Immunohistochemistry and ultrastructure of myoepithelium and modified myoepithelium of the ducts of human major salivary glands: histogenetic implications for salivary gland tumors

The organization of salivary gland ducts, especially the presence or absence of myoepithelial cells, is central to histogenetic approaches to the classification of salivary gland tumors. Striated and excretory ducts are reported to be devoid of myoepithelial cells but do contain basal cells. To investigate the nature of such basal cells, tissue sections of normal human salivary glands were examined by means of immunohistochemical, ultrastructural, and fluorescent microscopic techniques. With the use of a mouse monoclonal anticytokeratin antibody (3 12C8-1) that, in salivary glands, is specific for myoepithelial cells, these cells associated with acini and intercalated ducts were strongly stained, as were the basal cells of striated and excretory ducts in each case. Ultrastructurally, some basal cells of both striated and excretory ducts had narrow, elongated cellular processes or the main portion of the cell containing parallel arrays of microfilaments with linear densities and micropinocytotic vesicles, whereas in other basal cells tonofilament bundles predominated. A similar range of cytoplasmic features existed in myoepithelial cells associated with acinar and intercalated duct cells. In addition, some duct basal cells have a complement of actin filaments similar to classic myoepithelium of acini and intercalated ducts. Striated and excretory ducts of human salivary glands, therefore, contain fully differentiated and modified myoepithelial cells, both of which express a specific cytokeratin polypeptide that is absent from duct luminal and acinar cells. Differentiation patterns in the intralobular and interlobular ducts suggest that these regions of salivary gland parenchyma cannot be excluded as histogenetic sites for the induction of salivary gland tumors in which neoplastic myoepithelial cells have been shown to have a major role.     

A review of the proliferative capacity of major salivary glands and the relationship to current concepts of neoplasia in salivary glands

The classification of salivary gland tumors relies heavily on histogenetic postulates. One of these, the semipluripotential reserve cell theory, suggests that certain reserve cells in specific segments of the duct system of major and minor salivary glands are critical to the development of neoplasms in these glands. However, direct evidence in support of this hypothesis is unavailable. This survey of proliferative capacity in normal salivary gland is based on a review of data in the literature, our observations of DNA synthetic and mitotic activity in developing rat and human salivary gland, and autoradiographic studies of induced cell proliferation in rat salivary gland. Autoradiography of neonatal rat salivary gland after tritiated thymidine administration, and electron microscopy of these tissues, reveals that as well as duct basal cells, luminal cells at all levels of the duct system and even acinar cells are capable of DNA synthesis and mitosis. Indeed, in such studies, more luminal than basal cells are seen in mitosis. In adult rat salivary gland induced to undergo hyperplasia, more acinar cells than intercalated duct cells are in the S phase of the cell cycle. However, cycling cells were observed even in striated ducts and, importantly, both basal and luminal cells of major interlobular excretory ducts are also labeled. Similar findings are present in fetal and adult human salivary glands. From such observations, it is evident that dividing cells are not limited to basal cells of excretory ducts and luminal cells of intercalated ducts, so that there is no support for the semipluripotential bicellular reserve cell hypothesis. However, there is considerable evidence for a multicellular theory of tumor histogenesis; that is, any of the multiplicity of cell types in normal salivary gland have the potential to give use to any of the various types of tumor occurring in this organ.     

Kimura病的病理学分析

目的:探讨Kimura病(Kimura’s disease,KD)的临床病理学特点,提高对该病的认识及诊断。方法:分析和观察7例KD的临床资料、病理组织学表现及免疫组织化学特征。结果:7例KD患者均为男性,发病年龄21～73岁,主要表现为头颈部皮下或大唾液腺的无痛性肿块,组织学上以淋巴组织增生为主,可见淋巴滤泡形成,生发中心扩大,滤泡间见血管增生,大量嗜酸性粒细胞浸润。免疫组织化学显示KD中的淋巴滤泡表达B细胞抗原,滤泡间的淋巴细胞多表达T细胞标记。结论:KD是一种少见的淋巴组织增生性疾病,需与部分富含淋巴组织的肿瘤鉴别,组织病理学及免疫组化对其诊断具有重要意义。     

P63蛋白在人胚涎腺发育中的表达及意义

目的探讨P63蛋白在涎腺上皮干细胞发育中的作用及干细胞存在的可能位置。方法收集不同发育阶段的合法流产人胚24例、正常涎腺组织标本10例,对切片行常规HE染色和免疫组织化学SP法染色。结果组织切片见涎腺发育从早期上皮芽增生分支形成树枝状上皮条索,然后形成管腔,最终分支末端细胞增生膨大分化为导管、肌上皮和腺泡细胞。P63的表达从胚胎早期上皮芽中的广泛阳性表达到阳性细胞逐渐减少,呈现区域化散在分布特征,正常成人涎腺中阳性表达细胞仅少量存在于闰管、分泌管、排泄管管壁基底侧。结论P63在维系涎腺上皮性干细胞的生存和分化状态中可能具有重要作用,正常成人涎腺上皮性干细胞仅少量存在于导管管壁基底侧。     

口腔淋巴上皮囊肿3例报道

对3例口腔淋巴上皮囊肿进行临床病理分析,该囊肿的好发部位为口底,临床上常诊断为黏液腺囊肿等囊性疾病。镜下观察淋巴上皮囊肿以囊壁内衬复层鳞状上皮及纤维囊壁存在大量淋巴样组织为其特点。目前认为。口腔淋巴上皮囊肿可能来源于舌下腺或小唾液腺分泌管。由于慢性刺激,分泌管上皮发生鳞状化生,化生上皮的腔面细胞脱落后引起周围淋巴细胞浸润,表现为淋巴上皮囊肿。本文结合文献进行讨论,为类似病例的预防和诊断提供参考,为临床诊断和治疗提供借鉴。     

Marginal zone B-cell lymphoma of minor salivary gland representing tumor-forming amyloidosis of the oral cavity. A case report

We report here a case of mucosa-associated lymphoid tissue (MALT)-type lymphoma arising from the minor salivary gland of the oral cavity exhibiting tumor-forming amyloidosis. The patient was a 64-year-old Japanese woman who presented with 4-year history of a left soft palate mass. Despite multiple and multifocal recurrences including the lip, soft palate, tongue, oral base and vocal code and soft palate, the tumor remained localized in the upper aerodigestive tract, and the patient did not develop multiple myeloma during the course of disease. Histologically, the majority of the lesion was occupied by amyloid deposition. Only the periphery of the lesion contained numerous plasmacytoid cells, along with occasional centrocyte-like cells. In addition, lymphoepithelial lesion and follicular colonization were noted. The present case indicates that primary minor salivary gland MALT-type lymphoma appears to be the cause of tumor-forming amyloidosis of the upper aerodigestive tract including the larynx.     

Adenomatous ductal proliferation of the salivary gland

OBJECTIVE: The objective of this study is to report a series of patients with adenomatous ductal proliferation of the salivary gland and to investigate the nature and histogenesis of this process. STUDY DESIGN: The histologic and immunohistochemical studies of 13 patients with adenomatous ductal proliferation of the salivary gland were performed. RESULTS: Ten cases coexisted with other diseases, such as salivary gland tumor or chronic parotitis. Most of the lesions were limited to 1 or 2 lobules and showed prominent ductal proliferation with some acinar cell complexes. The proliferative ducts had a compact growth pattern with little stroma. Dedifferentiation of acinar cells, identified by the loss of their secretory granules and appearing similar to intercalated duct epithelium, was seen in the early stages of adenomatous ductal proliferation. CONCLUSION: Acinar cells play a role in the histogenesis of salivary gland tumors because acinar cells clearly participate in the formation of the proliferative ducts.     

Immunohistochemical and histologic study of cervical lymphoepithelial cysts

Four cases of lateral cervical cysts were reported. All cyst walls were lined with keratinized stratified squamous epithelium, and contained lymph follicles with well-defined germinal centers. Ectopic salivary gland tissue was found in one case. Histochemical examination by the immunoperoxidase method revealed the existence of carcinoembryonic antigen (CEA). However, alpha-feto protein (AFP) and amylase were not detected in any of the cysts. The cyst fluid contained high levels of CEA and high titers of salivary type amylase, but AFP was negative. These results do not support any one of the theories concerning the etiology of cervical lymphoepithelial cysts. It seems likely that cysts derive from both epithelial remnants of the branchial apparatus and from salivary gland inclusions in lymph nodes.     

腭部涎腺肿瘤116例临床分析

目的探讨腭部涎腺肿瘤的临床病理类型、诊断及治疗方法。方法对在1983年至2006年问住院治疗的116例腭部涎腺肿瘤病人的临床病理类型、诊断、治疗、预后进行分析和总结。结果116例中良性肿瘤71例（61．21％）,以多形性腺瘤最为多见。恶性肿瘤45例（38．79％）,以腺样囊性癌最多见,黏液表皮样癌次之。肿瘤发生在软腭者38例,硬腭者33例,软硬腭交界处者45例。114例经外科手术治疗,95例获3年以上随访,良性肿瘤复发率为7．4％,恶性肿瘤复发率为22．0％。结论腭部涎腺肿瘤治疗以手术切除为主,应重视术前组织学诊断,尽量避免术后复发及并发症的发生。     

Incidental Langerhans cell histiocytosis of the parotid gland resembling marginal zone B-cell lymphoma: a case report

Langerhans cell histiocytosis (LCH) manifesting as a parotid gland mass is an extremely rare clinical presentation. We report a case of LCH involving the bilateral parotid glands in an 81-year-old Japanese female. Pathologically, the lesion was characterized by numerous lymphoid follicles, dense lymphoplasmacytoid infiltrate and cystic dilatation of the parotid gland duct in addition to nodular and diffuse proliferation of LCs. Moreover, both LCs and small T-lymphocytes invaded the ductal epithelium forming a lymphoepithelial lesion-like morphology. The present case indicates that LCHs should be added to the different diagnosis for marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type involving the salivary glands.     

Nodular hyperplasia of oncocytes in mouse submandibular glands

Multinodular hyperplastic foci of oncocytes found in mouse submandibular glands were examined ultrastructurally, and their morphogenesis discussed. The oncocytic foci showed lobular architecture surrounded by myoepithelial cells, and tubular formations were frequently present. The cytoplasm of the oncocytes was distended by tightly-packed and non-oriented mitochondria which varied in size and shape. Furthermore, varying numbers of electron-dense fine granules, which were remnants of secretory granules of granular duct cells, were scattered in the cytoplasm. Within the salivary gland parenchyma neighboring the hyperplastic foci of oncocytes, intermediate-type cells between oncocytes and normal salivary gland epithelia were found. The result of the present study shows that the oncocytic change has a tendency to be more frequent in the granular ducts and less in the striated ducts, and that some oncocyte-transformed cells proliferate to form nodular hyperplastic foci.     

Nodular hyperplasia of oncocytes in mouse submandibular glands

Multinodular hyperplastic foci of oncocytes found in mouse submandibular glands were examined ultrastructurally, and their morphogenesis discussed. The oncocytic foci showed lobular architecture surrounded by myoepithelial cells, and tubular formations were frequently present. The cytoplasm of the oncocytes was distended by tightly-packed and non-oriented mitochondria which varied in size and shape. Furthermore, varying numbers of electron-dense fine granules, which were remnants of secretory granules of granular duct cells, were scattered in the cytoplasm. Within the salivary gland parenchyma neighboring the hyperplastic foci of oncocytes, intermediate-type cells between oncocytes and normal salivary gland epithelia were found. The result of the present study shows that the oncocytic change has a tendency to be more frequent in the granular ducts and less in the striated ducts, and that some oncocyte-transformed cells proliferate to form nodular hyperplastic foci.     

An immunohistochemical study of kallikrein in the rat parotid and exorbital lacrimal glands.

In the parotid gland, kallikrein was found by the direct immunofluorescence technique in the cytoplasm of the intralobular and interlobular striated duct cells and as a luminal rim in the main excretory ducts. Kallikrein-specific fluorescence was not found in the exorbital lacrimal gland which lacks striated ducts. The function of glandular kallikreins may be associated with striated ducts or similar structures elsewhere.     

Calcifications in a clear cell mucoepidermoid carcinoma of the hard palate

Although calcification is a common finding in inflammatory salivary gland disorders, salivary gland tumour rarely shows calcifications. A case of clear cell mucoepidermoid carcinoma (MEC) of the hard palate with extensive intratumoural calcifications visible on computed tomography (CT) scans and histologic sections is described. The calcification in the salivary gland tumour of the palate recognized by a CT scan should be considered in the differential diagnosis of a MEC. The mechanism of the intratumoural calcification in our case is speculated to be a result of a secretory function of the tumour cells.     

Primary malignant lymphoma of the salivary gland: a tumor of mucosa-associated lymphoid tissue

The clinical, morphologic and immunohistochemical features of 10 cases of the low-grade mucosa-associated lymphoid tissue (MALT) lymphoma of salivary glands are described. Although the initial histologic diagnosis in nine of these cases was myoepithelial sialadenitis, the diagnosis of primary salivary gland MALT lymphoma was based on the demonstration of light chain restriction and on morphologic characteristics. Histologic study showed a characteristic cytology, which included centrocytoid cells (composed of small centrocytes and monocytoid B cells) and a varying degree of plasma cell differentiation; the occurrence of epithelial or acinar invasion by neoplastic centrocytoid cells; and the presence of reactive lymph follicles among the neoplastic cells. Furthermore, multinucleate giant cells resembling Warthin-Finkeldey cells were detected in seven cases. In the light of these findings, cases previously diagnosed as myoepithelial sialadenitis require careful assessment and nine out of 32 cases are, in reality, examples of primary salivary gland MALT lymphomas. Immunohistochemical analysis of paraffin sections revealed the following characteristic immunophenotype of MALT lymphoma: L26, KiB3 and LN2 positive, and a monotypic immunoglobulin pattern (predominantly IgM/kappa). It was of interest that salivary gland parenchyma, infiltrated by neoplastic centrocytoid cells, reacted with LN3 for cells expressing human leukocyte antigen-DR (HLA-DR) antigens. Whereas salivary gland epithelia devoid of a neoplastic invasion were invariably negative for LN3. This suggests a lymphocyte-mediated role in salivary epithelial HLA-DR expression. It appears that HLA-DR expression is an inducible phenomenon in MALT lymphomas of salivary gland.     

A histochemical study of rat salivary gland acid phosphatase

Male Sprague-Dawley rats received 4 mg pilocarpine/100 g body wt intraperitoneally or physiological saline as control and were killed at various intervals. Acid phosphatase was reacted on frozen sections from soft palate, parotid and submandibular glands using sodium-alpha-naphthyl acid phosphate as substrate. Various inhibitors were added to the incubation medium. The strongest acid phosphatase activity was in the parotid gland acinar and proximal secretory duct cells; the mucous minor glands of the palate were completely negative. Activity was found in the acinar cells, proximal secretory duct cells, granular and striated duct and excretory duct cells. Pilocarpine injection slightly reduced the activity up to 6 h after injection. Cupric chloride added to the incubation medium lowered the overall activity. Fluoride and molybdate inhibited the acid phosphatase reaction in all structures. Tartrate inhibited the reaction in all structures except the submandibular striated duct cells. The tartrate-resistant activity may be a Na+K+-dependent ATPase involved in re-absorbing water and electrolytes from the primary saliva.     

Ultrastructural morphology and cellular differentiation in acinic cell carcinoma

Acinic cell carcinomas, in some instances, contain a component of intercalated duct cells. However, the manner in which this element is integrated within the more obvious acinar cells, as well as the role neoplastic intercalated duct cells play in determining morphologic patterns in acinic cell tumors, has not been fully investigated. Ultrastructural study and immunostaining with antibodies to cytokeratins and to S-100 protein carried out in nine cases of parotid acinic cell carcinoma suggest two basic differentiation patterns. In three cases, the lesions were essentially composed of acinar cells (with variation in the number and form of secretory granules), and one of these tumors was unique in having ultrastructural evidence of differentiated myoepithelial cells. In the second group of six cases, there was light microscopic, ultrastructural, and immunohistochemical evidence of a significant component of intercalated duct cells. By means of both immunostaining (intercalated ducts were positive for keratin and S-100 protein; acinar cells were negative for both antigens) and electron microscopy, flattened-to-cuboidal intercalated duct cells were noted to enclose and, presumably, to be involved in the formation of microcystic spaces. Acinic cell carcinomas with a more solid growth pattern contained groups of intercalated duct cells positive for keratin and S-100 protein. Ultrastructurally, these cells were organized into well-formed ducts related to nests of acinar cells. Acinic cell carcinoma is another class of salivary gland tumor in which there can be an integrated proliferation of intercalated duct and acinar cells and, infrequently, of myoepithelial cells, all organized in a simulation of the intercalated duct-acinar unit of the normal salivary gland.     

Soft palate preservation after tumor resection with transoral laser microsurgery

Background: Management and preservation of the soft palate is dependent on clinical stage and tumor histology. However, available literature is scarce regarding the palate preservation with the use of laser CO2. Objectives: We report the results obtained after management with laser surgery and soft palate preservation in three patients with salivary gland neoplasms. Method: Three patients with minor salivary gland tumors were treated by means of transoral laser microsurgery. All tumors were assessed using magnetic resonance imaging. All tumors were >3 cm. Soft palate function was preserved and reconstruction was performed with primary closure. Patients began oral feeding the same day and were discharged after 24 h. Conclusions: Transoral laser microsurgery is recommended for treatment of soft palate tumors. This treatment can be considered a better option when compared with other modalities such as radio- or chemoradiotherapy which require a longer time of treatment, are more expensive and tend to produce significant toxicity. Key words:Laser CO2, neoplasms, salivary gland.     

Scanning electron microscopic study of Warthin's tumor

Three cases of Warthin's tumors were studied with a scanning electron microscope. The free surface of the epithelium was composed mainly of round or ovoid dome-like structures bearing microvilli and apocrine protrusions. Ciliated epithelial cells were detected in 2 of the tumors. The tumor epithelium encircled various amounts of cellular debris resembling degenerate lymphoid cells. A few tiny cystic spaces were also found. Within the lymphoid stroma, tightly packed lymphocytes, a meshwork of reticulum cells and medullary cord-like structures were observed. Our findings support the concept that Warthin's tumors develop from heterotopic salivary gland ducts within pre-existing lymph nodes.     

Scanning electron microscopic study of Warthin's tumor

Three cases of Warthin's tumors were studied with a scanning electron microscope. The free surface of the epithelium was composed mainly of round or ovoid dome-like structures bearing microvilli and apocrine protrusions. Ciliated epithelial cells were detected in 2 of the tumors. The tumor epithelium encircled various amounts of cellular debris resembling degenerate lymphoid cells. A few tiny cystic spaces were also found. Within the lymphoid stroma, tightly packed lymphocytes, a meshwork of reticulum cells and medullary cord-like structures were observed. Our findings support the concept that Warthin's tumors develop from heterotopic salivary gland ducts within pre-existing lymph nodes.