Effects of guanabenz and guanfacine on postsynaptic α2-adrenoceptors in the rat submaxillary and parotid glands

Summary The effects of two ₂-agonists (guanfacine and guanabenz) on both the submaxillary and parotid gland of the rat were studied. Whereas guanfacine in doses ranging between 1,000 and 30,000 g/kg i.v. produced an immediate and persistent secretion of saliva from the submaxillary gland, guanabenz in doses as high as 40,000 g/kg did not induce measurable secretion either from the parotid or the submaxillary gland. Secretion clicited by guanfacine was not modified by yohimbine (300 g/kg) but was abolished by prazosin (100 g/kg).In both glands, low doses of either guanabenz (10 g/kg) or guanfacine (100 g/kg) markedly inhibited the secretory responses induced by noradrenaline, methacholine and substance P, but not that induced by isoprenaline. The inhibition caused by the ₂-agonists was greater for noradrenaline than for either methacholine or substance P. Blockade of ₂-adrenoceptors with yohimbine (300 g/kg) did not modify the response to noradrenaline, methacholine or substance P in either gland. However, the same dose of yohimbine injected 5 min before the ₂-agonists prevented the inhibitory effects of guanfacine and guanabenz on the response induced by either one of the three sialagogic agents. Guanabenz (10 g/kg) did not modify the increase in mean blood pressure observed after the different doses of noradrenaline employed to induce salivary secretion. Guanabenz (10 g/kg) and guanfacine (100 g/kg) did not change the time course of the secretion elicited by either noradrenaline, methacholine or substance P, since the degree of inhibition was of similar magnitude at all the periods of time analyzed.The results obtained give further support to the hypothesis that activation of ₂-adrenoceptors in the submaxillary as well as parotid gland of the rat inhibits secretory responses which are mediated by either muscarine, substance P and ₁-receptors and not those elicited by -adrenoceptors.Partially supported by grants no. 3111 k/83 CONICET and Res 40-5/4/84 SUBCYT     

Number of cortisol time-points and dexamethasone suppression test sensitivity for major depression

Failure to suppress cortisol secretion after administration of dexamethasone has been reported to be a diagnostic marker for major depression and to have prognostic implications when repeated after antidepressant treatment. The pulsatile pattern of cortisol secretion suggested to us that increasing the number of post-dexamethasone cortisol determinations might significantly increase the sensitivity of the dexamethasone suppression test (DST) for major depression. With a conventional two-point DST (1600 h and midnight), 5% of 20 normal volunteers, 8% of 13 inpatients with non-major depressions, and 31% of 65 inpatients with primary major depression failed to suppress. With six post-dexamethasone points (0800 h, 1200 h, 1600 h, 2000 h, 2200 h, midnight), the respective percentages were 10, 15 and 44%. The additional points increased the sensitivity from 31 to 44%, mostly by identifying more major depressives with a "late escape" pattern. If a clinician is using the DST to establish a marker for major depression that can be repeated to monitor response to treatment and the likelihood of relapse, then perhaps the increased sensitivity of the six-point DST would be helpful, despite a modest decrease in specificity from 94 to 88%.     

43例涎腺粘液表皮样癌的临床分析

目的：探讨涎腺粘液表皮样癌（MEC）的组织学分型和临床分期与手术预后的关系,为临床确定理想的治疗方案提供参考和依据。方法：对43例得到病理学证实的涎腺MEC的发病部位、临床表现及基组织学分型、TNM分类和临床分期与手术治疗预后的相关性进行分析。结果：在得到长期随访的36例中,6例出现局部复发或区域淋巴结转移,其中在组织学上属高分化型4例,低分化型2例;属临床Ⅰ、Ⅱ期1例,Ⅲ、Ⅳ期5例;现生存23例,死亡13例,其中死于MEC4例,死于其他疾病9例;死于MEC的4例均属临床Ⅲ、Ⅳ期。这表明MEC术后的复发转移率和病死率与其组织学分型无明显相关（P＞0．05）,而与临床分期关系密切（P＜0．01）,临床Ⅰ、Ⅱ期MEC的手术预后明显优于Ⅲ、Ⅳ期。结论：对于临床Ⅲ、Ⅳ期的MEC应高度重视原发灶手术切除的彻底性及相应区域的淋巴结清扫。对手术切除不彻底的病例,可考虑术后放疗。     

Salivary Intraductal Carcinoma Arising within Intraparotid Lymph Node: A Report of 4 Cases with Identification of a Novel STRN-ALK Fusion

Intraductal carcinoma (IDC) is a rare salivary gland tumor that is considered analogous to ductal carcinoma in-situ of the breast, demonstrating a complex neoplastic epithelial proliferation surrounded by a continuous layer of presumed non-neoplastic myoepithelial cells. It is subcategorized into intercalated duct, apocrine, and hybrid subtypes based on morphologic and immunohistochemical features, with frequent NCOA4-RET and TRIM27-RET fusions, respectively, seen in intercalated duct and hybrid tumors. However, as an expanding clinicopathologic spectrum of IDC has been documented, controversy has emerged as to whether this tumor type is best defined by its intraductal growth pattern or distinctive molecular and immunophenotypic differentiation. Here, we further explore the nature of IDC by evaluating four cases that arose within intraparotid lymph nodes. These intercalated-duct phenotype tumors with diffuse S100 protein expression demonstrated a crowded and complex epithelial proliferation arranged in cystic, cribriform, and micropapillary architecture, surrounded by an intact myoepithelial cell layer, and were completely intranodal. Of two tumors with tissue available for molecular analysis, one demonstrated a NCOA4-RET fusion and one harbored a STRN-ALK fusion that is novel to IDC. Not only does the intranodal presence of IDC present a challenging differential diagnosis, but the complex nature of this proliferation within lymph node tissue raises questions as to whether the myoepithelial component of IDC is actually non-neoplastic in nature. Furthermore, identification of a STRN-ALK fusion expands the genetic spectrum of IDC and adds to evidence of an emerging role for ALK in salivary gland tumors. Further attention to the nature of the myoepithelial cells and documentation of alternate fusion events in IDC may inform continued discussion about its appropriate classification.     

YAP1-MAML2-Rearranged Poroid Squamous Cell Carcinoma (Squamoid Porocarcinoma) Presenting as a Primary Parotid Gland Tumor

Porocarcinoma (synonym: malignant eccrine poroma) is a rare aggressive carcinoma type with terminal sweat gland duct differentiation. The squamous variant of porocarcinoma is even less frequent and might be indistinguishable from conventional squamous cell carcinoma (SCC). We herein describe the first case of a carcinoma presenting as a primary parotid gland malignancy in a 24-year-old male without any other primary tumor. Total parotidectomy and neck dissection were performed followed by adjuvant chemoradiation. The patient remained alive and well 10 months after diagnosis. Histology showed keratinizing SCC infiltrating extensively the parotid gland with subtle poroid cell features. Oncogenic HPV infection was excluded by DNA-based testing. NGS analysis using the TruSight RNA fusion panel (Illumina) revealed a novel YAP1-MAML2 gene fusion. This gene fusion was reported recently in a subset of cutaneous porocarcinoma and poroma. This case of poroid SCC (or squamoid porocarcinoma) adds to the differential diagnosis of SCC presenting as parotid gland tumor and highlights the value of molecular testing in cases with unusual presentation.Electronic supplementary materialThe online version of this article (10.1007/s12105-020-01181-9) contains supplementary material, which is available to authorized users.     

Multifocal Parotid Oncocytic Cystadenomatosis: A Rare Process that Can Mimic Malignancy

Multifocal cystic oncocytosis (MCO) is a rare, benign process accounting for approximately 0.1% of salivary gland lesions. Salivary oncocytosis is characterized by multiple unencapsulated solid nodules of oncocytic cells derived from transformed striated ducts. MCO is a variant of salivary oncocytosis which manifests as cystically dilated striated ducts. It is difficult to obtain a definitive preoperative diagnosis of MCO; therefore, these lesions are commonly treated with surgery. We report the unique case of a 66-year-old male who previously underwent a superficial left parotidectomy for a pleomorphic adenoma. Four years later, he presented with clinical and radiographic suspicion of a multifocal recurrent pleomorphic adenoma. The patient subsequently underwent a revision parotidectomy. However, final pathology confirmed a diagnosis of MCO. Although MCO is commonly treated with surgery due to lack of a definitive preoperative diagnosis, surgery is unnecessary outside of diagnostic, functional or cosmetic considerations. Thus, if a patient with parotid oncocytosis treated by superficial parotidectomy develops disease re-manifestation in the residual deep lobe, further surgery is not indicated. There is no risk of malignant progression in this process. We report on this unusual entity as it may mimic salivary malignancy or, as in this case, recurrence of benign disease.     

A case report of a rare nasopharyngeal myoepithelial dominant pleomorphic adenoma

IntroductionPleomorphic adenoma is the most common benign salivary gland neoplasm. The majority of cases occur in the major salivary glands; however, they can also originate from the minor salivary glands. The nasopharynx is an uncommon site, but it has been reported in the literature. The characteristic difference of our report from the literature is the young age of our patient and his previous unremarkable medical or surgical history.The objective of this report is to present a case of salivary gland pleomorphic adenoma, discuss radiological and histopathological findings and treatment options.Case presentationHerein we report a case of a 25-year-old male patient presenting with a long-term history of snoring, mouth breathing, and progressive left nasal obstruction. After examining the patient and confirming the diagnosis, patient successfully underwent tumor resection using a combined transnasal/transoral endoscopic approach with no complications following surgery and significant improvement of the previously reported symptoms.DiscussionPleomorphic adenoma of the minor salivary glands can occur anywhere throughout the distribution sites of these glands such as: along the upper aerodigestive tract, parapharyngeal fat spaces, soft palate, the sinonasal, and nasopharyngeal areas.ConclusionThe occurrence of pleomorphic adenoma in uncommon sites has been reported in the literature, and the nasopharynx is considered to be one of these uncommon sites. The mainstay of treatment for nasopharyngeal pleomorphic adenoma is surgical excision as they can grow to giant sizes if left untreated.     

涎腺肿瘤抗凋亡基因 bcl-2表达产物的分布及意义

目的 :探讨抗凋亡基因bcl 2蛋白与涎腺肿瘤的关系。方法 :利用免疫组化LSAB法 ,检测4 2例腺样囊性癌、15例多形性腺瘤和 5例正常涎腺组织中bcl 2基因产物的表达与分布。结果 :4 2例腺样囊性癌 37例阳性 ,阳性率 88 1%。 15例多形性腺瘤阳性率 10 0 % ,但阳性细胞少 ,主要分布于上皮丰富的腺管样结构 ,而鳞状上皮及粘液软骨区为阴性。 5例正常涎腺组织中 ,导管上皮细胞少数散在阳性 ,腺泡细胞阴性。结论 :bcl 2蛋白在涎腺肿瘤组织不同的肿瘤细胞中具有不同的凋亡能力 ;在上皮成分中广泛过量表达 ,可能参与了涎腺肿瘤的形态发生。     

董酒珍酒对小鼠血清睾酮皮质醇等的影响

目的　研究贵州产名酒董酒、珍酒的保健作用。方法　采用氢化可的松 (以下简称氢可 )肌注 (每日 1次 ,连续 3d)复制小鼠阳虚症模型 ,用放免法测血清睾酮、皮质醇水平及心、肝、肾、睾丸组织形态学的变化 ,并比较董酒、珍酒对其的影响。结果　肌注氢可的各组血清皮质醇浓度明显增加 ,与正常组比较 ,差异具显著性 (P <0 .0 5 ) ;单纯阳虚组血清睾酮浓度虽不降低 ,但睾丸组织中生精状况差 ;而在阳虚 饮酒组 (董酒或珍酒组 ) ,血清睾酮浓度明显降低 (P <0 .0 5或P <0 .0 1) ,但睾丸组织中生精活跃 ,可见较多的精母细胞、精子细胞等精子发育良好。结论　董酒、珍酒可降低阳虚小鼠血清睾酮水平 ,但对其睾丸生精功能似有一定促进作用 ,其机制有待阐明。