Small cell carcinoma of the major salivary glands

Small cell carcinoma is primarily a pulmonary neoplasm that rarely arises in extrapulmonic sites including salivary glands of the head and neck. Twelve cases of small cell carcinoma of salivary gland origin were retrieved from the Armed Forces Institute of Pathology files. Six tumors occurred in the parotid gland and six in the submandibular gland. Tumors were classified into two categories: those with areas of histologically typical small cell carcinoma (7 cases) and those with areas of typical small cell carcinoma with foci of ductal differentiation (5 cases). Follow-up information was available in all 12 cases. Electron microscopy was done on eight tumors; only one demonstrated round electron dense intracytoplasmic neurosecretory granules. These observations further support evidence in the literature suggesting most of the small cell carcinomas of salivary gland origin are not true neuroendocrine ("oat cell") carcinomas, but actually are small cell ductal carcinomas. These tumors appear to have a better prognosis than small cell carcinoma of the lung or nonsalivary gland sites in the head and neck region, with an estimated 2- and 5-year survival of 70 and 46%, respectively.     

Immunohistochemistry of germ cell and trophoblastic neoplasms

The immunoprofiles of 121 germ cell and trophoblastic neoplasms were defined, using a battery of antibodies against cytokeratin (CK), vimentin (VIM), epithelial membrane antigen (EMA), placental alkaline phosphatase (PLAP), S-100 protein, leukocyte common antigen (LCA), UCHL-1, LN-2, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), chromogranin A, Leu-7, alpha-fetoprotein (AFP), alpha-1-antitrypsin (AAT), and the beta subunit of human chorionic gonadotropin (BHCG). In addition to 85 neoplasms of testicular origin, the cases included eight ovarian germ cell tumors and 28 extragonadal neoplasms. All tissues had been subjected to formalin fixation and paraffin embedding. Similar immunoreactivity patterns were seen in gonadal and extragonadal neoplasms, gestational and nongestational choriocarcinomas, components of mixed germ cell tumors and their pure counterparts, and metastatic and primary lesions. Placental alkaline phosphatase was a sensitive marker of germ cell differentiation, and expression of this marker in the absence of EMA appeared to be a staining pattern unique to germ cell tumors. Both LCA and S100 were absent in neoplastic germ cells, and thus were useful in differentiating these tumors from malignant lymphoma and malignant melanoma, respectively. Cytokeratin was helpful in distinguishing seminomas/dysgerminomas from nonseminomatous germ cell tumors, although 10% of seminomas showed focal or diffuse cytokeratin reactivity. Finally, 75% of all germ cell neoplasms displayed NSE, calling the specificity of this determinant into question.     

Leu-7 in small cell neoplasms. An immunohistochemical study with ultrastructural correlations

In an effort to delineate the distribution of the Leu-7 antigen in small cell neoplasms, 283 paraffin-embedded examples of such tumors were studied immunohistochemically. These included 125 malignant lymphomas, 94 neuroendocrine carcinomas, 13 adenocarcinomas, 14 squamous carcinomas, four malignant melanomas, six neuroblastomas, four nephroblastomas (Wilms' tumors), six primitive neuroectodermal neoplasms, three "Askin" tumors, ten Ewing's sarcomas, and four embryonal rhabdomyosarcomas. Histologic diagnoses were verified by the use of electron microscopic study or independent immunostains. Overall, 44% of small cell neuroendocrine carcinomas expressed Leu-7, whereas nonendocrine carcinomas were uniformly nonreactive for this determinant. All neuroblastomas yielded immunopositivity, as did three primitive neuroectodermal tumors, three rhabdomyosarcomas, two "Askin" tumors, one nephroblastoma, one Ewing's sarcoma, and one malignant melanoma. None of the small cell lymphomas were Leu-7 positive. These results suggest that Leu-7 is a specific neuroendocrine marker in cases of small cell carcinoma, but its sensitivity is lower than that of other "endocrine" determinants. Reactivity patterns for Leu-7 in other small cell tumors demonstrate no specificity for any given line of cellular differentiation. However, the shared expression of this antigen by neuroblastomas, neuroectodermal tumors, Ewing's sarcomas, and Wilm's tumors contributes further to the hypothesis that these neoplasms may be related histogenetically.     

Small cell carcinoma of the prostate. II. Immunohistochemical and electron microscopic studies of 18 cases

To evaluate the histogenesis of small cell carcinoma of the prostate, 18 cases of this tumor (9 pure small cell and 9 combined adeno- and small cell carcinoma) were studied using immunohistochemical methods. Seven of the small cell components also were assessed by electron microscopic examination. Using neuron-specific enolase (NSE), prostatic acid phosphatase (PAP), and prostate-specific antigen (PSA) on tissue sections, three distinctive immunostaining patterns of small cell carcinoma components were identified: staining positive for NSE and negative for PSA and PAP (10 cases), staining positive for PSA and PAP and negative for NSE (3 cases), and negative reaction for all three antigens (5 cases). Electron microscopic study demonstrated neurosecretory granules in two cases. Based on the immunostaining and electron microscopic findings, small cell carcinomas of the prostate appear to be a heterogeneous group of tumors. Some of them are neuroendocrine carcinomas whereas others are poorly differentiated adenocarcinomas or, possibly, reserve cell carcinomas. Differences in immunostaining patterns or presence and absence of adenocarcinoma component do not reflect any differences in the uniformly poor prognosis of small cell carcinomas, in which median survivals is 7.7 months. The authors believe that, because of such heterogeneity, small cell carcinomas of the prostate arise from multipotential prostatic epithelium and that an origin from specific neuroendocrine cells need not be implicated.     

CD56在小细胞癌组织中的表达及其对诊断的作用

背景与目的:小细胞癌(smallcellcarcinoma,SCC)是恶性度及死亡率高的少见恶性肿瘤,临床病理目前常用神经特异性烯醇化酶(neuron-specificenolase,NSE),触突素(synaptophysin,SYN),嗜铬蛋白(chromograninA,CgA)标记协助诊断,本项目拟研究CD56在小细胞癌组织中的表达并探讨把CD56作为临床病理诊断小细胞癌的标记分子的可能性。方法:收集小细胞癌病例标本共80例,包括肺原发病例42例,其中伴淋巴结转移20例;食管原发病例21例,结直肠原发病例17例。另外随机选取肺非小细胞癌38例作为对照(肺鳞癌26例,肺腺111癌12例),其中淋巴结转移28例。所有标本用CD56,NSE,Syn,CgA,CK和EMA进行免疫组化染色。结果:CD56在肺小细胞癌肿瘤组织及其淋巴结转移灶组织中阳性率显著高于在肺非小细胞癌中阳性率,其在肺小细胞癌原发灶阳性率为90.5%(38/42),转移灶为90.0%(18/20),其在肺非小细胞癌原发灶阳性率为7.8%(3/38),转移灶为3.5%(1/28)(H=85.731,P<0.001),它在小细胞癌肿瘤组织中阳性率明显高于NSE,CgA,CK与EMA的阳性率,其阳性率分别为:CD5686.3%(69/80),Syn78.8%(63/80),CgA73.8%(59/80),EMA66.3%(53/80),CK61.3%(49/80),NSE56.3%(45/80)(H=38.871,P<0.001)。CD56在肺、食管及结直肠小细胞癌中阳性率比较无显著差异,其阳性率分别为肺90.5%(38/42),食管81.0%(17/21),结直肠82.4%(14/17)(H=1.651,P=0.438)。结论:CD56在小细胞癌组织中无论是原发灶还是淋巴结转移灶的阳性率均高,且无器官特异性;CD56可作为临床病理诊断小细胞癌的阳性标记物。     

Large cell neuroendocrine tumors of the lung. Clinical significance and histopathologic definition

Twenty-five cases of neuroendocrine tumors of lung, including bronchial carcinoids (eight), malignant (atypical) carcinoids (nine), and large cell undifferentiated carcinomas (LCAC) with neuroendocrine differentiation (eight) were analyzed. All carcinoids (BC) could be diagnosed by light microscopy; all patients with these tumors are alive without disease. Five of nine malignant carcinoids (MC) could be recognized histologically; four of nine were called LCAC and required electron microscopy for diagnosis. Survival correlated best with stage of diagnosis. High-grade neuroendocrine carcinomas (LCAC-NE) required electron microscopy for their diagnosis. Seven were LCAC histologically; one was diagnosed as malignant carcinoid (MC). Such tumors resemble small cell anaplastic carcinomas ultrastructurally and behaviorally. All eight patients with such high-grade tumors died of their disease; three of eight had no nodal metastases at the time of resection. This experience suggests it is clinically important to distinguish neuroendocrine neoplasms since behavior is predictable on the basis of morphology.     

Isoenzyme pattern of enolase in the diagnosis of neuroendocrine bronchopulmonary tumors

Electrophoretic separation of enolase isoenzymes and the measurement of enolase activity were performed in 25 lung tumor extracts. In 13 neuroendocrine (NE) tumors (nine small cell lung carcinoma [SCLC], three atypical NE tumors, and one carcinoid tumor), the NE differentiation was assessed by ultrastructural determination of neurosecretory granule (NSG) density. Twelve non-NE lung tumors also were studied (three adenocarcinomas, four epidermoid, two composite, two large cell undifferentiated carcinomas, and one lymphoma). Four normal lung tissues and 1 human brain were used as controls. The gamma gamma isoenzyme was present at a high level (mean +/- SE, 12 +/- 3%) in all NE carcinomas and consistently absent in all non-NE tumors as well as in normal lung. The alpha gamma isoenzyme was found in significantly higher proportion in NE carcinomas (mean +/- SE, 29 +/- 2%) than in non-NE tumors (mean +/- SE, 8 +/- 1%) (P less than 0.0001), despite an equally high level of total enolase activity in both groups of tumor. The separation of alpha gamma and gamma gamma isoenzymes of enolase allows for the accurate diagnosis of NE tumors and NE components of atypical NE carcinomas, and the gamma gamma isoenzyme, in contrast to gamma chain detection by immunoassay, can be considered to be a specific marker in itself of NE differentiation in lung neoplasms.     

Pleomorphic (giant cell) carcinoma of the intestine. An immunohistochemical and electron microscopic study

Pleomorphic (giant cell) carcinomas have been described in the lungs, thyroid, pancreas, and gallbladder. Two pleomorphic carcinomas of the small bowel and two of the large bowel are presented. On light microscopic study, the carcinomas were solid, without squamous or glandular differentiation. The tumors were composed of the following three cell types: gemistocytic (giant) cells, smaller polygonal cells, and spindle cells, with identical immunohistochemical reactions. A panel of monoclonal and polyclonal antibodies was applied. All tumors were found to coexpress keratin and vimentin. A positive reaction for neuron-specific enolase (NSE) was found in three tumors and a positive reaction for chromogranin was found in one tumor. On electron microscopic study, intracytoplasmic whorls of intermediate filaments were seen in the perinuclear area. Dense core "neurosecretory" granules were rarely seen. Intestinal pleomorphic carcinomas are histologically identical to pulmonary giant cell carcinomas. The prognosis is poor due to early tumor spread, with only a few months of postoperative survival. The pleomorphic carcinomas have some of the differentiation characteristics of carcinoid tumors and are best regarded as poorly differentiated variants of neuroendocrine carcinomas.     

Neuroendocrine carcinomas of the upper airways: a small case series with histopathological considerations

Neuroendocrine carcinomas are rare tumors. In the head and neck region they are most common in the larynx, where they represent 0.5-1% of epithelial cancers. Diagnosis requires the recognition of the typical neuroendocrine architecture and morphology and the immunohistochemical confirmation of neuroendocrine differentiation. In the 1991 WHO classification laryngeal neuroendocrine carcinomas have been divided into carcinoids, atypical carcinoids, small cell carcinomas and paragangliomas. Atypical carcinoids in the head and neck region usually show an aggressive behavior analogous to poorly differentiated carcinomas, and are resistant to chemo- and radiotherapy. For this reason, it was recently proposed to change their designation to "moderately differentiated neuroendocrine carcinomas". We present the clinical and histopathological features of 2 moderately differentiated neuroendocrine carcinomas of the larynx, one large cell poorly differentiated neuroendocrine carcinoma of the oropharynx, and one small cell carcinoma of the minor salivary glands of the tongue. The patient with small cell carcinoma was free from disease 26 months after radical surgery, while the other patients showed liver, lung and bone metastases 18, 26 and 24 months after the diagnosis despite radical surgery or concomitant intra-arterial chemotherapy and radiotherapy.     

14例宫颈小细胞神经内分泌癌临床病理分析

目的:探讨宫颈小细胞神经内分泌癌的临床病理特征、诊断与鉴别。 方法:通过回顾性方法收集2015年1月至2017年12月共14例宫颈小细胞神经内分泌癌。分析其临床特点、病理形态特征和免疫组化标记。 结果:最常见的临床表现是接触性阴道流血流液、不规则阴道流血、腹部包块、隐痛。体格检查最常见为宫颈糜烂、宫颈肥大和萎缩。光学显微镜检查:细胞较小,大小不一,分散分布在间质血管周围,圆形或者梭形,胞浆较少而核染色较深,粗颗粒状,核仁不明显或者无核仁,核分裂象多见甚至有坏死。免疫组化检测:PCK(+)、EMA(+)、CGA(+)、CD45(-)、CD56(+)、CK8/18(+)、SYN(+)、NSE(+)、Ki-67(+,80%~95%)。 结论:宫颈小细胞神经内分泌癌确诊需联合组织病理学及免疫组织化学检查,其恶性程度高,预后差,易复发,准确的病理诊断对临床治疗具有重要的作用。     

Neuroendocrine features in poorly differentiated and undifferentiated carcinomas of the cervix

Neuroendocrine or argyrophil cell carcinoma of the cervix has recently been accepted as a distinct clinical-pathological entity. The histologic pattern of these carcinomas is usually poorly differentiated or undifferentiated. Twenty patients with a histologic diagnosis of small cell carcinoma, undifferentiated carcinoma, poorly differentiated adenocarcinoma, or poorly differentiated, adenosquamous carcinoma of the cervix were evaluated for neuroendocrine features. The results of studies to detect neurosecretory granules were positive in seven of the 20 cases. Not only small cell carcinomas, but also tumors classified as undifferentiated carcinoma and poorly differentiated, adenosquamous carcinoma contained cytoplasmic granules consistent with neuroendocrine carcinoma of the cervix. The prognosis for survival appears poorer for patients having tumors with neurosecretory granules after controlling for stage and histologic grade of the neoplasm.     

Reevaluation of pulmonary neoplasms resected as small cell carcinomas. Significance of distinguishing between well-differentiated and small cell neuroendocrine carcinomas

The clinicopathologic features of 50 cases of surgically resected small cell carcinoma were reevaluated (doubly blinded). Two pulmonary carcinomas were excluded because neuroendocrine features could not be demonstrated; two additional cases also were excluded because the tumors grossly invaded the chest wall and their pulmonary origin was not substantiated. Thirty-four tumors were confirmed to be small cell neuroendocrine carcinoma (SCNC). Only seven of 11 (64%) patients with T1N0,T2N0 tumors survived more than 1 year; one of 11 (9%) patients survived more than 2 years. In 12 cases, the diagnosis was changed to well-differentiated neuroendocrine carcinoma (WDNC). Of these, nine of nine (100%) patients with T1N0,T2N0 tumors survived more than 1 year; six of eight (75%) patients survived more than 2 years. These observations strongly indicate that a significant number of long-term survivors with the diagnosis of small cell carcinoma may, in fact, have a distinctly less aggressive type of pulmonary neuroendocrine carcinoma. It was concluded that the distinction between small cell and well-differentiated types of neuroendocrine carcinomas has significant prognostic and therapeutic implications.     

Small cell carcinomas of the parotid gland. A clinicopathologic study of three cases

Clinical, histological and ultrastructural features of three small cell carcinomas arising in the parotid gland are presented. The light microscopic appearance of two of the neoplasms suggested neuroendocrine cell derivation, confirmed by electron microscopy in both instances. The fine structure of the third neoplasm suggested intercalated duct cell differentiation. The possibility that both types of neoplasm may arise from the same primitive precursor cell is considered. The findings from this study confirm the occurrence of two different types of small cell carcinoma of salivary gland origin. A distinction between duct cell and neuroendocrine subtypes may be impossible by conventional light microscopic evaluation.     

非小细胞肺癌神经内分泌分化的检测及意义

 目的　探讨非小细胞肺癌 (NSCLC)的神经内分泌 (NE)分化状况、免疫组化检测指标及其意义。方法　采用SP免疫组化法检测 113例NSCLC中神经元特异性烯醇化酶 (NSE)、突触素 (SYN )和嗜铬素A(CgA)的表达。 结果　NSCLC中NSE、SYN、CgA的阳性率分别为 5 3.10 %、2 6 .5 5 %、6 .19% ,NSE与SYN联合检测 ,其阳性率为 2 1.2 4 %。 3种NE标记物在不同组织学类型NSCLC中的表达无显著性差异。SYN阳性率随肿瘤分化程度降低而增高。NSE与SYN、SYN与CgA表达之间显著相关。 结论　NSCLC的NE分化与组织学类型无关 ,与分化程度有关。NSE和SYN联用是判断NE分化的较好指标     

Serum neuron-specific enolase in diagnosis and follow-up of gastrointestinal neuroendocrine tumors.

Neuron-specific enolase (NSE), the glycolytic isoenzyme of the enolase gamma-gamma dimer, is a specific marker for the diffuse neuroendocrine system and derivative tumors (NET). Serum levels of NSE were measured in 39 patients with NET of the gastrointestinal tract (including 3 gastric and 13 intestinal carcinoid tumors, 6 gastrinomas, 3 insulinomas, 1 glucagonoma, 2 mixed islet cell tumors, 11 neuroendocrine pancreatic carcinomas), in 15 healthy subjects and in 15 nonendocrine gastric, pancreatic, and intestinal tumors. Thirty-six of the 39 patients had elevated circulating levels of NSE, 2 insulinomas and 1 gastrinoma had values below 12 ng/ml like healthy subjects and nonendocrine tumors. No significant difference of serum NSE was found between 23 'functioning' and 16 'nonfunctioning' NET. Fourteen of the NET were malignant, and NSE circulating values were significantly higher than those of nonmalignant forms. After curative surgery serum NSE decreased significantly. NSE can be considered a reliable marker in the differential diagnosis between endocrine and nonendocrine neoplasms, in the clinical detection of silent endocrine tumors and in the follow-up of NET.     

Heterotransplantation of small cell lung carcinoma into nude mice. Stability of the phenotypic characters

In order to validate xenografted small cell lung carcinomas (SCLC) for biological studies, the authors established 12 lung neuroendocrine (NE) tumors (eight typical SCLC and four atypical NE tumors [ANE]) by heterotransplantation onto nude mice. Their characterization was performed using serial ultrastructural, enzymatic, and immunohistochemical methods on primary tumors and after xenografts. These were subclassified into epithelial (one), neuroendocrine (three), and multidifferenciated (eight) types. The phenotypic characters (cytokeratins, neurofilaments, neurone-specific enolase) and the proliferative rate (Ki 67 labelling) of original tumor were maintained until the last passage studied. Although further acquisition of subsets of cytokeratin or neurofilaments was observed in some cases, the authors could not detect any morphologic and/or biological spontaneous change comparable to those described in in vitro cell lines. In addition, ANE are not quite identical to variant subclasses described in vitro. The authors conclude that the stability of heterotransplanted SCLC is an advantage in further biological studies.     

Pulmonary large cell carcinoma expressing neuroendocrine markers: the morphological, biological, and neuroendocrine features of their cell lines and surgical cases.

A cell line expressing neuroendocrine (NE) markers, designated as KTS9, was established from a human large cell carcinoma of the lung using serum-free medium, ACL-3. KTS9 cells showed morphological characteristics of large cell undifferentiated carcinoma (LCUC) and expressed some general NE markers including neuron-specific enolase (NSE), protein gene product (PGP) 9.5, neural cell adhesion molecule (N-CAM), synaptophysin and neurofilaments (NF) of 200 kd. Some cells of this cell line were positive to chromogranin-A (CG-A), but did not express Leu7 or aromatic L-amino acid decarboxylase (AADC). Such a cell line derived from LCUC with NE properties has not previously been reported. The biological and NE properties of the KTS9 cell line were compared with those of 2 surgical cases of LCUC with NE markers and of the KTA7 cell line previously reported to derive from large cell carcinoma and to possess NE markers such as alpha-hCG, PGP9.5 N-CAM and AADC. Tumor cells of 2 large cell carcinomas expressed NSE, PGP9.5, N-CAM and NF. The KTS9 and KTA7 cell lines and 2 large cell carcinomas were thus considered to be LCUCs with NE differentiation. Both lines had the morphological characteristics of LCUC, relatively short doubling time and discordant expression of NE markers, indicating them to be closely related to the variant type of small cell carcinoma cell lines and thus possibly to represent high-grade malignancy. They may be useful for examining the biological behavior and NE features of large cell-type NE tumors of the lung.