Sclerosing polycystic adenosis of the submandibular gland: Two case reports

BACKGROUNDSclerosing polycystic adenosis (SPA) is a rare disease of salivary glands, similar to fibrocystic disease of the breast. It occurs over a wide age range and exhibits a slight female preference. Most SPA cases have occurred in the parotid gland. The exact nature of SPA is unclear, but its tumor nature has recently been proposed. Although SPA has a good prognosis after adequate surgery, atypical lesions might occur, ranging from mild dysplasia to carcinoma in situ in some cases. To the best of our knowledge, only five cases of SPA in the submandibular gland have been reported to date. Here, we present two new cases of SPA involving the submandibular gland.CASE SUMMARYA 50-year-old woman and a 52-year-old woman were referred to Tongji Hospital in Wuhan, China, with complaints of moderate pain, recurrent swelling, and a mass in the submandibular area. After admission, the two cases of the submandibular mass were examined physically. The boundary of the submandibular tumor was clear, and the range of motion was good. After preoperative examinations, surgery was performed on a selective basis. Postoperative histopathological examination revealed a well-defined mass with acinar structures, ducts, or cystic dilated glands of various sizes scattered in a large number of proliferative sclerosing stroma. There were flat and cuboidal cells, and eosinophils in the duct epithelium. There was also a eosinophilic substance in the lumen of dilated cysts. No atypical epithelial hyperplasia, invasive growth, or carcinoma in situ was found. Based on the above findings, the mass was diagnosed as SPA. Both patients have remained asymptomatic and no recurrence or distant metastasis had occurred by the 7-mo and 5-year follow-up, respectively.CONCLUSIONSPA is a rare disease of the salivary gland. Even though it has a good prognosis after adequate surgery, atypical lesions may occur from mild dysplasia to carcinoma in situ. However, no recurrence, distant metastasis, or mortality has been reported for submandibular gland SPA. Clinicians and pathologists should be familiar with the characteristics of SPA in the submandibular gland to avoid misdiagnosis and overtreatment.     

Effective chemotherapy for submandibular gland carcinoma ex pleomorphic adenoma with lung metastasis after radiotherapy: A case report

BACKGROUND Only a few cases of carcinoma ex pleomorphic adenoma arising in the submandibular gland have ever been reported,all with a poor prognosis. The standard treatment for salivary gland carcinoma ex pleomorphic adenoma is surgical resection combined with postoperative radiotherapy,but the necessity of chemotherapy as well as the most appropriate treatment regimen for patients with distant metastasis after radiotherapy remains controversial.CASE SUMMARY This report presents the case of a 73-year-old woman who suffered submandibular gland carcinoma ex pleomorphic adenoma. She accepted surgery to remove the mass; she was found to have lung metastasis after radiotherapy.Her condition was controlled by chemotherapy with liposomal doxorubicin plus cisplatin.CONCLUSION The positive clinical outcome in the patient reveals that this chemotherapy regimen may be an alternative treatment for such a condition.     

Antioxidant parameters and lipid peroxidation in salivary glands of streptozotocin-induced diabetic rats

BACKGROUND: There is evidence suggesting an unbalance between oxidant and antioxidant status associated with diabetes. Considering that salivary function is essential for the maintenance of oral and systemic health, this study was designed to examine the levels of reduced and oxidized glutathione and the activities of the antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, in salivary gland of streptozotocin-induced diabetic rats. METHODS: The content of malondialdehyde was determined in the blood and in the salivary glands. The antioxidant status was investigated in the submandibular and parotid salivary glands. RESULTS: Diabetic rats showed an increase in the content of malonaldehyde in the blood and in the submandibular salivary gland, but not in the parotid gland. Both forms, reduced and oxidized glutathione content present higher values in the diabetic submandibular gland compared with controls. No difference in the activity of superoxide dismutase between the diabetic and control glands was observed in either gland. Catalase showed higher specific activity in the parotid gland of the diabetic rats than control; however, in the submandibular gland, only when expressed as unit per gland was it higher than control. The specific activity of glutathione peroxidase was higher in the diabetic parotid gland than control; however, in the submandibular gland, its activity per gland was lower than controls. CONCLUSION: The streptozotocin-induced diabetes in rats caused different results comparing the submandibular and parotid salivary glands.     

下颌下腺主导管结扎可激活损伤组织中的干/祖细胞

背景：成体干细胞的伦理学问题较少,而且某些操作技术比较成熟,利用成体干细胞进行组织工程化涎腺的构建具有十分诱人的吸引力和极其重要的应用前景。目的：建立下颌下腺主导管结扎的涎腺组织损伤大鼠模型,探讨涎腺组织损伤模型中成体干/祖细胞存在的可能性及可能位置。方法：SD大鼠统一行右侧下颌下腺主导管结扎,1周后处死大鼠取出两侧腺体,通过苏木精-伊红染色、PAS糖原染色及细胞角蛋白19、Bcl-2、Ki-67等指标的免疫组织化学测定,对正常涎腺组织与建立的损伤模型组织进行比较。结果与结论：同一只大鼠,结扎侧与对照侧体积、质量有明显的差异。对照侧下颌下腺组织呈卵圆形,色泽红润,表面光滑,有完整包膜,质地柔软;结扎后腺体萎缩,组织形态欠规整,色泽暗红,包膜充血,质地变韧,周围组织血管代偿性扩张。主导管结扎的组织损伤模型可导致PAS阳性腺细胞的消失和细胞角蛋白19阳性的小导管上皮细胞增殖,并有在未结扎的腺体中很少见到的小丛层粘连蛋白阳性细胞出现在导管周围,而抑制细胞凋亡的Bcl-2和提示增殖活跃度的Ki-67的表达均有所增强。可见下颌下腺组织中可能存在着定位于涎腺周围导管区的下颌下腺干/祖细胞;下颌下腺主导管结扎导致的组织损伤模型是一种能有效激活下颌下腺组织中干/祖细胞的方法。     

Sonographic appearances of malignant lymphoma of the salivary glands.

PURPOSE: We undertook this retrospective study to describe the sonographic findings in patients with malignant lymphoma of the major salivary glands. METHODS: We reviewed the sonograms and medical records of 7 patients with histologically proven lymphoma of the parotid (3 patients) or submandibular glands (4 patients). RESULTS: Primary lymphoma was found in 1 parotid gland and 2 submandibular glands. The remaining 4 cases were secondary lymphomas. One patient had been diagnosed with Sj?gren's syndrome and had been followed up with sonography. In parotid glands, both parenchymal and intraparotid nodal lymphomas were found. All submandibular gland tumors were parenchymal. Intraparotid nodal involvement appeared as multiple small nodules with relatively smooth margins, whereas the parenchymal parotid and submandibular gland lymphomas were larger (25 to 45 mm in longitudinal diameter) and showed various degrees of margin irregularity. All tumors were hypoechoic relative to the normal parenchyma. The primary parotid lymphoma and intraparotid nodal lymphomas had a homogeneous echotexture; the secondary parotid lymphomas and submandibular gland lymphomas were heterogeneous. One submandibular gland lymphoma showed intratumoral echogenic stripes. Neither calcification nor cystic degeneration was observed within the lesions. CONCLUSIONS: Lymphomas of the salivary glands present a variety of sonographic appearances, ranging from multiple small, hypoechoic nodules to an irregularly shaped heterogeneous mass without cystic areas or calcifications.     

小涎腺腺样囊性癌周围神经浸润MRI诊断

目的通过分析3例小涎腺腺样囊性癌,提高对小涎腺腺样囊性癌周围神经浸润的认识和MRI诊断。方法收集3例病理证实的小涎腺腺样囊性癌病例资料,回顾性分析其MRI表现。结果 2例发生于口腔的小涎腺,1例起源于颌下腺间隙。3例均以周围神经病变为主要临床表现。MRI上表现为神经根、干、海绵窦结节样增粗,异常强化。结论 MRI可显示小涎腺腺样囊性癌沿神经周围扩散转移,有助于术前诊断。     

小鼠下颌下腺发育中转化生长因子β受体的表达

背景：小鼠的下颌下腺是研究唾液腺的发育的良好模型,转化生长因子β是器官发育和疾病中重要的生长因子,但是在下颌下腺中转化生长因子β受体的表达以及作用机制至今并不明确。目的：观察胚胎小鼠下颌下腺发育过程中转化生长因子βⅠ型受体和Ⅱ型受体以及p-ERK1／2的表达,揭示转化生长因子β在小鼠涎腺发育中的作用。方法：取C57BL／6J小鼠胚胎期第14.5天的标本,使用转化生长因子βⅠ型受体和Ⅱ型受体以及p-ERK1／2抗体,对小鼠的下颌下腺进行免疫组化染色。取新生小鼠标本,大体观察下颌下腺,并且使用苏木精-伊红染色观察其形态。结果与结论：①小鼠出生时,下颌下腺位于下颌骨下方;苏木精-伊红染色发现小鼠下颌下腺的腺泡、导管和闰管细胞也已经分化完成。②在胚胎期第14．5天,转化生长因子βⅠ型和Ⅱ型受体在腺泡上皮和导管上皮内高表达,而腺体上皮细胞外的间充质没有表达。③p-ERK1／2主要也是表达在下颌下腺的上皮细胞中,与转化生长因子βⅠ型受体和Ⅱ型受体在下颌下腺中的表达基本一致。说明在小鼠下颌下腺的发育过程中,转化生长因子β蛋白可能通过与上皮细胞表面的受体结合,激活ERK信号通路来调节涎腺腺泡和导管的发育。     

Neurotrophic factor GDNF promotes survival of salivary stem cells

Stem cell–based regenerative therapy is a promising treatment for head and neck cancer patients that suffer from chronic dry mouth (xerostomia) due to salivary gland injury from radiation therapy. Current xerostomia therapies only provide temporary symptom relief, while permanent restoration of salivary function is not currently feasible. Here, we identified and characterized a stem cell population from adult murine submandibular glands. Of the different cells isolated from the submandibular gland, this specific population, Lin^–CD24⁺c-Kit⁺Sca1⁺, possessed the highest capacity for proliferation, self renewal, and differentiation during serial passage in vitro. Serial transplantations of this stem cell population into the submandibular gland of irradiated mice successfully restored saliva secretion and increased the number of functional acini. Gene-expression analysis revealed that glial cell line–derived neurotrophic factor (Gdnf) is highly expressed in Lin^–CD24⁺c-Kit⁺Sca1⁺ stem cells. Furthermore, GDNF expression was upregulated upon radiation therapy in submandibular glands of both mice and humans. Administration of GDNF improved saliva production and enriched the number of functional acini in submandibular glands of irradiated animals and enhanced salisphere formation in cultured salivary stem cells, but did not accelerate growth of head and neck cancer cells. These data indicate that modulation of the GDNF pathway may have potential therapeutic benefit for management of radiation-induced xerostomia.     

Hemangioma with phleboliths in the sublingual gland: as a cause of submental opacity

Hemangiomas are the most common lesions of the major salivary glands during infancy and early childhood. Changes in blood flow dynamic within hemangioma results in thrombus and phleboliths. There have been a number of reports of hemangiomas with phleboliths in parotid and submandibular glands. We present the first case of a hemangioma with multiple phleboliths in the subligual gland as a cause of submental opacity, and discussed the diagnosis of radiopaque masses in the sublingual and submental regions.     

High-resolution real-time ultrasonography of the submandibular salivary gland

Twenty "normal" volunteers underwent real-time ultrasound scanning of their submandibular salivary glands in an attempt to define the normal anatomy and ultrasound characteristics of these glands and their adjacent anatomy. It is possible to define the entire gland and portions of its duct, which measures less than 3 mm in diameter. Adjacent structures are easily seen and are constant in their relationships to the gland. Three case reports demonstrate the usefulness of this approach to various clinical problems. Real-time ultrasonography is an easily applied, non-ionizing modality to image the submandibular fossa.     

二维超声联合声触诊组织成像定量技术诊断唾液腺干燥综合征

目的 观察二维超声联合声触诊组织成像定量（VTIQ）技术诊断唾液腺干燥综合征（SS）的价值。方法 收集43例SS患者（SS组）和60例非SS患者（对照组）,观察并对比其唾液腺病灶二维超声评分及剪切波速度（SWV）,绘制受试者工作特征（ROC）曲线,评估二维超声评分、VTIQ及二者联合诊断唾液腺SS的效能。结果 SS组唾液腺二维超声评分及唾液腺SWV均明显高于对照组（P均<0.01）。以2.12、2.38 m/s为唾液腺（腮腺、下颌下腺）SWV最佳截断值,其诊断唾液腺SS的敏感度、特异度、约登指数和曲线下面积（AUC）分别为83.70%、88.30%、0.72和0.90;以二维超声评分2分为最佳截断值,其诊断唾液腺SS的敏感度、特异度、约登指数和AUC分别为76.70%、90.00%、0.67和0.91;以二维超声评分为1分且唾液腺SWV=2.12、2.38 m/s为最佳截断值,联合诊断唾液腺SS的敏感度、特异度、约登指数和AUC分别为95.30%、60.00%、0.55和0.78。结论 二维超声联合VTIQ技术有助于诊断唾液腺SS。     

Immunohistochemical study on the excretion of a drug (methamphetamine) by salivary glands

We have succeeded in the immunohistochemical demonstration of methamphetamine; and in the present study, we used this technique to determine the topographic distribution of exogenously administered methamphetamine in mouse major salivary glands. Positive reactions for methamphetamine were localized in the striated duct portion of the major salivary glands and granular duct in the submandibular glands. Time course of the decrease in immunohistochemical reactivity of the ducts was very similar to that for reported methamphetamine levels in plasma or saliva. These results show that through the striated ducts of the major salivary glands and the granular ducts of the submandibular glands, MA is excreted into saliva; however, the mechanism by which MA is excreted into saliva is unknown.     

Agenesis of a submandibular gland with compensatory pseudotumoral hypertrophy of the contralateral gland: Sonographic findings

Agenesis of a submandibular gland with compensatory hypertrophy of the contralateral gland is an extremely rare disorder. Most reported cases of unilateral submandibular agenesis have been asymptomatic without any associated facial anomalies. We report a case of submandibular gland hypertrophy mimicking a mass that was detected incidentally. The absence of the contralateral submandibular gland and associated contralateral sublingual gland hypertrophy was confirmed by typical imaging findings. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound 41 :15–17, 2013     

Local adeno-associated virus-mediated interleukin 10 gene transfer has disease-modifying effects in a murine model of Sjögren's syndrome

Female nonobese diabetic (NOD) mice develop spontaneous autoimmune sialadenitis and loss of salivary flow, and are a widely used model of Sj?gren's syndrome. We examined the feasibility of local salivary gland immunomodulatory gene delivery to alter these sequelae in NOD mice. We constructed recombinant adeno-associated virus (rAAV) vectors encoding either human interleukin 10 (rAAVhIL-10) or beta-galactosidase (rAAVLacZ, control vector). Mice received rAAVhIL-10 or rAAVLacZ by retrograde submandibular ductal instillation either at age 8 weeks (early, before onset of sialadenitis), or at 16 weeks (late, after onset of sialadenitis). As a systemic treatment control, separate mice received intramuscular delivery of rAAVhIL-10 at each time point. Both submandibular and intramuscular delivery of vector led to low circulating levels of hIL-10. After submandibular administration of rAAVhIL-10, salivary flow rates at 20 weeks for both the early and late treatment groups were significantly higher than for both rAAVLacZ-administered and untreated mice. Systemic delivery of rAAVhIL-10 led to improved salivary flow in the late treatment group. Inflammatory infiltrates in submandibular glands, however, were significantly reduced only in mice receiving rAAVhIL-10 locally in the salivary gland compared with mice receiving this vector intramuscularly, or rAAVLacZ or no treatment. In addition, after submandibular rAAVhIL-10 delivery, NOD mice exhibited significantly lower blood glucose, and higher serum insulin, levels than all other groups, indicating some systemic benefit of this treatment. These studies show that expression of hIL-10 by rAAV vectors can have disease-modifying effects in the salivary glands of NOD mice, and suggest that local immunomodulatory gene transfer may be useful for managing the salivary gland pathology in Sj?gren's syndrome.     

Human parathyroid hormone is secreted primarily into the bloodstream after rat parotid gland gene transfer

Hypoparathyroidism is a hormone deficiency syndrome that leads to low blood calcium levels and for which current replacement therapy is inadequate. Gene transfer to salivary glands leads to safe and abundant secretion of therapeutic protein into either saliva or the bloodstream. We previously reported the successful transduction of rat submandibular glands with an adenoviral vector encoding human parathyroid hormone (Ad.hPTH), but unfortunately most of the hPTH was secreted into saliva. Because submandibular and parotid glands are morphologically and functionally different, we hypothesized that hPTH sorting might be different in parotid glands. After 2 days, the pattern of hPTH secretion from transduced parotid glands of intact rats was reversed from that of transduced submandibular glands, that is, most transgenic hPTH was detected in serum (5?×?10(10) viral particles per gland; the saliva-to-serum ratio of total hPTH secreted was 0.04). Vector copies were localized to the targeted parotid glands, with none detected in liver or spleen. Ad.hPTH next was administered to parotid glands of parathyroidectomized rats. Two days after delivery no hPTH was detectable in saliva, but high levels were found in serum, leading to normalization of serum calcium and a significant increase in the urinary phosphorus-to-creatinine ratio. This study demonstrates for the first time differential sorting of transgenic hPTH between submandibular and parotid glands, suggesting that hPTH may be a valuable model protein for understanding the molecular basis of transgenic secretory protein sorting in these exocrine glands. We also show the clinical potential of salivary gland hPTH gene therapy for patients with hypoparathyroidism.     

自体颌下腺显微移植再造泪腺治疗重症干眼病的护理

探讨自体颌下腺移植再造泪腺治疗重症干眼病的护理方法，对8例(12侧)重症干眼病患者行自体颌下腺显微移植治疗。术前进行受区皮肤准备，术后重点观察移植后颌下腺的存活状态、移植部位的血运及角膜上皮的修复情况，康复期对患者及家属进行有针对性的护理指导。随访1个月至3年，所移植颌下腺全部存活，眼干症状均明显改善，视力提高。     

基质金属蛋白酶9在涎腺肿瘤中的表达及意义

目的探讨基质金属蛋白酶9（MMP-9）在涎腺肿瘤中的表达及其与涎腺肿瘤侵袭性生物学行为的关系,为涎腺肿瘤临床治疗寻找新思路提供理论依据。方法手术切除且资料完整的涎腺肿瘤存档蜡块共140例,多形性腺瘤32例;基底细胞腺瘤28例;腺样囊性癌40例,其中,癌细胞转移16例,无转移24例,神经侵润18例,无神经侵润22例;黏液表皮样癌40例。另选取10例手术切除的正常涎腺组织作为对照。采用免疫组化PV-9000两步法检测80例涎腺恶性肿瘤、60例良性肿瘤和10例正常涎腺组织的MMP-9表达,计算每例切片中细胞的阳性率并进行对比分析。结果MMP-9在80例涎腺恶性肿瘤、60例涎腺良性肿瘤和10例正常涎腺组织中阳性表达率分别为72．5％、30．0％、10．O％,差异有统计学意义（X^2=32．12,P〈0．01）。腺样囊性癌组织癌细胞转移组MMP-9的阳性表达率93．75％（15／16）,癌细胞未转移组阳性表达率为66．67％（16／24）,差异有统计学意义（X^2=4．038,P〈0．05）。MMP-9在正常涎液腺组织、粘液表皮样癌组、腺样囊性癌组中的阳性表达率分别为10．0％（1／10）、67．5％（27／40）、77．5％（31／40）,三组阳性率比较差异有统计学意义（X2=16．263,P〈0．01）。腺样囊性癌组织中有神经浸润者的MMP-9的阳性表达率为94．44％（17／18）明显高于无神经浸润者的阳性率63．63％（14／22）,差异有统计学意义（X^2=5．389,P〈0．05）。结论MMP-9与涎腺恶性肿瘤的浸润、转移有关,可作为预测转移潜能的指标。     

超声评分法诊断干燥综合征涎腺病变

目的 研究超声评分法对干燥综合征涎腺病变的诊断价值.方法 由两名医师对103例腮腺和颌下腺4个腺体的声像图进行评分,进行统计分析确定诊断最佳阈值及其诊断效力.结果 两名医师评分结果的Kappa值为0.80.疾病组腮腺、颌下腺评分和总评分均明显高于对照组.腮腺、颌下腺评分和总评分的ROC曲线下面积分别为0.98、0.95、0.99,总评分的最佳诊断阈值为8,诊断敏感性、特异性、阳性预测值和阴性预测值分别为93%、97%、95%、95%.结论 腮腺和颌下腺4个腺体的超声评分法评价干燥综合征涎腺病变具有较高的诊断价值.     

Pleomorphic adenoma originating from the trachea showing the appearance of a follicular tumor of the thyroid on ultrasonography

Pleomorphic adenoma (PA) is the most common tumor of the salivary gland. This report presents a case of a PA originating from the trachea that looked like a thyroid neoplasm on ultrasonography, showing a well-circumscribed, hypovascular, solid, and hypoechoic tumor within the thyroid. The tumor was resected with the right lobe of the thyroid and the first tracheal ring, which revealed a PA impacted within the thyroid. PAs originating outside of the salivary glands are rare, and there have been no reports of PAs arising from the lateral side of the trachea. This report describes the first reported, and unique, case of this type of tumor.     

Imaging of the major salivary glands

The major salivary glands, submandibular, parotid and sublingual glands play an important role in preserving the oral cavity and dental health. Patients with problems of the major salivary glands may present with symptoms such as dry mouth, dysphagia and obstruction of duct, inflammation, severe dental caries or swelling. Imaging plays an important role in visualization of morphology and function, to establish a diagnosis, for treatment, and for surgical planning. There are several options for diagnostic imaging: plain radiography, sialography, ultrasound (US), magnetic resonance imaging (MRI), computed tomography (CT), salivary gland scintigraphy and ¹⁸F‐FDG positron emission tomography (PET). We present an overview of the modalities in relation to common salivary gland disease.