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The histogenesis of carcinosarcomas of the uterus is not clear yet. The different histologic structures of a collisions-tumor which is characterized by a secondary intermingling of sarcomatous and carcinomatous elements are described, and their etiolgy and pathogenesis are discussed.
Presentation of a new case of vesical carcinosarcoma in a 49 year-old male patient. The tumour's pathoanatomical study showed an epithelial pattern of transitional and squamous cells and a sarcomatous pattern composed of rabdomiosarcoma, osteochondrosarcoma and pleomorphous indifferentiated sarcoma with giant multinuclear cells. Histogenesis, signs and symptoms, and treatment, as well as the need of performing an immunohistochemical study for its diagnosis are discussed.
Vesical carcinosarcoma is a very poor prognosis, infrequent tumour normally presenting with haematuria and for which the only treatment available is radical cystectomy. Here we present a new case of this tumour in a 61 year-old male with a brisk evolution to death.
The clinicopathologic feature of one carcinosarcoma of the renal pelvis is reported. The tumor occurred in a 51-year-old woman with a long standing history of renal calculi. The epithelial component was consistent with squamous cell carcinoma, whereas the sarcomatous component was composed of pleomorphic spindle cells. The immunohistochemical studies demonstrated obvious epithelial and mesenchymal reactivity respectively. The tumor progressed rapidly with widespread metastases and the patient died one month after operation.
We report a case of carcinosarcoma of the minor salivary glands of the left palatine tonsil, an especially rare location. Imaging characteristics assessed at CT, MR imaging, and angiography are presented. In addition, we describe our experience with preoperative therapeutic endovascular embolization of this hypervascular tumor.
The authors analyse and comment on a case of carcinosarcoma of the gallbladder which they have recently observed. Given the rarity of this form of cancer, it is interesting to note that this case presents some peculiar aspects which have not been recorded in the few cases previously published on the subject. The peculiarities are such that they require a revision of what have until now been considered as intrinsic characteristics in the clinical observation of this kind of cancer. The authors maintain that the peculiarities of this case concern: a) the clinic onset of the illness and the relative aspecific symptomatology: b) that fact that laboratory tests did not signal any biochemical alteration; c) that the instrumental investigation's results pointed toward a non neoplastic pathology; d) that even the intra-operatory examination did not reveal any suspicious element; and last but by no means least the good survival of the patient which is definitely superior to other cases already reported in literature. The neoplasia, which manifested itself through a hemorrhage in the gallbladder, represented in fact the very initial stage of the illness, a condition rarely observed.
Histologic, immunohistochemical and ultrastructural features of a case of carcinosarcoma of the lung are described. The biphasic pattern of this neoplasm is characterized by the presence of a carcinomatous component that corresponds to an adenosquamous carcinoma, and a sarcomatous component with rhabdomyoblastic differentiation. Since the biphasic sarcomatoid carcinoma has an aggressive clinical behaviour, immunohistochemical expression of prognostic markers, such as Ki-67 and p53 is evaluated to individuate differences between the carcinomatous and the sarcomatous components of the tumor. The higher p53 expression and Ki-67 positivity in the former, suggests that the carcinomatous component probably represents the more aggressive portion of the tumor. Moreover, P53 expression is nuclear in both carcinomatous and sarcomatous areas, thus it is likely that the biphasic sarcomatoid carcinoma of the lung is monoclonal in origin.
A 67-year-old man was admitted to our hospital with blood sputum. Adenocarcinoma was diagnosed by sputum cytological examination. A chest X-ray film showed a tumor shadow in the lower field of the right lung. The middle and lower lobes were resected and lymph node dissection was performed. Tumor was composed of well differentiated adenocarcinoma and spindle cell sarcomatous element, and diagnosed as so-called carcinosarcoma. Pathological staging was IIIA by pT1N2M0. Postoperative chemotherapy was not performed for side effect, so radiotherapy only was done. He died of recurrence and metastasis after about 1 postoperative year.
This article presents three cases of carcinosarcoma of the lung which is considered to be a rare neoplasm. The authors describe supposed etiology, clinical symptoms, preoperative diagnostic difficulties, surgical interventions performed, postoperative course and follow-up. The role of modern histopathological techniques like use of monoclonal antibodies reaction against keratin, vimentin and neurofilaments in differential diagnosis is emphasized. Short review of other authors reports is presented.
The authors report a case of carcinosarcoma (malignant mesodermal mixed tumor of the urinary bladder. We discuss the histological criteria of positive and differential diagnosis, the histogenesis, as well as their biological behavior.
A 64-year-old male complained of right hypochondralgia and was admitted to our hospital. A large tumor (10 x 15 x 10 cm) of the right diaphragm was detected involving the middle and lower lobe of the lung. Microscopic and immunohistochemical examinations showed that bronchiolo-alveolar cell carcinoma was interposed in the sarcoma-like lesion, and this tumor was diagnosed as a so-called carcinosarcoma of the lung.
We present a new case of carcinosarcoma of the bladder. This tumor is generally considered to be a rare one, has an uncertain aetiology and very poor prognosis, composed by mesenchymal and epithelial elements. It is an aggressive tumor with a short clinical course. At present radical cystectomy is the treatment of choice.
BACKGROUND: Epidermal growth factor receptor (EGFR) and c-erbB-2 (also known as HER-2/neu) oncoprotein (p185erbB-2) are members of the subfamily of tyrosine kinase, transmembrane receptors often implicated in human carcinogenesis. We hypothesize that expression of EGFR and p185erbB-2 adds useful prognostic and histogenetic information regarding female genital tract carcinosarcomas (FGTCSs). METHODS: Paraffin sections from 82 FGTCS (61 endometrium, 14 ovary, 5 cervix, and 2 fallopian tube), 56% of which exhibited heterologous elements, were stained using anti-EGFR (clone 31G7, Triton Diagnostics, Alameda, CA) and anti-p185erbB-2 (clone CB11, Novocastra Labs, UK). RESULTS: EGFR reactivity was present in 11 (13.4%) FGTCSs (55% carcinomatous component [CC] only, 18% sarcomatous component [SC] only, and 27% in both). EGFR was associated with adenosquamous histology of the CC (P < 0.05) and heterologous rhabdomyosarcomatous differentiation in the SC (P < 0.05); no other histopathologic features were correlated. p185erbB-2 reactivity was present in 79 (87.8% strong [S], 78% membrane [M], and 8.5% weak) FGTCSs (1% CC only, 0% SC only, and 99% in both). p185erbB-2 did not correlate with histopathologic features or EGFR. Seventy-seven patients had clinical follow-up for longer than 12 months. Approximately 49.3% and 72.3% of patients had recurrent disease by 12 and 80 months, respectively; all but 1 were dead from disease. 27% of patients were disease free after 15 to 307 months (median, 77 months; mean, 92 months). EGFR, but not p185erbB-2 expression predicted disease recurrence (P < 0.05). Recurrent disease was associated with Stage greater than I (P < 0.0001), vascular space invasion in resection specimens (P < 0.01), and deep myometrial invasion in hysterectomies (P < 0.05). EGFR was associated with Stage greater than I and did not help predict recurrence in good prognosis groups. CONCLUSIONS: p185erbB-2 overexpression in both CC and SC of FGTCS suggests a common carcinogenic mechanism for both components and supports the conversion-histogenesis hypothesis implicating a dominant role for the CC with the SC arising as a metaplastic change from the CC. EGFR may be expressed in either component and indicates aggressive biologic behavior; however, its prognostic utility is limited by its low predictive value for recurrence (40.3%), inability to foretell recurrence in good prognosis groups, and dependence on stage. High frequency of overexpression and dismal prognosis make FGTCS patients good candidates for trials of therapeutic strategies involving the p185erbB-2 receptor manipulations.
The putative role of cellular or solvent volume in protrusive activity and locomotion has been investigated in blebbing Walker carcinosarcoma cells using hypertonic media. Blebbing, locomotion, and cell polarity are completely suppressed by 0.2 M sorbitol. The response occurs in two steps. In a first step, i.e. within 10 sec after the addition of sorbitol, blebbing and locomotion are inhibited and this is associated with an average cell volume reduction by 17% (corresponding to a reduction in solvent volume by 38%). It clearly precedes suppression of cell polarity (pre-existing protrusions, tail) occurring in a second step within 5 to 10 min after addition of sorbitol without additional reduction in the cell or solvent volume. The relative amount of F-actin does not correlate with the decrease in cell volume, suppression of blebbing, locomotion, and cell polarity. A significant decrease in the relative amount of F-actin is found only at volume reductions which are higher than those required to completely suppress blebbing, locomotion, and cell polarity. F-actin staining occurs preferentially along the cell membrane in isotonic as well as in hypertonic media. The results are best compatible with the hypothesis that hydrostatic pressure rather than actin polymerization at the front is the direct force driving the membrane forward during bleb formation. Cells with lamellipodia show a similar response to hypertonic media, suggesting that basically similar mechanisms may operate in both forms of protrusions.
The dynamic events at the front of locomoting blebbing Walker carcinosarcoma cells [Keller and Bebie, Cell Motil. Cytoskeleton 33:241-251, 1996] are interpreted on the basis of an analysis of the actin cytoskeleton and its relationship to the plasma membrane in fixed cells using a novel double-staining procedure. The data show that blebs are formed where cortical actin is locally depolymerized and/or by detachment of the plasma membrane from more or less intact cortical actin layers. Dissociation between the cortical actin layer and the plasma membrane, which is stimulated by microtubule disassembly, is achieved by forward movement of the plasma membrane, rather than by retraction of the actin layer. Therefore, the detached actin layers form a boundary between the newly forming protrusions and the rest of the cell. They can be associated with "constriction rings," which we have termed "restriction rings." Detached actin layers can impede entry of organelles and the nucleus into the protrusions and thereby compartmentalize the cytoplasm. Later, detached cortical actin layers depolymerize, allowing for relaxation of the restriction rings and for forward movement of cytoplasmic organelles and the nucleus. Actin may repolymerize along the detached plasma membrane allowing for a new cycle to occur. Estimates indicate that the actin polymerization/depolymerization cycles may be largely confined to the front of blebbing cells. The findings suggest that the dynamic events at the front of blebbing metazoan cells are similar to those previously found in Amoeba proteus [Grebecki, Protoplasma, 154:98-111, 1990] but different from those found in lamellipodia.
The metabolic effects of total parenteral nutrition (TPN) solutions containing different profiles of individual amino acids were investigated in the rats bearing Walker 256 carcinosarcoma. The rats were subcutaneously inoculated with 10(7) tumor cells and 6 days later were continuously infused intravenously for 8 days with three different TPN solutions. The experimental and control solutions were composed of high concentrations of branched chain amino acids (BCAA) and arginine (high Arg + BCAA TPN), high concentrations of BCAA (high BCAA TPN) and regular amino acids (regular TPN), respectively, and were isonitrogenous, isocaloric, and isovolemic. Rats receiving subcutaneous injection of saline rather than tumor cells received high Arg + BCAA TPN as pair-fed controls. The flooding dose method of 14C-leucine was used for the analysis of protein synthesis. With the feeding of high Arg + BCAA TPN, the tumor-bearing rats revealed a smaller increase of tumor volume and lower tumor fractional rates of growth (Kg) and synthesis (Ks) as well as protein synthesis (PS), compared with the high BCAA TPN and regular TPN in tumor-bearing rats. There were no significant differences of Ks and PS in liver and muscle between TPN groups, whereas tumor-bearing rats infused with high Arg + BCAA TPN displayed higher levels of whole-body Ks and PS than other TPN groups in tumor-bearing rats and pair-fed nontumorous rats. Except for liver RNA content which showed a lower level in tumor-bearing rats with high Arg + BCAA TPN, no other differences of DNA and RNA contents were found in tumor, liver, and muscle of the different TPN groups. The current results indicate that individual amino acids can influence tumor growth and protein metabolism, and that arginine, in combination with BCAA, may reduce tumor growth through a reduction in protein synthesis.
Spontaneously migrating Walker carcinosarcoma cells usually form lamellipodia at the front. Combined treatment with 10(-5)M colchicine and 10(-7)M latrunculin A produces large defects in the cortical F-actin layer at the leading front and suppresses lamellipodia. However, the cortical actin layer at the rear is intact and shows myosin IIA accumulation. These cells, showing no or little detectable cortical F-actin at the front and no morphologically recognisable protrusions, migrate faster than control cells with lamellipodia and an intact cortical actin layer. This documents that the cortical actin layer or actin-powered force generation at the front is redundant for locomotion. Colchicine and latrunculin A have synergistic effects in compromising the cortical layer at the front and in increasing the speed of locomotion, but antagonistic effects on the relative amount of F-actin per cell. Colchicine but not latrunculin A, can increase the proportion of polarised and locomoting cells under appropriate conditions. Locomotion and polarity of cells treated with latrunculin A and colchicine is inhibited at latrunculin A concentrations >10(-7)M, by the myosin inhibitor BDM or the ROCK inhibitor Y-27632. Colchicine and Y-27632 have antagonistic effects on polarity and the speed of locomoting cells. The data show that locomotion of metazoan cells, which normally form lamellipodia, can be driven by actomyosin contraction behind the front (cell body, uropod). They are best compatible with a cortical contraction/frontal expansion model, but they are not compatible with models implying that actin polymerisation or actomyosin contraction at the front drive locomotion of the cells studied.
We show that diacylglycerols, like phorbol myristate acetate (PMA), suppress cell polarity and locomotor activity of Walker carcinosarcoma cells in a dose-dependent fashion in vitro. OAG and diC8 show significant activity at concentrations above 3 x 10(-5) M. The inhibitory effect on locomotion is due to a reduction in the proportion of locomoting cells rather than gradual lowering of the speed of individual cells. Measurement of protein kinase C (PKC) activity in isolated fractions showed a substantial reduction of the total cellular PKC activity and of the activity in the cytosolic fraction following incubation of cells with 10(-8) M PMA for 30 min. In contrast, the total and relative PKC activity associated with the membrane fraction was increased by PMA. The effect of H-7, an inhibitor of PKC as well as of cAMP-dependent kinase, has been tested. H-7 suppressed cell polarity of "unstimulated" control cells (ID50 = 6.5 microM H-7), colchicine-stimulated cells (ID50 = 92 microM H-7) or cells treated with both PMA and colchicine (ID50 = 15 microM H-7), in a dose-dependent fashion. The locomotor activity of the cells was also suppressed. LTB4 had no clearcut activity in this system. Our findings suggest that diacylglycerols and H-7 are of interest as physiological or pharmacological stop signals for tumor-cell locomotion. Contrary to our expectations, PMA and diacylglycerols vs. H-7 did not produce opposing or antagonistic effects on cell polarity and locomotion. This similarity may be due to down-regulation of PKC by PMA and inhibition of PKC by H-7. However, the mechanisms underlying these novel effects of diacylglycerols and of H-7 on cell polarity and locomotion may be even more complex; they require further studies.