence after tamoxifen treatment appears to be an indication for the possible carcinogenic potency of tamoxifen.

Aged↗

Morphological and functional differentiation of Kirsten murine sarcoma virus-transformed rat adrenocortical cell lines.

This study was undertaken to examine relationships of the phenotype of malignant cells to target cell properties and to events early in the transformation process. Eighteen transformed lines were obtained by Kirsten murine sarcoma virus infection of cells from adrenal glands of rats ages 4 to 30 weeks, at first or second passages in culture. They were grown either as fibroblastic adrenocortical stem cells or as more differentiated epithelial cells, depending on culture conditions. Of 14 lines examined for their capacity to synthesize corticosteroids, 11 converted [14C]pregnenolone to progesterone, and one converted to deoxycorticosterone. In vivo, seven lines produced tumors resembling pleomorphic carcinomas, six lines grew as sarcomas, four grew as mixed tumors, and one line produced anaplastic tumors. Distinguishing features in culture of the carcinoma-producing lines were early onset and rapid progression of morphological transformation, a noncohesive epithelial cell form in some lines, lack of extracellular matrix, and, possibly, and origin in older animals. In contrast, sarcoma-producing cells were fibroblastic and cohesive, produced extracellular matrix, and transformed morphologically after longer and less well-defined periods in culture. The variation in histopathology was unrelated to the differentiation of the target cells and to the capacity of the transformed cells to synthesize corticosteroids. The results show that adrenocortical cells, transformed by Kirsten murine sarcoma virus after short-term culture, usually retain some functional differentiation and sometimes resemble human adrenocortical carcinomas histologically. The susceptibility of adrenocortical cells to Kirsten murine sarcoma virus raises the possibility that mesodermally derived epithelia in general may be target tissues for C-type sarcoma viruses.

Adrenal Cortex↗

[Sarcomatoid carcinoma of the colon: report of a case and review of the literature].

Sarcomatoid carcinomas or carcinosarcoma are rare tumors composed of mixed carcinoma cells and mesenchymal cells. Thirteen cases with colorectal involvement have been published to date. We report a case of sarcomatoid carcinoma of the colon in a 67-Year-old woman hospitalized with a history of anemia and bloody stools. The patient underwent a left hemicolectomy. Immunohistochemistry revealed two cell components (undifferentiated carcinomatous and sarcomatous components). The patient died of her tumor 2 Months after the operation. Our review of the literature stresses the poor prognosis associated with colonic sarcomatoid carcinoma.

Aged↗

Fine needle aspiration cytology of hepatoblastoma. Recognition of subtypes on cytomorphology.

OBJECTIVE: To delineate the cytomorphologic appearances of hepatoblastoma (HBL) in the largest series to date and to evaluate the feasibility of subtyping on fine needle aspiration cytology (FNAC). STUDY DESIGN: Papanicolaou- and May-Grünwald-Giemsa-stained smears of aspirates from 26 cases of HBL were analyzed by 2 observers. Histologic material, available in 15 cases, was correlated. A cytology grouping system was proposed on the basis of which all cases were classified. RESULTS: The ages of the patients ranged from 4 months to 9 years. Twenty-five cases were categorized as epithelial HBL, with epithelial fragments showing a trabecular arrangement and acinar formation in all, and extramedullary hemopoiesis in 20 cases. It was possible to differentiate fetal and embryonal areas on FNAC. Six cases showed only fetal elements (cytology group F), characterized by cells with abundant cytoplasm and a small, rounded nucleus resembling a normal fetal hepatocyte. The chromatin was finely granular, with a single, central nucleolus. Pleomorphism and mitoses were not seen, and the nuclear/cytoplasmic ratio was < or = 1/3. Fourteen cases showed, in addition to fetal elements, an embryonal component characterized by cells with scant cytoplasm, a pleomorphic nucleus, N/C ratio of > or = 3/1, coarsely granular chromatin and 2-4 angulated nucleoli. Mitoses were seen in these cells (1-4/1,000 cells). Of these 14 cases, 6 showed predominantly fetal and scant embryonal cells, while 8 cases showed fetal and embryonal components in equal amounts (cytology groups Fe and FE, respectively). Four cases showed predominantly embryonal cells (cytology group E). One case was unclassifiable (U). On histology, 8 of 14 cases were of mixed epithelial and mesenchymal type, but mesenchymal tissue was not seen on the corresponding cytology. The cytology grouping system correlated well with histology. One case was small cell undifferentiated HBL and resembled a round cell tumor without differentiation. Macrotrabecular arrangement was not seen on cytology but was seen on histology in 1 case. CONCLUSION: Epithelial HBL can be easily diagnosed in aspirates further classified into fetal and embryonal subtypes, which may be of prognostic relevance. The proposed cytology grouping system is effective in semiquantification of the observed subtypes.

Biopsy, Fine-Needle↗

Primitive streak mesoderm-like cell lines expressing Pax-3 and Hox gene autoinducing activities.

Differentiating P19 embryonal carcinoma (EC) cells transiently express an endogenous activity capable of inducing Pax-3 expression in adjacent P19 stem cells (Pruitt, Development 116, 573-583, 1992). In the present study, expression of this activity in mesodermal cell lineages is demonstrated. First, expression of the mesodermal marker Brachyury correlates with expression of Pax-3-inducing activity. Second, the ability of leukemia inhibitory factor (LIF) to block mesoderm differentiation at two different points is demonstrated and correlated with the inhibition of Pax-3-inducing activity. Finally, two mesodermal cell lines that express Pax-3-inducing activity were derived from P19 EC cells. Each of these lines expresses high levels of the mesodermal marker Brachyury and high levels of Oct-3/4 (which is down-regulated at early times during mesoderm differentiation) suggesting that these lines are early mesodermal derivatives. Unlike EC or embryonic stem cell lines, each of the two mesodermal derivatives autoinduces Hox gene expression on aggregation even in the presence of LIF. Following aggregation, anterior-specific genes are expressed more rapidly than more posterior genes. These observations directly demonstrate the ability of murine mesodermal derivatives to autoinduce Hox gene expression in the absence of signals from other cell lineages. Similar to the Pax-3-inducing activity, signals from mesodermal cell lines were sufficient to induce HOX expression in adjacent P19 stem cells in cell mixing assays. These observations are consistent with the previous suggestion (Blum, M., Gaunt, S. J., Cho, K. W. Y., Steinbeisser, H., Blumberg, B., Bittner, D. and De Robertis, E. M. (1992) Cell 69, 1097-1106) that signals responsible for anterior-posterior organizer activity are localized to the anterior primitive streak mesoderm of the mouse embryo.

Animals↗

Immunohistochemical study of a case of malignant müllerian mixed tumor in comparison with the activity of normal uterine tissue.

A case of malignant Müllerian mixed tumor of the uterus, exhibiting a histology of heterologous osteosarcomatous differentiation, is presented. Special emphasis is placed on the characteristic immunohistochemical reactivity of the tumor tissue in comparison with that of normal uterine tissue in the proliferative phase. Keratin, cytokeratin, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), and human chorionic gonadotropin (HCG) were found only in the carcinomatous element. However, neuron specific enolase (NSE), S-100 protein (S 100) and vimentin were identified in almost all tumor tissue elements. Desmin and actin were not stained in any elements. Myoglobin was only detected weakly in the squamous carcinomatous element. Undifferentiated cell element, composed of small, round, spindle, or polygonal cells showed positive reactions to NSE and S 100, but not to any other antibodies. As compared to the reactivities of the normal proliferative endometrium, the glandular epithelial cells were positive with NSE, S 100, vimentin and CEA, but the stromal cells were only positive with vimentin. Such a multitudinous and concomitant expression of antigenicity to the different tumor elements indicates a close relationship to its mesodermal Müllerian origin, and NSE, S 100 and vimentin might be most adequate indicators of these types of tumors.

Adenocarcinoma↗

Cutaneous mesenchymal hamartoma with mixed myogenous differentiation.

A 3-month-old infant girl presented with a polypoid lesion in the perianal region. No changes in this lesion had been noted since birth. Microscopic examination of the excised specimen showed a mixture of mesenchymal elements, dominated by haphazard thin fascicles of skeletal muscle. Collagen and vascular changes were also apparent. Immunohistochemistry showed positive staining for muscle-specific actin and desmin in the fascicular components of the lesion, and smooth muscle actin, desmin, and h-caldesmon positivity in a haphazard collection of muscle fibers in the deep dermis and anal submucosa. Numerous Verhoeff-van Gieson positive elastic fibers were also noted. Hamartomas containing skeletal muscle have rarely been reported outside of the head and neck region. They must be distinguished from a variety of other tumors, including juvenile rhabdomyoma, benign Triton tumor, and rhabdomyosarcoma.

Cell Differentiation↗

Fine needle aspiration cytology of mesenchymal hamartoma of the liver. A case report.

BACKGROUND: Mesenchymal hamartoma (MH) of the liver constitutes the third or fourth most common tumor of the liver in childhood and occurs most commonly in the first two years of life. MHs of the liver are seldom aspirated, and reports on the role of fine needle aspiration (FNA) in the diagnosis of MH are scarce. Clinically, cytologically and even histologically, MH can be mistaken for a number of reactive and neoplastic hepatic lesions that may occur in children under 2 years of age. CASE: A 10-month-old Pakistani female presented with a history of a right-sided, nonpainful abdominal swelling. Abdominal computed tomography showed a large, partly solid and partly cystic, heterogeneous hepatic mass. FNA cytology showed clusters of both epithelial and mesenchymal/spindle-shaped cells with pieces of loose connective tissue. A cytologic differential diagnosis of mesenchymal hepatic hamartoma and hepatoblastoma of the possible mixed mesenchymal/epithelial subtype was rendered. The histopathologic diagnosis of the resected tumor mass was benign mesenchymal hamartoma of the liver. CONCLUSION: In children under 2 years of age who present with partly solid and partly cystic hepatic masses, the possibility of MH of the liver should be considered. FNA has a role in the diagnosis of MH. The cytopathologist should be aware of the patient's age, radiologic features and cytologic appearances of this rare, benign neoplasm. Histologic examination of tru-cut biopsies and immunohistochemical stains can help to exclude other pediatric neoplasms that may show cytologic features similar to or mimicking those of MH.

Biopsy, Needle↗

Rhabdomyosarcoma of the liver associated with long-term oral contraceptive use. Possible role of estrogens in the genesis of embryologically distinct liver tumors.

We report a case of rhabdomyosarcoma arising in a 34-year-old woman with a 16-year history of oral contraceptive use. This is the first reported case of hepatic rhabdomyosarcoma associated with oral contraception. The tumor did not grossly or microscopically involve biliary structures or gall bladder. It was mostly comprised of undifferentiated spindle cells that were histologically similar to embryonal sarcoma. Foci of cells showing rhabdomyoblastic differentiation blended into poorly formed muscle bundles. No epithelial neoplasm was identified by either morphologic or immunohistochemical analysis. A review of the literature reveals that, although the incidence is low, mesenchymal neoplasms of the liver have been associated with oral contraceptive use. Furthermore, there is now evidence that a multipotential progenitor cell exists that can give rise to both epithelial and mesenchymal neoplasms. Thus, there may be a common precursor cell on which estrogens could act, and which could give rise to epithelial, mesenchymal, or mixed neoplasms. Finally, we suggest that embryonal sarcomas of the liver can undergo further differentiation to more well-defined mesencymal elements.

Actins↗

Classification of odontogenic tumours. A historical review.

Using the term odontome for any tumour arising from the dental formative tissues, Broca suggested a classification of odontogenic tumours (OTs) in 1869. From 1888 to 1914, Bland-Sutton and Gabell, James and Payne modified tumour terminology, while maintaining Broca's odontome concept. Thoma and Goldman's classification (1946) divided the OTs into tumours of ectodermal, mesodermal and mixed origin and abolished the general term odontome. The Pindborg and Clausen classification (1958) based on the idea that the reciprocal epithelial-mesenchymal tissue interactions were also operating in the pathogenesis of OTs. In 1966, WHO established a Collaborating Centre for the Histological Classification of Odontogenic Tumours and Allied Lesions (including jaw cysts) headed by Dr Jens Pindborg. In 1971, the first authoritative WHO guide to the classification of OTs and cysts appeared followed in 1992 by a second edition. In 2002, Philipsen and Reichart produced a revision of the 1992-edition and in 2003, the editors of the WHO Blue Book series: 'WHO Classification of Tumours' decided to produce a volume on the Head and Neck Tumours including a chapter on Odontogenic Tumours and Bone Related Lesions. In July of 2005 this volume was published by IARC, Lyon.

History, 19th Century↗

A human prostatic epithelial model of hormonal carcinogenesis.

The effects of stromal and hormonal environment on the immortalized but nontumorigenic human prostatic epithelial cell line BPH-1 were investigated in an in vivo model. BPH-1 cells were recombined with rat urogenital sinus mesenchyme (UGM), and the tissue recombinants were grafted to the renal capsule of adult male athymic mouse hosts. BPH-1 + UGM recombinants formed solid branching epithelial cords with a well-defined basement membrane. The cords canalized to form ductal structures. The mesenchymal cells formed thick sheets of well-differentiated smooth muscle surrounding the epithelium, reinforcing the idea that the epithelium dictates the patterning of prostatic stromal cells. When hosts carrying BPH-1 + UGM tissue recombinants were exposed to testosterone propionate and 17-beta-estradiol (T + E2), the tissue recombinants responded by forming invasive carcinomas, demonstrating mixed, predominantly squamous as well as adenocarcinomatous (small acinar and mucinous) differentiation. When either untreated or T + E2-treated hosts were castrated, epithelial apoptosis was observed in the grafts. When tumors were removed and regrafted to fresh hosts they grew rapidly. Tumors were serially regrafted through six generations. Histologically these tumors consisted largely of focally keratinizing squamous cell carcinoma with high-grade malignant cytological features. BPH-1 cells grown in the absence of UGM survived at the graft site but did not form tumors or organized structures. This behavior was not influenced by the presence or absence of T + E2 stimulation. These data show that an immortalized, nontumorigenic human prostatic epithelial cell line can undergo hormonal carcinogenesis in response to T + E2 stimulation. In addition, the data demonstrate that the stromal environment plays an important role in mediating hormonal carcinogenesis.

Animals↗

[Tumor and tumor-like benign mesenchymal lesions of the breast].

All the spectrum is encompassed of those miscellaneous pathologic entities occurring in the mammary stroma which are on record up to date other than "mixed fibroepithelial" tumors (fibroadenomas and phyllodes tumors) and tumors both "pure" and "mixed" originating from myoepithelium (adenomyoepitheliomas and pleomorphic adenomas). Also they were excluded those dysreactive-autoimmune diseases (sarcoidosis, sclerosing lymphocytic lobulitis, lobular granulomatous mastitis) and those inflammatory-infectious conditions (tuberculosis, actinomycosis, foreign body reactions, Mondor's disease) which can mimick breast tumors clinically or on image analysis, but on the contrary not evoking the idea of a tumor on histology. Specifically, inflammatory pseudotumor, myofibroblastoma, leiomyoma, neurinoma/neurofibroma, benign fibrous histiocytoma, hemangiopericytoma, fibromatosis, nodular fascitis, variants of lipoma, mesenchymoma, amartoma and its variants, hemangiomas, pseudoangiomatous hyperplasia of stroma, amyloid tumor, granular cell tumor, are consecutively described and discussed, with a large list of references enclosed to each rubric. Most of the pictures are taken from personally observed lesions of the breast. Only few pictures referred to are from their analogue lesions which occurred in soft parts of other locations, with specific mention of that when it was the case. Of note after reviewing the literature the fact that no glomus tumor, nor Kaposi's sarcoma either sporadic or in the context of any immunodeficiency, nor myelolipoma has been recorded yet.

Breast Neoplasms↗