Sarcomatoid carcinoma of the renal pelvis with giant cell tumor-like features: Case report with immunohistochemical findings

Sarcomatoid transitional cell carcinoma is a rare entity, in which a malignant, overtly epithelial component coexists with areas having a sarcoma-like appearance. Histological distinction of sarcomatoid carcinomas from carcinosarcomas is often difficult and immunohistochemistry is a helpful diagnostic adjunct in the correct diagnosis. In the present report, we describe an uncommon case of sarcomatoid transitional cell carcinoma of the renal pelvis, associated with giant cell tumor-like features. Immunoperoxidase staining for cytokeratin was positive in spindle cell component, indicating an epithelial origin. The carcinomatous component showed a diffuse membranous reactivity for E-cadherin, whereas the reactivity was sporadic and weaker in the sarcomatoid component, suggesting that the decrease of E-cadherin expression might be associated with the acquisition of sarcomatous morphology. Osteoclast-like multinucleated giant cells were positive for CD68 and negative for p53 oncoprotein, suggesting that they represent a non-neoplastic component that is reactively induced in the tumor stroma.     

A case of carcinosarcoma arising in the submandibular gland.

A 54-year-old man presented with an 8-year history of a hard asymptomatic mass of the left submandibular area. Total excision of the left submandibular gland with radical neck dissection was performed under a diagnosis of a submandibular tumor, probably a malignant mixed tumor. The pathologic diagnosis was carcinosarcoma consisting of carcinomatous and sarcomatous elements. The epithelial component was composed of squamous cell carcinoma, undifferentiated carcinoma, and adenocarcinoma. The nonepithelial component was composed of chondrosarcoma, osteosarcoma, spindle cell sarcoma, rhabdomyosarcoma, and liposarcoma. In the central area of the tumor, a few remnants of benign pleomorphic adenoma were identifiable. The finding suggested that in our patient, the carcinosarcoma arose from a preexisting pleomorphic adenoma. In view of the expected aggressive nature of the tumor, the patient was treated with postoperative radiotherapy of 60 Gy total, in 30 daily fractions of 2 Gy, and chemotherapy. He currently remains well and free of disease 24 months after treatment.     

Metanephric adenosarcoma in a young adult: morphologic, immunophenotypic, ultrastructural, and fluorescence in situ hybridization analyses: a case report and review of the literature.

Metanephric neoplasms are uncommon renal tumors that arise in both children and adults. They may be composed of small epithelial cells or benign stroma, or both, and are termed metanephric adenoma, metanephric stromal tumor, or metanephric adenofibroma, respectively. Thus far, these tumors have been known for their benign behavior. We present the case of a 21-year-old woman who developed a neoplasm composed of a renal epithelial component identical to metanephric adenoma combined with a malignant spindle cell sarcoma. The epithelial component was positive for pankeratin AE1/3, whereas the sarcomatous component was negative for epithelial markers and positive for vimentin, CD34, and CD117. No smooth muscle differentiation was apparent in the sarcoma by immunohistochemistry or ultrastructural analysis. By fluorescent in situ hybridization analysis of the sarcomatous component there was monosomy of the X chromosome, but no apparent variation from the normal diploid pattern for chromosomes 3, 7, 12, and 17. We conclude that the spectrum of metanephric neoplasia should be expanded to include malignant stromal variants, and we propose the term "metanephric adenosarcoma" for the present case.     

Sarcomatoid renal cell carcinoma with scant carcinomatous components

A 30‐year‐old male underwent radical nephrectomy for a right renal tumor 15 cm in diameter. On microscopic examination of initial 17 sections, the tumor consisted of pleomorphic giant cells and spindle neoplastic cells. There was no carcinomatous component. Immunohistochemically, the neoplastic cells were negative for keratin and epithelial membrane antigen but positive for vimentin. The giant cells were also scatteringly, weakly positive for myoglobin. At that time a diagnosis of rhabdomyosarcoma of the kidney was made. However, further microscopic examination of another eight sections revealed small areas of clear cell‐type renal cell carcinoma (RCC) which transited to sarcomatous components and led to a diagnosis of sarcomatoid RCC. The patient underwent three cycles of adjuvant chemotherapy. He has been free of the disease for 14 months after nephrectomy.     

Schwannoma-Like Pleomorphic Adenoma: A Case Report with Review of the Literature

Pleomorphic adenoma is a common benign salivary gland tumor, which represents about 66 % of benign neoplasms of the salivary glands. Although it can occur in any salivary gland, it is most frequently found in the parotid. Pleomorphic adenomas are renowned for their cytomorphological and architectural heterogeneity that are characterized by intermixed epithelial and mesenchymal-like components. We report a rare case of pleomorphic adenoma of the parotid gland with prevalent schwannoma-like features mimicking a benign schwannoma. Microscopically the tumor showed a prevalence (about 95 %) of schwannoma-like areas with focal (about 5 %) epithelial component with tubular organization. The tumor showed positive immunoexpression for cytokeratin, S-100 protein, and focal expression of p63, CD10 and smooth muscle actin. To the best of our knowledge only six cases of schwannoma-like pleomorphic adenoma have been reported in the literature. The differential diagnosis between this entity and neurogenic and myogenic tumors is discussed.     

Sarcomatoid carcinoma of the urinary bladder: report of a case

The patient was a 78-year-old man with gross hematuria. A non-papillary and non-pedunculated tumor was found on the posterior wall of the bladder by cystoscopic examination. Total cystectomy with construction of ileal conduit was performed. Histologically, the tumor was composed of carcinomatous and sarcomatous elements. The carcinomatous element was compatible with grade 3 transitional cell carcinoma. The sarcomatous element was composed of osteosarcomatous, chondrosarcomatous pattern and undifferentiated malignant spindle cell component. Immunohistochemical examination demonstrated the presence of keratin, cytokeratin and epithelial membrane antigen in both carcinomatous and sarcomatous elements. Therefore, we diagnosed this tumor as sarcomatoid carcinoma. The patient has remained well without any evidence of recurrence for 10 months after operation.     

Malignant mesodermal mixed tumor of the bladder: report of a case

An 81-year-old woman was admitted to our clinic due to gross hematuria. A large bulky pedunculated mass was found in the bladder by cystoscopic examination. Subtotal cystectomy and bilateral cutaneostomy was performed on January 12, 1987. Histologically the tumor was composed of carcinomatous and sarcomatous elements. The carcinomatous element was composed fundamentally of grade 2, transitional cell carcinoma with numerous foci of squamous metaplasia. The sarcomatous element was composed of myxosarcomatous, chondro-sarcomatous pattern and non-differentiated malignant spindle cell component. Immunohistochemical examination demonstrated the presence of cytokeratin and epithelial membrane antigen in the spindle cell and more obvious carcinomatous regions, using the avidin-biotin conjugated immunoperoxidase technique. The patient died 3 months after operation. Autopsy findings showed multiple organ metastasis which were composed of carcinomatous and sarcomatous elements.     

Gliosarcoma arising in oligodendroglial tumors ("oligosarcoma"): a clinicopathologic study

Gliosarcomas are morphologically biphasic tumors composed of glial and sarcomatous elements. Only rare examples of gliosarcoma with oligodendroglial components have been reported. Seven patients with oligodendroglial tumors and a sarcomatous component were identified. Fluorescence in situ hybridization for 1p/19q was sought in glial and sarcomatous regions in all cases. Their mean age at diagnosis of gliosarcoma was 48 years (range 36 to 68) (F:M ratio=5:2). At first resection, the tumors included grade II oligodendroglioma (n=3), grade III oligodendroglioma (n=1), grade II oligoastrocytoma (n=1), and grade III oligoastrocytoma (n=2). The sarcomatous component developed in recurrent/progressive tumors in 6 cases but was a focal finding at first tumor resection in 1 and included fibrosarcoma (n=5), leiomyosarcoma (n=1), or pleomorphic myogenic sarcoma (n=1). Rhabdoid change was a focal finding in the sarcomatous component of 1 tumor. The glial component expressed both glial fibrillary acidic protein and S-100 in all cases, whereas the sarcomatous component at least focally showed smooth muscle actin (n=6), CD34 (n=4), S-100 protein (n=3), and epithelial membrane antigen (n=2) reactivity. Fluorescence in situ hybridization studies demonstrated 1p/19q codeletion in 5 cases, showed no evidence of deletion in 1 case, and technically failed in 1 case. Three of the 5 cases demonstrated 1p/19q codeletion in the sarcomatous component as well. Gliosarcomas with oligodendroglial elements are rare. The relatively frequent presence of 1p/19q codeletion in both glial and sarcomatous components supports the notion that the sarcomatous component represents a metaplastic change occurring in the glial element, the same mechanism active in classic astrocytic gliosarcomas.     

Pleomorphic carcinomas of the lung show a selective distribution of gene products involved in cell differentiation,cell cycle control,tumor growth,and tumor cell motility: a clinicopathologic and immunohistochemical study of 31 cases

We investigated 31 cases of pleomorphic carcinomas of the lung, with a double component of neoplastic epithelial cells and of spindle and/or giant cells. To correlate the morphologic diversity of these two cell components with their immunophenotype, we evaluated the expression of several gene products involved in cell differentiation (cytokeratins, epithelial membrane antigen, carcinoembryonic antigen, vimentin, S-100 protein, smooth muscle actin, desmin), cell cycle control and apoptosis (p53, p21Waf1, p27Kip1, FHIT), tumor growth (proliferative fraction, assessed by Ki-67 antigen, and microvascular density, assessed by CD34 immunostaining), and tumor cell motility (fascin). We found the epithelial component to be significantly more immunoreactive for cytokeratins, epithelial membrane antigen, carcinoembryonic antigen, cell cycle inhibitors p21Waf1, p27Kip1 and tumor suppressor gene FHIT, whereas the sarcomatoid component, independent of tumor stage and size, was more immunoreactive for vimentin, fascin, and microvascular density. Accordingly, we suggest a model of tumorigenesis whereby the mesenchymal phenotype of pleomorphic cells is likely induced by the selective activation and segregation of several molecules involved in cell differentiation, cell cycle control, and tumor cell growth and motility. Whether pleomorphic carcinomas of the lung are tumors with a dismal prognosis still remains an unsettled issue. In our series, however, stage I pleomorphic carcinomas have the same clinical behavior as ordinary non-small cell lung cancer, and only a high proliferative index (Ki-67 labeling index >35%) is associated with a worse prognosis in these tumors.     

A case of carcinosarcoma of the urinary bladder

A 66-year-old woman visited our hospital complaining of painful, irritative urinary symptoms and macroscopic hematuria. Cystoscopy revealed a non-papillary tumor covered with necrotic tissue on the right side of the posterior wall of the bladder. Transurethral resection was performed ; histologically, the tumor was found to be composed of carcinomatous and sarcomatous elements. The carcinomatous element consisted of urothelial and squamous cell carcinomas. The sarcomatous element was composed of osteosarcoma, chondrosarcoma and spindle cell sarcoma. Immunohistochemical examination showed that the carcinomatous component was positive for cytokeratin and the sarcomatous component was positive for S-100 protein. The patient underwent total cystectomy with ileal conduit under the diagnosis of carcinosarcoma. Pathological examination showed no residual tumor. She was followed up with no signs of recurrence or metastasis. Computed tomography (CT) at nine months following surgery showed no evidence of recurrence. However, thirteen months after the operation, she complained of lower abdominal pain, and CT demonstrated a bulky intrapelvic tumor and right hydronephrosis. Her condition worsened rapidly and she died one month later.     

Carcinosarcoma of the extrahepatic bile duct

A rare case of a carcinosarcoma of the extrahepatic bile duct demonstrating interesting features is described. A 75-year-old woman with a history of choledocholithotomy presented with acute obstructive suppurative cholangitis. Ultrasonography and computed tomography showed a thickened choledochal wall, with calcification. Percutaneous transhepatic and endoscopic retrograde cholangiography revealed a round filling defect accompanied by an irregular obstruction in the common bile duct. Carcinosarcoma was diagnosed from a protruding lesion in the common bile duct obtained by intraoperative frozen sectioning, and pylorus-preserving pancreatoduodenectomy was performed. Histological examination by light microscopy showed a transition between the carcinomatous and sarcomatous components and positive immunoreactivity for epithelial markers in the sarcomatous component. The patient died of a local recurrence 2 years after the surgery. Polypoid growth and ossification in the tumor could be representative features of carcinosarcoma of the extrahepatic bile duct.     

Genetic alterations in urinary bladder carcinosarcoma: evidence of a common clonal origin

The cellular origin of carcinosarcoma of the bladder is unknown. We addressed this issue by using microsatellite analysis for loss of heterozygosity (LOH) in both the carcinomatous and sarcomatous components of 6 bladder tumors. We tested 40 microsatellite markers from 19 human chromosomes and compared the genetic alterations between the two separately isolated components. The potential relevance of the E-cadherin pathway was also evaluated by immunohistochemistry. All 6 cases revealed identical LOH on chromosomal arms 9p, 9q, 8p, and 8q, corresponding to relatively early events in bladder carcinogenesis. Discordant losses between two alleles in the remaining chromosomes, associated with progression, were seen in all tumors with a trend toward a higher incidence in the more advanced tumors (N1M1 and N1Mx). E-cadherin was strongly expressed in the carcinomatous components (5 of 6), whereas most of sarcomatous elements displayed absence of the protein product (4 of 6). These results indicate that both the carcinomatous and sarcomatous components of carcinosarcoma are derived from a common stem cell. Downregulation of E-cadherin may define one of the pathways responsible for conversion of epithelial cells to the sarcomatous phenotype.     

Polypoid carcinoma of the esophagus. A unifying term for "carcinosarcoma" and "pseudosarcoma"

Polypoid carcinomas with spindle-cell sarcomatous features have been designated either as carcinosarcoma or pseudosarcoma. The distinction between these two tumors has depended on the presence of "intermingling" of the carcinomatous and sarcomatous components in so-called carcinosarcoma. But unlike the carcinosarcoma, the sarcomatous component in pseudosarcoma has been considered benign. A polypoid tumor of the esophagus in a 57-year-old male was predominantly composed of spindle cell, sarcomatous cells. The presence of adjacent intraepithelial epidermoid carcinoma with transitional and ultrastructural features confirmed the epithelial origin of this tumor. Because of the absence of "intermingling," the primary tumor was considered to be a pseudosarcoma. However, our postmortem examination showed metastases composed of both carcinomatous and sarcomatous features. A review of the literature on carcinosarcomas and pseudosarcomas shows that only one case of pseudosarcoma reported by Hughes and Cruickshank showed a similar situation and indicates that the sarcomatous component in pseudosarcomas has the same metastatic potentiality as has been reported in carcinosarcomas. We conclude from these studies a basic similarity of the carcinosarcoma and pseudosarcoma. The term polypoid carcinoma is proposed for both these lesions.     

Primary intracranial sarcomatoid carcinoma arising from a recurrent/residual epidermoid cyst of the cerebellopontine angle: a case report

Primary intracranial squamous cell carcinomas (SCCs) are rare and mostly associated with an intracranial epidermoid or dermoid cyst. Sarcomatoid carcinoma is a rare biphasic tumor composed of both carcinomatous and sarcomatous components and has not previously been reported as a primary intracranial tumor. Here, we present a case of a 60-year-old man with a primary intracranial sarcomatoid carcinoma, arising from the remnants of the previously resected epidermoid cyst in the cerebellopontine angle. The resected material had portions of an epidermoid cyst lined by normal and dysplastic squamous epithelia and invasive keratinizing SCC. This area was in continuity with areas of highly pleomorphic, anaplastic sarcomatoid cells. Brisk mitotic activity and extensive areas of necrosis were found. On immunohistochemical staining, the cells of the conventional SCC were positive for cytokeratin 5/6, pancytokeratin, epithelial membrane antigen, p63, and p53. The sarcomatoid cells were diffusely and strongly positive for vimentin, p53, smooth muscle actin, and, focally, muscle-specific actin. Occasional sarcomatoid cells coexpressed cytokeratin 5/6, pancytokeratin, p63, and S100 protein. The patient subsequently developed leptomeningeal spread and died 4 months after the second surgery. This rare entity expands the morphologic spectrum encountered in primary intracranial carcinoma.     

Immunoprofile of a carcinosarcoma of the submandibular gland.

Carcinosarcomas are a very rare group of true malignant tumors of the salivary gland. As the name indicates, the tumor is composed of an epithelial and a mesenchymal component, both malignant. We report a case of carcinosarcoma of the submandibular gland in an 86-year-old woman. The epithelial component showed a squamous carcinoma phenotype, whereas the mesenchymal component was morphologically similar to a fibrosarcoma. The epithelial component was strongly positive for CK13, CK14, and AE1/AE, and groups of positive cells were seen for CK19 and vimentin. The whole mesenchymal component was positive for vimentin, negative for cytokeratins, and focal cells were positive for smooth- muscle actin. Both components were strongly positive for P53 and Cyclin D1, and focally positive for MDM2. Rare multinucleated giant cells showed expression of CD68, and focal dendritical cells on carcinomatous nests were positive for S-100. The CK7, CK8, Factor XIIIa, c-erbB-2, P16, CDK-4, Rb1, and E2F-1 were not detected in these 2 groups of malignant cell populations.     

Endometrioid carcinomas of the uterine corpus with sex cord-like formations, hyalinization, and other unusual morphologic features: a report of 31 cases of a neoplasm that may be confused with carcinosarcoma and other uterine neoplasms

We describe a series of unusual endometrioid carcinomas (ECs) of the uterine corpus characterized in significant part by cords of epithelioid cells, spindle cells, and a hyalinized stroma that sometimes formed osteoid. These features, particularly when prominent, produced an appearance strikingly different from that of conventional EC, sometimes resulting in problems in differential diagnosis, especially with a malignant mullerian mixed tumor (carcinosarcoma). The 31 patients ranged in age from 25 to 83 years (mean, 52 years). The proportion within each stage were as follows: stage Ia, 9.7%, stage Ib, 45.2%, stage Ic, 9.7%, stage IIb, 16.1%, stage IIIc 3.2%, and stage IV, 3.2%. In 4 patients (12.9%), staging information was not available. On microscopic examination, typical EC, which accounted for 10% to 90% of the tumor, was admixed in 90% of cases with cords of epithelioid or spindle cells within a hyalinized stroma. In 3 cases, the tumor contained cords of cells without a hyalinized stroma. Areas with a diffuse growth of fusiform cells suggesting endometrial stromal cells were also occasionally seen in minor amounts. Seventy percent of the tumors exhibited squamous differentiation, and in 50% of the tumors there was a background of endometrial hyperplasia. Two thirds of the tumors were grade 2 and the remainder were grade 1. Vascular space invasion was identified in seven tumors. On immunohistochemical analysis, the typical EC component was strongly positive for keratin, whereas the keratin staining was more focal and variable in the epithelial cells in the cords. Muscle markers (desmin, actin), CD10, and inhibin were negative in the latter. Overexpression of p53 was found in only 1 case. Eighty-three percent of the patients were alive with no evidence of disease on follow-up (range, 2-115 months; mean, 34.4 months). The clinical features, including a typically low stage and generally good prognosis, and histologic findings are different from those of malignant mullerian mixed tumors that are characterized by both high-grade carcinomatous and sarcomatous components and an aggressive clinical course. Confusion with other neoplasms, particularly those with sex cord-like growth, such as uterine tumors resembling ovarian sex cord tumors and epithelioid smooth muscle tumors, may also arise. We refer to tumors with the features described herein as "corded and hyalinized endometrioid carcinomas," a designation that reflects their two most striking and consistent features. Corded and hyalinized endometrioid carcinomas are yet another example of the protean phenotype of endometrioid adenocarcinomas of the female genital tract that has been appreciated only in the last two decades.     

Mullerian adenosarcomas: an immunophenotypic analysis of 35 cases

Mullerian adenosarcomas (MAs) are rare mixed mesenchymal and epithelial neoplasms that occur most commonly in the uterus. Although the epithelial component is typically benign, the mesenchymal component of most adenosarcomas morphologically resembles that observed in endometrial stromal tumors and is responsible for their clinical behavior. Thus, the differential diagnosis usually includes not only low-grade endometrial stromal tumors, but also adenofibroma, carcinosarcoma, and embryonal rhabdomyosarcoma especially in small samples. The objective of this study was to ascertain the immunophenotypic profile of the epithelial and mesenchymal components of MAs and delineate possible differences between conventional mesenchymal areas and areas of sarcomatous overgrowth. Representative sections from 35 MAs, 28 of them without sarcomatous overgrowth (MA-NSO) and 7 with sarcomatous overgrowth (MA-SO), were included in the study. Thirty tumors arose in the uterus, 4 were pelvic, and 1 originated in the colon. Adequate blocks were selected and immunostained for estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), CD10, WT1, smooth muscle actin, desmin, AE1/3 cytokeratin, CD34, calretinin, inhibin, c-kit, and Ki-67. The mesenchymal component expressed ER in 21/27 MA-NSOs but in only 1/7 MA-SOs (65% overall). PR was expressed in 21/26 MA-NSOs and 4/7 MA-SOs (76% overall), whereas AR was positive in 10/27 MA-NSOs and 5/7 MA-SOs (35% overall). CD10 was expressed in 23/28 MA-NSOs but in only 2/7 MA-SOs (71% overall), and WT1 positivity was seen in 22/27 MA-NSOs and 6/7 MA-SOs (79% overall). Sixty-seven percent of MAs expressed smooth muscle actin, 32% desmin, including both examples of MA-SOs with rhabdomyoblastic differentiation, and 25% expressed AE1/3 cytokeratin. CD34 expression was found in 35% of the tumors, but it was almost always patchy in distribution and weak in intensity, as was calretinin expression, seen only in 12% of the cases. Expression of c-kit and inhibin in greater than 5% of the tumor cells was not encountered. The median and mean Ki-67 labeling indices were 10% and 12%, respectively (range, <5% to 40%). The median and mean Ki-67 indices were both 5% in MA-NSOs compared with 30% and 28%, respectively, in MA-SOs. The epithelial compartment demonstrated expression for ER (24/32), PR (23/31), and AE1/3 cytokeratin (33/33); rare cases expressed CD10 (4 cases) and AR (1 case). In summary, the immunophenotype of most MAs resembled that of endometrial stromal tumors (positive for ER, PR, WT1, and CD10, with variable expression of muscle markers, AR and cytokeratin). The proliferative rate in the stromal component was strongly related to the presence of sarcomatous overgrowth. ER, PR, and CD10 expression was lost in MA-SOs relative to conventional low-grade stromal areas of mullerian/mesodermal adenosarcomas, reflecting the "dedifferentiation" of this component.     

Sarcomatoid carcinoma of the urinary bladder with a spontaneous perforation: a case report

A 65-year-old woman was referred to our clinic with gross hematuria. Cystoscopy revealed a non-papillary and non-pedunculated tumor on the left lateral wall of the bladder. A piece of necrotic tissue obtained from the bladder irrigation was histologically squamous cell carcinoma. A perforation at the left lateral wall of the bladder was found on the cystogram. Bone scintigraphy showed multiple metastases and computed tomography scans showed multiple lymph node metastases in the pelvic cavity. The clinical diagnosis was bladder carcinoma of T4N2M1 stage with an abscess due to a spontaneous perforation. Total cystectomy with bilateral ureterocutaneostomy was performed. She died due to sepsis 13 days after the operation. Histologically, the tumor was composed of carcinomatous and sarcomatous elements. The carcinomatous element was compatible with squamous cell carcinoma and the sarcomatous element was composed of undifferentiated malignant spindle cells. Immunohistochemical examination showed that the carcinomatous component was positive for keratin and human chorionic gonadotropin (HCG) and the spindle cell component positive for vimentin, desmin and HCG. Therefore, we diagnosed the tumor as sarcomatoid carcinoma. We reviewed 56 cases of carcinosarcoma of the bladder in Japan and discussed the clinicopathology of the disease.     

Benign metastasizing pleomorphic adenoma of the parotid gland: a clinicopathologic puzzle

BACKGROUND: Pleomorphic adenoma constitutes the most common benign parotid gland tumor. Local recurrence after surgical treatment (lateral or total parotidectomy) has been described in 1% to 5% of cases. Malignant degeneration has been reported in 2% to 9% of cases of pleomorphic adenoma of salivary gland origin. Metastasizing pleomorphic adenomas without histologic evidence of malignancy have rarely been reported. Metastatic lesions have been discovered in bone, lymph nodes, the lung, oral cavity, pharynx, skin, liver, retroperitoneum, kidney, calvarium, and central nervous system. To the best of our knowledge, we hereby report the first case of pleomorphic adenoma of the parotid gland metastasizing to the ipsilateral maxilla. METHODS: We simultaneously examined apoptosis-related protein expression and markers of cell-proliferation activity in our case of benign pleomorphic adenoma metastasis and compared outcome with a control group of primary parotid pleomorphic adenomas. RESULTS: Analysis of p53, Bcl-2, MIB1, CD 105, p27, and p21 expression did not reveal significant differences between metastasizing pleomorphic adenoma of the salivary gland and the control group of primary parotid pleomorphic adenomas. CONCLUSIONS: Clinical rather than pathologic evidence seems to justify inclusion of metastasizing salivary pleomorphic adenoma in the group of low-grade malignant salivary tumors.