弥漫性特发性肺神经内分泌细胞增生伴微小瘤形成1例并文献复习

目的 探讨弥漫性特发性肺神经内分泌细胞增生伴微小瘤形成的临床及病理特点.方法 对1例弥漫性特发性肺神经内分泌细胞增生伴微小瘤形成进行光镜和免疫组化检测并文献复习.结果 弥漫性特发性肺神经内分泌细胞增生及微小瘤常继发于肺间质性疾病,好发于中年人或非吸烟老年女性,临床表现为干咳和气短等气道堵塞症状,病情进展极其缓慢,体征可不明显.镜下表现为在支气管扩张、慢性炎细胞浸润、肺间质弥漫纤维化的基础上出现多灶性神经内分泌细胞增生(直径<5 mm),增生的细胞可局限于支气管和细支气管上皮或突破基膜向间质浸润.细胞呈短梭形或椭圆形,大小相对一致,核分裂象罕见.免疫组化染色Syn、CgA、CD56强阳性;广谱CK、CK-L、CK-H阳性;增殖指数Ki-67较低,p63、Vim等阴性.结论 弥漫性特发性肺神经内分泌细胞增生伴微小瘤形成是类癌的癌前病变,临床表现不明显,常为偶然发现,确诊主要靠病理学检查及免疫组化,临床处理以密切随访为主,必要时可行外科治疗,预后好.     

肺微瘤型类癌5例报道并文献复习

目的探讨肺微瘤型类癌(carcinoid tumourlet)的临床病理学特征、免疫表型及病因学。方法对5例肺微瘤型类癌(其中4例伴肺支气管扩张症1,例伴肺腺癌)进行临床病理观察,应用免疫组化Super Vision两步法检测其特异性标记物。结果肺微瘤型类癌常伴发可导致肺部严重纤维化的疾病,亦可见于无基础炎性疾病的肺组织。肿瘤多位于小气道附近,细胞大小较一致,核呈卵圆形及短梭形,未见核分裂及坏死。免疫标记:肿瘤组织CK、EMA、TTF-1呈弱阳性,CgA、Syn、NSE、CD56及VEGF呈强阳性。结论肺微瘤型类癌具有典型类癌的病理特征和免疫表型,可能是典型类癌发生的早期阶段。气道炎症及肺纤维化导致的缺氧并非微瘤型类癌发生的必要条件,可能有其他分子机制参与微瘤型类癌的发生。     

53BP1蛋白表达缺失与前列腺腺癌临床病理的关系

目的 探讨p53结合蛋白1(53BP1)在前列腺腺癌及癌旁良性前列腺组织、前列腺高级别上皮内瘤变、良性前列腺增生中的表达及其与临床病理的关系和意义.方法 对50例前列腺腺癌根治标本的癌及癌旁良性前列腺组织、20例前列腺高级别上皮内瘤变、20例良性前列腺增生标本应用免疫组织化学EnVision两步法检测53BP1在以上病变组织中的表达,并探讨其与前列腺腺癌发生及临床病理的相关性.结果 53BP1蛋白在良性前列腺增生上皮、高级别上皮内瘤变、癌旁良性前列腺上皮、前列腺腺癌细胞中阳性表达呈递减趋势,且在良性前列腺增生上皮、高级别上皮内瘤变、癌旁良性前列腺上皮的表达显著高于前列腺腺癌细胞 (P=0,0.015,0),在癌旁良性前列腺上皮及高级别上皮内瘤变中的表达显著低于良性前列腺增生上皮(P=0,0.035),而癌旁良性前列腺上皮与高级别上皮内瘤变的差异无统计学意义(P=0.658).53BP1在低年龄组中表达明显低于高年龄组(P=0.001),而与其他病理参数无关.结论 53BP1作为抑癌基因,其表达的缺失与前列腺腺癌发生有关,它有可能成为前列腺腺癌的早期指示因子,预示前列腺腺癌的发生可能.     

早期胃印戒细胞癌免疫表型的临床病理意义

目的 探讨胃、肠免疫表型标志物在早期胃印戒细胞癌中的表达及其与临床病理参数和预后的相关性.方法 免疫组织化学EnVision法检测91例早期胃印戒细胞癌中胃免疫表型标志物MUCI、MUCSAC、MUC6和肠免疫表型标志物MUC2、CDX2的表达,并根据肿瘤细胞胃、肠免疫表型标志物表达水平的差异,将早期胃印戒细胞癌分为3种类型:胃型、肠型和混合型.结果 胃型、混合型和肠型印戒细胞癌分别为53例(58.2%)、22例(24.2%)和16例(17.6%).胃、肠免疫表型标志物表达水平与印戒细胞癌形态学分型无相关性(P>0.05).两种肠免疫表型标志物MUC2和CDX2在早期黏膜下层浸润癌中阳性表达率均显著高于黏膜内癌,差异有统计学意义(均P<0.01).两种胃免疫表型标志物MUCSAC和MUC6在早期黏膜下层浸润癌中的阳性表达率分别为52.9%(18/34)和20.6%(7/34)均显著低于黏膜内癌91.2%(52/57)和31.6%(18/57),差异有统计学意义(P<0.01和P<0.05).在淋巴结转移阳性组和脉管浸润阳性组中,MUC2和CDX2的阳性表达率均明显高于无淋巴结转移组和无脉管浸润组,差异有统计学意义(P<0.05).随着肿瘤病变范围的扩大,CDX2阳性表达率明显增高,差异有统计学意义(P<0.05).肠型印戒细胞癌比胃型印戒细胞癌更多见于早期黏膜下层浸润癌且有更高的淋巴结转移率(P=0.000和P=0.003).生存分析显示,肠型和混合型印戒细胞癌5年生存率明显低于胃型印戒细胞癌(P<0.05).结论 肠型胃印戒细胞癌临床生物学行为和预后均较胃型印戒细胞癌差.胃、肠免疫表型标志物的胃印戒细胞癌分型有助于评估预后并有可能指导治疗.     

喉大细胞神经内分泌癌

目的：探讨喉大细胞神经内分泌癌的临床及病理特征。方法：复习2例患者的临床病史，肿瘤组织的病理形态和免疫表型及相关文献。结果：2例患者均为男性，以声音嘶哑、喉部不适为主要表现；病变均位于声门上，以具有丰富嗜酸性胞质，巢状排列为肿瘤细胞的形态特征，免疫组化表达神经内分泌肿瘤标志物。2例均因短期内发生肿瘤广泛转移而死亡，结论：喉大细胞神经内分泌癌属于高度恶性的肿瘤。形态上需与低分化鳞癌，甲状腺样癌，肺神经内分泌癌，副神经节瘤和无色素性黑色素瘤等相鉴别。     

气道上皮IL-25促进哮喘气道重塑

目的:通过检测白细胞介素-25(IL-25)在嗜酸细胞性哮喘(EA)及非嗜酸细胞性哮喘(NEA)患者的血清、诱导痰及气道上皮中的表达,探讨其在支气管哮喘气道重塑中的作用。方法:选取初诊的哮喘患者55例,健康对照组27例,所有受试者均进行肺通气功能检查,然后采集空腹静脉血及诱导痰。据诱导痰中嗜酸性粒细胞(EOS)的比例将哮喘患者分为EA组和NEA组。采用ELISA检测血清及诱导痰中IL-25的水平,同时对其中的10例EA组患者、10例NEA组患者及10例健康对照者行电子支气管镜气道黏膜活检,免疫组织化学技术分析IL-25在气道上皮的表达,HE染色测量气道重塑的重要指标-基底膜厚度,并行血清及诱导痰中IL-25的水平与基底膜平均厚度的相关性分析。结果:与正常对照组相比,EA和NEA组哮喘患者的肺功能轻度受损。ELISA结果显示哮喘患者血清及诱导痰中IL-25的水平明显高于对照组(P<0.05),而EA和NEA组哮喘患者间差异无统计学意义(P>0.05)。免疫组织化学结果显示哮喘患者气道上皮IL-25的表达明显高于对照组,HE染色显示气道黏膜下的基底膜厚度明显增加(P<0.05)。相关性分析显示哮喘患者血清及诱导痰中IL-25水平与气道黏膜下基底膜平均厚度成正相关。结论:IL-25可能有促进哮喘气道重塑的作用,嗜酸性粒细胞与基底膜厚度无明显相关性,其在哮喘气道重塑中的作用可能是有限的。     

卵巢复合性神经内分泌癌二例临床病理学分析

目的探讨卵巢复合性神经内分泌癌的临床病理特征。方法对2018年9月至2019年1月武汉大学人民医院2例卵巢复合性神经内分泌癌行组织病理学、免疫组织化学表型分析。结果镜下见2例肿瘤均可见2种成分。其中一种成分为神经内分泌癌,另一种成分为卵巢恶性上皮性肿瘤,免疫组织化学结果显示:2例肿瘤中的神经内分泌癌成分均表达嗜铬素粒A、突触素和CD56,例1中子宫内膜样癌细胞角蛋白(CK)7、ER、PR、波形蛋白阳性。例2中黏液性癌CK7阳性。最终诊断为1例卵巢复合性小细胞癌(肺型)伴子宫内膜样癌,1例为卵巢复合性大细胞神经内分泌癌伴黏液性癌。结论卵巢复合性神经内分泌癌是一种罕见的高度恶性混合性肿瘤,预后较差,术前及术中诊断困难,免疫组织化学检测可辅助诊断。     

血管周上皮样细胞分化肿瘤的研究进展

血管周上皮样细胞分化的肿瘤(neoplasms with perlvascular epithelioid cell differentiation,PEComa)是一组较少见组织学和免疫表型上具有血管周上皮样细胞特征的间叶肿瘤,瘤细胞胞质透明或嗜酸性颗粒状,免疫组化检测表达黑色素瘤抗体HMB45、Melan—A(A103)及肌源性抗体SMA。包括肝肾血管平滑肌脂肪瘤(angiomyolipoma,AML)、肺的透明细胞“糖”瘤(clear cell“sugar”tunlour of the hmg．CCST)、     

十二指肠神经节细胞性副神经节瘤3例临床病理分析

目的探讨神经节细胞性副神经节瘤(gangliocytic paraganglioma,GP)临床病理特征、诊断、鉴别诊断、治疗及预后。方法回顾性分析3例十二指肠GP的临床病理学特征、免疫表型、治疗及预后,并复习相关文献。结果3例患者内镜下均表现为十二指肠黏膜下病变,隆起于肠腔;组织学上肿瘤由3种不同类型的细胞混合组成:梭形的施万细胞、上皮样神经内分泌细胞和神经节样细胞。免疫表型:梭形细胞表达SOX-10、NF、NSE、CD56、Syn、S-100蛋白,上皮样细胞表达CKpan、CAM5.2、NSE、CD56、Syn、CgA、PR,神经节样细胞表达NSE、CD56、Syn、CgA、Calretinin、PR、NF。结论GP属于罕见的神经内分泌肿瘤,多发于十二指肠,内镜提示十二指肠黏膜下病变时应考虑该病可能,确诊依赖于组织病理学特征及免疫表型,治疗以内镜下切除和外科手术切除为主,患者预后较好。     

泌尿系统神经内分泌肿瘤16例临床病理分析

目的探讨泌尿系统神经内分泌肿瘤(neuroendocrine tumors,NETs)的临床病理学特征、诊断及鉴别诊断、治疗及预后。方法回顾性分析16例泌尿系统NETs(膀胱11例、输尿管1例、肾脏4例)的临床病理特点、免疫表型、诊断及鉴别诊断、治疗及预后,并复习相关文献。结果 16例NETs中男性11例,女性5例;年龄48～84岁,平龄65岁;小细胞癌10例,副神经节瘤4例,类癌及不典型类癌各1例;12例患者有随访资料,其中6例死亡,均为小细胞癌(3～21个月),6例存活,包括4例膀胱副神经节瘤(7～88个月)、1例肾类癌(14个月)和1例膀胱小细胞癌合并尿路上皮癌(42个月)。结论 NETS发生在泌尿系统中较为罕见,主要为小细胞癌、副神经节瘤及类癌。根据其典型组织形态及神经内分泌免疫组化标志物(Syn、CgA、CD56)阳性鉴别,需谨慎排除转移可能。副神经节瘤及类癌预后较好,小细胞癌侵袭性高,预后差。     

On the origin of the so-called tumorlets of the lung

A light and electron microscopic study of multiple tumorlets in a 66 year old female is presented. Clinically the patient had had chronic obstructive lung disease with bronchiectasis of the right upper lobe. Aside from severe bronchiectatic alterations, the resected lobe showed typical tumorlets. On electron microscopic study, these were shown to consist of cells containing large numbers of a neurosecretory type of granule, which was identical to those present in the bronchial counterpart of the intestinal argentaffin (Kulchitsky) cell, as well as in pulmonary carcinoid and oat cell carcinoma cells. Our studies suggest the possibility of a histogenetic relationship between tumorlets, bronchial carcinoid tumors, and oat cell carcinoma, the cell of origin in each case being the bronchial counterpart of the intestinal argentaffin cell.     

Sox10-positive sustentacular cells in neuroendocrine carcinoma of the lung

Tsuta K, Raso M G, Kalhor N, Liu D C, Wistuba I I & Moran C A
(2011) Histopathology  58, 276–285
Sox10‐positive sustentacular cells in neuroendocrine carcinoma of the lung Aims: Sustentacular cells are found in approximately half of pulmonary carcinoid tumours. However, most studies of sustentacular cells have used the less‐specific antibody to the S100 protein, and any correlation between the presence of sustentacular cells and other clinicopathological factors is unclear. The aim of this study was to analyse the significance of sustentacular cells in pulmonary neuroendocrine carcinomas (NECs). Methods and results: A Sox10 antibody was used to investigate 113 pulmonary NECs. Sustentacular cells were observed in 66.7% of typical carcinoid (TC) and 58.3% of atypical carcinoid (AC) cases, but not in high‐grade NECs. Sustentacular‐rich tumours had a statistically significant correlation with peripheral locations. We found no statistical differences in age, gender, smoking history, overall survival, or the occurrence of lymph node metastasis. In all but one case, when sustentacular cells were present in the primary site, they were also present in the metastatic lymph nodes. The presence of sustentacular cells differed in morphological subtypes, with the spindle pattern being the most common subtype. Conclusions: Sox10‐positive sustentacular cells were observed in carcinoid tumours but not in high‐grade NECs. Sustentacular‐rich carcinoid tumours did not show a correlation with the occurrence of lymph node metastasis or survival. The sustentacular cells found differed in morphological subtypes.     

11q13 Allelic Imbalance Discriminates Pulmonary Carcinoids from Tumorlets : A Microdissection-Based Genotyping Approach Useful in Clinical Practice

Pulmonary tumorlets are minute neuroendocrine cell proliferations believed to be precursor lesions to pulmonary carcinoids. Little is known of their molecular pathogenesis because of their small size. Using tissue microdissection, we evaluated 11q13 region allelic imbalance in the pathogenesis of pulmonary tumorlet/carcinoid lesions. The int-2 gene was selected because of its chromosomal location at 11q13 in close proximity to MEN1, a tumor suppressor gene frequently mutated in familial forms of neuroendocrine cancer. Three cohorts of patients were studied: subjects with typical carcinoid tumors and coexisting tumorlets (n = 5), typical carcinoids without tumorlets (n = 6), and tumorlets alone without carcinoid lesions (n = 5). A total of 11 carcinoids and 11 tumorlets were microdissected from 4-micrometer-thick histological sections. Genotyping was designed to detect allelic imbalance of the int-2 gene and involved DNA sequencing of two closely spaced deoxynucleotide polymorphisms. Subjects shown to be informative were evaluated for allelic imbalance in tumorlet/carcinoid tissue. Eight of 11 (73%) carcinoids manifested allelic, in contrast to only one of 11 (9%) of tumorlets. Int-2 allelic imbalance was significantly associated with carcinoid tumor formation (P < 0.01). In patients having both carcinoid tumors and tumorlets, the latter showed allelic balance and were thus discordant in genotype with coexisting carcinoid excluding pathogenesis of tumorlets from intramucosal spread from carcinoid tumors. Int-2 allelic imbalance was shown to be an early event in carcinoid tumor formation by virtue of the absence of allelic imbalance for other common cancer-related gene disturbances involving 11p13 (Wilms' tumor), 3p25 (von-Hippel-Lindau), and 17p13 (p53). Demonstration of 11q13 allelic imbalance by microdissection/genotyping may be a useful discriminatory marker for pulmonary neuroendocrine neoplasia.     

Human chorionic gonadotropin in lung and lung tumors. Immunohistochemical study on unbalanced distribution of subunits

To demonstrate unbalanced distribution of subunits of human chorionic gonadotropin (hCG) in the lung and lung tumors and to clarify its significance in differentiation and carcinogenesis of the lung, immunohistochemistry was performed on human fetus, infant, and adult lungs, and endocrine and nonendocrine tumors of the lung. Tissues were immunostained for alpha-subunits and for beta-subunits of glycoprotein hormones (hCG, luteinizing hormone, follicle stimulating hormone, and thyroid stimulating hormone), serotonin, and gastrin-releasing peptide. Immunoreactive alpha-subunit was first identified in endocrine-like cells at the 39th gestational week, and was found in all infant lungs and two-thirds of adult lungs. The hCG beta-immunoreactive cells were extremely rare in an adult lung, and were not found in fetus or infant lungs. The alpha-subunit-containing cells were present in neuroepithelial bodies, tumorlets, carcinoid tumors, and small cell carcinomas of the lung (SCCL). There were occasionally alpha-subunit-containing cells in non-SCCL but one of the carcinomas also contained many serotonin-positive and gastrin-releasing peptide-positive cells in the same region. All alpha-subunit-immunoreactive cells lacked immunoreactivity for beta-subunits of glycoprotein hormones, except some for hCG beta in one carcinoid tumor. Immunoreactive cells for isolated hCG beta appeared much more frequently in non-SCCL than in SCCL. Most non-SCCL containing hCG beta-positive cells did not show alpha-subunit-immunoreactivity. Thus, immunohistochemical distribution of hCG-subunits was unbalanced and hCG-subunits may be expressed through an independent mechanism, commonly in the lung and lung tumors. The significance of isolated alpha-subunit is further discussed in light of multidirectional differentiation of lung neoplasms (14, 17).     

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia with a Central and Peripheral Carcinoid and Multiple Tumorlets: A Case Report Emphasizing the Role of Neuropeptide Hormones and Human Gonadotropin-Alpha

We report a case of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). We performed immunohistochemical analysis of 17 neuropeptides and human gonadotropin-alpha (hCGα), a trophoblastic peptide that promotes the proliferation of neuroendocrine cells. A 51-year-old woman with no history of smoking was found to have a nodule in the right middle lobe. Upon examination, the nodule was found to comprise diffuse linear and nodular neuroendocrine cell hyperplasia (NECH), numerous pulmonary tumorlets merging with one peripheral carcinoid, and an additional central carcinoid. Immunohistochemical analysis revealed diffuse but intense expression of the general neuroendocrine markers CD56, synaptophysin, and chromogranin A, together with gastrin-releasing peptide (GRP), calcitonin, and hCGα throughout the carcinoids, tumorlets, and NECH. Positive staining was also noted for adrenocorticotropic hormone, corticotropin-releasing hormone, met-enkephalin, vasoactive intestinal polypeptide, neurotensin, and growth hormone-releasing hormone in a few isolated cells of the carcinoids and the tumorlets, but staining for these proteins was entirely negative in the NECH lesions. The presence of these neuropeptides in neuroendocrine tumors might explain the presence of neuropeptide-producing tumors of the lungs, cases of which have been reported over the last 30 years. The preoperative serum proGRP level was high but returned to normal after surgical intervention, indicating that GRP was produced and secreted by carcinoids, tumorlets, and/or NECH lesions. It is also probable that neuroendocrine cells secreted GRP into the interstitium in a paracrine manner, leading to the development of dense fibrosis around the tumorlets. During the preoperative and postoperative periods, no evidence of bronchiolitis obliterans was noted, in contrast to some previously reported cases of DIPNECH.     

Expression of vascular endothelial growth factor (VEGF) and its receptors (VEGF-R1 [Flt-1] and VEGF-R2 [KDR/Flk-1]) in tumorlets and in neuroendocrine cell hyperplasia of the lung

Pulmonary tumorlets and neuroendocrine (NE) cell hyperplasia are part of a continuous spectrum of NE-cell hyperplasia, going from NE hyperplasia to carcinoid. Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen that has been shown to be increased in hypoxic lung. We hypothesized that tumorlets and NE-cell hyperplasia, which occur frequently in this context, were partly responsible for VEGF secretion. Immunohistochemical analysis of VEGF and both VEGF-R1 and VEGF-R2 was performed on paraffin sections of 12 lung tissues containing tumorlets and NE-cell hyperplasia in parallel with a control group of 11 lung specimens. VEGF and its receptor expressions were compared in bronchial epithelial cells and endothelial cells in both groups. VEGF and its receptors were consistently expressed in tumorlets and in NE-cell hyperplasia. When compared with control group lungs, the staining score for VEGF in lung bearing tumorlets was significantly higher in endothelial cells, but was not different in bronchial epithelial cells. VEGF-R1 expression was significantly increased both on bronchial epithelial cells (P = 0.001) and endothelial cells (P = 0.006), and VEGF-R2 expression was significantly increased on endothelial cell (P = 0.044). There was a significant positive correlation between the level of expression of VEGF and VEGF-R1 (P = 0.04) in both control groups and lung bearing tumorlets, but there was no significant correlation between VEGF and VEGF-R2 expression (P = 0.1). We concluded that VEGF is highly expressed in localized NE cell proliferations without potential of malignancy and might participate in local development of fibrosis.     

Tumorlets of the Lung- An Ultrastructural Study

A tumorlet of the lung is a minute tumorlike lesion found in damaged lungs in close association with the bronchioles. Histochemical and ultrastructural studies identify proliferating cells in the tumorlets as Kultschitzky-type cells. However, the pathological significance of the tumorlets, whether they are hyperplastic or neoplastic, is still controversial. Previous ultrastructural studies on the tumorlets have been carried out on formalin-fixed lung tissues. The case examined in this study was of typical tumorlets found in a so-called middle lobe syndrome of the lung of a 52-year-old woman. Tumorlets were located within the bronchiolar mucosa surrounded directly by a basal lamina and by the bronchiolar nonendocrine epithelial cells. There were no signs of invasion into the surrounding connective tissues or into lymphaticlike spaces. Between the covering bronchiolar epithelial cells and the subjacent proliferating Kultschitzky cells, specific sites of cell-to-cell attachment were noted. This finding, in addition to previously reported clinicopathological characteristics, indicates that the proliferating Kultchitsky-type cells in the tumorlets might be nonneoplastic and that tumorlets are due to hyperplasia of pure Kultschitzky-type cells, thus resembling neuroepithelial bodies of the lung.     

Expression of the alpha subunit of human chorionic gonadotropin in normal and neoplastic neuroendocrine cells. An immunohistochemical study

The alpha subunit of human chorionic gonadotropin (HCG) was localized Immunohistochemically in paraffin sections of normal human tissues and neuroendocrine tumors. A small subset of dispersed neuroendocrine cells was positive in normal adult tissues, including gastric antrum, urachal remnant, anal glands and prostate. Positive cells were consistently present in perinatal lung but rare in adult lung. In contrast, the beta subunit was absent from these cells. Seventy-two of 151 extrapituitary neuroendocrine tumors (48%) were alpha subunit-positive. Thirty-three of 37 bronchial carcinoids (92%) were immunoreactive, with a high percentage of the tumors (54%) containing moderate to large numbers of positive cells. The alpha subunit was further demonstrated in 9 of 45 small cell lung carcinomas (20%), 19 of 35 extrapulmonary carcinoids (54%), 3 of 11 islet cell tumors (27%) and 8 of 13 medullary thyroid carcinomas (62%). Two of three malignant islet cell tumors were positive. Positive cells were usually few in number, except for two small cell lung carcinomas, two rectal carcinoids, one thymic carcinoid and one malignant islet cell tumor. Pheochromocytomas (n = 10) were negative. Eleven of 19 pulmonary tumorlets (58%) were alpha subunit-immunoreactive. A few beta subunit-positive cells were detected in only 6 lung lesions. The physiological significance of the imbalance of expression of HCG subunits by certain neuroendocrine cells and their tumors remains unknown.     

Expression of the Alpha Subunit of Human Chorionic Gonadotropin in Normal and Neoplastic Neuroendocrine Cells

The alpha subunit of human chorionic gonadotropin (HCG) was localized Immunohistochemically in paraffin sections of normal human tissues and neuroendocrine tumors. A small subset of dispersed neuroendocrine cells was positive in normal adult tissues, including gastric antrum, urachal remnant, anal glands and prostate. Positive cells were consistently present in perinatal lung but rare in adult lung. In contrast, the beta subunit was absent from these cells. Seventy two of 151 extrapituitary neuroendocrine tumors (48%) were alpha subunit positive. Thirty three of 37 bronchial carcinoids (92%) were immunore-active, with a high percentage of the tumors (54%) containing moderate to large numbers of positive cells. The alpha subunit was further demonstrated in 9 of 45 small cell lung carcinomas (20%), 19 of 35 extrapulmonary carcinoids (54%), 3 of 11 islet cell tumors (27%) and 8 of 13 medullary thyroid carcinomas (62%). Two of three malignant islet cell tumors were positive. Positive cells were usually few in number, except for two small cell lung carcinomas, two rectal carcinoids, one thymic carcinoid and one malignant islet cell tumor. Pheochromocytomas (n=10) were negative. Eleven of 19 pulmonary tumorlets (58%) were alpha subunit immunoreactive. A few beta subunit positive cells were detected in only 6 lung lesions. The physiological significance of the imbalance of expression of HCG subunits by certain neuroendocrine cells and their tumors remains unknown. Acta Pathol Jpn 39: 413 419, 1989.