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1.
AIMS: To determine the prevalence of sustentacular cells across the range of pulmonary neuroendocrine tumours: typical and atypical carcinoid tumours and large cell and small cell neuroendocrine carcinomas. METHODS AND RESULTS: Sustentacular cells were sought in 80 pulmonary neuroendocrine tumours by immunolabelling for S100 protein, nerve growth factor receptor and glial fibrillary acidic protein. Intratumoural macrophages and Langerhans cells were identified with the KP 1 (CD68) and CD1A antibodies. S100-positive sustentacular cells were present in 25 of 30 typical carcinoids, 200 of 25 atypical tumours, six of 10 large cell carcinomas and six of 15 small cell lesions. They were most numerous in the typical carcinoids but very few in the small cell carcinomas, their prevalance being clearly related to grade of differentiation and, in particular, to the degree of architectural organization. CONCLUSIONS: Sustentacular cells are often found in pulmonary neuroendocrine tumours, especially better-differentiated lesions with a well-developed architecture. their prevalence clearly reflecting the degree of structural organization. Whether their prevalence is a useful prognostic indicator within a particular group of such tumours, such as the atypical carcinoids or the large cell carcinomas, as appears to be the case with paragangliomas, is unclear. 相似文献
2.
Neuroendocrine tumours of the lung comprise low [typical carcinoid (TC)], intermediate [atypical carcinoid (AC)] and high‐grade [small‐cell lung cancer (SCLC) and large‐cell neuroendocrine carcinoma (LCNEC)] malignancies, while a pre‐invasive lesion [diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH)] may generate a subset of peripheral carcinoid tumours. These neoplasms are differentiated conventionally based on mitotic rate, presence of necrosis and cytological details, according to the 2015 World Health Organisation (WHO) classification. Clinical data and molecular alterations distinguish carcinoids and high‐grade carcinomas into two separate categories. Previous studies have demonstrated a significantly higher rate of chromosomal aberrations in carcinomas (e.g. 3p and 17p deletions), but restriction of multiple endocrine neoplasia type 1 (MEN1) mutations to carcinoids. High‐grade carcinomas are also characterised by TP53 and RB1 gene inactivation. In this review, a critical analysis of the diagnostic and prognostic role of Ki67 labelling index and a concise discussion of the most relevant findings regarding molecular characterisation of lung neuroendocrine neoplasms are reported. In addition, we illustrate how the development of promising therapeutic strategies based on the identification of molecular targets (mTOR inhibitors in carcinoids and targeting of the Notch ligand DLL3 in SCLC) may require the assessment of predictive biomarkers, even in the group of neuroendocrine tumours of the lung. 相似文献
3.
Selim M H Rizvi Joseph Goodwill Eric Lim Yoong K Yap Athol U Wells David M Hansell Peter Davis Syed Abdel-Ghani Peter Goldstraw & Andrew G Nicholson 《Histopathology》2009,55(3):332-337
Aims: To evaluate the frequency of neuroendocrine cell hyperplasia (NEH) in resected neuroendocrine tumours and non-neuroendocrine cell carcinomas and to study its relationship to selected clinical parameters.
Methods and results: Random blocks without tumour from resected typical carcinoids (TCs, n = 46), atypical carcinoids (ACs, n = 14), large cell neuroendocrine carcinomas (LCNECs, n = 18), small cell carcinomas (SCLCs, n = 22), adenocarcinomas (ADENOs, n = 26) and squamous cell carcinomas (SCCs, n = 18) were stained for CD56 and evaluated for linear proliferations, cell aggregates (>4 CD56+ cells), and tumourlets (<5 mm with basement membrane invasion). There was a statistically significant difference between the frequency of NEH in all neuroendocrine tumours (TC/AC/LCNEC/SCLC, 35/100, 35%) ( P = 0.009) when compared with non-neuroendocrine carcinomas (ADENO/SCC, 6/44, 14%) and in the frequency of NEH in TC (21/46, 46%) versus all other tumours (AC/LCNEC/SCLC/SCC/ADENO, 20/98, 20%) ( P = 0.001). There was increased frequency of NEH in peripheral TCs (8/13, 62%) compared with central TCs (14/33, 43%) ( P = 0.33). There was no association between smoking history and NEH. Clinical and imaging data showed no evidence of an increased frequency of obliterative bronchiolitis in patients with NEH.
Conclusions: NEH is significantly increased in the background lung of neuroendocrine tumours when compared with non-neuroendocrine carcinomas, supportive data for NEH having neoplastic potential. 相似文献
Methods and results: Random blocks without tumour from resected typical carcinoids (TCs, n = 46), atypical carcinoids (ACs, n = 14), large cell neuroendocrine carcinomas (LCNECs, n = 18), small cell carcinomas (SCLCs, n = 22), adenocarcinomas (ADENOs, n = 26) and squamous cell carcinomas (SCCs, n = 18) were stained for CD56 and evaluated for linear proliferations, cell aggregates (>4 CD56+ cells), and tumourlets (<5 mm with basement membrane invasion). There was a statistically significant difference between the frequency of NEH in all neuroendocrine tumours (TC/AC/LCNEC/SCLC, 35/100, 35%) ( P = 0.009) when compared with non-neuroendocrine carcinomas (ADENO/SCC, 6/44, 14%) and in the frequency of NEH in TC (21/46, 46%) versus all other tumours (AC/LCNEC/SCLC/SCC/ADENO, 20/98, 20%) ( P = 0.001). There was increased frequency of NEH in peripheral TCs (8/13, 62%) compared with central TCs (14/33, 43%) ( P = 0.33). There was no association between smoking history and NEH. Clinical and imaging data showed no evidence of an increased frequency of obliterative bronchiolitis in patients with NEH.
Conclusions: NEH is significantly increased in the background lung of neuroendocrine tumours when compared with non-neuroendocrine carcinomas, supportive data for NEH having neoplastic potential. 相似文献
4.
Enhancer of zeste homolog 2, the catalytic subunit of polycomb repressive complex 2, is a histone methyltransferase and plays an important role in cell proliferation and cell cycle regulation. It has been shown to be overexpressed in a number of malignant neoplasms. This study aimed to determine the expression pattern of enhancer of zeste homolog 2 in neuroendocrine tumors of the lung and the potential of enhancer of zeste homolog 2 to serve as a biomarker to segregate carcinoids from high-grade neuroendocrine carcinomas. Fifty-four cases, including 25 typical carcinoids, 7 atypical carcinoids, 9 large-cell neuroendocrine carcinomas, and 13 small-cell lung carcinomas, were immunohistochemically studied using a monoclonal antibody against enhancer of zeste homolog 2. All 13 small-cell lung carcinomas demonstrated moderate to strong nuclear staining with 12 exhibiting more than 90% of tumor cells staining. All 9 large-cell neuroendocrine carcinomas were moderately to strongly positive for enhancer of zeste homolog 2, with 6 cases having staining in more than 80% of tumor cells. In contrast, all 25 typical carcinoids and 6 atypical carcinoids showed only rare scattered enhancer of zeste homolog 2-positive tumor cells, with 1 case of atypical carcinoid exhibiting moderate staining in 40% of tumor cells. A subsequent validation study of the 14 specimens of lung or mediastinal lymph node biopsy and fine-needle aspiration, including 6 small-cell lung carcinomas, 2 large-cell neuroendocrine carcinomas, 5 typical carcinoids, and 1 atypical carcinoid, was performed. Enhancer of zeste homolog 2 was diffusely and strongly positive in all small-cell lung carcinomas and large-cell neuroendocrine carcinomas, even with severe crush artifact, whereas it was only positive in rare tumor cells in carcinoids. These findings support the formulation that enhancer of zeste homolog 2 may play an important role in the regulation of biologic behavior of high-grade neuroendocrine carcinomas and as a diagnostically useful marker in distinguishing high-grade neuroendocrine carcinomas from carcinoids. 相似文献
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6.
LKB1 protein expression in neuroendocrine tumors of the lung 总被引:1,自引:0,他引:1
Amin RM Hiroshima K Iyoda A Hoshi K Honma K Kuroki M Kokubo T Fujisawa T Miyagi Y Nakatani Y 《Pathology international》2008,58(2):84-88
During a recent investigation of LKB1 gene abnormality in lung lesions, strong expression of LKB1 protein in normal neuroendocrine (NE) cells of the bronchial epithelium was found. Because LKB1 functions as a tumor suppressor gene, the question of whether alteration of LKB1 expression is related to the development of pulmonary NE tumors of various grades was investigated. LKB1 immunohistochemistry was examined in a total of 68 primary pulmonary NE tumors consisting of 30 specimens of small cell lung carcinoma (SCLC), 23 large cell neuroendocrine carcinomas (LCNEC), two atypical carcinoids, and 13 typical carcinoids. Loss or low expression (<20% immunoreactive cells) of LKB1 protein expression was more frequently observed in high-grade NE tumors (SCLC and LCNEC; 45/53, 84.9%) than in typical and atypical carcinoids (3/15; 20%). The difference in LKB1 immunoreactivity between the high-grade NE tumors and the carcinoid group was statistically significant ( P < 0.0001). In conclusion, marked reduction of LKB1 expression in high-grade NE tumors of the lung suggests a possible role of LKB1 inactivation in its tumorigenesis. Although a few previous studies indicated rare genetic alterations of LKB1 in SCLC, further studies including analysis of other NE tumors and focusing on epigenetic abnormalities of LKB1 gene are warranted. 相似文献
7.
Abnormal p53 expression in lung neuroendocrine tumors. Diagnostic and prognostic implications. 总被引:2,自引:0,他引:2
M Roncalli C Doglioni D R Springall M Papotti A Pagani J M Polak N B Ibrahim G Coggi G Viale 《Diagnostic molecular pathology》1992,1(2):129-135
The diagnostic and prognostic implications of p53 immunostaining have been investigated in 59 pulmonary neuroendocrine tumors, including typical carcinoids (n = 15), so-called "atypical carcinoids" (n = 22), and small cell lung carcinomas (SCLCs; n = 22). Immunocytochemistry was performed on formalin-fixed, paraffin-embedded samples using the monoclonal antibody PAb1801, which has been shown to be suitable for staining fixed and embedded tissue sections. p53 immunoreactivity was restricted to atypical carcinoids (45% of the cases being immunoreactive) and to SCLCs (which were positively stained in 59% of the cases), whereas it was consistently lacking in typical carcinoid tumors. When the group of the so-called "atypical carcinoids" was further reclassified, p53 immunostaining was strictly confined to those cases belonging to the histologically more aggressive subsets (well differentiated neuroendocrine carcinoma subsets II and III). Within the same tumor type, however, p53 immunoreactivity did not correlate with the clinical outcome of the disease and was not predictive of the length of survival. The data indicate that abnormal p53 expression (which is strictly dependent on structural abnormalities of the p53 gene) is detectable in the majority of neuroendocrine carcinomas of the lung and might represent a useful adjunct in the differential diagnosis of pulmonary neuroendocrine neoplasms, particularly in routinely fixed and embedded small bronchoscopic biopsies. 相似文献
8.
Pulmonary neuroendocrine tumors, especially small cell carcinoma and typical carcinoids, are the most common cause of ectopic Cushing syndrome (CS). Sometimes these adrenocorticotropic hormone (ACTH)-producing tumors are too small to localize, and it may take a long time to identify them. This report describes the case of a 27-year-old-man with CS. This CS was due to the ectopic ACTH produced by the pulmonary atypical carcinoids, which were recognized at the disseminated stage 5 years after the initial presentation of CS. Microscopically, multiple whitish nodules (up to 1.0 cm in diameter) of the wedge-resected lung were composed of small round cells appearing to be typical neuroendocrine but were diagnosed as atypical carcinoid, based on the findings of focal necrosis, high mitotic rates and multiple endolymphatic tumor emboli. Immunohistochemically, tumor cells robustly stained for ACTH. The delay of diagnosis is, in part, attributable to the pulmonary tuberculosis (one of the complications of hypercortisolism), because the pulmonary tuberculosis presented in the form of multiple nodules throughout the lung. In addition, this patient had a Crooke's cell hyperplasia of the pituitary gland, which represents the reactive change of corticotrophs exposed to the excess cortisol rather than neoplastic change leading to CS. 相似文献
9.
The intraoperative diagnosis of pulmonary neuroendocrine tumors can be difficult. Frozen section diagnosis was requested on 87 neuroendocrine tumors including 58 typical carcinoids, 8 atypical carcinoids, 18 large cell neuroendocrine carcinomas, and 3 small cell carcinomas from 2405 patients that underwent frozen section diagnosis at Cedars-Sinai Medical Center from 2002 to 2007. The deferral and error rate for carcinoid tumors was 4.13% and 7.5%, respectively, and resulted in 4 unnecessary lobectomies and 2 second thoracotomies. The most common errors included misdiagnoses as lymphoma, squamous carcinoma or metastasis from breast carcinoma. Thirty one pathologic features were evaluated in the 66 carcinoid tumors and 10 frozen sections each of lymphoma, squamous cell carcinoma, and metastatic breast carcinoma. Seven pathologic features were significant by chi square test at P > .05. Positive likelihood ratios identified 11 pathologic features that were useful for the diagnosis of carcinoid tumor from other neoplasms. The applicability of the 11 pathologic features was tested with a group of pathologists, resulting in significant improvement in diagnostic accuracy as measured by pre and posttests. The value of evidence-based pathology and Bayesian statistics to evaluate complex differential diagnoses in pathology is discussed. 相似文献
10.
Immunohistochemical markers of small cell carcinoma and related neuroendocrine tumours of the lung 总被引:7,自引:0,他引:7
B J Addis Q Hamid N B Ibrahim M Fahey S R Bloom J M Polak 《The Journal of pathology》1987,153(2):137-150
A selected group of 263 pulmonary neuroendocrine tumours comprised 156 small cell carcinomas, five combined cell carcinomas, nine atypical carcinoid/small cell carcinomas, 32 atypical carcinoids, ten large cell/small cell carcinomas, and 51 carcinoid tumours. These were compared with a group of 109 non-small cell carcinomas, using four markers of neuroendocrine differentiation to determine differences in reactivity between the two groups and among the variants of neuroendocrine tumour. The antibodies used were neuron-specific enolase (NSE), protein gene product (PGP) 9.5, human bombesin, and the C-terminal flanking peptide of human bombesin (CTP). Most small cell carcinomas, carcinoid tumours, and atypical carcinoid variants showed immunoreactivity for both NSE and PGP 9.5 but a significant number of non-small cell carcinomas, mainly squamous cell carcinomas, were also positive (11 and 35 per cent, respectively). Bombesin was specific for neuroendocrine tumours, being demonstrable in 35 per cent carcinoids and 24 per cent small cell carcinomas, but staining was focal and often confined to scattered cells. Diffuse strongly positive immunoreactivity for CTP was seen in the majority of malignant neuroendocrine tumours, but only 12 per cent of carcinoid tumours were positive and non-small cell carcinomas were negative. CTP is therefore of potential value as a specific marker of malignant neuroendocrine tumours, particularly if the amount of biopsy material is limited and the tumour is an unusual variant, such as atypical carcinoid or large cell-small cell carcinoma. 相似文献
11.
Cytohistology of papillary carcinoid and emerging concept of pulmonary neuroendocrine neoplasms
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Grace C. H. Yang 《Diagnostic cytopathology》2016,44(1):52-60
This timely review starts by reporting the clinical, cytologic and histologic features of a morphologic variant of pulmonary carcinoid tumor forming exclusively of papillae. This growth pattern is so rare that it was not included in 2014 WHO classification of pulmonary neuroendocrine neoplasms. The current concept is reviewed, and example of spindle cell carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma are illustrated with fine needle aspiration cytology, surgical and clinical follow‐up. Finally, the new findings in cell biology and molecular biology that led to the emerging concept that carcinoids and high‐grade neuroendocrine lung carcinomas are separate biological entities are reviewed and summarized in a tumorigenic module. Diagn. Cytopathol. 2016;44:52–60. © 2015 Wiley Periodicals, Inc. 相似文献
12.
Toru Igarashi Shi-Xu Jiang Toru Kameya Hisao Asamura Yuichi Sato Kanji Nagai Isao Okayasu 《Modern pathology》2004,17(10):1259-1267
A total of 111 pulmonary neuroendocrine tumors comprising 13 typical carcinoids, five atypical carcinoids, 44 large-cell neuroendocrine carcinomas and 49 small-cell carcinomas were immunohistochemically studied for dysregulated cyclin B1 expression and disruption of the Rb/p16/cyclin D1 pathway (Rb pathway), and the results were correlated with tumor proliferation activity and clinical outcome. Overexpression of cyclins B1 and D1, respectively, was detected in no and 15% typical carcinoids, 20 and 20% atypical carcinoids, 84 and 32% large-cell neuroendocrine carcinomas, 84 and 10% small-cell carcinomas. Loss of Rb and p16 expression, respectively, was observed in no and 14% typical carcinoids, no and 40% atypical carcinoids, 49 and 18% large-cell neuroendocrine carcinomas, 84 and 8% small-cell carcinomas. In summary, 29% typical carcinoids, 20% atypical carcinoids, 78% large-cell neuroendocrine carcinomas and 93% small-cell carcinomas had Rb pathway aberrations. Rb pathway aberration was mostly attributed to Rb loss in small-cell carcinomas, while p16 loss and/or cyclin D1 overexpression besides Rb loss also played an important role in large-cell neuroendocrine carcinomas, while cyclin D1 overexpression was the only cause of Rb pathway aberration in carcinoid tumors. Thus, both cyclin B1-associated G2/M arrest and Rb-mediated G1 arrest are consistently compromised in high-grade large-cell neuroendocrine carcinoma and small-cell carcinoma, but are generally intact or occasionally altered in carcinoid tumor; the mechanisms involved in Rb pathway aberration among the tumor categories are different, reflecting a genetic divergence among the individual tumor categories. Cyclin B1 expression closely correlated with the Ki-67 labeling index either in the individual tumor categories or overall tumors (P < 0.0001, r = 0.742), suggesting that cyclin B1 is one of the key factors regulating cell proliferation in pulmonary neuroendocrine tumors. Neither cyclins B1 and D1, Rb, p16, nor Ki-67 correlated with patient survival in individual tumor categories, suggesting that the prognostic significance of these factors is tumor-type specific. 相似文献
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The reliability of prealbumin as a diagnostic marker was studied in 60 cases of bronchopulmonary carcinoid tumours. There were differences in the incidence of positivity between typical and atypical carcinoids (well differentiated neuroendocrine carcinomas). Seventy five per cent of the carcinoid tumours were positive for prealbumin; (86.7% typical and 63.3% atypical carcinoids). In 15 cases, which were Grimelius negative, 10 were prealbumin positive. Only 8.3% carcinoids were negative with both prealbumin and Grimelius stains. Ten squamous, 10 adeno- and 10 small cell carcinomas showed only occasional scattered prealbumin positive cells. It is concluded that prealbumin is a useful marker for bronchopulmonary carcinoid tumours. It is cheap, readily available, and should be considered part of routine diagnostic procedures for the diagnosis of carcinoid tumours. 相似文献
15.
Kawauchi S Okuda S Morioka H Iwasaki F Fukuma F Chochi Y Furuya T Oga A Sasaki K 《Human pathology》2005,36(10):1096-1100
Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a newly introduced category of the revised World Health Organization classification. We reported a case of cervical LCNEC with cytogenetic analysis by comparative genomic hybridization (CGH). The cervical tumor showed moderately increased mitotic activity (8-14 mitotic figures per 10 high-power fields) and focal necrosis, which made it problematic to differentiate from atypical carcinoid. CGH analysis failed to detect chromosome 11q loss that has been reported to be characteristic of pulmonary atypical carcinoids. Furthermore, chromosome 3q amplification, which has been detected frequently in pulmonary small cell carcinomas and LCNECs but not in pulmonary typical and atypical carcinoids, was the most remarkable chromosomal aberration. Although CGH reports are extremely rare in neuroendocrine tumors of the uterine cervix, specific chromosomal aberrations may be useful in their distinction. 相似文献
16.
Sturm N Rossi G Lantuéjoul S Laverrière MH Papotti M Brichon PY Brambilla C Brambilla E 《Histopathology》2003,42(2):156-166
AIMS: Monoclonal antibody 34betaE12 (Ck34betaE12) recognizes a set of cytokeratins (1, 5, 10, 14) expressed in normal stratified squamous epithelium. We have recently reported its expression in squamous cell carcinoma and basaloid carcinoma, in contrast to large cell neuroendocrine carcinoma, an entity with overlapping morphological features with basaloid carcinoma. We have now examined the role of Ck34betaE12 in discriminating between neuroendocrine and non-neuroendocrine proliferations. METHODS AND RESULTS: We performed an immunohistochemical study of 228 cases, comprising the whole spectrum of lung neuroendocrine proliferations and tumours. All cases of neuroendocrine cell hyperplasia (n = 15), tumorlet (n = 23), typical carcinoid (n = 27) and atypical carcinoid (n = 23) were completely negative for Ck34betaE12. Although the neuroendocrine cells of small cell lung carcinoma and large cell neuroendocrine carcinoma were consistently negative, a strong and diffuse positive staining was found in the non-neuroendocrine components of combined small cell carcinoma (three of eight cases) and combined large cell neuroendocrine carcinoma (11 of 12 cases). In addition, scattered Ck34betaE12+ cells were noted in 11 of 64 (17%) large cell neuroendocrine carcinoma and in seven of 56 (12.5%) small cell carcinoma, which were not obviously histologically combined. This heterogeneity of high-grade neuroendocrine tumours was not observed in carcinoids which lack Ck34betaE12 clusters of reactive cells. There was mutual exclusion between expression of neuroendocrine markers and that of Ck34betaE12. CONCLUSION: We conclude that 34betaE12 expression excludes the neuroendocrine nature of tumour cells and uncovers the real frequency of combined forms in high-grade neuroendocrine tumours. 相似文献
17.
Tiziana D'Adda Lorena Bottarelli Cinzia Azzoni Silvia Pizzi Massimo Bongiovanni Mauro Papotti Giuseppe Pelosi Patrick Maisonneuve Tommaso Antonetti Guido Rindi Cesare Bordi 《Modern pathology》2005,18(6):795-805
Association of X chromosome allelic losses with tumor malignancy has been identified in foregut but not in midgut endocrine neoplasms. The aim of this study was to investigate the association of deletions on X chromosome with malignancy in lung neuroendocrine tumors, another family of foregut neoplasms comprising four categories with increased malignancy: typical and atypical carcinoids, large cell neuroendocrine and small cell lung carcinomas. To evaluate loss of heterozygosity, DNA extracted from nine typical carcinoids, 17 atypical carcinoids, six large cell neuroendocrine carcinomas and five small cell lung carcinomas was PCR-amplified for 18 microsatellite markers spanning the whole X chromosome. All tissue samples were formalin-fixed and paraffin-embedded. X chromosome losses were absent in typical carcinoids, whereas they were found in nine out of 17 atypical carcinoids and in five out of six large cell neuroendocrine carcinomas (involving 28 and 70% of informative loci, respectively). On the contrary, deletions on X chromosome were an extremely rare event in small cell lung carcinomas. In atypical carcinoids, the presence of losses was associated with larger tumor size, higher pT status and advanced stage. No death occurred in atypical carcinoid patients without deletions on X chromosome, whereas all atypical carcinoid patients who had died from disease showed allelic losses. In conclusion, X chromosome allelic losses, absent in benign 'typical' carcinoids, progressively increased in frequency from intermediate-grade 'atypical' carcinoids to high-grade large cell neuroendocrine carcinomas. These results extend the association of deletions on X chromosome with malignancy, already demonstrated in other foregut endocrine neoplasms, to lung neuroendocrine tumors. The absence of X chromosome allelic losses in small cell lung carcinomas underlines a striking difference from large cell neuroendocrine carcinomas, possibly linked to different pathogenetic mechanisms of these two highly aggressive neuroendocrine lung tumors. 相似文献
18.
hASH1 expression is closely correlated with endocrine phenotype and differentiation extent in pulmonary neuroendocrine tumors. 总被引:5,自引:0,他引:5
Shi-Xu Jiang Toru Kameya Hisao Asamura Atsuko Umezawa Yuichi Sato Jun Shinada Yasuaki Kawakubo Toru Igarashi Kanji Nagai Isao Okayasu 《Modern pathology》2004,17(2):222-229
The human homolog 1 of the Drosophila neurogenic achaete-scute genes, hASH1, is specifically expressed in fetal pulmonary neuroendocrine cells and in some neuroendocrine tumor cell lines. However, no data have been gathered regarding its in vivo expression in tumors. hASH1 mRNA expression was investigated by in situ hybridization in 238 surgically resected lung carcinomas, and the correlations between hASH1 expression status and immunostaining results of neuroendocrine markers chromogranin A, neural cell adhesion molecule, gastrin-releasing peptide and calcitonin, and clinical outcome were analyzed. hASH1 expression was detected in 2/20 (10%) adenocarcinomas, 4/30 (13.3%) typical carcinoids, 11/13 (84.6%) atypical carcinoids, 38/67 (56.7%) large-cell neuroendocrine carcinomas and 56/78 (71.8%) small-cell carcinomas, respectively, but not in any squamous cell carcinoma (0/21) or large-cell carcinoma (0/9). The 2 hASH1+ adenocarcinomas also expressed multiple neuroendocrine markers. Thus, hASH1 expression was restricted to lung cancers with neuroendocrine phenotypes. However, not all neuroendocrine tumors expressed hASH1. Within the entities of large-cell neuroendocrine carcinoma and small-cell carcinoma, hASH1 expression correlated very closely with chromogranin A, gastrin-releasing peptide and calcitonin expression (P<0.0001, r=0.852), but was not related to neural cell adhesion molecule expression (P=0.8892), suggesting that hASH1 expression, at least in lung cancer, is associated with endocrine phenotype expression other than 'neuroendocrine differentiation' in a broad sense. The fact that hASH1 was virtually absent in almost fully differentiated typical carcinoids, but was expressed in most, if not all, less differentiated atypical carcinoids as well as large-cell neuroendocrine carcinomas and small-cell carcinomas, suggests that hASH1 expression in lung cancer imitates its early and transient expression in fetal development, and that hASH1 is instrumental in the establishment, but not in the maintenance, of a cellular endocrine phenotype. Finally, hASH1 expression correlated with a significantly shortened survival in small-cell carcinoma patients (P=0.041). 相似文献
19.
《Diagnostic Histopathology》2023,29(2):114-120
Thymic epithelial tumours include the subcategory of thymic neuroendocrine neoplasms, which comprise a spectrum of entities that mirrors their counterparts in the lung, i.e. typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma. These tumours are classified according to the current WHO classification for lung tumours, and their relevant histomorphological and immunohistochemical criteria will be discussed in this brief review. Thymic neuroendocrine neoplasms do, however, also have clinical and molecular characteristics which set them apart from their pulmonary relatives, and recent research has provided valuable insights into possible molecularly-informed classification systems, which broadly align with classical categories, but also show some discrepancies. The most salient recent studies in that respect will also be discussed, as will the avenues for locally ablative therapy and possibilities for systemic treatment. 相似文献
20.
M.N. SHEPPARD 《Histopathology》1997,30(5):478-480
Pulmonary typical carcinoid tumours are generally easy to diagnose with their uniform cells, carcinoid growth pattern and lack of mitoses. However, nuclear pleomorphism, which is common in other neuroendocrine tumours, is not emphasized in pulmonary carcinoid tumours. Three cases of typical carcinoid tumours, because of marked nuclear pleomorphism on frozen section, were misdiagnosed as non-small cell carcinomas. 相似文献