Elastosis and other stromal reactions in benign and malignant breast tissue: an ultrastructural study.

The stroma and stromal reaction in normal breast, benign, and malignant breast tissue was studied by electron microscopy. Elastosis is the main stromal response in infiltrating duct and lobular carcinomas. Medullary carcinoma elicits no significant elastosis but intraductal carcinoma has significant local elastosis. Benign conditions such as fibroadenoma and sclerosing adenosis produced no significant elastosis. The high number of elastic fibers and the high microfibril:elastin ratio indicate that most of the elastic fibers are recently secreted, probably by fibroblasts and myofibroblasts. The factors stimulating the increased production of elastic fibers and the prognostic significance of elastosis remain unclear.     

Expression and mutation patterns of p53 in benign and malignant salivary gland tumors

The expression and mutation patterns of p53 were studied in a series of 68 benign pleomorphic adenomas and 237 malignant salivary gland tumors. p53 overexpression (nuclear staining exceeding 10%) was detected in 20% of the malignant salivary gland tumors, with the highest prevalence observed in polymorphous low grade adenocarcinoma, squamous cell carcinoma, and carcinoma ex pleomorphic adenoma and the lowest in adenoid cystic carcinoma and acinic cell carcinoma. In contrast, none of the 68 benign pleomorphic adenomas had nuclear staining exceeding 10%. SSCP and nucleotide sequence analysis of exons 4 to 9 of p53 in 19 malignant tumors revealed 9 mutations in 7 tumors. Our findings indicate that p53 may be a useful marker to help discriminate between benign and malignant salivary gland tumors.     

The role of immune surveillance in malignant transformation of benign salivary gland tumors

Pleomorphic adenoma (PA), the most common salivary gland tumor, is a benign tumor that carries a risk of malignant transformation to various histologies of carcinoma ex pleomorphic adenoma (CA exPA). Recently, genomic analyses have provided deeper insights into the molecular biology of salivary gland cancers. However, the molecular processes that underlie the progression from PA to CA exPA are largely unknown. In this study, we used RNAseq data from CA ex PA of myoepithelial (n = 24) or salivary duct histology (n = 6), de novo myoepithelial carcinoma (n = 16) and de novo salivary duct carcinoma (n = 10), and compared their constituent immune tumor microenvironments. We found that increasing levels of immune infiltration and activation were associated with a generally lower probability of cancer developing ex-PA, suggesting that immune surveillance may constrain the malignant transformation of benign salivary tumors. More immunologically infiltrated tumors were more likely to have developed de novo. Taken together, these data suggest a role for tumor escape from immune surveillance in the development of CA exPA. The immune-cold microenvironments of CA ex PA tumors may in part explain their more aggressive clinical behavior.     

Amyloid stroma in a tubular carcinoma of palatal salivary gland: a histochemical and ultrastructural study.

Amyloid as defined by positive Congo red green birefringence and STB red birefringence was observed in the stroma of a tubular carcinoma of minor salivary gland origin. The amyloid exhibited additional histochemical characteristics of immunamyloid, viz., positive DMAB-nitrate and DC-reactions and spontaneous autofluorescence. Electron microscopic studies of the epithelial tumor cells displayed large amounts of cytoplasmic microfilaments similar to those present in the extracellular amyloid masses. It is suggested that the amyloid is derived from spontaneous assembly or polymerization of cytoplasmic microfibrils of the dying tumor cells as has been proposed for the amyloid associated with the calcifying epithelial odontogenic tumor (CEOT).     

Minor salivary gland tumors. A histologic and immunohistochemical study

Clinical, histologic, and immunohistochemical data were reviewed and evaluated on 238 oral minor salivary gland tumors. Benign neoplasms accounted for 65% of the total. Pleomorphic adenomas were the most common of all neoplasms, and mucoepidermoid carcinomas were the most frequently encountered malignancies. Pleomorphic adenomas and adenoid cystic carcinomas stained positive for S-100 protein. Immunohistochemistry was believed to be of potential assistance in diagnosis of salivary gland tumors and in prediction of histogenesis.     

Management of malignant sublingual salivary gland tumors

The majority of tumors of the sublingual gland are malignant, with adenoid cystic carcinoma and mucoepidermoid carcinoma being the most frequent. Many other malignant tumor types have also been reported. The sublingual gland anatomically is not a unit organ and while it is described anatomically as being confined to the anterior floor of the mouth, salivary tissue may be located laterally along the submandibular duct and posterior floor of the mouth. Diagnosis should be suspected when any thickening or raised lesion presents in this area and a biopsy performed to confirm malignancy before planning further treatment. Surgery is the treatment of choice, and should include an en-block resection of the anterior floor of mouth as a minimum, and may include a portion of mandible, as well as a supraomohyoid neck dissection. Adjuvant radiotherapy should be considered in most of the patients after surgical excision.     

Radiation therapy in the treatment of malignant salivary gland tumors.

A retrospective analysis of 52 patients with malignant salivary gland tumors is reported. Seventeen patients received early postoperative radiation therapy and 16 (94%) were free of local or regional disease 2-14 years following initiation of therapy, although 14 were considered at high risk of developing local recurrence. Two subjects (12%) developed distant metastases and 14 (82%) were completely disease-free. Survival and disease-free status of patients treated for recurrent or inoperable disease were much worse with two of 13 disease-free at 45 and 168 months respectively. Various workers have reported recurrence rates after surgery along at 25-38% and over 50% for many histological types. On the basis of this report early postoperative radiation therapy is recommended to reduce the risk of postsurgical recurrence. Prognostic trends relating to both histological type and location of primary disease are discussed.     

Gamma radiation sensitivity and risk of malignant and benign salivary gland tumors: a pilot case-control analysis

BACKGROUND: The salivary gland is a highly radiosensitive organ. Exposure to gamma radiation is a risk factor for both malignant (MSTs) and benign salivary gland tumors (BSTs), but the exact mechanisms remain unknown. The objectives of the current study were to determine whether gamma radiation-induced chromatid breaks increase the risk of MSTs and BSTs and whether there is any difference in risk between these two diseases. METHODS: The authors performed a pilot case-control study of 57 patients with salivary gland diseases (45 patients with MSTs and 12 patients with BSTs) and 105 cancer-free controls. Peripheral blood lymphocytes from these participants were cultured and exposed to gamma radiation (1.5 grays). Five hours later, metaphase spread slides were evaluated. The chromatid breaks in 50 well-spread metaphase slides were counted to determine the average number of chromatid breaks per cell (b/c). RESULTS: Multivariate logistic regression analyses revealed that gamma radiation-induced b/c values greater than the median of the controls were a significant risk factor for salivary gland tumors (adjusted odds ratio [OR], 17.25; 95% confidence interval [CI], 4.92-60.49). The risk remained significant for MSTs (adjusted OR, 40.45; 95% CI, 5.27-310.17) but was of borderline significance for BSTs (adjusted OR, 4.73; 95% CI, 0.94-23.87) when these tumors were analyzed separately. CONCLUSIONS: In the current study, high levels of chromatid breaks in lymphocytes induced by gamma irradiation were associated with an independent risk for MSTs and were likely to increase the risk of BSTs. However, larger studies are needed to verify these findings.     

Fast neutron radiotherapy for advanced malignant salivary gland tumors

Thirty-two patients with inoperable, recurrent, or gross residual malignant salivary gland tumors received fast neutron radiotherapy at the University of Washington. Eleven patients were treated with low energy neutrons alone, four received a combined photon-low energy neutron treatment regimen ("mixed beam"), and 17 were treated with high energy neutrons alone. Patients treated for microscopic residual tumor after a surgical resection were excluded from this study. With a minimum follow-up period of one year, (maximum 12 years), the overall locoregional tumor control rate for the entire series was 81%. The 5-year locoregional tumor control rate was 69%. The overall 5-year survival rate was 33% (50% for T3 tumors and 0% for T4 tumors). Compared to results obtained with conventional photon and/or electron treatment for advanced salivary gland tumors, fast neutron radiotherapy appears to offer a significant advantage.     

实时超声弹性成像对涎腺结节良恶性诊断的Me ta分析

目的：系统评价实时超声弹性成像中的弹性评分法对于区分涎腺结节良恶性的诊断价值。方法：计算机检索PubMed、Embase、High Wire Press、Ovid、中国学术期刊网全文数据库（CNKI）至2016年5月31日,检索语言为英文和中文。选取应用超声弹性评分法区别涎腺结节良恶性的文章。合并敏感度、特异度、诊断比值比（DOR）评价超声弹性评分法区别涎腺结节的诊断准确性。进行综合接受者工作特征曲线（SROC）,计算曲线下面积（AUC）和Q*值来分析超声弹性评分法区别涎腺结节的综合诊断价值。结果：最终纳入11篇研究,包含642名患者,共计691个结节。超声弹性评分法区别涎腺结节的合并敏感度、特异度、诊断比值比分别为：0．77（95％CI：0．68～0．84）,0．74（95％CI：0．65～0．82）,10．12（95％CI：4．67～21．94）。综合SROC曲线下面积为0．82,Q*指数为0．7623。结论：实时超声弹性对于诊断腮腺及颌下腺结节的良恶性方面有一定的诊断价值,它可以作为一个辅助工具与传统超声联合使用,提高腮腺及颌下腺结节诊断的准确度。     

Malignant salivary gland tumors

A retrospective review of 403 patients with salivary gland tumors seen between 1958 and 1980 and a mean follow-up of 10 years is reported. The median age was 58 (7-94) years and the male to female ratio 1.3:1. There were 293 (72%) parotid, 83 (21%) submaxillary and 27 (7%) tumors developed at other sites. Among these were 84 (22%) mucoepidermoid (all degrees of differentiation), 87 (22%) adenocystic carcinomas, 70 (17%) adenocarcinomas, 25 (6%) acinic, 26 (6%) squamous cell, 44 (11%) undifferentiated, 52 (13%) mixed and 12 (3%) nonspecified carcinomas. A painless lump was the first symptom in 338 (84%) patients. The first planned treatment was surgery in 110 (27%), radiotherapy in 50 (12%), and surgery and radiotherapy combined in 239 (59%) patients. Following the first treatment, the primary parotid tumor was controlled by surgery in 17/70 (24%), by irradiation in 6/39 (15%) and surgery and radiation combined in 134/182 (74%) patients. Altogether, regional metastases developed in 36 (12%) and distant metastases in 36 (12%) of 293 patients with parotid tumors. For the submandibular tumors the primary tumor was controlled by surgery in 9/31 (29%), 0/4 (0%) by irradiation, and in 32/46 (70%) by surgery and irradiation. Here, regional and distant metastases developed in 16/84 (19%) and 19/84 (23%) patients. Among the other sites the primary tumor was controlled by surgery in 4/9 (44%), 0/7 (0%) by irradiation, and in 8/11 (73%) by surgery and radiotherapy combined. In this group 4/27 (15%) and 5/27 (18%) patients developed regional and distant metastases. The 5- and 10-year cause specific survival rates were 65 and 59% for the parotid tumors, 61 and 48% for the submaxillary tumors and 62 and 52% for the other sites. These results clearly demonstrate the advantages of combining surgery and radiotherapy as the first planned treatment for most tumors.     

Labial salivary gland tumors

A study was conducted on labial salivary gland tumors from four oral pathology laboratories. Of the 103 identified tumors, 87 (84.5%) were from the upper lip, whereas 16 (15.5%) were from the lower lip. Of the 87 upper lip tumors, 80 (92.0%) were benign. Forty-three of these were monomorphic adenomas and 37 were pleomorphic adenomas. Seven malignant tumors of the upper lip were as follows: four adenoid cystic carcinomas, two acinic cell carcinomas, and one adenocarcinoma. Of the 16 lower lip tumors, 15 (93.8%) were malignant. Thirteen of these were mucoepidermoid carcinomas and two were acinic cell carcinomas. The only benign lower lip tumor was an intraductal papilloma. These results confirm the findings of previous investigations, showing that minor salivary gland tumors are much more common in the upper lip than the lower lip, but that lower lip tumors are more likely to be malignant.     

The role of radiotherapy in the treatment of malignant salivary gland tumors

PURPOSE: We analyzed the role of primary and postoperative low linear energy transfer radiotherapy in 538 patients treated for salivary gland cancer in centers of the Dutch Head and Neck Oncology Cooperative Group, in search for prognostic factors and dose response. METHODS AND MATERIALS: The tumor was located in the parotid gland in 59%, submandibular gland in 14%, oral cavity in 23%, and elsewhere in 5%. In 386 of 498 patients surgery was combined with radiotherapy, with a median dose of 62 Gy. Median delay between surgery and radiotherapy was 6 weeks. In the postoperative radiotherapy group, adverse prognostic factors prevailed. Elective radiotherapy to the neck was given in 40%, with a median dose of 50 Gy. Primary radiotherapy (n = 40) was given for unresectable disease or M(1), with a dose range of 28-74 Gy. RESULTS: Postoperative radiotherapy improved 10-year local control significantly compared with surgery alone in T(3-4) tumors (84% vs. 18%), in patients with close (95% vs. 55%) and incomplete resection (82% vs. 44%), in bone invasion (86% vs. 54%), and perineural invasion (88% vs. 60%). Local control was not correlated with interval between surgery and radiotherapy. No dose-response relationship was shown. Postoperative radiotherapy significantly improved regional control in the pN(+) neck (86% vs. 62% for surgery alone). A rating scale for different sites, T stage, and histologic type may be applied to calculate the risk of disease in the neck at presentation, and so indicate the need for elective neck treatment. A marginal dose-response was seen, in favor of a dose > or =46 Gy. A clear dose-response relationship was shown for patients treated with primary radiotherapy. Five-year local control was 50% with a dose of 66-70 Gy. CONCLUSIONS: Postoperative radiotherapy with a dose of at least 60 Gy is indicated for patients with T(3-4) tumors, incomplete or close resection, bone invasion, perineural invasion, and pN(+). In unresectable tumors, a dose of at least 66 Gy is advisable.     

Small cell undifferentiated carcinoma of salivary gland origin: an ultrastructural study.

A case of small cell carcinoma of salivary gland was studied by light and electron microscopy. Light microscopy showed sheets of small uniform cells with scanty cytoplasm and pyknotic nuclei. Electron microscopy showed two distinct cell types; an electron-lucent epithelial-appearing cell, and a denser cell with processes containing bundles of filaments and other features suggesting myoepithelial differentiation. Neurosecretory granules were absent. These findings support a salivary duct origin, and are evidence against a neurendocrine derivation for this tumor.