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At least 19 recordsLinked to original sources
PubMed1987

Nuclear DNA content in squamous cell carcinoma, small cell carcinoma, and bronchiolo-alveolar carcinoma of the lung.

Nuclear DNA content in individual, morphologically identified tumor cells from 33 squamous lung carcinomas, 20 small cell lung carcinomas, and 10 bronchiolo-alveolar carcinomas were analyzed by means of cytophotometry on Feulgen-stained histologic and cytologic specimens. Twenty-eight of the squamous cell carcinomas and 17 of the small cell carcinomas had high and scattered DNA values, indicative of high malignancy potentials. None of the bronchiolo-alveolar carcinomas showed such high DNA values. These results are in line with clinical experience that squamous cell and small cell carcinoma are associated with rapid progression and death in patients, whereas bronchiolo-alveolar carcinomas have a more indolent course.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2006

[A case of endocrine cell carcinoma (small cell carcinoma) of duodenum].

Extra-ampullary duodenal endocrine cell carcinoma is extremely rare. A 65-year-old woman visited our hospital, complaining of epigastralgia, anorexia and vomiting. She was admitted for suspected duodenal or pancreas head tumor by abdominal CT. Fiberscopic examination revealed a circumferential tumor in the extra-ampullary duodenal second portion. Histopathological findings of biopsy specimen showed a small cell carcinoma, and positive immunohistochemical staining for synaptophysin revealed this tumor to be endocrine cell carcinoma. Pylorus-preserving pancreaticoduodenectomy with partial transversocolectomy was performed, and intraoperative washing cytology detected tumor cells in the peritoneal cavity. Although she discharged from hospital uneventfully, she died 11 months later of multiple liver metastases and peritoneal dissemination. This case showed the high malignant potential of this tumor.

Aged↗
PubMed1987

Expression of the C-terminal peptide of human pro-bombesin in 361 lung endocrine tumours, a reliable marker and possible prognostic indicator for small cell carcinoma.

Small cell carcinoma of the lung is a highly malignant tumour. Its known biological products which include bombesin, do not allow the prediction of tumour behaviour. Molecular biology has revealed the amino acid sequence of human pro-bombesin, which consists of a signal peptide, the bioactive bombesin molecule and a C-terminal peptide. We have raised a rabbit antiserum to the first (N-terminal) 21 amino acids of the predicted C-terminal peptide. A total of 505 (361 neuroendocrine) surgically resected pulmonary tumours were evaluated for the presence of immunoreactive bombesin and C-terminal peptide. Strong immunostaining was obtained with the antiserum to the C-terminal peptide of human pro-bombesin in 70% of the small cell carcinomas (175/250), in 63% of atypical (aggressive) carcinoids (31/49) but only in 16% of benign carcinoids (10/62). In contrast, bombesin immunostaining was focal and only moderately strong and the relative proportion of positive cases was quite evenly distributed amongst the neuroendocrine tumours: 35% of carcinoids (22/62), 22% of atypical carcinoids (11/49) and 25% of small cell carcinoma (62/250). None of the squamous, adeno, or large cell undifferentiated carcinomas were immunoreactive for bombesin or the C-terminal peptide. Radioimmunoassay and chromatography of extracts of tumours recovered from wax blocks revealed high concentrations of C-terminal peptide immunoreactivity (241 +/- 66 pmol/g of tissue) in all 12 small cell carcinomas studied, moderate concentrations in carcinoid tumours (50 +/- 7 pmol/g) and none in non-small cell carcinomas. Patients with tumours showing immunoreactivity to the C-terminal peptide of human pro-bombesin had a significantly shorter survival time than those without immunoreactive peptide (185 +/- 16.49 days, mean +/- SEM, and with 1128 +/- 226 days, respectively P greater than 0.02). The apparent presence of the C-terminal peptide of human pro-bombesin in higher concentrations than bombesin in the more malignant class of endocrine tumours, mainly small cell carcinomas associated with the poorest prognosis, suggests that the antiserum to this C-terminal peptide is not only a useful pathological marker but may prove to be of value in investigating the biological behaviour of small cell carcinomas and predicting the clinical course of the disease.

Bombesin↗
PubMed1994

MIC2 analysis of small cell carcinoma.

Small cell carcinomas (SCCs) and peripheral neuroectodermal tumors (PNETs) are two distinct neoplasms that show considerable histologic, immunohistochemical, and clinical overlap, but differ in their therapies and prognoses. In an attempt to further diagnostically distinguish the two, 33 SSCs were analyzed from both pulmonary and extrapulmonary sites for the MIC2 gene product, a cell surface antigen strongly and reliably expressed in PNETs and Ewing's sarcoma (ES). Two of the 33 SCCs stained positively, but the staining was less intense than that seen with PNET and ES. The remaining 31 tumors did not stain. These data indicate that, in combination with a panel of immunohistochemical stains, analysis of neuroendocrine tumors for MIC2 expression may be useful in distinguishing between small cell carcinomas of both pulmonary and extrapulmonary origins and soft tissue PNETs.

12E7 Antigen↗
PubMed2006

[Collision cancer of squamous cell carcinoma and small cell carcinoma of the lung; report of a case].

We report a rare case of a primary collision cancer in the lung consisting of squamous cell carcinoma and small cell carcinoma. A 65-year-old man with an abnormal shadow in the right S6 was diagnosed as squamous cell carcinoma by transbronchial lung biopsy. A right lower lobectomy with mediastinal lymph node dissection was performed. The pathological stage of squamous cell carcinoma was IIIA (T2N2M0). The other element diagnosed by pathological examination was small cell carcinoma of which pathological stage was IA (T1N0M0). Each element was clearly distinguished and touched each other. Following the operation, the patient received systemic chemotherapy against small cell carcinoma with cisplatin and irinotecan hydrochloride for 1 course, and cisplatin and etoposide for 3 courses. Since the prognosis of collision cancer is generally reported to be influenced by more advanced element of cancer, the prognosis of the present case is suspected to be dependent on the squamous cell carcinoma.

Aged↗
PubMed1989

Bronchoscopic "resection" of small cell carcinoma.

Small cell carcinoma of the bronchus frequently presents as a widely disseminated tumor with a large central primary lesion. A patient with peripheral shadowing on a chest radiograph is reported in whom bronchoscopy revealed endobronchial tumor of the small cell type. The patient underwent lobectomy, but residual carcinoma could not be identified in the operative specimen, and the patient has remained disease-free for 2.5 years post-resection.

Biopsy↗
PubMed2000

Analysis of thyroid transcription factor-1 and cytokeratin 20 separates merkel cell carcinoma from small cell carcinoma of lung.

Merkel cell carcinoma needs to be separated from small cell carcinoma metastatic from visceral sites to skin. Pulmonary small cell carcinoma is the most common primary site of small cell carcinoma. We evaluated the immunophenotypic characteristics of 21 Merkel cell carcinomas and 33 small cell carcinomas of lung using thyroid transcription factor-1 and cytokeratin 20. Thyroid transcription factor-1 was 100% specific for the diagnosis of small cell carcinoma of lung associated with a diagnostic sensitivity of 85%. Cytokeratin 20 was present in 95% of Merkel cell carcinomas; however, 33% of small cell carcinoma of lung were also positive. Both antibodies typically demonstrate diffuse and intense staining of their respective tumor cells. We conclude that thyroid transcription factor-1 is a sensitive and specific marker for small cell carcinomas of lung and that a combination of thyroid transcription factor-1 and cytokeratin 20 is indicated to assist in the differentiation of metastatic small cell carcinoma of lung from merkel cell carcinoma.

Biomarkers, Tumor↗
PubMed1982

Histogenetic classification of lung carcinomas. small cell carcinomas studied by light and electron microscopy.

Forty-six small cell carcinomas of the lung identified by light microscopy were also studied by electron microscopy in an attempt to subclassify them histogenetically. Thirty were subclassifiable into neuroendocrine secretory, mucus secretory, or epidermoid categories on the basis of their differentiated structural features; 16 were too poorly differentiated to assign to any specific cell type and were designated null. In addition to histogenetic separation, electron microscopy revealed a spectrum of average cell differentiation within each subclass except null. The widest spectrum occurred in the most frequent subclass, the neuroendocrine group. This study clearly demonstrated that the light microscopic diagnosis of small cell carcinoma does not identify a morphologically homogeneous process. Whether histogenetic separation and/or some assessment of the relative degree of differentiation have any consistent clinical value remains to be shown; however, combined light and electron microscopy should improve the precision of the initial diagnosis over that of light microscopy alone.

Carcinoid Tumor↗
PubMed1998

p27KIP1 in human lung cancers: differential changes in small cell and non-small cell carcinomas.

Small cell lung cancers (SCLCs) and non-small cell lung cancers (NSCLCs), two major categories of human lung cancers, have been shown to exhibit considerably different clinicopathological, biological, and molecular genetic characteristics. Inactivation of cyclin-dependent kinase inhibitors is now thought to play an important part in the pathogenesis of this fatal disease. In the present study, we show that in vitro p27KIP1 expression was associated with cell density-dependent growth inhibition in human lung epithelial cells in vitro, whereas in vivo, p27KIP1 expression in lung cells showed an inverse correlation with proliferative activity in the developing and adult normal lungs. Our immunohistochemical examination of 166 lung tumor specimens also revealed a striking difference in p27KIP1 expression between SCLCs and NSCLCs. Of 149 NSCLCs, 107 (72%) showed reduced p27KIP1 expression, with 8 being virtually negative. Furthermore, p27KIP1 expression status was found to be a significant prognostic factor for patient survival in the analysis of the 149 primary, resected NSCLC cases (P = 0.03 by the log-rank test). In contrast, all SCLC specimens thus far examined exhibited significantly increased staining when compared to the corresponding normal lung epithelium. These findings provide additional evidence for the heterogeneity prevalent in human lung cancers and suggest that p27KIP1 might play distinct biological roles in the pathogenesis of the two major histological categories, warranting additional studies to elucidate the functional consequences of such differences.

Adult↗
PubMed2005

Prognostic significance of p27Kip1, p45Skp2 and Ki67 expression profiles in Merkel cell carcinoma, extracutaneous small cell carcinoma, and cutaneous squamous cell carcinoma.

AIMS: To compare the immunohistochemical expression of prognostic markers p27(Kip1), p45(Skp2) and Ki67 in Merkel cell carcinoma (primary neuroendocrine carcinoma of the skin, MCC), small cell neuroendocrine carcinoma of lung and urinary bladder (SNC), and cutaneous squamous cell carcinoma (SCC). METHODS AND RESULTS: Immunohistochemistry was performed using antibodies directed against p27(Kip1), p45(Skp2) and Ki67 on 72 tumour cases: 24 MCC, 25 SCC, and 23 SNC (15 from the lung and eight from the urinary bladder). Percentages of positive cells were determined for each marker and statistically analysed. Expression profiles on MCC and SCC were significantly different for all three markers. MCC and SNC exhibited significant similarities in their p27(Kip1) and p45(Skp2) expression profiles. In contrast, MCC and SNC differed significantly in their Ki67 proliferation indices, which were much higher in SNC. Additionally, MCC cases showed an association between increased proliferation indices and the appearance of local recurrence(s) and/or metastases. CONCLUSION: The immunohistochemical profile of MCC differs from that of SCC, in spite of their common oncogenesis and the supposed metaplastic origin of MCC, and resembles that of SNC, except for Ki67 levels, which were higher in the latter (characterized by greater biological aggressiveness). High levels of Ki67 also appear to be a prognostic factor in MCC.

Analysis of Variance↗
PubMed1990

[Combined radiotherapy-chemotherapy in inoperable bronchial carcinoma (small cell carcinoma excluded)].

When treated by irradiation alone, non small cell carcinomas of the lung usually experience a very poor outcome. Consequently, more interest is being focussed on radiotherapy and chemotherapy association. The analysis of a randomized trial comparing irradiation alone to a sequential or an alternated combination of radio and chemotherapy did not reveal any clear advantage of the association of both therapies on each technique used alone. It is only when using concurrent irradiation and chemotherapy that some encouraging results are reported. Several non randomized studies used radio and chemotherapy prior to surgery, aiming at increasing the resectability rate. However, the criteria for initial unresectability were not homogeneous and it is not yet clear if such an association really allowed the state of surgical resection to be improved. In the near future it could be worth considering the use of radiosensitizing drugs, synchroneously given with an irradiation delivered with a multiple daily fractionation. This technique would possibly lead to a therapeutic gain, by increasing the local control rate and reducing the metastasis rate, while keeping it to an acceptable level of toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

B-cell specific activation protein encoded by the PAX-5 gene is commonly expressed in merkel cell carcinoma and small cell carcinomas.

PAX-5 is a B cell specific transcription factor crucial for B cell ontogeny and has been detected in most of human B-cell lymphomas. In mouse, PAX-5 is also highly expressed in the central nervous system under tight temporal and spatial controls during embryogenesis. In humans, however, detection of PAX-5 in cells other than B lymphocytes has rarely been reported. We have encountered cases of Merkel cell carcinoma expressing PAX-5 during our routine evaluation of lymphoma. Because Merkel cell carcinoma is a small blue round cell tumor constantly in the differential diagnosis of lymphoma, we expanded our study in an effort to determine if PAX-5 is significantly expressed in neuroendocrine tumors. Based on our immunohistochemistry results using a monoclonal anti-PAX5 antibody with paraffin-embedded tissue sections, we report herein that PAX-5 was detected in 29 of 31 (93.5%) of Merkel cell carcinoma and 22 of 30 (73.3%) of small cell carcinoma, but in none of 17 cases of carcinoid tumor. Furthermore, the staining intensity of PAX-5 in Merkel cell carcinoma was frequently comparable with that in most B-cell lymphomas. We conclude that expression of PAX-5 is not confined to the B cell lineage and is frequently associated with neuroendocrine carcinomas.

B-Lymphocytes↗
PubMed2003

Diagnostic findings of bronchial brush cytology for pulmonary large cell neuroendocrine carcinomas: comparison with poorly differentiated adenocarcinomas, squamous cell carcinomas, and small cell carcinomas.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) of the lung has been proposed as a new disease entity. To establish diagnostic features, bronchial brush cytologic findings were evaluated. METHODS: Bronchial brush cytology material of 20 LCNECs was evaluated by light microscopy and stained immunocytochemically with protein gene product 9.5 (PGP9.5), neuron-specific enolase, and neural cell adhesion molecule antibodies. The findings were compared with those for 19 poorly differentiated adenocarcinomas (ACs), 18 poorly differentiated squamous cell carcinomas (SCCs), and 20 small cell lung carcinomas (SCLCs). RESULTS: Frequently observed characteristic cytologic findings of LCNECs were necrotic background (90.0%), large tumor cell size (90.0%), naked nuclei (90.0%), and nuclear streaking (90.0%). Nuclei in all LCNECs showed a fine granular chromatin pattern and possessed one or a few nucleoli. Indian-filing and rosette arrangements were observed in less than one-half of the LCNECs. In poorly differentiated ACs and SCCs, these features were less frequent, whereas thick nuclear membranes were observed more often. In SCLCs, tumor cell adhesions and Indian-filing or nuclear molding were observed more frequently than in LCNECs, whereas a necrotic background, tumor cell clusters, large tumor cells, and nucleoli were less prominent. The majority of LCNECs (80.0%) had a positive immunocytochemical reaction for PGP9.5, in contrast to the low positive reactions for ACs (42.1%) and SCCs (30.8%). CONCLUSIONS: Large cell neuroendocrine carcinomas can be diagnosed preoperatively by bronchial brush cytology using reliable parameters, including tumor cell size, naked nuclei, thin nuclear membranes, nuclear streaking, high PGP9.5 positivity, and a necrotic background.

Adenocarcinoma↗
PubMed2006

Immunohistochemical distinction between merkel cell carcinoma and small cell carcinoma of the lung.

We assessed the usefulness of several immunohistochemical stains in distinguishing these two neoplasms, including cytokeratin 7, cytokeratin 20 (CK20), neuron-specific enolase, chromogranin, synaptophysin, neurofilaments (NF), thyroid-transcription factor-1 (TTF-1), CD56 antigen, S-100 protein, vimentin, c-erbB-2 oncoprotein, and CD117 antigen. All 13 cases of Merkel cell carcinoma evaluated were positive for CK20, and negative for TTF-1. Twelve of 13 Merkel cell carcinoma cases were positive for NF. Eleven of 13 cases of small cell lung carcinoma were positive for TTF-1. All small cell lung carcinoma cases were negative for NF, and all but one were negative for CK20. In terms of the remaining antigens, there were no differences of significance between the two neoplasms. These findings suggest that a set of three immunohistochemical stains, including CK20, NF, and TTF-1, is useful in affording a distinction between Merkel cell carcinoma and small cell lung carcinoma.

Adult↗
PubMed2006

Immunohistochemical differential diagnosis between large cell neuroendocrine carcinoma and small cell carcinoma by tissue microarray analysis with a large antibody panel.

To elucidate additional phenotypic differences between large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC), we performed tissue microarray (TMA) analysis of surgically resected LCNEC and SCLC specimens. Immunostaining with 48 antibodies was scored based on staining intensity and the percentage of cells that stained positively. Four proteins were identified as significantly expressed in LCNEC as compared with SCLC: cytokeratin (CK)7, 113 vs 49 (P < .0301); CK18, 171 vs 60 (P < .0008); E-cadherin, 77 vs 9 (P < .0073); and beta-catenin, 191 vs 120 (P < .0286). Immunostaining of cross-sections containing LCNEC and SCLC components revealed significant expression of CK7, CK18 and beta-catenin in the LCNEC component compared with the SCLC component in 2 of 3 cases. Our results indicate that significant expression of CK7, CK18, E-cadherin, and beta-catenin is more characteristic of LCNEC than of SCLC, and these findings provide further support that these tumor types are separate entities morphologically and immunophenotypically, if not biologically.

Biomarkers, Tumor↗
PubMed1997

Cytokeratin 20 immunoreactivity distinguishes Merkel cell (primary cutaneous neuroendocrine) carcinomas and salivary gland small cell carcinomas from small cell carcinomas of various sites.

Cytokeratin 20 (CK20) is a low-molecular-weight cytokeratin (CK) that shows restricted expression in the gastrointestinal epithelium, urothelium, and Merkel cell. Recent studies have suggested that since Merkel cell (primary cutaneous neuroendocrine) carcinomas are consistently CK20-positive, this feature may help to distinguish it from pulmonary small cell carcinomas. However, only limited numbers of these tumors have been studied, and the pattern of CK20 expression in other small cell carcinomas has not been established. Therefore, we studied CK20 expression in small cell carcinomas from a wide variety of sites. Immunohistochemical study was performed on paraffin sections using CK20 antibody, coupled with antigen retrieval by pressure cooking in citrate buffer. The cases included 34 Merkel cell carcinomas and 89 small cell carcinomas from various sites (pulmonary, 37; gastrointestinal tract, nine; pharynx and tongue, two; sinonasal tract, three; salivary gland, five; larynx, nine; breast, two; thymus, three; uterine cervix and corpus, 12, prostate, three; urinary bladder, two; kidney, one; pancreas, one). In addition, all cases were immunostained with pan-CK (MNF-116) and low-molecular-weight CK (CAM5.2) antibodies to ascertain their epithelial nature. With the exception of one case, all Merkel cell carcinomas were CK20-positive; and 30 of the 33 cases showed a punctate pattern. Almost 100% of tumor cells were positive, except for two cases that showed staining of 10% and 30% of tumor cells, respectively. Among the other small cell carcinomas, only five cases were CK20-positive, including one of 37 pulmonary (40% cells positive in punctate pattern), one of 11 cervical (10% cells positive), and three of five salivary gland (100% cells positive). We conclude that CK20-positivity in a small cell carcinoma of uncertain origin strongly predicts a diagnosis of Merkel cell carcinoma, especially if the majority of tumor cells are positive. A negative CK20 reaction can practically rule out Merkel cell carcinoma, provided that an effective antigen retrieval technique is used and appropriate staining is obtained with other cytokeratin antibodies. The frequent CK20 positivity observed in salivary gland small cell carcinomas in this series suggests that at least some of them may be more closely related biologically to Merkel cell carcinoma than to pulmonary-type small cell carcinoma. This may explain why they are far less clinically aggressive than other small cell carcinomas.

Biomarkers, Tumor↗
PubMed2005

Distinguishing small cell carcinoma from non-small cell carcinoma of the lung: correlating cytologic features and performance in the College of American Pathologists Non-Gynecologic Cytology Program.

CONTEXT: The cytologic features of small cell carcinoma of the lung are well described. Nevertheless, some small cell carcinomas may be difficult to reproducibly distinguish from non-small cell carcinomas, and this distinction carries significant clinical importance. OBJECTIVE: To correlate the cytologic features of individual cases of small cell carcinoma of the lung in fine-needle aspiration specimens from the College of American Pathologists Non-Gynecologic Peer Comparison Cytology Program with the frequency of misclassification as non- small cell carcinoma. DESIGN: We reviewed 1185 interpretations of 23 different cases of small cell carcinoma in lung fine-needle aspiration specimens and correlated the cytologic features noted in these cases with performance in the program. RESULTS: Cases were divided into those that were frequently misclassified as non-small cell carcinoma (at least 10% of the responses, 11 cases) and those that were infrequently misclassified as non-small cell carcinoma (<5% of all responses, 12 cases). All cases had areas on the slides with classic features of small cell carcinoma. However, 10 of 11 cases that were frequently misclassified as non-small cell carcinoma had cells with either increased cytoplasm (4 cases), cytoplasmic globules (so-called paranuclear blue bodies) (3 cases), or apparent intracytoplasmic lumina (3 cases). These features were not identified in cases that were infrequently misclassified (P = .005). In addition, cases more frequently misclassified as non-small cell carcinoma tended to show better overall cellular and group preservation. CONCLUSIONS: Frequent misclassification of small cell carcinoma as non-small cell carcinoma in lung fine-needle aspiration specimens in this program correlates strongly with the presence of cytoplasmic features that may suggest non-small cell carcinoma or with the presence of paranuclear blue bodies. Misclassification in this program may reflect a variety of factors, including the variation in the cytologic features of individual cases, but also the lack of wide recognition that some features of non-small cell carcinoma may also be noted in well-preserved cases of small cell carcinoma.

Biopsy, Fine-Needle↗