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A case of carcinosarcoma of the urinary bladder characterized by electron microscopy and immunohistochemistry is described. The use of these studies in poorly differentiated bladder neoplasms and in suspected cases of carcinosarcoma is encouraged. Increased accuracy in characterizing these tumors will permit a better understanding of their natural history and response to therapy.
Cervical sarcomas and carcinosarcomas are exceedingly rare. The clinicopathologic characteristics, management and outcome of a patient with cervical carcinosarcoma is presented.
An unusual low-grade metaplastic carcinoma (müllerian carcinosarcoma) of the uterine corpus occurring in a 45-year-old woman is presented. The tumor was polypoid and showed an initial invasion into the myometrium. The epithelial component was composed of low-grade endometrioid glands that focally showed an unusual oxyphilic change of the cytoplasm. These cells contained only a small amount of mitochondria detected with antimitochondrial antibody. The stromal component contained small round cells of bland appearance and appeared to arise from epithelial cells through a metaplastic process, as a gradual transition between epithelial and stromal cells was often seen. An invasive marginal zone of the tumor showed endometrioid adenocarcinoma pattern without any stromal component. The proliferative activity generally was low. Interestingly, it was clearly accentuated in the epithelial component especially in the peripheral invasive areas, whereas it was very low in the stromal component. The course of disease was indolent. Low-grade müllerian carcinosarcoma is to be distinguished from other biphasic müllerian tumors.
We assessed the usefulness of Jun N-terminal kinase inhibitor (JNK-I) as an anti-angiogenic agent against a human uterine carcinosarcoma cell line (FU-MMT-1). JNK-I blocked FU-MMT-1-induced human arterial endothelial cell (HAEC) tube formation in an in vitro co-culture model. Cell proliferation of FU-MMT-1 or HAEC was inhibited by JNK-I. In addition, JNK-I blocked matrix metalloproteinase production but not vascular endothelial growth factor (VEGF) secretion in HAECs. Although low concentrations of JNK-I or TNP-470, an anti-cancer agent, did not separately block FU-MMT-1-induced tube formation, such tube formation was blocked by the combination of low concentrations of JNK-I and TNP-470 because TNP-470 blocked VEGF production, suggesting that JNK-I and TNP-470 had a synergistic effect and might be effective in patients with carcinosarcoma.
Carcinosarcoma of the gallbladder is a rare malignancy characterized by both malignant epithelial and mesenchymal components. The clinical behavior of this tumor is extremely aggressive. Only 26 cases have been reported in the world literature to date. We report the case of a 64-year-old woman who had fever associated with a right upper quadrant mass. An exploratory laparotomy through a right upper quadrant incision was performed at another institution, and the patient was thought to have severe acute cholecystitis that would require additional antibiotic therapy before attempted resection. She was referred to our center, where abdominal CT showed a 6.4 x 8.2 cm pericholecystic mass involving the hepatic flexure of the colon. The patient underwent cholecystectomy and hepatic wedge resection, pancreaticoduodenectomy, and right hemicolectomy. Pathologic examination of the surgical specimen revealed two histologic components consisting of squamous cell carcinoma and spindle cell sarcoma of gallbladder origin, consistent with carcinosarcoma. All seven lymph nodes in the pancreaticoduodenectomy specimen were negative for tumor. We present this case and a review of the literature and current treatment recommendations.
Carcinosarcoma (spindle cell carcinoma) of the esophagus is a rare neoplasm that shows squamous cell carcinoma (SCC) with a variable component of spindle cell sarcoma. Clinical and pathologic features of this neoplasm have been well documented, but the histogenesis has long been a matter of speculation and dispute. In an attempt to clarify the clonality and genetic relationships in the evolution of this neoplasm, we microdissected a total of 36 carcinomatous and sarcomatous foci from six esophageal carcinosarcoma (CS) and analyzed the allelic status with 25 microsatellite markers on chromosomal arms 3p, 5q, 6q, 8p, 9p, 11q, 13q, 17p, and 18q. In all cases, we found multiple and homogenous allelic losses in both the carcinomatous and sarcomatous components, strongly supporting the concept of monoclonal origin for this neoplasm. Homogeneous allelic losses were detected most frequently on 17p (5 cases), a chromosomal arm that included the p53 locus, followed by 3p, 11q, and 13q (3 cases); 9p (2 cases); and 8p and 18q (1 case). Moreover, five of the six cases showed additional or divergent allelic losses at more than one chromosomal locus at some of the microdissected foci, indicating genetic progression (2 cases) or genetic progression and divergence (3 cases). In four cases, the genetic changes indicated that an original clone of a pure SCC apparently acquired carcinosarcomatous or sarcomatous phenotype by successive genetic changes. On the other hand, we saw no evidence for tumors in which a sarcoma appeared to give rise to a carcinosarcomatous or carcinomatous subclone in the examined cases. In conclusion, our data support the concept that esophageal CS is derived from a single clone originating from a SCC. Furthermore, we showed genetic heterogeneity to accompany the phenotypic divergence, with patterns of genetic alterations that are consistent with both progression and divergence within individual tumors.
In this report, we present the first case of a vulvar carcinosarcoma with squamous carcinomatous and leiomyosarcomatous differentiation. Comparative genomic hybridization was used to analyze clonality of the two tumor components. A widely identical pattern of genetic imbalances in the comparative genomic hybridization analysis in both the carcinomatous and the sarcomatous tumor component strongly supported the concept of a bidirectionally differentiated neoplasm. In both tumor components and two lymph node metastases, an amplicon was detected on chromosome 11q12-q13, homing the cyclin D1 gene locus. In contrast, exclusively in the sarcomatoid component, a characteristic amplicon on 12q13-q14 was found. The cytogenetic profile of the lymph node metastases revealed an increase in imbalances compared with the primary tumor. In summary, we found strong indications for a clonal origin of the two tumor components in a vulvar carcinosarcoma and a good correlation of the histological morphology with the pattern of genetic imbalances.
True malignant mixed tumours of the salivary gland (carcinosarcoma) are rare tumours composed of both carcinomatous and sarcomatous components. They predominantly occur in the parotid gland. This report presents the clinical, histological and imaging findings of a carcinosarcoma arising in the deep lobe of the parotid. We present magnetic resonance imaging (MRI) findings of this tumour. MRI demonstrated heterogenous intermediate T2-W signal with a thick irregular enhancing rim was suggestive of a malignant lesion.
Primary hepatic carcinosarcoma is a rare malignant hepatic tumor containing both carcinomatous and sarcomatous elements. A 40-year-old man referred to our liver transplant team because of hepatic cirrhosis was on the waiting list, having undergone all liver tests, ultrasonography, and with normal serum alpha fetoprotein markers every 6 months to search for a tumor. He underwent a liver transplantation without complication. The pathologic findings of the original liver indicated carcinosarcoma. We have reviewed the literature on this subject.
OBJECTIVE: Uterine carcinosarcomas are highly aggressive neoplasms with no established effective adjuvant therapy. The aim of the present study was to compare between the outcome in three medical institutions in each of which a different postoperative treatment modality was preferred, namely, chemotherapy in one, whole pelvic irradiation (WPI) in another, and sequential treatment (i.e., chemotherapy followed by WPI) in the third. METHODS: The hospital records of all 49 uterine carcinosarcoma patients diagnosed and operated from 1995 to 2003 in the three institutions were reviewed. Non-parametric test was used to compare the median age between the treatment groups. Survival was calculated using the Kaplan-Meier method and compared by the log-rank test. Cox proportional hazard regression model was used to assess the effect of treatment type on survival after adjustment for stage. RESULTS: Only about half of the patients (51%) had stage I at diagnosis and the majority of the patients (83.7%) had postoperative adjuvant treatment. The overall 5-year survival of the 41 patients that had postoperative treatment was 49.6%. The highest median survival and 5-year survival rate was observed in the sequential treatment group. Controlling for stage, this treatment modality was associated with a significant decrease in mortality of about 80% when compared to postoperative chemotherapy alone, and a non-significant decrease in mortality of about 50% when compared to WPI alone (HR = 0.20; 95% CI 0.04-0.99, P = 0.049 and HR = 0.50; 95% CI 0.1-2.32, P = 0.4, respectively). CONCLUSIONS: The improved outcome in patients who received postoperative sequential treatment seems to indicate that further exploration of this treatment modality is justified.
BACKGROUND: Production of granulocyte colony stimulating factor (G-CSF) by solid tumors, including cervix cancers, is reported to be associated with an aggressive clinical course. CASE: A 64-year-old female with a locally advanced carcinosarcoma of the cervix presents with a WBC count of 48,000 cells/microl with no infectious causes. Her WBCs returned to normal during primary radiotherapy and then increased again with recurrence. She expired of progressive disease 10 weeks after primary therapy. Serum and pleural fluid levels of G-CSF were 1500 and 6000 pg/ml, respectively. Cancer cells secreted G-CSF in culture and recombinant G-CSF increased cancer cell proliferation. CONCLUSIONS: Like other sarcomas, carcinosarcomas can produce high levels of G-CSF and demonstrate an aggressive behavior that may be autocrine stimulation.
Primary cardiac carcinosarcoma is a rare cardiac tumor, and little is known about its natural history. We treated a man who had no evidence of a cardiac mass at initial echocardiography, but 19 months later he had a large biatrial tumor with left ventricular inflow obstruction. Only palliative resection could be achieved. Four months postoperatively extensive tumor recurrence was found, and he died a month later. Histologic examination showed cells with features of both rhabdomyosarcoma and adenocarcinoma, and the tumor was classified as a primary cardiac carcinosarcoma.
True carcinosarcoma of the prostate is a rare neoplasm, with only 9 cases well documented by immunocytochemistry and ultrastructural examination. We report a case of an unresectable pelvic tumor studied at autopsy. The primary prostatic neoplasm and pulmonary metastases were composed of well differentiated adenocarcinoma admixed with foci of leiomyosarcoma and osteosarcoma. The sarcomatous components showed reactivity with vimentin and desmin, did not express prostatic acid phosphatase (PAP) and prostate specific antigen (PSA), and contained myofilaments on electron microscopic examination. Positive staining of the carcinomatous component for PAP and PSA was noted. These findings confirm the mixed epithelial and mesenchymal components in primary and metastatic sites, and support the diagnosis of true prostatic carcinosarcoma.
We report a case of unilateral ureteral obstruction owing to carcinosarcoma of the distal ureter. Tumor recurred 6 months after ureteronephrectomy and the patient died 2 1/2 years later. A review of the literature revealed only 3 other cases of ureteral carcinosarcoma, all of which had a similar aggressive course. Recognition and separation of this entity from the more usual transitional cell carcinoma are important because of its apparent poorer prognosis.
We report a case of carcinosarcoma of the bladder. Total cystectomy with ileal loop urinary diversion was performed. Histologically, the bulk of the tumor tissue was rhabdomyosarcoma and adenocarcinoma. At distant areas from the bulk tumor transitional cell carcinoma was noted. The literature is reviewed and the clinicopathologic condition of carcinosarcoma of the bladder is discussed.
The clinical presentation, clinical course, and results of various treatment modalities of 17 patients with carcinosarcoma of the lung were reviewed. This group of patients was 0.2% of all Mayo Clinic patients with lung cancer who had been treated between 1971 and 1982. Most patients were men in the sixth decade of life who had a history of smoking. Ten of 17 neoplasms were located in the upper lobes. Noninvasive diagnostic tests had a low yield in detecting carcinosarcomas. Pulmonary resection with curative intent was performed in 15 of 17 patients; however, only 4 patients were alive at 6, 8, 28, and 39 months, respectively, postoperatively. The median survival was 1 year. Doxorubicin-based chemotherapeutic programs produced an objective response in two of four patients.
A carcinosarcoma of the lung, as well as the paratracheal lymph nodes from the same patient, were subjected to immunofluorescent labeling with antibodies to tissue-specific intermediate-filament subunits, including desmin, vimentin, and prekeratin. Within the tumor mass two distinct populations of malignant cells were found: prekeratin-positive cells, corresponding to the carcinomatous component of the tumor, and vimentin-positive cells, corresponding to the sarcomatous elements. Tumor cells were also detected in lymph node metastases in which only the prekeratin-containing carcinoma cells were found. In view of the strict specificity of antivimentin and anti-prekeratin for cells of mesenchymal or epithelial origin, respectively, it is proposed that the two components of the carcinosarcoma are derived from distinct cell types and are not morphologic variants of the same tumor.
Carcinosarcoma of the uterine cervix is a rare tumor. A case of carcinosarcoma of uterine cervix initially interpreted as sarcoma, NOS, is presented along with immunohistochemical findings.