An ultrastructural classification of carcinomas of the lung]

For the purpose of providing more accurate histological typing of lung carcinoma, it is necessary to classify carcinomas of the lung by electron microscopy. One hundred and fifty cases of resected lung carcinoma were examined under electron microscope. The results of ultrastructural typing of lung carcinoma were as follows: 1. carcinomas showed differentiated features of glandular and squamous epithelium, including squamous cell carcinoma (28 cases), adenocarcinoma (35 cases), and adenosquamous carcinoma (29 cases). Among them, some cases were associated with neuroendocrine differentiation. In addition, solid mucinous cell carcinoma (4 cases) and adenoid cystic carcinoma (2 cases) were seen. 2. Carcinomas showed differentiated features of bronchioloalveolar epithelium, subdividing into clara cell (9 cases), type II pneumocyte (3 cases), mucinous cell (5 cases) and mixed type (4 cases). 3. Carcinomas showed differentiated features of neuroendocrine cell (Kulchitsky cell), including well differentiated (carcinoid, 13 cases), intermediately differentiated (atypical carcinoid, 12 cases), and poorly differentiated (small cell carcinoma, 6 cases). Among them, some cases were associated with squamous differentiation. The ultrastructural classification was compared with histological classification of lung carcinomas and the differences between them are discussed.     

Immunocytochemical localization of neuron specific enolase in small cell carcinomas and carcinoid tumours of the lung

Carcinoid tumours and small cell carcinomas of the lung share many characteristics with normal neuroendocrine cells. While carcinoid tumours contain many dense-cored neurosecretory granules and are frequently argyrophil, small cell carcinomas are poorly granulated and rarely argyrophil, which casts doubt on their neuroendocrine nature. Immunostaining of the enzyme neuron specific enolase (NSE) was recently used to demonstrate the neuroendocrine components of the lung including nerves and neuroendocrine cells. We therefore used NSE immunostaining to investigate neuroendocrine differentiation in 79 lung tumours, including 18 bronchial carcinoids and 31 small cell carcinomas, and compared these results with those obtained with silver stains. Thirteen of the 18 carcinoids were reactive to silver, all other types being negative. NSE-immunoreactivity occurred in 16 carcinoids and 18 small cell carcinomas. None of the squamous cell carcinomas, large cell anaplastic carcinomas and adenocarcinomas examined showed NSE-immunoreactivity. Radioimmunoassay of extractable NSE from 10 fresh lung tumours correlated well with the immunostaining results, demonstrating large amounts in two small cell carcinomas (334 and 517 ng/mg protein) and three carcinoids (152, 908, and 1143 ng/mg protein). Values were much lower for four squamous cell carcinomas (31-44 ng/mg protein) and one large cell anaplastic carcinoma (30 ng/mg protein) and were accounted for by the presence of NSE-positive nerves and neuroendocrine cells in the surrounding lung. NSE immunostaining is a useful marker of neuroendocrine differentiation in lung tumours and should prove particularly valuable in the diagnosis of small cell anaplastic tumours and their metastases.     

The fine structure of large cell undifferentiated carcinoma of the lung. Evidence for its relation to squamous cell carcinomas and adenocarcinomas

The light microscopic diagnosis of large cell undifferentiated carcinoma of the lung is known to be highly subjective and shows poor interobserver reproducibility; the very existence of this tumor as a separate entity has been challenged. The ultrastructure of seven large cell undifferentiated carcinomas was examined in an attempt to determine whether they were merely poorly differentiated adenocarcinomas and squamous cell carcinomas, or actually represented an entirely separate class of tumors. Four large cell undifferentiated carcinomas demonstrated intra- and intercellular lumina and were designated adenocarcinomas. In three cases there were well formed desmosomes with numerous tonofilaments and intercellular bridges. These tumors were classified as squamous cell carcinomas. An eighth tumor metastatic to the abdominal wall also showed the features of squamous carcinoma. In addition, all tumors contained a variable population of primitive cells without identifying features. The large cell undifferentiated carcinomas were compared ultrastructurally with eight cases of poorly differentiated adenocarcinomas and squamous cell carcinomas classified by light microscopy. These tumors were morphologically similar, but contained fewer primitive cells and greater numbers of differentiated cells. Cells with a clear cytoplasm as seen by light microscopy were present in both the large cell undifferentiated and poorly differentiated groups; these cells contained variable amounts of glycogen but were otherwise similar to the nonclear cells. It is suggested that most of the subcategories of large cell undifferentiated carcinoma represent very poorly differentiated adenocarcinomas and squamous carcinomas.     

Cytological features of non-small cell carcinomas of the lung in fine needle aspirates.

Fifty eight lung tumours were typed according to the second World Health Organization histological classification and compared with the cytological appearances obtained by fine needle aspiration in a total of 47 primary non-small cell carcinomas. The presence of glands, cell balls, branching or papillary structures, cylindrical cells and nuclear grooving were major diagnostic indicators for adenocarcinoma. Cytoplasmic macrovacuoles were more common in adenocarcinomas (69%) than in squamous (37%) and large cell (50%) carcinomas. Two or more of these features were combined in all well and moderately differentiated adenocarcinomas and in 67% of poorly differentiated adenocarcinoma. The major cytological indicators for squamous carcinomas were the presence of keratin and eosinophilic spindle cells with glassy or laminated cytoplasm. Granular cytoplasm was not specific for any histological type. A combination of the major features for both adeno- and squamous carcinoma was present in 58% of adeno-squamous carcinomas, including some poorly differentiated types. Correct typing could be obtained in almost all the well and moderately differentiated carcinomas and in about two thirds of the poorly differentiated tumours using FNA, provided that combinations and not individual variables are considered.     

Kategorisierung der Tumoren der Cervix uteri

In the 2014 WHO classification, squamous cell precursor lesions are classified as low-grade and high-grade intraepithelial lesions. LSIL corresponds to CIN1, HSIL includes CIN2 and CIN3. Only adenocarcinoma in situ (AIS) is accepted as precursor of adenocarcinoma and includes the stratified mucin-producing intraepithelial lesion (SMILE). Although relatively rare, adenocarcinoma and squamous cell carcinoma can be mixed with a poorly differentiated neuroendocrine carcinoma. Most cervical adenocarcinomas are low grade and of endocervical type. Mucinous carcinomas show marked intra- and extracellular mucin production. Almost all squamous cell carcinomas, the vast majority of adenocarcinomas, and many rare carcinoma types are HPV related. For low grade endocervical adenocarcinomas, the pattern-based classification according to Silva should be reported. Neuroendocrine tumors are rare and are classified into low-grade and high-grade, whereby the term carcinoid is still used.     

Ultrastructural and molecular heterogeneity in non-small cell lung carcinomas: study of 110 cases and review of the literature

The authors reviewed a series of 110 surgical specimens of primary non-small cell lung carcinomas from the Department of Pathology at the Hospital Clinic, University of Barcelona Medical School, between 1987 and 1997. The sample included 25 squamous cell carcinomas, 60 adenocarcinomas, 14 large cell carcinomas, and 11 neuroendocrine tumors. Electron microscopic subcellular characteristics of the lung cancer cells were studied to define the squamous, adenoid, or neuroendocrine differentiation in each tumor. An immunohistochemical study for Cyclin D1 was performed in 96 cases. In 71 cases (65%) the author found a single ultrastructural differentiation, and in 30 cases (27%) ultrastructural differentiation was double: 25 adenosquamous and 5 adeno-neuroendocrine. In 3 cases a triple adeno-squamous-neuroendocrine differentiation was found. There were no cases of squamous-neuroendocrine differentiation. In 6 cases no differentiation of any kind could be found. Cyclin D1 overexpression was found in 58% of all tumors. The positive expression rates in squamous cell carcinoma and adenocarcinoma were 72% and 62%, respectively. In purely adenoid-differentiated tumors there was a strong association between high Cyclin D1 overexpression and differentiation (p=.006). In bronchioloalveolar carcinoma the positivity rate was 70%; all were heavy expressers, compared with 25% of heavy expressers in adenocarcinomas as a whole (p<.005). In purely squamous tumors differentiated ultrastructurally no relationship was found between high Cyclin D1 expression and degree of differentiation (p=.08). Lung cancers are morphologically and molecularly heterogeneous, and certain molecular alterations are related to specific subcellular characteristics.     

鼻咽原发性癌的组织学类型--30年经验总结

目的：提出既能与“国际接轨”又能充分反映在我国鼻咽癌病理学研究成就的鼻咽原发性癌组织学的方案。方法：在总结作者３０年来人事鼻咽癌病理学研究成果的基础上,参阅ＷＨＯ的组织学分类,并广泛征求同行的意见后,概括出本方案。结果：鼻咽原发性癌柯分为４种类型,即角化性鳞状细胞癌,非角化性癌、腺和原位癌。角化性鳞状细胞癌可按分化程序分为分化好、中等分化和分化差。非角化性癌是鼻咽癌高发区常见的癌,又可分为分化型。     

Poorly differentiated tumours of the anal canal: a diagnostic strategy for the surgical pathologist

Poorly differentiated malignancies affecting the anal canal are uncommon but pose diagnostic difficulties because of the wide range of normal cell types that may occur within a limited anatomical region. The range of lesions that may present as poorly differentiated tumours includes squamous cell carcinoma, adenocarcinoma, small and large cell neuroendocrine carcinoma, neuroendocrine carcinoma expressing epithelial cytokeratins and other patterns of mixed differentiation, undifferentiated carcinoma, malignant melanoma, lymphoma and secondary tumours. This review discusses the differential diagnosis of these neoplasms with the aid of short illustrative case studies.     

OV-TL 12/30 (keratin 7 antibody) is a marker of glandular differentiation in lung cancer

The immunoreactivity of OV-TL 12/30, a monoclonal antibody to keratin 7 was investigated on paraffin-embedded human lung cancer tissues of 61 patients. A modified AEC-immunoperoxidase method with pepsin pre-digestion was used. In normal lung tissue keratin 7 was found in bronchial and bronchiolar epithelium, pneumocytes and compound glands. Squamous metaplasia of the bronchial tree was negative. All 24 squamous cell carcinomas were negative irrespective of grade of differentiation. All differentiation grades of 20 adenocarcinomas including bronchioalveolar carcinomas were positive. Since six large cell anaplastic carcinomas did not react with keratin 7 antibody these tumours are considered to be of squamous cell rather than adenocarcinomatous origin. Small cell anaplastic carcinomas were negative in 10 of 11 cases. Our study demonstrates that this keratin 7 antibody is useful in differentiating between squamous cell carcinoma and adenocarcinoma of the lung and it may be particularly useful in making the correct diagnosis in small lung biopsy specimens.     

Extremely high Langerhans cell infiltration contributes to the favourable prognosis of HPV-infected squamous cell carcinoma and adenocarcinoma of the lung

AIMS: The infiltration of Langerhans cells in adenocarcinomas and squamous cell carcinomas of the lung was examined in relation to prognostic implications and human papillomavirus (HPV) infection. METHODS AND RESULTS: Samples from 62 adenocarcinoma and 59 squamous cell carcinoma patients in 1995-97, the prognosis of which had been followed up, were used. The Langerhans cells were demonstrated immunohistochemically using anti S100a and CD1 antibodies. Human papillomavirus (HPV) infection was examined by polymerase chain reaction (PCR) and nonisotopic in-situ hybridization (NISH) methods. Statistical analysis was carried out using the Kaplan-Meier method (Wilcoxon analysis) and multiple regression analysis. HPV infection was demonstrated in 12 cases (19.4%) of adenocarcinoma. The HPV-infected adenocarcinomas had abundant faintly eosinophilic cytoplasm, and were immunohistochemically positive for the surfactant apoprotein A. In the 59 cases of squamous cell carcinomas 19 were of the well differentiated form, and 29 and 11 were moderately and poorly differentiated cases, respectively. HPV was detected in 29 cases (49.2%) (13 well and 16 moderately differentiated cases). In all HPV-infected adenocarcinoma and squamous cell carcinoma cases, extremely large numbers of Langerhans cells (more than 100 per high-power field) were demonstrated in the tumour nests. In contrast, in the non-HPV-infected adenocarcinomas and squamous cell carcinomas, only a few (less than about 10 per high-power field) Langerhans cells were observed. The squamous cell carcinoma cases with high Langerhans cell infiltration, which were also infected with HPV, showed a significantly good prognosis (P = 0.007). The adenocarcinoma cases with high Langerhans cell infiltration tended to have a better prognosis than the cases with low Langerhans cell infiltration, but the difference was not statistically significant. The low number of highly infiltrated cases was insufficient for an adequate statistical analysis. Furthermore, there was no significant correlation between either Langerhans cell infiltration and smoking, or HPV infection and smoking, in either squamous cell carcinoma or adenocarcinoma cases. CONCLUSIONS: It was considered that the extremely high Langerhans cell infiltration in the tumours was caused by HPV infection. The extremely large number of Langerhans cells in the tumours contributes to the favourable prognosis for HPV-infected lung cancer.     

Differential distribution of the neuron-associated class III beta-tubulin in neuroendocrine lung tumors

OBJECTIVE: To study the immunoreactivity profile of the neuron-associated class III beta-tubulin isotype (beta III) in epithelial lung tumors. DESIGN: One hundred four formalin-fixed, paraffin-embedded primary and metastatic lung cancer specimens were immunostained with an anti-beta III mouse monoclonal antibody (TuJ1) and an anti-beta III affinity-purified rabbit antiserum. Paraffin sections from fetal, infantile, and adult nonneoplastic lung tissues were also examined. RESULTS: In the fetal airway epithelium, beta III staining is detected transiently in rare Kulchitsky-like cells from lung tissues corresponding to the pseudoglandular and canalicular but not the saccular or alveolar stages of development. beta III is absent in healthy, hyperplastic, metaplastic, and dysplastic airway epithelium of the adult lung. In contrast, beta III is highly expressed in small cell lung cancer, large cell neuroendocrine carcinoma, and in some non-small cell lung cancers, particularly adenocarcinomas. There is no correlation between expression of beta III and generic neuroendocrine markers, such as chromogranin A and/or synaptophysin, in pulmonary adenocarcinomas. Also, focal beta III staining is present in primary and metastatic adenocarcinomas (to the lung) originating in the colon, prostate, and ovary. beta III is expressed to a much lesser extent in atypical carcinoids and is rarely detectable in typical carcinoids and squamous cell carcinomas of the lung. The distribution of beta III in small cell lung cancer and adenocarcinoma metastases to regional lymph nodes and brain approaches 100% of tumor cells, which is substantially greater than in the primary tumors. CONCLUSIONS: In the context of neuroendocrine lung tumors, beta III immunoreactivity is a molecular signature of high-grade malignant neoplasms (small cell lung cancer and large cell neuroendocrine carcinoma) although its importance in atypical carcinoids must be evaluated further. In addition, beta III may be a useful diagnostic marker in distinguishing between small cell lung cancers and certain non-small cell lung cancers (poorly differentiated squamous cell carcinomas), especially in small biopsy specimens. To our knowledge, beta III is the only tumor biomarker that exhibits a substantially more widespread distribution in poorly differentiated than in better differentiated pulmonary neuroendocrine tumors. However, the significance of beta III phenotypes in non-small cell lung cancer, particularly adenocarcinoma, with respect to neuroendocrine differentiation and prognostic value, requires further evaluation.     

Histologic and immunophenotypic classification of cervical carcinomas by expression of the p53 homologue p63: a study of 250 cases

Recent studies of the p53 homologue p63 indicate that this gene is preferentially expressed in basal and immature cervical squamous epithelium. This study correlated p63 expression with morphologic phenotype and human papillomavirus (HPV) type in a wide range of cervical neoplasms. Two hundred fifty cases of cervical carcinoma, including squamous cell carcinoma (SCCA; n = 178), adenocarcinoma (ADCA; n = 28), adenosquamous carcinoma (ASCA; n = 8), neuroendocrine carcinoma (NECA; n = 15), and other variant or mixed types (n = 21) were studied. Ninety-seven percent of SCCA, 0% of ADCA, and 0% of SCUC showed strong (>75% v <30%) positivity for p63 (P<.001). p63 sharply distinguished SCCA (p63+) from ADCA (p63-), Large-cell, poorly differentiated carcinomas were distinguished as putative glandular (glassy cell) or squamous (lymphoepithelial-like or spindle cell) types based on p63 staining. Eight (73%) of 11 neuroendocrine tumors tested were chromogranin positive; all showed no or low (<30%) levels of p63 immunostaining. Absence of p63 was also associated with a subset of nonneuroendocrine undifferentiated carcinomas. Transitions from squamous to columnar or undifferentiated morphology coincided with loss of p63 expression. A strong association between HPV 16 and p63 positivity was identified because of the colocalization of both within tumors of squamous phenotype. p63 is a powerful marker for squamous differentiation and, when diffusely expressed, excludes a glandular or neuroendocrine differentiation. p63 may be useful for differentiating pure squamous or glandular from adenosquamous carcinomas, tracking shifts in differentiation within tumors, supporting (by its absence) the diagnosis of neuroendocrine carcinomas, and clarifying the spectrum of poorly differentiated carcinomas lacking either squamous or neuroendocrine differentiation.     

Non‐urothelial carcinomas of the bladder

Non‐urothelial carcinomas involving the bladder are uncommon and often diagnostically challenging. These carcinomas may show squamous, adenocarcinomatous or neuroendocrine features, with immunohistochemical stains aiding the diagnosis in only a subset of cases. The clinical history in non‐urothelial bladder carcinomas is important, given that the differential diagnosis often includes secondary involvement of the bladder by direct extension or metastasis from carcinomas at other sites. This paper will review non‐urothelial carcinomas in each of these three morphological categories, emphasising recent changes in diagnostic grouping and challenges in the histopathological diagnosis. Review of bladder cancers with squamous morphology will include discussion of conventional squamous cell carcinoma and verrucous carcinoma and their distinction from urothelial carcinoma with extensive squamous differentiation. Bladder carcinomas with adenocarcinomatous change will include primary bladder adenocarcinoma, urachal adenocarcinoma and tumours of Müllerian type. Finally, neuroendocrine neoplasms of the bladder, including well‐differentiated neuroendocrine tumour and neuroendocrine carcinomas, will be discussed. Associated surface findings, risk factors and prognostic features will be described.     

Pseudoangiosarcomatous carcinoma: a clinicopathological study of seven cases

Seven cases of carcinoma mimicking angiosarcoma occurring in skin (3 cases), breast (3) and lung (1) are described. The cutaneous, pulmonary and one of the breast carcinomas were poorly differentiated and squamous in type; the other two breast tumours were poorly differentiated ductal carcinomas with focal squamous differentiation. Histologically, the pseudoangiosarcomatous pattern was due to complex anastomosing channels and spaces lined by neoplastic cells. The spaces contained hyaluronic acid. The neoplastic cells exhibited cytokeratin positivity but yielded negative results with the endothelial cell markers, factor VIII-related antigen and CD 34 (QB-END/10). Two breast tumours showed binding of UEA-1. Ultrastructurally, unequivocal epithelial differentiation was demonstrated in six of the cases. Pathogenetically, these tumours appeared to be variants of acantholytic squamous cell carcinoma. Recognition of this unusual form of carcinoma is important, as an incorrect diagnosis of angiosarcoma may lead to inappropriate treatment and prognostication.     

Fine-needle aspiration cytology of metaplastic carcinoma of the breast

BACKGROUND: Metaplastic carcinoma of the breast encompasses a heterogeneous group of tumours with variable components of sarcomatoid, squamous or poorly differentiated carcinomas. AIM: To review a series of 19 cytological preparations of metaplastic carcinomas to assess diagnostic cytological features. METHODS: 17 cases of fine-needle aspirates of histologically proven metaplastic carcinomas (4 monophasic spindle cell carcinomas, 4 squamous cell carcinomas and 11 biphasic tumours) were reviewed, with an emphasis on the presence of poorly differentiated carcinoma, squamous cell carcinoma, atypical spindle cells, benign stromal fragments and necrosis. RESULTS: All cases were diagnosed as malignant, with 68% of cases showing moderate to high cellularity, and 47% showing necrosis. If the tumours were analysed according to the constituting components histologically, 7, 15 and 8 cases, respectively, possess poorly differentiated carcinoma cells, sarcomatoid malignant cells and squamous carcinoma cells, whereas these components were cytologically identified in 11, 10 and 7 cases, respectively. Dual tumour populations were identified in only 5 of the 11 biphasic carcinomas in the cytological preparations; and the stromal material was cytologically identified in the only case with chondroid stroma. CONCLUSIONS: Identification of metaplastic carcinoma in cytology remains problematic. There seems to be morphological overlap between various components. The identification of dual components, unequivocal squamous carcinoma cells and chondroid stroma is helpful for diagnosis, but it is uncommon. The presence of poorly differentiated carcinoma cells with a suggestion of focal spindle morphology is another clue to the suggestion of metaplastic carcinoma.     

34betaE12 Cytokeratin Immunodetection in the Differential Diagnosis of Small Cell Tumors of Lung

The group of small cell tumors of the lung includes fine following: (1) small cell carcinoma (SCC) of neuroendocrine (NE) origin, (2) poorly differentiated squamous carcinoma, (3) the rare basaloid (basal cell) carcinomas, and (4) malignant lymphomas, primitive neuroectodermal tumors (PNETs), and rhabdomyosarcomas. The differential diagnosis among these entities carries a heavy therapeutic impact but may be difficult in small biopsy specimens or in cytologic material, especially if necrosis or artifactual alterations are present. The use of additional techniques such as immunostaining for NE markers is not always helpful, since immunoreactive chromogranin A is detectable in only a small percentage of small cell carcinomas. It has recently been reported that in the aerodigestive tract 34betaE12 cytokeratin (CK) immunostaining selectively labels non-NE carcinomas, including squamous cell carcinoma, adenocarcinoma, and the rare basaloid carcinoma. We evaluated the role of such CK immunodetection in the differential diagnosis of small cell lung tumors in cytologic and biopsy specimens. Eighty-one lung tumors diagnosed by means of endoscopic bronchial biopsy, fine needle aspirate, or bronchial washing were collected. They included 43 small cell NE carcinomas and 38 cases used as controls (comprehensive of 2 large cell neuroendocrine carcinomas, 4 carcinoid tumors, 30 cases of non-NE lung carcinomas, 2 cases of bronchial infiltration by non-Hodgkin lymphomas). 34betaE12 CK immunoreactivity was found in 29/30 cases of non-NE carcinomas, but in only 3/43 SCCs. The latter showed positivity in only a few scattered cells. The 2 cases of bronchial infiltration by malignant lymphoma as well as the 4 cases of carcinoid tumors and the 2 cases of large cell neuroendocrine carcinomas were negative. These findings were confirmed in the surgical specimens of operatedon cases. We conclude that, in lung carcinoma biopsies showing a small cell pattern, presence of 34betaE12 CK immunoreactivity favors a non-NE carcinoma, whereas its absence supports the diagnosis of SCC. Int J Surg Pathol 8(4):317-322, 2000     

Differential expression of neural-cadherin in pulmonary epithelial tumours

Aims:  Neural (N)-cadherin belongs to a group of transmembrane molecules with a crucial role in tissue morphogenesis and maintenance of an epithelioid phenotype and increased N-cadherin expression is implicated in tumour progression and dedifferentiation. The aim was to determine whether evaluation of N-cadherin in pulmonary tumours might assist in identifying lesions with more aggressive potential.
Methods and results:  One hundred and fifty-five pulmonary lesions were analysed for N-cadherin expression using immunohistochemistry, including neuroendocrine hyperplasia ( n  = 3), typical carcinoid ( n  = 59), atypical carcinoid ( n  = 12), small cell lung carcinoma ( n  = 11), large cell neuroendocrine carcinoma ( n  = 12), adenocarcinoma ( n  = 35) and squamous cell carcinoma ( n  = 23). Lymph node status was correlated with immunohistochemical expression. N-cadherin expression was demonstrated in all cases of neuroendocrine hyperplasia, 96% of typical carcinoids, 83% of atypical carcinoids, 63% of the small cell lung carcinomas and 32% of large cell neuroendocrine carcinomas. Over 90% of the adenocarcinomas and 100% of the squamous cell carcinomas were negative. Increased N-cadherin expression in typical carcinoids was associated with negative lymph node status ( P  < 0.001).
Discussion:  N-cadherin is differentially expressed in pulmonary tumours and is predominantly observed in neuroendocrine lung lesions with high expression in typical and atypical pulmonary carcinoids. The level of expression of N-cadherin between types of lung tumours does not appear to indicate malignant potential or aggressive behaviour.     

LUNG TUMOURS IMMUNOREACTIVE FOR PARATHYROID HORMONE RELATED PEPTIDE: ANALYSIS OF SERUM CALCIUM LEVELS AND TUMOUR TYPE

Secretion by tumours of parathyroid hormone-related peptide (PTHrP) in quantities sufficient to raise circulating levels results in the syndrome of humoral hypercalcaemia of malignancy (HHM). Since HHM is commonly associated with squamous carcinoma of lung and rarely with adenocarcinoma or lung neuroendocrine tumours, immunopositivity was related to tumour type, to assess whether this difference was due to a low general incidence of PTHrP expression in the latter two groups. Seventy-six of 82 tumours were immunopositive: 22 of 22 squamous carcinomas, 21 of 25 small cell lung carcinomas, 14 of 15 carcinoids, and 19 of 20 adenocarcinomas. These data confirm and extend previous observations on squamous and neuroendocrine tumours but are in contrast with previous findings in adenocarcinoma, which have suggested that only a small proportion of cases express the peptide. They suggest that the differences in incidence of HHM in the various tumour types are due to patterns of secretion, rather than differences in expression of PTHrP. The second aim of this study was therefore to assess whether tumours immunopositive for PTHrP, but not associated with HHM, might secrete PTHrP at levels which might result in more subtle changes in calcium metabolism. Preoperative calcium levels were analysed in a series of 56 patients with immunopositive lung tumours of all types. One small cell carcinoma was associated with hypercalcaemia, but there was no evidence of any other alteration in serum calcium. These data indicate that the majority of tumours expressing PTHrP do not secrete it in amounts sufficient to alter calcium metabolism.     

人肺癌冷冻蚀刻法透射电镜观察

用冷冻蚀刻透射电镜法,观察18例人类肺癌(6例鳞癌,6例腺癌,3例小细胞癌,3例大细胞癌)。结果表明,各型肺癌细胞间显示不同的连接特征:未分化癌细胞膜常平直并行。鳞癌细胞多为指状镶嵌,桥粒较多。腺癌细胞可见紧密连接。高分化癌细胞核膜孔数目较少,而低分化和未分化癌细胞核膜孔数目明显增多。作者认为,肺癌细胞随分化程度降低核膜孔数量增多,可能与其生长速度、代谢功能有关。观察细胞生物膜和细胞间连接结构,冷冻蚀刻技术优于超薄切片技术。