Polymorphous low-grade adenocarcinoma of submandibular gland origin

A case of polymorphous low-grade adenocarcinoma (PLGA) in the submandibular gland is reported. A 72 year old woman presented with a 5 year history of a gradually expanding tumor in the submandibular region. The surgical specimen revealed a relatively well demarcated tumor, 35 × 35 × 20 mm in size. Macroscopically, necrosis and hemorrhage were not seen in the solid tumor. Histologically, the tumor growth pattern was variable, composed of tubular, papillary, solid, trabecular and cribriform structures. Immunohistochemically, some tumor cells were positive for epithelial membrane antigen (EMA), S-100 protein, keratin, and carcino-embryonic antigen (CEA). Electron microscopically, prominent microvilli projected into the luminal spaces, and basal lamina and hemidesmosomes were seen in the tumor cells adjacent to the connective tissues. The submandibular gland is an extremely rare location for PLGA. To the authors' knowledge, this is the first case of its kind reported in the English literature.     

Hybrid carcinoma of the salivary gland: salivary duct adenocarcinoma adenoid cystic carcinoma

AIMS: Hybrid tumours of the salivary gland are rare neoplasms that have been described only in the parotid and palate. Their recognition is important particularly when the component tumours have different biological behaviours. The occurrence of a submandibular hybrid tumour has not been reported. METHODS AND RESULTS: We describe a case of a 36-year-old woman with a hybrid carcinoma composed of salivary duct adenocarcinoma and adenoid cystic carcinoma of the right submandibular gland. There was no evidence of a pre-existing or concurrent pleomorphic adenoma. The presence of the two components was verified by differential immunohistochemical staining using a panel of cytokeratin, vimentin, smooth muscle actin and S100. The patient subsequently developed metastases to the pelvis, lumbar, vertebra and wrist. The clinical course in this patient was consistent with the behaviour of the salivary duct adenocarcinoma component. CONCLUSIONS: The histogenesis of hybrid tumours is largely unknown, but in this case it may represent diverging differentiation of luminal tumour cells. Because some histological features of different salivary gland tumours overlap, immunohistochemistry is a valuable tool especially when used to delineate the components of a hybrid tumour.     

Stromal melanocytosis of an adenoid cystic carcinoma arising from the palatal minor salivary gland

An unusual case of adenoid cystic carcinoma arising from the palatal minor salivary gland in a 63-year-old Japanese female is reported. In addition to the characteristic histopath-ologic features of adenoid cystic carcinoma, spindle- and dendritic-shaped cells containing excessive amounts of melanin pigment were densely and widely distributed in the stroma resulting in a blue nevus-like appearance. Neither melanocytes nor melanin pigments were seen within the parenchyma. The possible histogenesis of melanocytes in the stroma of the salivary gland carcinoma is discussed, although no firm conclusion could be drawn.     

涎腺基底细胞腺瘤和腺癌与腺样囊性癌的比较观察

目的 研究涎腺基底细胞腺瘤和基底细胞腺癌与腺样囊性癌的形态学特征、免疫表型和鉴别诊断。方法 对5例基底细胞腺瘤，5例基底细胞腺癌和7例腺样囊性癌进行了免疫组化和双重免疫电镜(2例)的观察。结果 基底细胞腺瘤和基底细胞腺癌在免疫表型方面非常相似；基底细胞腺瘤(癌)与腺样囊性癌之间在免疫表型和超微结构方面有一定的差别。结论 基底细胞腺瘤和基底细胞腺癌的鉴别诊断基于两者的生长方式和组织学特征。免疫组化和免疫电镜观察有助于基底细胞腺瘤(癌)与腺样囊性癌的鉴别诊断。     

Polymorphous low-grade adenocarcinoma of the salivary glands

Six cases of polymorphous low-grade adenocarcinoma (terminal duct adenocarcinoma) of the minor salivary glands are presented. In all but one there was a history of a painless intra-oral mass of fairly long duration. The histopathological appearances were characterized by cytological uniformity in a variety of morphological patterns, including tubular, solid, fascicular and cribriform areas. At a cellular level, the tumours possessed regular, often vesicular nuclei and generally eosinophilic cytoplasm. Five of the patients are still alive, although one had recurrent disease 16 years after her original operation; none died of their tumour. These findings are compared with those of six salivary adenoid cystic carcinomas, a neoplasm with many similar histological features, but with a much worse prognosis. The microscopic differences were mainly cytological and, to a lesser extent, morphological. The immunohistochemical reactions of the two tumours were not sufficiently dissimilar to be of practical value. Polymorphous low-grade adenocarcinoma has only rarely been reported in Britain, but we believe it deserves wider recognition as a distinct clinicopathological entity and, in particular, separation from adenoid cystic carcinoma.     

Polymorphous low-grade adenocarcinoma of the salivary glands with transformation to high-grade carcinoma

AIMS: Polymorphous low-grade adenocarcinoma of the minor salivary glands is an infiltrative neoplasm characterized by bland-looking tumour cells arranged in diverse architectural patterns. It is considered to be of low-grade malignant potential in that nodal metastases are seen in only a minority, and distant spread is rare. Even more unusual is the transformation of polymorphous low-grade adenocarcinoma to a histologically high-grade carcinoma, i.e. dedifferentiation. In this paper, we describe the clinicopathological and immunohistochemical findings in two further examples. METHODS AND RESULTS: Two patients presented each with a tumour of the palate. Histopathological examination showed the typical morphological, cytological and immunohistochemical features of a polymorphous low-grade adenocarcinoma. In one case there was a second component of high-grade carcinoma showing nuclear atypia, markedly increased mitotic activity and MIB1 index, as well as prominent zones of necrosis. It expressed epithelial markers and androgen receptors, and thus resembled salivary duct carcinoma. Similar tumour tissue was observed in one of the cervical nodal metastases, which was biopsied at the same time as the palate. In the second patient, a high-grade component was discovered when the tumour recurred in the palate 13 years after the initial biopsy. Whilst morphologically similar to that in first case, there were significant immunohistochemical differences such as retention of some of the polymorphous low-grade adenocarcinoma profile and absence of androgen receptor expression. CONCLUSIONS: Polymorphous low-grade adenocarcinoma was first described relatively recently, and as experience with it continues to accumulate, it is becoming clear that late recurrences and metastases, whilst still infrequent, may not be quite as rare as previously thought. Reports of histological transformation are even scarcer, and most occurred at least 13 years after the polymorphous low-grade adenocarcinoma was initially recognized. It is a real possibility that this phenomenon, like clinical progression, may also be encountered more often as time passes. Therefore, we believe that, whilst polymorphous low-grade adenocarcinoma is certainly far less aggressive than, for example, adenoid cystic carcinoma, it nevertheless remains a true malignancy with a potential to prove fatal in a minority of patients.     

涎腺腺样囊性癌和基底细胞腺瘤的免疫表型及临床病理特征

目的观察CK7、Calponin、CD117、Ki-67在涎腺腺样囊性癌(adenoid cystic carcinoma,ACC)和基底细胞腺瘤(basal celladenoma,BCA)中的免疫表型及其病理组织形态学差异,以提高对该类肿瘤鉴别诊断的认识。方法对发生于涎腺的26例BCA和17例ACC进行临床和病理组织形态观察并免疫组化标记(CK7、Calponin、CD117、Ki-67)。结果临床特点为两种肿瘤的发病年龄相似,但发生部位不同,ACC好发于腮腺以外的小涎腺,BCA多数发生于腮腺;病理特点为前者表现为浸润性生长并累及周围组织;免疫组化显示两种肿瘤存在免疫表型差异:其中CD117在ACC和BCA之间的强阳性率差异有统计学意义(P<0.05);Ki-67在BCA和ACC之间的强阳性率差异有统计学意义(P<0.01)。结论 ACC具有浸润性生长的生物学特征,病理特点上与BCA鉴别主要基于两者的生长方式和组织形态学检查,CD117和Ki-67免疫组化标记有助于其鉴别诊断。     

Salivary carcinomas with papillae: Cytology and histology analysis of polymorphous low-grade adenocarcinoma and papillary cystadenocarcinoma

We retrospectively compared fine-needle samplings (FNS) from two recently individualized low-grade papillary salivary carcinomas, polymorphous low-grade adenocarcinoma (PLGAC) and papillary cystadenocarcinoma (PCAC), to define the cytologic criteria allowing the correct diagnosis. Twelve PLGACs in 10 patients and 5 PCACs in 4 patients were investigated by FNS preoperatively. In both entities, smears contained variable proportions of malignant cells, occasionally arranged in pseudopapillary formations. In contrast to PCAC, PLGAC showed stromal fragments and hyaline globules resembling pleomorphic adenoma or adenoid cystic carcinoma. Cytologic diagnoses of malignancy were established in 10 (83.3%) PLGACs and in 4 (80%) PCACs. Two (16.7%) PLGACs were misdiagnosed as pleomorphic adenoma, and 1 (20%) PCAC as a salivary cyst. Diagn. Cytopathol. 1998;19:244–249. © 1998 Wiley-Liss, Inc.     

Prognostic value of apoptosis and apoptosis-associated proteins in salivary gland adenoid cystic carcinoma

The purpose of the present study was to investigate the level of apoptosis and expressions of p53, mdm2 and bcl-2 proteins in salivary gland adenoid cystic carcinoma (ACC) to determine potential relationships among apoptosis, apoptosis-associated proteins and clinical cumulative survival. Thirty-nine formalin-fixed, paraffin-embedded cases, cribriform (17), tubular (13) and solid (9), were studied by immunohistochemistry. Apoptosis detection and analysis were determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL). There was an inverse significance between the apoptotic index (AI) and bcl-2 expression (P = 0.018), whereas no correlation was found between the AI and either p53 or mdm2 expression (P = 0.416 and P = 0.456). Co-expression of p53 and mdm2 was found in 22 cases (P = 0.037). Patients with p53-positive tumors had a worse prognosis than those with p53-negative tumors (P = 0.014). Patients with a high AI had a better cumulative survival than patients with a low AI (P = 0.038). The present study suggests that p53 expression and AI can be useful as prognostic values; bcl-2 protein plays a role in the down-regulation of apoptosis and is also potentially useful as a prognostic parameter in salivary gland ACC.     

RNAi knockdown of C-erbB2 expression inhibits salivary gland adenoid cystic carcinoma SACC-83 cell growth in vitro

Objective

To knockdown the C-erbB2 gene in salivary gland adenoid cystic carcinoma SACC-83 cells using RNA interference, and determine the effect of silencing C-erbB2 on cell proliferation.

Methods

C-erbB2-siRNA was transfected into SACC-83 cells. RT-PCR and immunohistochemistry were used to detect C-erbB2 expression in SACC-83 cells. Cell proliferation was measured by the MTT assay and gene knockdown was achieved by RNA interference. Apoptosis was analyzed by flow cytometry.

Results

Compared with the control, C-erbB2 mRNA expression was decreased in the C-erbB2-siRNA transfection group, and immunohistochemical analysis indicated that C-erbB2 protein expression was decreased. After C-erbB2-siRNA was transfected for 48 h, absorbance at 570 nm (MTT) was 0.185±0.021 compared with 0.354±0.034, 0.299±0.053, and 0.314±0.049 in the blank control, liposome control and negative control siRNA groups, respectively. The differences were statistically significant (P < 0.05) between the C-erbB2-siRNA group and the control groups. Following the C-erbB2 knockdown, the percentage of apoptotic cells was 5.63% compared with 2.04%, 2.85%, and 2.98% in the three control groups, respectively. Proliferation of SACC-83 cells was inhibited, and early apoptotic cells were increased.

Conclusion

RNA interference can effectively silence C-erbB2 gene expression and inhibit growth of SACC-83 cells, which indicates the potential of targeting this gene as a novel gene therapy approach for the treatment of salivary gland adenoid cystic carcinoma.     

涎腺腺样囊性癌中ADAM-17的表达及临床意义

目的探讨ADAM-17在涎腺腺样囊性癌(salivary adenoid cystic carcinoma,SACC)中的表达及临床意义。方法收集48例SACC石蜡组织和20例新鲜组织,分别采用免疫组化EnVision两步法和RT-PCR法检测SACC组织中ADAM-17蛋白和mRNA表达水平,并分析其与临床病理学参数之间的相关性。结果 ADAM-17蛋白在48例SACC组织中阳性率为72.9%(35/48),ADAM-17mRNA水平在20例SACC中平均相对表达量为(0.40±0.18),两者的表达均高于正常对照组,差异具有统计学意义(P<0.001),两者的表达与肿瘤的大小、TNM分期和患者的生存时间均有相关性。结论 ADAM-17在SACC中高表达,可能介导癌组织生长、侵袭和转移,其有望成为一个新的治疗靶点。     

Fine-needle sampling of salivary gland lesions III. cytologic and histologic correlation of 75 cases of adenoid cystic carcinoma: Review and experience at the Institut Curie with emphasis on cytologic pitfalls

Fine-needle sampling (FNS) of 75 adenoid cystic carcinomas, including 44 primary tumors, 18 local recurrences, 10 lymph node, and 3 distant metastases, was performed in 66 patients. Concordant cytologic diagnoses were established in 68 tumors (90.7%), whereas 4 (5.4%) were classified as malignant (adenocarcinoma), 1 (1.3%) as suspicious, and 1 (1.3%) as pleomorphic adenoma. The material was insufficient for cytologic evaluation in 1 (1.3%) tumor. Adenoid cystic carcinoma is, in our opinion, easy to diagnose using the FNS technique. Diagn. Cytopathol. 17:36–41, 1997. © 1997 Wiley-Liss, Inc.     

涎腺腺样囊性癌的免疫组织化学及免疫电镜观察

采用抗平滑肌的肌动蛋白（ａｃｔｉｎ）、肌球蛋白（ｍｙｏｓｉｎ）、Ｓ—１００蛋白和胶质纤维酸性蛋白（ＧＦＡＰ）对４例涎腺腺样囊性癌进行免疫组化和免疫电镜研究。结果发现，该癌中肿瘤性肌上皮细胞对抗ａｃｔｉｎ、ｍｙｏｓｉｎ和Ｓ—１００蛋白反应阳性，对抗ＧＦＡＰ反应阴性。这些细胞衬里在囊样腔隙周边、小导管外周或散在于上皮团块中；肿瘤性腺上皮细胞对上述抗体反应阴性。讨论了肿瘤性肌上皮细胞的分化趋向和免疫特性。     

Fine-needle sampling of salivary gland lesions V: Cytology of 22 cases of acinic cell carcinoma with histologic correlation

Fine-needle sampling (FNS) of 22 acinic cell carcinomas, including 17 primary tumors, 4 local recurrences, and 1 lymph node metastasis was performed preoperatively in 17 patients. Cytologic diagnoses were concordant with histology in 3 (13.7%) cases, whereas 15 (68.2%) cases were cytologically classified as malignant, 2 (9.1%) as suspicious, and 1 (4.5%) as benign (pleomorphic adenoma). The material was unsatisfactory for cytologic evaluation in 1 (4.5%) case. Preoperative FNS technique is, therefore, useful in acinic cell carcinoma with a concordant malignant/suspicious rate of 91%. Diagn. Cytopathol. 1997;17:347–352. © 1997 Wiley-Liss, Inc.     

Acinic-cell carcinoma,papillary-cystic variant: a diagnostic dilemma in salivary gland aspiration

Fine-needle aspiration (FNA) plays a pivotal role as the initial diagnostic modality of choice when dealing with salivary gland (SG) lesions. Due to the heterogeneous nature of most SG neoplasms, cytologic interpretation on FNA can be quite challenging. This is particularly valid when dealing with rare tumor types, such as the papillary-cystic variant of acinic-cell carcinoma (ACC-PCV), resulting in a high rate of false-negative cytologic diagnoses. Seven cases of ACC-PCV diagnosed on tissue resection with a prior FNA performed in cytology were studied. Material consisted of Diff-Quik and Papanicolaou stained cytologic smears, as well as hematoxylin-eosin stained cell block and histopathologic sections. In no case did the FNA performed prior to the surgical resection eventuate in a cytopathologic diagnosis of cancer. A retrospective morphologic review of the smears disclosed several characteristics common to all 7 cases, i.e., mostly tightly cohesive fragments of neoplastic epithelium seen as monolayered sheets or with a prominent papillary architecture, high nuclear:cytoplasmic ratio ductal-type epithelium, cystic material and degenerated cellular debris, histiocytes, cells with squamoid and metaplastic oncocytic changes, vacuolated and pigmented histiocyte-like tumor cells, and lack of a predominant single-cell component or naked neoplastic cell nuclei. ACC-PCV represents a rare yet significant cause of false-negative results for cancer on SG aspirations. An erroneous interpretation may occur due to lack of experience in dealing with this tumor type, the rarity of published literature on ACC-PCV, and a predominantly cystic, somewhat variegated appearance of the tumor mimicking other benign and malignant SG lesions.     

Extra-salivary gland presentations of adenoid cystic carcinoma: a report of three cases

Adenoid cystic carcinoma (ACC) is a malignant neoplasm most commonly originating in salivary glands of the head and neck area. When ACC presents outside of these locations, the diagnosis may become more challenging. We describe three cases of ACC presenting in extra-salivary gland sites. Two cases were metastatic; in case 1 the initial presentation was widespread bony metastasis of unknown primary origin. The other metastatic case (case 2) was from a patient presenting with a pleural effusion and a history of previously treated metastatic pulmonary ACC. The pleural effusion cytology was unusual in that exfoliated ACC cells were present in the effusion itself, a rare occurrence. Case 3 was a primary bronchial ACC. In conclusion, ACC can present in various body sites and cytologists must consider this neoplasm when presented with a basaloid carcinoma of uncertain origin.