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PubMedDate not supplied

The comparative role of immunohistochemistry and electron microscopy in the identification of myogenic differentiation in soft tissue pleomorphic sarcomas.

There is increasing evidence that histological classification of pleomorphic soft tissue sarcomas is prognostically useful, since a number of studies have provided evidence that myogenic differentiation is associated with a more aggressive clinical behavior. The aim of the current study was to analyze the role of electron microscopy in comparison with immunohistochemistry in the classification of soft tissue pleomorphic sarcomas. Thirty-nine pleomorphic sarcomas of the somatic soft tissues for which material for immunohistochemical and ultrastructural analysis was available were selected for this study. Cases were classified according to the criteria of the WHO classification of soft tissue tumors on the basis of the histologic appearance and of the results of immunohistochemical analysis, and then diagnoses were reconsidered at the light of the results of the ultrastructural analysis. The group of myogenic sarcomas included 13 leiomyosarcomas, 8 myofibrosarcomas, and 1 rhabdomyosarcoma, while the group of nonmyogenic sarcomas included 11 undifferentiated pleomorphic sarcomas/malignant fibrous histiocytomas (MFH), 4 myxofibrosarcomas, and 2 liposarcomas. Overall, there was a good concordance between immunohistochemistry and electron microscopy in recognizing myogenic differentiation in soft tissue pleomorphic sarcomas. Discrepancies included 1 case showing no immunoreactivity for muscle markers, which displayed ultrastructural features allowing reclassification as leiomyosarcoma, and 2 cases initially classified as undifferentiated pleomorphic sarcoma/MFH, which were reclassified as myofibrosarcomas after ultrastructural analysis. Ultrastructural analysis allowed the identification of pleomorphic sarcomas with myofibroblastic phenotype, a category that is not identifiable based on histologic and immunohistochemical profile. Notably, fibronexus junction was identified in tumor cells of 4 pleomorphic myofibrosarcomas, while 2 other lesions showed putative fibronexus junction structures, consisting of electron-dense straight fibrils adjacent to the cell surface, not clearly in continuity with cytoplasmic actin filaments. In conclusion, the results indicate that immunohistochemistry and electron microscopy can usefully complement each other in the classification of soft tissue pleomorphic sarcomas.

Actins↗
PubMed2001

Pleomorphic leiomyosarcoma: clinicopathologic and immunohistochemical study with special emphasis on its distinction from ordinary leiomyosarcoma and malignant fibrous histiocytoma.

Pleomorphic leiomyosarcoma (PLMS) was recently described as a morphologic variant of leiomyosarcoma; however, its diagnostic criteria, as shown by morphologic features and biologic behavior, remain controversial. We describe 28 cases of pleomorphic sarcoma with pleomorphic areas in more than two thirds of the tumor and an ordinary leiomyosarcomatous fascicular area covering less than one third as PLMS. PLMS comprised 8.6% of all the leiomyosarcomas (322 cases) registered in our institute. Patients ranged in age from 31 to 89 years (average, 57.9 years). Seventeen patients (60.7%) were male and 11 were female. Tumor location was as follows: the extremities in 17 cases, the retroperitoneum or abdominal cavity in 7 cases, the chest/abdominal wall in 3 cases, and the scalp in 1 case. Histologically, all cases showed at least small foci of fascicles consisting of smooth muscle tumor cells, in addition to pleomorphic areas mimicking storiform-pleomorphic malignant fibrous histiocytoma. The border between pleomorphic and leiomyosarcomatous fascicular areas was sharp in 3 cases, gradual in 2 cases, and blending in 23 cases. Sixteen cases (57.1%) showed a typical storiform pattern, 6 cases revealed extensive stromal hyalinization, 6 cases showed a chronic inflammatory infiltrate, 2 cases had the foci of foamy xanthomatous cells, and 7 cases contained myxoid malignant fibrous histiocytoma-like areas covering less than 50% of the tumor. The tumors had a tendency to be of a morphologically higher grade (10 tumors were French Federation of Cancer Centers grade 2, 18 were grade 3). Five of 28 cases (18%) showed rhabdoid features. Immunohistochemically, all of the 28 tumors examined showed a positive reactivity for at least one smooth muscle marker (desmin, muscle-specific actin, and alpha-smooth muscle actin) in the leiomyosarcomatous fascicular areas. In the pleomorphic areas the expression of smooth muscle markers (desmin 10 of 28, muscle-specific actin 13 of 28, and alpha-smooth muscle actin 14 of 28) was significantly reduced, compared with that in leiomyosarcomatous fascicular area (desmin 18 of 28, muscle-specific actin 26 of 28, and alpha-smooth muscle actin 24 of 28). No significant difference was observed between the MIB-1 labeling index in the leiomyosarcomatous fascicular areas (26.10 on average) and that in the pleomorphic areas (26.17 on average). However, the MIB-1 labeling index in PLMS was significantly higher than that in ordinary leiomyosarcoma (n = 20, 12.86 on average) or storiform-pleomorphic malignant fibrous histiocytoma (n = 16, 16.63 on average). In 23 patients follow-up data were available with a duration of 1-239 months. Eleven patients developed metastases, and lung accounted for the most common site of metastasis (9 cases). Fifteen of 23 patients (65.2%) died of disease. Our results indicate that PLMS should be differentiated from ordinary leiomyosarcoma because of its high proliferative activities and rather aggressive biologic behavior.

Adult↗
PubMed2005

Immunophenotypic characterization of high grade pleomorphic sarcomas: a demographic and immunohistochemical study in a major referral center of Pakistan.

OBJECTIVE: Immunophenotypic characterization of high grade (pleomorphic) sarcomas and determination of their frequency, mean/median age, sex preferences and common sites in Pakistani patients. METHODS: This study included 134 consecutive cases of high grade (pleomorphic) sarcomas diagnosed in adults above the age of 15 years in the section of histopathology at theAga Khan University Hospital, Karachi during a period of two years. These high grade (pleomorphic) sarcomas were immunophenotyped using a panel including antibodies against Vimentin, Desmin, Smooth muscle Actin, S 100, CD34, CD68 and Cytokeratin etc by indirect immunoperoxidase. RESULTS: Of the 134 cases which were characterized, 38.1% were pleomorphic leiomyosarcoma, followed by pleomorphic rhabdomyosarcoma 14.9%, Malignant Peripheral Nerve Sheath Tumour 9%, pleomorphic liposarcoma 3.7% and pleomorphic storiform Malignant Fibrous Histiocytoma 0.7%. Thirty three percent of cases could not be characterized further. Mean/ median age for Leiomyosarcoma was 50/50, for Rhabdomyosarcomas 33/22, for MPNST 42/41, for Liposarcoma 52/50 and for Malignant Fibrous Histiocytoma 46/46 respectively. The commonest site for leiomyosarcoma was lower limb (43%), for rhabdomyosarcoma head and neck (42%), for MPNSTthorax (36.4%) and for liposarcoma abdomen (50%). CONCLUSION: It was concluded that the most common pleomorphic sarcoma occurring in our adult population was Leiomyosarcoma, and that immunohistochemical stains are essential in most cases for further characterization of pleomorphic high grade sarcoma.

Adult↗
PubMed1995

Immunohistochemical pattern of Bcl-2- and PTHrP-positive cells in primary, in recurrent and in carcinoma in pleomorphic adenomas.

Forty-seven samples of paraffin-embedded formalin-fixed (and 25 related frozen) sections of 27 primary pleomorphic adenomas, 15 recurrent pleomorphic adenomas and 5 carcinomas in pleomorphic adenomas were studied to analyse their immunohistologic patterns with respect to the ratio of the expression of 'normally' and 'aberrantly' differentiated cell types. In primary pleomorphic adenoma PTHrP-positive cells are seen in the inner layer of tubulo-ductal structures, in part of the cells in the mucoid, chondroid, or myxochondroid matrix, and in the squamous metaplastic areas. Bcl-2-positive cells are found in the outer layer of tubulo-ductal structures, in part of the cells in the mucoid, chondroid, or myxochondroid matrix, and around the squamous metaplastic areas. In one case of primary pleomorphic adenoma, which recurred later, the positivity for Bcl-2 is more intense and seen in the periphery of this tumour with a predominantly myxoid pattern. In recurrent pleomorphic adenomas, which also mostly showed a predominantly myxoid pattern, the positivity for Bcl-2 showed a pattern similar to the primary-to-recur tumour. PTHrP-positive cells are found less frequently than Bcl-2-positive cells. In carcinoma in pleomorphic adenoma, the benign part shows the features of primary pleomorphic adenoma with its Bcl-2 and PTHrP-positivity patterns. The malignant part strongly shows Bcl-2-positive cells in the periphery of the tumour. We conclude that the maintained presence of Bcl-2 and PTHrP-positive cells in the tumours we studied shows the variable capacity of tumour cells to differentiate.

Adenoma, Pleomorphic↗
PubMed1995

Diagnostic criteria for neoplastic myoepithelial cells in pleomorphic adenomas and myoepitheliomas. Immunocytochemical detection of muscle-specific actin, cytokeratin 14, vimentin, and glial fibrillary acidic protein.

OBJECTIVE: Markers for normal salivary gland myoepithelium were used to determine the extent of their expression in the neoplastic myoepithelial (nonluminal) cells of pleomorphic adenomas and then in the tumor cells in myoepitheliomas and to gather information necessary to establish diagnostic criteria, especially muscle actin expression, for myoepitheliomas. STUDY DESIGN: Methanol/acetic acid-fixed and paraffin-embedded tissue was used to immunohistochemically study expression of intermediate and smooth-muscle actin filaments in nonluminal cells in 14 pleomorphic adenomas and to compare this to their expression in five myoepitheliomas. RESULTS: In routine histologic sections, the morphologic variants of nonluminal tumor cells--spindle, stellate, polygonal, angular, and plasmacytoid--in pleomorphic adenoma mirror the spectrum of tumor cells in myoepitheliomas. Immunocytochemical similarities are also apparent. Two specific markers for myoepithelial cells in the normal salivary gland, muscle-specific actin and cytokeratin 14, were both variably, independently, and never uniformly expressed in nonluminal cells of pleomorphic adenoma and tumor cells in myoepitheliomas regardless of their morphology. Cytokeratin 14 in addition labels basal cells of excretory ducts. Both muscle-specific actin and cytokeratin 14 preferentially localized to single layers of periductal cells in pleomorphic adenomas, angular, polygonal, and plasmacytoid cells preferentially expressed cytokeratin 14. Similar patterns were noted in the three myoepitheliomas with reasonable expression of the two markers. Only isolated single cells or small groups of plasmacytoid cells in four pleomorphic adenomas with a significant component of these cells and the two plasmacytoid myoepitheliomas immunostained for muscle-specific actin and cytokeratin 14. In both tumor types, vimentin was nearly uniformly expressed in nonluminal tumor cells of all morphologic types, including plasmacytoid cells. CONCLUSIONS: The range and transition of morphology of nonluminal cells in pleomorphic adenomas is reflected in myoepitheliomas. Incomplete or absent expression of the myoepithelial/basal cell markers, muscle-specific actin, and cytokeratin 14, and the general expression of vimentin is common to both tumors. Because these findings apply to the majority of plasmacytoid cells in pleomorphic adenomas, tumor cells with a similar morphology and immunoprofile are to be expected in myoepitheliomas; the term plasmacytoid myoepitheliomas is thus appropriate regardless of the presence or absence of muscle-specific actin.

Actins↗
PubMed2001

Histopathology of pleomorphic adenoma in the parotid gland: a prospective unselected series of 100 cases.

OBJECTIVES/HYPOTHESIS: Histopathological characteristics of pleomorphic adenomas, especially of capsular alterations such as thin capsule areas, capsule-free regions, capsule penetration, satellite nodules, and pseudopodia in the different subtypes, are described. STUDY DESIGN: Prospective unselected series of 100 consecutive cases from 1997 to 2000. METHODS: Light microscopic examination and semiquantitative analysis of the pleomorphic adenomas. RESULTS: Fifty-one (51%) pleomorphic adenomas were classified as myxoid (stroma-rich) type, 35 (35%) specimens as cellular type, and 14 (14%) as classic subtype. Ninety-seven percent of all tumors showed areas with thin (<20 microm) capsule independent of the tumor subtype. Tumors of myxoid subtype showed the absolute greatest regions of a thin capsule. Especially, tumors of myxoid type (71%) often had a distinct focal absence of encapsulation with tumor merging into normal parotid gland tissue; 11% of the cellular subtype and 43% of the classic subtype presented capsule-free areas. Thirty-three percent of the myxoid pleomorphic adenomas, 23% of the cellular subtype, and 21% of the classic subtype had satellite nodules or pseudopodia. CONCLUSIONS: Almost all pleomorphic adenomas have focally thin capsules. One-fourth of all pleomorphic adenomas contain abnormalities such as satellite nodules or pseudopodia. More than two-thirds of pleomorphic adenomas of the myxoid (stroma-rich) subtype and at least half of all tumors show a focal absence of the capsule. Therefore, enucleation or local dissection of the pleomorphic adenoma is not a sufficient surgical treatment of this special tumor entity. We recommend, depending on the location of the tumor, a lateral or total parotidectomy as the treatment of choice.

Adenoma, Pleomorphic↗
PubMedDate not supplied

Myofilament localization and immunoelectron microscopic detection of muscle-specific actin in neoplastic myoepithelial cells in pleomorphic adenomas and myoepitheliomas.

Elucidating the cellular characteristics of the nonluminal or myoepithelial cells of pleomorphic adenomas is one approach to establishing the diagnostic criteria for myoepitheliomas. Ultrastructural features of nonluminal tumor cells in 22 pleomorphic adenomas and of tumor cells in 9 myoepitheliomas were assessed from micrographs of routinely fixed and epoxy resin-embedded samples. Recognizable myofilaments were only moderately prominent in 1 myoepithelioma. In the rest of the cases, irrespective of whether nonluminal cells of pleomorphic adenomas or tumor cells of myoepitheliomas were spindle, angular, round, or plasmacytoid in form, myofilaments were noted only in one third of the cases and were present even in these in a small proportion of the tumor cells. Intermediate filament accumulations and basal lamina were more frequent findings associated with nonluminal tumor cells. Six pleomorphic adenomas and 2 myoepitheliomas had been fixed in half-strength glutaraldehyde and embedded in LR White resin for immunoelectron microscopic detection of muscle-specific actin. In 3 (2 pleomorphic adenomas and myoepitheliomas) of these 8 cases, readily visualized bands of filaments in many tumor cells were strongly labeled by the colloidal gold probe detecting muscle-specific actin even when myofilaments were minimal and infrequent in 2 cases and undetectable in the third by routine transmission electron microscopy. Lack of myofilament detection by immunocytochemistry or routine electron microscopy does not exclude a diagnosis of pleomorphic adenoma or myoepithelioma when growth patterns and cytology indicate such diagnoses. Immunoelectron microscopy, in fact, shows that muscle-specific actin can be detected even when myofilaments or muscle actin are apparently absent or minimal by routine electron microscopy or immunohistochemistry, respectively. Because examples of pleomorphic adenoma and myoepithelioma each with similar histologic and cytologic features of the myoepitheliomatous cells can have variable degrees or complete absence of expression of myofilaments or muscle-specific actin, the time-honored term myoepithelial for the nonluminal cells of pleomorphic adenomas and the term myoepithelioma are legitimate even in the absence of those markers that are specific for normal myoepithelial cells.

Actins↗
PubMed1997

Fine-needle aspiration cytology of pleomorphic lobular carcinoma of the breast. Comparison with the classic type.

BACKGROUND: The pleomorphic variant of invasive lobular carcinoma shares the typical infiltrating histologic pattern of classic invasive lobular carcinoma, but differs from it in its nuclear pleomorphism and aggressive behavior. The purpose of this study was to describe the fine-needle aspiration (FNA) cytologic findings of the pleomorphic variant of lobular carcinoma and to compare them with those of classic lobular carcinoma. METHODS: Among 405 breast FNA performed in 1995, 7 examples of classic infiltrating lobular carcinoma and 4 cases of this neoplasm's pleomorphic variant were identified; all were histologically confirmed. The FNA from three of the four pleomorphic variant cases and from two of the seven classic lobular carcinoma cases were diagnostic of malignancy; these were evaluated for a variety of cytologic criteria, which were graded from 0 to 3. RESULTS: Although exhibiting many cytologic features in common with the classic type, such as indian files and cytoplasmic vacuoles, the FNA of the pleomorphic variant differed in their tendency to yield greater cellularity, larger cell size, and, particularly, more pleomorphic nuclei. CONCLUSIONS: The FNA cytologic findings of the pleomorphic variant of lobular carcinoma are characteristically hybrid between those of classic lobular carcinoma and ductal carcinoma.

Biopsy, Needle↗
PubMed2004

Prognostic implication of p53 protein expression in relation to nuclear pleomorphism and the MIB-1 counts in breast cancer.

BACKGROUND: A close correlation of the p53 protein expression to nuclear pleomorphism and proliferative activity in breast cancer has been reported. The prognostic implications of p53 protein expression, however, in relation to nuclear pleomorphism and proliferative activity in breast cancer remain controversial. PATIENTS AND METHODS: Nuclear pleomorphism and immunohistochemical reactivity for p53 protein and MIB-1 were evaluated on formalin-fixed paraffin-stored sections from 250 patients with breast cancer for whom the median follow-up duration was 6.4 years. RESULTS: p53 protein expression was positive in 66 (26.4%) of 250 cases. Nuclear pleomorphism was grade I or II in 169 (67.6%) cases and grade III in 81(32.4%)cases. The MIB-1 counts were more than 10% in 102 (40.8%) cases and less than 10% in 148 (59.2%) cases. There was a close correlation between p53 protein expression and nuclear pleomorphism (p<0.0001) and between p53 protein expression and MIB-1 counts (p<0.0001). Univariate analyses showed the 66 cases with positive p53 protein expression to have a significantly (p=0.0284) worse disease free survival (DFS) than the 184 cases with negative p53 protein expression. A multivariate analysis, however, on the variables including all of p53 protein expression, nuclear pleomorphism and MIB-1 counts indicated the MIB-1 counts (p=0.0041) as well as the lymph node status to be independently significant factors for DFS, while neither p53 protein expression nor nuclear pleomorphism were independently significant factors for DFS. CONCLUSION: The present study demonstrated that the p53 protein expression, nuclear pleomorphism and MIB-1 counts all demonstrated prognostic significance for breast cancer, while the most significant prognostic indicator among these three biological parameters was the MIB-1 counts.

Adult↗
PubMed1995

Immunohistochemistry of MyoD1 in adult pleomorphic soft tissue sarcomas.

Adult pleomorphic rhabdomyosarcomas are difficult to distinguish from other pleomorphic soft tissue sarcomas. Immunostaining with the monoclonal antibody MyoD1 5.8A has recently shown promise as a sensitive and specific marker of rhabdomyosarcomas of childhood. To determine the usefulness of MyoD1 in distinguishing adult pleomorphic rhabdomyosarcoma from other pleomorphic sarcomas, we studied 21 cases of pleomorphic sarcoma, including six cases diagnosed as rhabdomyosarcoma. Immunostaining was accomplished using monoclonal antibodies against MyoD1, desmin, alpha-smooth-muscle actin, and muscle-specific actin on cryostat sections of frozen tumor. All cases of pleomorphic rhabdomyosarcoma stained positively with both desmin and MyoD1. Five cases diagnosed as nonrhabdomyosarcomatous pleomorphic sarcomas stained positively with desmin, but only one showed weak MyoD1 positivity. Three of these five cases were also positive with alpha-smooth-muscle actin. The results of this study suggest that the sensitivity and specificity of the MyoD1 antibody in the differential diagnosis of adult pleomorphic soft tissue sarcomas approaches that seen in pediatric rhabdomysarcomas.

Adult↗
PubMedDate not supplied

Recurrent pleomorphic adenoma: uninodular versus multinodular disease.

BACKGROUND: While treatment of previously untreated pleomorphic adenoma is relatively straightforward, recurrent pleomorphic adenoma presents a management problem with increased risk of injury to the facial nerve and an increased risk of malignant transformation in recurrent disease. AIMS: The objectives of this study were to review the management of recurrent pleomorphic adenoma in our unit to identify factors that might help treatment of future cases. METHODS: We reviewed the management of pleomorphic adenoma at our department over an eight-year period from 1990-1998 and present our experience of recurrent pleomorphic adenoma of the parotid gland and parapharyngeal space. RESULTS: Twelve patients were treated with recurrent pleomorphic adenoma. In 10 of these, the site of recurrence was in the parotid gland with the remainder occurring in the parapharyngeal space. Type of recurrence was uninodular or multinodular, the former being easier to treat. Three patients required adjuvant radiotherapy. None of our patients had permanent facial nerve damage. CONCLUSIONS: In order to prevent recurrence of pleomorphic adenoma of the parotid gland, we recommend formal superficial parotidectomy for first time surgery.

Adenoma, Pleomorphic↗
PubMed2003

Immunohistochemical evaluation of cartilage-derived morphogenic protein-1 and -2 in normal human salivary glands and pleomorphic adenomas.

Cartilage-derived morphogenic protein (CDMP)-1 and -2 belong to the bone morphogenetic protein (BMP) family in the transforming growth factor (TGF)-beta superfamily. CDMP-1 and CDMP-2 were reported to play essential roles in limb cartilage and limb-joint formation in developing mice. Although pleomorphic adenoma of the salivary glands is an epithelial tumor, it frequently shows ectopic cartilaginous formation. These findings suggested that CDMP-1 and -2 may play essential roles in chondroid formation in salivary pleomorphic adenoma. To evaluate this hypothesis, we examined the expression and localization of CDMP-1 and -2 immunohistochemically in 20 normal human salivary glands and 35 pleomorphic adenomas. CDMP-1 was immunolocalized in the striated ducts and the intercalated ducts in the normal salivary glands. CDMP-1 was immunolocalized in the cuboidal neoplastic myoepithelial cells around the chondroid areas of the pleomorphic adenomas, whereas these molecules were not localized in the spindle-shaped neoplastic myoepithelial cells of the myxoid element or the lacuna cells of the chondroid element in these tumors. CDMP-2 was expressed neither in normal salivary glands nor any of the elements of the pleomorphic adenomas. Type-II collagen and aggrecan were immunolocalized throughout the matrix around the lacuna cells of the chondroid element, whereas type-X collagen was not immunolocalized in any epithelial or stromal elements, including the chondroid elements. Aggrecan was deposited not only on the chondroid matrix, but also on the myxoid stroma and intercellular spaces of the tubulo-glandular structures, whereas chondromodulin-I was deposited on the chondroid matrix. These results indicated that the cuboidal neoplastic myoepithelial cells around the chondroid areas expressed CDMP-1 and suggested that this molecule may play a role in the differentiation of neoplastic myoepithelial cells in pleomorphic adenoma. The phenotype of the lacuna cells was similar to that of mature to upper hypertrophic chondrocytes of the authentic cartilage. In conclusion, pleomorphic adenoma expressed CDMP-1 but not CDMP-2.

Adenoma, Pleomorphic↗
PubMed2005

Vascular endothelial growth factor in salivary pleomorphic adenomas: one of the reasons for their poorly vascularized stroma.

To better understand the poorly vascularized background of the stroma of pleomorphic adenomas, we attempted to determine the expression of molecules related to blood vessels and hypoxic conditions in pleomorphic adenoma. Surgical specimens and tumor cells in primary culture of salivary pleomorphic adenomas were used for immunohistochemistry for CD31, vascular endothelial growth factor (VEGF) and its receptors Flk-1 and Flt-1, as well as for hypoxia markers, such as hypoxia-inducible factor-1alpha (HIF-1alpha) and lactate dehydrogenase-1 (LDH). At the same time, alternative splicing modes of the VEGF gene and expression levels of the HIF-1alpha gene were analyzed in surgical specimens by means of reverse-transcription polymerase chain reaction (RT-PCR) and direct sequencing of the PCR products. In addition to co-immunolocalization with CD31+ vascular endothelial cells, VEGF and its receptors were demonstrated in normal duct epithelial and myoepithelial cells as well as in tumor cells in ductal structures and in myxochondroid stromata. Immunolocalizations for HIF-1alpha and LDH were confirmed in the VEGF-positive area. Immunofluorescence signals for VEGF and others were confirmed in pleomorphic adenoma cells in culture. RT-PCR results showed that there were at least four splicing modes of the VEGF gene, among which VEGF(121) was most enhanced, and higher HIF-1alpha levels in pleomorphic adenomas. The results suggest that pleomorphic adenoma cells produce VEGF in several functional forms for their own proliferation or differentiation, and that the VEGF expression is controlled by hypoxic circumstances of poorly vascularized pleomorphic adenomas.

Adenoma, Pleomorphic↗
PubMed2001

Cartilage-specific matrix protein chondromodulin-I is associated with chondroid formation in salivary pleomorphic adenomas: immunohistochemical analysis.

Chondromodulin-I (ChM-I) is a novel cartilage-specific matrix protein. In the growth plates of the long bones, ChM-I was shown to be expressed in mature to upper hypertrophic chondrocytes, and to be deposited in the cartilage matrix. As ChM-I strongly inhibits angiogenesis, cartilage is avascular. Also, ChM-I has bifunctional activity against chondrocyte proliferation. On the other hand, pleomorphic adenomas of the salivary glands frequently have chondroid elements. To elucidate the relationship between chondroid formation and hypovascularity in salivary pleomorphic adenomas, we immunohistochemically examined the expression and localization of ChM-I in 35 cases of this tumor. ChM-I was immunolocalized to the lacunae in the chondroid elements of pleomorphic adenomas (100%). Type II collagen and aggrecan were immunolocalized throughout the matrix around lacuna cells of the chondroid element (100%, 91.7%), and ChM-I was infrequently immunolocalized to the spindle-shaped myoepithelial cells in the myxoid element (37.5%). Fibroblast growth factor-2 was strongly immunolocalized to the lacuna cells in the chondroid element (100%), among the neoplastic myoepithelial cells in the myxoid elements (96.9%), and on the basement membranes around the solid nests of neoplastic myoepithelial cells (71.4%). Although CD34 is a marker of endothelial cells, CD34 was expressed in the endothelial cells in only a few areas around the epithelial elements and in the fibrous element of pleomorphic adenomas. No signals for CD34 were observed in chondroid elements in pleomorphic adenomas (P < 0.001), but a few signals were seen in the myxoid elements (P < 0.05). These findings suggested that lacuna cells and neoplastic myoepithelial cells expressed ChM-I, and that this molecule may play an important role in hypovascularity and chondroid differentiation in pleomorphic adenoma. In conclusion, pleomorphic adenoma expressed ChM-I, which is involved in hypovascularity and chondroid formation in this type of tumor.

Adenoma, Pleomorphic↗
PubMed1999

Immunohistochemical localization of the bone morphogenetic protein-6 in salivary pleomorphic adenomas.

Salivary pleomorphic adenomas are often associated with chondroid tissue formation. We have found that bone morphogenetic proteins (BMP), especially BMP-2, may play an important role in ectopic chondrogenesis in this tumor. Bone morphogenetic protein-6 was reported to be related to the osteogenic metastasis of prostatic carcinomas. The relationship between BMP-6 expression and chondroid tissue formation is investigated. Twenty-three pleomorphic adenomas were examined immunohistochemically. The overexpression of BMP-6 was observed in 10 pleomorphic adenomas of the major salivary glands (43. 5%), and no evidence of BMP-6 expression in any of the nine pleomorphic adenomas of the palate. Bone morphogenetic protein-6 was immunolocalized in the lacuna cells of the chondroid tissue, in which type II collagen was localized. Bone morphogenetic protein-6 was expressed in inner ductal cells of the tubulo-glandular structures in the pleomorphic adenomas. This finding indicates that BMP-6 may be associated with the differentiation of inner ductal cells. Bone morphogenetic protein-6 was expressed weakly in neoplastic myoepithelial cells in the myxoid areas, which may be related to the production of extracellular matrices. Bone morphogenetic protein-6 has a role in chondroid formation, and also tubulo-glandular differentiation in pleomorphic adenomas. In conclusion, a large portion of pleomorphic adenomas of the salivary gland origin, but not of palate origin, was shown to overexpress BMP-6 protein.

Adenoma, Pleomorphic↗
PubMed2004

Elevated expression of cyclooxygenase-2 in adenocarcinoma of the parotid gland: insights into malignant transformation of pleomorphic adenoma.

Pleomorphic adenoma, the most common type of tumor of the parotid gland, may transform into a malignant tumor. In the current study, we investigated whether the expression of cyclooxygenase-2 (COX-2) is elevated in adenocarcinoma as compared to pleomorphic adenoma. Ten pleomorphic adenomas and 10 adenocarcinomas were examined. The tumor specimens were immunohistochemically stained with antibodies against COX-2 and Ki-67. The labeling indices of COX-2 in pleomorphic adenoma and adenocarcinoma were 6.0% +/- 4.1% and 16.1% +/- 4.6%, respectively, and those of Ki-67 in pleomorphic adenoma and adenocarcinoma were 0.77% +/- 0.62% and 6.9% +/- 6.6%, respectively. The labeling indices of both COX-2 and Ki-67 were significantly greater (p < .001) in adenocarcinoma than in pleomorphic adenoma. Together with the biological effects of COX-2, these results suggest that overexpression of COX-2 plays a crucial role in the pathogenesis of malignant transformation of pleomorphic adenoma in the parotid gland.

Adenocarcinoma↗
PubMed1999

Pleomorphic adenoma with nuclear palisading arrangement of modified myoepithelial cells: histopathologic and immunohistochemical study.

Pleomorphic adenomas with a nuclear palisading arrangement of spindle-shaped modified myoepithelial cells (MMCs), suggesting the appearance of palisading leiomyoma or Antoni's A type of neurilemmoma, are quite rare, and its cytologic nature has been poorly understood. This paper reports histologic and immunohistochemical findings of palisading MMCs in two cases of pleomorphic adenoma. Histologically, foci of spindle-shaped MMCs with nuclei in a palisading arrangement were scattered in the myxoid areas. Near the large foci of spindle-shaped MMCs with nuclear palisading arrangements, tiny foci of spindle-shaped MMCs forming nuclear palisading or rosette-like arrangements were seen. Such nuclear palisading arrangements of MMCs were suggestive of differentiation or transformation of MMCs into cells that were more smooth muscle in nature, supported by occasional existence of palisading leiomyoma in the myometrium and gastrointestinal tract. However, immunohistochemical findings of palisading MMCs in pleomorphic adenoma were similar to those of non-palisading MMCs, and showed no evidence of smooth muscle differentiation; neither palisading nor non-palisading MMCs in pleomorphic adenoma expressed desmin, muscle specific actin (HHF-35), alpha smooth muscle actin, or myoglobin. The biologic significance and formative mechanism of nuclear palisading arrangement of MMCs in pleomorphic adenoma could not be determined in the present study. However, if the MMCs with nuclear palisading arrangements in pleomorphic adenoma, presented here, are aspirated for cytologic diagnosis or are included in a small biopsy specimen, the correct diagnosis of pleomorphic adenoma may be confused by a suspicion of myogenic or neurogenic tumor.

Adenoma, Pleomorphic↗
PubMed2000

[The expression and mechanism study of BMP in pleomorphic adenoma].

OBJECTIVE: One important pathological character of pleomorphic adenomas is that there is chorndriod component in the epithelial tumors. It is well known that bone morphogenetic protein (BMPs) plays important roles in the morphogenesis of hard tissue by inducing mesenchymal cells to differentiate into osteoblasts and chondroblasts in vivo. So we examined the expression of BMP and BMP2 mRNA in pleomorphic adenomas to study the pathological mechanism of chorndriod tissue formation. METHODS: Using ABC immunohistochemistry method, 6 specimens of pleomorphic adenomas were examined with BMP antibody. Reverse transcriptase-polymerase chain reaction (RT-PCR) methods were developed for detecting BMP2 mRNA expression with special primers used to amplify the BMP2 cDNA mature domain fragment. The total RNA was extracted from frozen 6 specimens of pleomorphic adenoma and then reversed to cDNA by reverse transcription using AMV reverse transcriptase. PCR conditions were 94 degrees C for 20 seconds, 60 degrees C for 30 seconds, and 72 degrees C for 1 minute, 40 cycles, followed by extension for 30 minute at 72 degrees C. The reaction products were analyzed by electrophoresis. RESULTS: BMP expression could be found in all of the specimens of pleomorphic adenoma examined by immunohistochemistry method. BMP2 RT-PCR product was detected in only 5 specimens that showed BMP2 mRNA existed in 5 specimens. CONCLUSION: These results may be helpful to study the mechanism of pleomorphic adenoma. It is speculated that BMP secreted by tumor cells may play important roles in origin of osteoid tissue in pleomorphic adenoma by inducing neoplastic myoepithelial cells to differentiate to chondrocytes.

Adenoma, Pleomorphic↗