Immunohistochemical localization of members of the transforming growth factor (TGF)-β superfamily in normal human salivary glands and pleomorphic adenomas

Although pleomorphic adenoma is the most common type of salivary gland epithelial tumor, it frequently contains "mesenchymal"-like components, including myxoid or chondroid tissues. We reported previously that chondroid tissue formation in pleomorphic adenoma was associated with overexpression of bone morphogenetic proteins (BMPs) by neoplastic myoepithelial cells. BMPs belong to the transforming growth factor (TGF)-beta superfamily, so we hypothesized that pleomorphic adenoma may express TGF-betas and that these molecules may regulate mesenchymal-like tissue formation. To evaluate this hypothesis, we immunohistochemically examined TGF-beta1, -beta2 and -beta3 expression and localization in normal salivary glands and in 43 cases of pleomorphic adenomas. There was no evidence of TGF-beta1 expression in normal salivary glands or pleomorphic adenomas. Signals for TGF-beta2 in the normal salivary glands were observed in the intercalated ducts, while in pleomorphic adenomas they were observed in the inner ductal cells of the tubulo-glandular structures. Signals for TGF-beta3 in the normal salivary glands were observed in mucous cells, whereas in pleomorphic adenomas they were observed in the solid nests of neoplastic myoepithelial cells, in the portion showing squamous metaplasia, and in the inner ductal cells of tubulo-glandular structures. TGF-betas induce ectopic cartilage formation in vivo, but chondroid tissues in pleomorphic adenomas showed only weak TGF-beta3 expression. TGF-beta may be related to differentiation of the inner ductal cells and the neoplastic myoepithelial cells. In conclusion, pleomorphic adenomas expressed TGF-beta2 and -beta3, which may be associated with differentiation of the inner ductal cells and neoplastic myoepithelial cells.     

Immunolocalisation of cartilage-derived retinoic acid-sensitive protein in pleomorphic adenoma of the parotid salivary gland

Pleomorphic adenoma of the parotid salivary glands often contains chondroid elements and may exhibit cartilaginous and osseous differentiation, although the latter is extremely rare. Twenty-nine pleomorphic adenomas (PAs) of the parotid gland were examined immunohistochemically for the distribution of cartilage-derived retinoic acid-sensitive protein (CD-RAP), a recently described marker of chondrocytes, which may be important in the morphogenesis and development of the salivary gland. In the normal parotid gland, the ductal cells expressed CD-RAP, but not the myoepithelial cells. In the pleomorphic salivary adenomas, the duct-like cells, but not the myoepithelial cells, expressed CD-RAP. Since many authorities consider myoepithelial cells to be the source of the chondroid matrix, it is surprising that these cells do not express the chondrocytic marker, CD-RAP. Putative neoplastic myoepithelium in the pleomorphic adenoma and some cells in the myxochondroid areas expressed S-100 and calponin.     

Immunohistochemical localization of fibroblast growth factors (FGFs) and FGF receptor-1 in human normal salivary glands and pleomorphic adenomas

Basic and acidic fibroblast growth factors (bFGF and aFGF) are heparin-binding growth factors, and promote fibrogenesis and angiogenesis. We investigated the immunohistochemical localization of bFGF, aFGF, and FGF receptor-1 in pleomorphic adenomas. In the normal salivary glands, bFGF was localized in the basement membranes of intercalated ducts, acini and basal cells of the excretory ducts, while aFGF was localized focally in the intercalated ductal cells and basal cells of the excretory ducts. In pleomorphic adenomas, bFGF was immunolocalized in the basement membranes around the solid nests of myoepithelial cells, around the neoplastic myoepithelial cells in the myxoid areas, and in the lacuna cells in the chondroid areas. In contrast, chondroid areas exhibited no immunoreactivity with aFGF. Positive signals for aFGF were localized in luminal cells of the tubuloglandular structures in pleomorphic adenomas. FGF receptor-1 immunolocalized in the lacuna cells and myoepithelial cells in the solid and myxoid areas. These observations suggest that bFGF and FGF receptor-1 produced by myoepithelial cells inhibited terminal differentiation and enchondral ossification in pleomorphic adenomas. These results also suggest important roles for FGFs in the formation of various structures with mesenchymal-like histology.     

Immunohistochemical demonstration of bone morphogenetic protein-2 and type II collagen in pleomorphic adenoma of salivary glands

Immunohistochemical investigation of bone morphogenetic protein-2 (BMP-2) and type II collagen, two cartilage-associated proteins, was undertaken using monoclonal antibodies in 20 cases of salivary pleomorphic adenoma (PA) in order to explore their possible roles in chondroid differentiation of this tumor. Other salivary gland tumors, including adenoid cystic carcinoma (17 cases), polymorphous low-grade adenocarcinoma (10 cases), basal cell adenoma (3 cases), basal cell adenocarcinoma (1 case), and epithelial-myoepithelial carcinoma (2 cases), were also examined for comparison. In PA, BMP-2 immunoreactivity was detected in the luminal and non-luminal cells of the tubulo-ductal structures, plasmacytoid cells, and other scattered tumor cells in solid areas. In addition, tumor cells in chondroid areas in most cases (14/15), and stellate cells in myxoid areas in many cases (7/19), were also intensely labeled for BMP-2. Furthermore, BMP-2 was also detected in the non-neoplastic ductal cells in salivary glands, whereas no other salivary gland tumors were positively stained for this protein. Type II collagen was localized in the intercellular matrix of chondroid areas and in a few chondroid differentiating cells in myxoid areas, confirming its cartilage-specificity. A proportional relationship was observed between BMP-2 expression and chondroid formation, although BMP-2 was also stained in occasional PAs without chondroid formation. It is speculated that BMP-2 might be secreted by tumor cells and play a role in chondroid formation in PA by inducing some tumor cells to produce type II collagen and other chondroid matrical substances, like glycosaminoglycans. The expression of BMP-2 is specific to PA and may possibly be used as a useful marker in differentiating PA from other salivary gland tumors.     

Immunocytochemical localization of bone morphogenetic proteins (BMPs) in salivary gland pleomorphic adenoma

The localization of bone morphogenetic protein (BMP)-1, -2, -3 and transforming growth factor (TGF)-β in normal salivary gland and pleomorphic adenoma of the salivary gland has been examined immunocytochemically. Tumor cells with BMP immunostaining in pleomorphic adenoma were associated with some solid cellular and tubuloglandular patterns, and with stellate cells in the myxoid area. In addition, in the chondroid area of three pleomorphic adenomas, chondrocyte-like cells were positive for BMPs. It is speculated that BMPs secreted by the tumor cells play a role in the formation of the chondroid component in pleomorphic adenoma by inducing some tumor cells, probably neoplastic myoepithelial cells, to differentiate to chondrocytes by metaplastic change. No tumor cells specifically immunostained with TGF-β were found. TGF-β was positive in fibrous and hyalinized stroma. In the submandibular gland, only anti-BMP-1 antibody specifically reacted to apical portions of degenerated serous acinar cells.     

Immunohistochemical study of the distribution of S-100 protein in pleomorphic adenomas of minor salivary glands.

Twelve pleomorphic adenomas of minor salivary gland origin were examined for the distribution of S-100 protein, detected using the peroxidase-antiperoxidase (PAP) method. Strong S-100 protein immunoreactivity was noted in areas containing plasmacytoid cells, stellate and spindle cells against a myxochondroid or hyalinous stroma, and solid epithelial areas. Tubular and duct-like structures showed variable stainability. Stromal tissue and normal salivary glands were generally negative for S-100 protein. These findings were compared with those reported elsewhere.     

Immunohistochemical study in pleomorphic adenomas of human parotid gland--with special reference to cytoskeletal filamentous proteins

The purpose of this immunohistochemical study was to know the degree and direction of differentiation, the mechanism of mesenchymal appearance, and histogenesis in pleomorphic adenomas which were obtained from surgical removed specimens. All specimens were fixed in 10% neutral phosphoate buffered formalin, and embedded in paraffin. Sections were steined with the avidin-biotin peroxidase complex method for keratin, vimentin, desmin and S-100 protein, the peroxidase-antiperoxidase method for lysozyme, and the direct immunoperoxidase method for IgA and secretory component. Normal salivary glands were employed as controls. 1. Solid portion of pleomorphic adenomas were consisted of the focal hypline cells and scattered the duct cell-like cells. The hyaline cells were positive for vimentin and S-100 protein, and the duct cell-like cells were positive for keratin. But one case was found the bundles of spindle-shaped cells which was similar to myoepithelial cells were positive for actin and another case was consisted of the focal duct cell-like cells were observed. 2. In the tubular portion, the duct-like structures were classified into three types. One type was mono-layered structure, another type was double-layered structure and the other type is duct-like structure in the solid portion. Any inner layer of the duct-like structure were positive for keratin. 3. Double-layered duct-like structures were most common type. Among the double-layered structures, hyaline cells mostly made up the outer layered structures. At times, the spindleshaped cells of the outer layer were found. This structures were similar to intercalated portion of normal salivary glands. In one case, inner and outer layer was consisted of keratin positive cells, but outer layer was steined for keratin stronger than inner. This structure was similar to excretory duct of normal salivary glands. 4. IgA and sc were seen at inner cells and in luminal accumulation of the duct-like structures. 5. In the myxoid regions, stellate cells or spindle cells were positive for vimentin, S-100 protein and partial positive for desmin. In the chondroid regions, chondrocyte-like cells were positive for vimentin and S-100 protein. These results seemed to suggest that pleomorphic adenomas were composed of duct cell-like cells and hyaline cells. Duct cell-like cells consisted of the duct-like structure in order to transport secretion which was similar to the duct of normal salivary glands.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunohistochemical characterization of functional markers in human minor salivary gland tumors

The distribution of carcinoembryonic antigen (CEA), secretory component (SC), immunoglobulin A (IgA), immunoglobulin M (IgM), J-chain, and lysozyme in tumors of minor salivary glands was investigated using an immunoperoxidase method. Although CEA was demonstrated in both benign and malignant tumors, its distribution was relatively more common and with increased staining intensity in malignant tissues. In pleomorphic adenomas, the distribution of SC was similar to that of IgA and J-chain, suggesting the presence of secretory IgA in the epithelial cells. However, some neoplastic epithelial cells contained SC but not IgA and J-chain. No IgM was detected in such cells. Lysozyme could be demonstrated only in pleomorphic adenomas. Mucocpidermoid tumors and adenoidcystic carcinomas were negative for lysozyme. These findings suggest that some neoplastic ductal epithelial cells of pleomorphic adenomas retain functional characteristics of normal epithelial cells.     

Immunohistochemical evaluation of the Ca2+-binding S-100 proteins S-100A1, S-100A2, S-100A4, S-100A6 and S-100B in salivary gland tumors

The Ca²⁺-binding S-100 proteins are involved in the regulation of a number of cellular processes and an altered expression has been reported in several neoplastic tissues. Tissue specimens of normal salivary glands (n = 23). pleomorphic adenomas (n=60). basal cell adenomas (n=6). canalicular ademomas (n=2), myoepitheliomas (n = 2). adenoid cystic carcinomas (n=26) and adenocarcinomas NOS (n=11) were evaluated for the expression of S-100A1, S-100A2. A-100A4, S-100A6 and S-100B by using highly specific polyclonal and monoclonal antibodies generated against the recombinant human protein. In normal salivary glands, the ductal cells showed mild to intense immunoreactivity for S-100A 1, S-100A2. S-100A4and S-100A6, while S-100B was observed in nerve fibers in the connective tissue. The normal myoepithelial cells were unreactive. In pleomorphic adenoma, the luminal tumor cells of the duct-like structures showed moderate to intense immunoreactivity for S-100A2. while reactivity for S-100A 1. S-100A4 and S-100A6 was relatively weak. The non-luminal cells, also termed neoplastic myoepithelial cells, showed immunoreactivity for S-100B, while tumor cells in the solid, myxoid and chondroid areas were immunoreactive for S-100A 1. S-100A4, S-100A6 and S-100B. The non-luminally located tumor cells in basal cell adenomas and canalicular adenomas, and numerous tumor cells in clusters in myoepitheliomas were intensely reactive for S-100A2. In adenoid cystic carcinomas and in adenocarcinomas not otherwise specified, the luminal cells forming the tubular or cribriform structures were markedly positive for S-100A2 and/or S-100A6. Squamous metaplastic cells in salivary tumors showed intense immunoreactivity for S-100A2. The results of the present study suggest that the majority of the tumor ceils in salivary neoplasms, despite the most heterogeneous tumor cell differentiation, express S-100 proteins more heterogeneously than the normal glandular ducts. The salivary ducts in normal glands, the luminal tumor cells and squamous metaplastic cells in the neoplastic lesions were intensely immunoreactive for S-100A2 as compared to S-100A1, S-100A4orS-100A6. In contrast, the non-luminal tumor cells showed a rather heterogeneous expression of the S-100 proteins.     

Immunohistochemical characterization of functional markers in human minor salivary gland tumors

The distribution of carcinoembryonic antigen (CEA), secretory component (SC), immunoglobulin A (IgA), immunoglobulin M (IgM), J-chain, and lysozyme in tumors of minor salivary glands was investigated using an immunoperoxidase method. Although CEA was demonstrated in both benign and malignant tumors, its distribution was relatively more common and with increased staining intensity in malignant tissues. In pleomorphic adenomas, the distribution of SC was similar to that of IgA and J-chain, suggesting the presence of secretory IgA in the epithelial cells. However, some neoplastic epithelial cells contained SC but not IgA and J-chain. No IgM was detected in such cells. Lysozyme could be demonstrated only in pleomorphic adenomas. Mucoepidermoid tumors and adenoidcystic carcinomas were negative for lysozyme. These findings suggest that some neoplastic ductal epithelial cells of pleomorphic adenomas retain functional characteristics of normal epithelial cells.     

Immunohistochemical localization of fibroblast growth factor-1 (FGF-1), FGF-2 and fibroblast growth factor receptor-1 (FGfR-1) in pleomorphic adenoma of the salivary glands

Fibroblast growth faclor-1 (FGF-l) and FGF-2 are heparin-binding polypeplides that are potent mitogens for neoplastic cells. In this study, fibroblast growth factor-1 (FGF-l), FGF-2, and fibroblast growth factor receptor-1 (FGfR-1) were immunohistochemically analyzed in 10 patients with pleomorphic adenoma of the salivary gland by using specific monoclonal antibodies. The tumor tissues were histopathologically classified as: tubular, solid, myxoid or chondroid. Both FGF-1 and FGF-2 were immunohistochemically identified in the tumor cells of all histological types. In addition, immunoreactive FGF-2 was also found in the basement membrane of tubular type tumor cells. Conversely. FGfR-1-positive tumor cells were essentially confined to the tubular and solid areas of tumors. Tumor cells in the myxoid and chondroid areas were FGfR-1 immunonegative. These results suggest that the co-expression of FGF and its receptor appears to be related to the proliferative activity of tumor cells in the tubular and solid areas, whereas loss of FGF receptor expression may be associated with the differentiation of tumor cells into myxoid and chondroid tissue types.     

TENASCIN AND FIBRONECTIN IN PLEOMORPHIC ADENOMA OF THE SALIVARY GLAND

Objectives:

To analyze the expression and distribution pattern of extracellular matrix components in pleomorphic adenomas of the major and minor salivary glands and to compare the morphological findings of these tumors with the immunohistochemical expression, considering the different types of stroma predominating in each case.

Methods and Results:

The expression of tenascin (TN) and fibronectin (FN) was analyzed in 23 cases of pleomorphic adenomas, 11 major and 12 minor salivary gland tumors, by the streptavidin-biotin method using anti-tenascin and anti-fibronectin antibodies. In addition, the immunohistochemical results were correlated with the morphological findings of the lesions. All cases analyzed were immunoreactive for the antibodies used. Fibronectin showed strong labeling in fibrous and chondroid stroma, while labeling was weak in hyaline and myxoid stroma. Tenascin expression was more intense in fibrous and chondroid stroma and moderate in hyaline and myxoid stroma.

Conclusions:

No difference in the expression of these proteins was observed between major and minor salivary gland tumors.     

In vitro evaluation of the suppressor potential of conditioned medium from benign myoepithelial cells from pleomorphic adenoma in malignant cell invasion

J Oral Pathol Med (2012) 41 : 610–614 Tumoral invasion process is the result of a complex interaction between the tumor cells and microenvironment which plays an important role in modulating the growth and invasion of the cancer. The myoepithelial cells, present in glandular organs such as the breast and salivary glands, seem to exert paracrine effects on the glandular epithelium, acting as natural tumor suppressors. To verify the influence of the benign myoepithelial cells in the invasion of malignant cells, simulating an in situ carcinoma ex pleomorphic adenoma, we have cultured three different high‐potential invasive malignant tumors (breast ductal adenocarcinoma, melanoma and oral squamous cell carcinoma) in conditioned medium of myoepithelial cells from salivary gland pleomorphic adenomas using transwell chambers with 8‐μm pores membrane coated with matrigel. After 96 h, quantitative analyses of the results were performed by calculating the invasion index (number of cells that invaded in relation to the total number of cells). The results showed that there was a reduction of the invasion index mean for the three different malignant tumors. This study supports a tumoral suppressor function of the myoepithelial cells from pleomorphic adenoma in in vitro invasion process.     

Immunolocalization of α2, α5, and α6 integrin subunits in salivary tissue and adenomas of the parotid gland

The localization of the integrin subunits α₂, α₅, α₆ was studied immunohistochemically in samples of normal salivary gland and in a series of 8 pleomorphic adenomas, 5 Warthin's tumors, and 2 basal cell adenomas. In normal salivary tissue, acinar and ductal cells expressed α₂ and α₆ chains at the basal cell pole facing the basement membrane. α₂ also localized at sites of cell-cell contact. No staining of the epithelial component was seen with α₅. The polarized expression of α₂ and α₆, subunits was retained in salivary adenomas. These subunits were present at the basal cell pole of solid nests, tubules and ducts of pleomorphic adenomas, as well as of the basal layer of the epithelium of Warthin's tumor, and of the trabecular structures of basal cell adenomas. The α₅ subunit was consistently expressed only by cells embedded in the myxoid or chondroid matrix of pleomorphic adenomas. We conclude that the pattern of a integrin subunit expression in salivary adenomas may be related to the "epithelial" or "mesenchymal" phenotype of the neoplastic cells.     

Nucleolar organizer regions (NORs) evaluation of lingual salivary glands of chronic alcoholics

BACKGROUND: Chronic alcoholism has been associated with structural and physiological changes in salivary glands. Studies on a variety of pathologies have suggested that variation in number of nucleolar organizer regions (NORs) reveals conditions of cellular activity. The aim of this work was to examine, through the AgNOR technique, changes in number and size of NORs in lingual salivary glands of chronic alcoholics. METHODS: Samples of mucous and serous lingual salivary glands were obtained from tongues from autopsies of individuals whose cause of death was hepatic alcoholic cirrhosis. Lingual organs from individuals whose cause of death was accidental were used as controls. Number and size of the AgNORs and nuclear area, in ductal and acinar cells, were evaluated through a digital image analyzer. RESULTS: Statistical analysis revealed differences (P < or = 0.05) in number of AgNORs in mucous acini and ductal cells. Also, we observed changes in the area of the NORs. CONCLUSION: These results suggest that in alcoholics the activity of glandular cells, mainly in ductal epithelium, could be affected, modifying synthesis, transport and salivary secretions.     

Polymorphous Low Grade Adenocarcinoma: Literature Review and Report of Lower Lip Lesion with Suspected Lung Metastasis

Polymorphous low grade adenocarcinoma (PLGA) is an uncommon tumour that affects minor salivary glands mainly. It was known to be clinically benign and histologically polymorphic; sometimes misdiagnosed as pleomorphic adenomas, monomorphic adenomas, malignant pleomorphic adenomas, adenoid cystic carcinomas and adenocarcinoma not otherwise specified. More information about PLGA is cumulating in the current literature with new evidences suggesting that the tumour may not be as indolent as it was previously thought. A thorough understanding of the clinical and histological behaviour of the lesion has serious implications in management. Here, a case of lower lip lesion with suspected lung metastasis is reported to exemplify how the clinical behaviour of the lesion may affect management.     

Flow cytometric S-phase fraction contributes to diagnosis of diploid malignant salivary gland tumours

DNA ploidy studies on salivary gland tumours have shown that the proportion of aneuploid cases, although confined to the malignant entities, is considerably lower than for other solid malignancies. To analyse whether the S-phase fraction (SPF) may contribute to discrimination of diploid malignant from benign tumours, DNA flow cytometric data from 45 different malignant salivary gland tumours was compared with that of 121 pleomorphic adenomas. All benign tumours were diploid. Twelve malignant tumours contained aneuploid cell populations. The SPF values for diploid malignancies ranged between 0.9% and 11.0% (mean 3.9%), and between 0.5% and 7.9% (mean 2.7%) for pleomorphic adenomas. A 4% cut-off value gained statistical significance for discriminating diploid malignant tumours from pleomorphic adenomas (P<0.01). The sensitivity for SPF>4% was 46% and the positive predictive value was 40%. A sensitivity of 60% and a positive predictive value of 54% was achieved by combining aneuploidy and SPF>4%. These results show that DNA flow cytometry may contribute to diagnostic assessment in salivary gland tumours.     

2456例唾液腺肿瘤临床病理分析

目的探讨唾液腺肿瘤的发病、病理类型等临床特点。方法收集中山大学孙逸仙纪念医院口腔颌面外科1973年1月至2018年12月间确诊的唾液腺肿瘤病例2456例患者的相关资料,回顾分析其性别、年龄、病理类型、发病部位、良恶性构成比等特点。结果46年间收治的唾液腺肿瘤患者2456例,女性比例占41.9%,男性占58.1%,40~60岁年龄段为发病高峰,其中良性肿瘤1863例(75.9%),恶性肿瘤593例(24.1%),良恶性之比为3.1∶1。良性肿瘤构成比前2位是多形性腺瘤(58.7%)、Warthin瘤(33.6%),恶性肿瘤构成比前2位是黏液表皮样癌(27.7%)、腺样囊性癌(26.1%)。最常见的良性肿瘤多形性腺瘤的好发部位是腮腺、腭部、颌下腺,而恶性肿瘤中粘液表皮样癌则常见于腮腺和腭部的小唾液腺。本组资料中唾液腺肿瘤发病呈逐年递增的趋势,近10年病例占总病例数的53.3%。结论唾液腺肿瘤病人数量逐年增加;唾液腺肿瘤的总发生率男性高于女性;大唾液腺以良性肿瘤为主,小唾液腺恶性肿瘤多见;多形性腺瘤、Warthin瘤、黏液表皮样癌最常见;40~60岁是唾液腺良、恶性肿瘤高发年龄段。     

Multiple tumours of the salivary glands—Terminology and nomenclature

Multiple tumours of the salivary glands are very rare and their combinations according to histological classification of the tumours, localisation and origin (origin in independent topographical areas or in the same tissue) are diverse.The following two categories can be distinguished: common occurrence of multiple salivary gland tumours with identical histology, or with different histology. In either group the tumours can be unilateral or bilateral, synchronous or metachronous. The most common multiple tumours with an identical histology are Warthin tumours and pleomorphic adenomas. Bilateral occurrence has been observed especially in oncocytomas, acinic cell carcinomas and basal cell adenomas. In the group of multiple tumours with differing histology, Warthin tumours and pleomorphic adenomas show a number of combinations with other adenomas or carcinomas of the salivary glands. Notable also is the simultaneous occurrence of salivary gland tumours with other oral tumours or extraglandular tumours, especially thyroid carcinomas and breast carcinomas.Multiple salivary gland tumours must be distinguished by nomenclature from tumours with biphasic differentiation and hybrid tumours. Tumours with biphasic differentiation are defined as regular, recurring mixtures of two cellular components in the same tumour and have a corresponding term in the tumour classification. Hybrid tumours are very rare and are composed of two different tumour entities within the same topographical area. Each of the tumour entities conforms with an exactly defined tumour category.     

涎腺多形性腺瘤的纤维粘连素和层粘蛋白的表达和分布

纤维粘连素（ＦｉｂｒｏｎｅｃｔｉｎＦＮ）是细胞外基质蛋白；层粘蛋白（ＬａｍｉｎｉｎＬＭ）是基底膜成分，两者均对细胞的生长、分化、极向化和移动等行为起重要介导作用，本文采用免疫组织化学方法观察ＦＮ和ＬＭ在正常涎腺及涎腺多形性腺瘤的分布和表达，正常腺体中ＦＮ的表达定位于闰管细胞胞浆；ＬＭ定位于各级导管细胞胞浆，导管及腺泡的基底膜，多形性腺瘤中ＦＮ阳性细胞分散在肿瘤上皮结构区，在玻璃样、粘液样和软骨样间质中的变异肌上皮细胞ＦＮ呈强阳性，ＬＭ阳性见于肿瘤上皮细胞的邻接面和玻璃样间质中的变异肌上皮细胞，软骨样间质ＬＭ阴性