Bronchial brushing during fiberoptic bronchoscopy for the cytodiagnosis of lung cancer: comparison with sputum and bronchial washings.

In a study of 50 cases of bronchogenic carcinoma in which brushings and washings during fiberoptic bronchoscopy, as well as sputum cytopathologic examinations were performed in the same patients, accuracy rates were respectively: 76 per cent, 76 per cent and 56 per cent. The main cytologic differences setting brush apart from wash and sputum specimens referred to the arrangement of tumor cells as well as the distribution of chromatin within their nuclei. These differences appeared related to cell degeneration which was minimal in brush materials and maximum in sputum specimens. Only six cases were assigned a different cell type of bronchogenic carcinoma when brush cytopathologic diagnoses were compared with results obtained by biopsy or lobectomy specimens. Our findings are consistent with the view that the brush technique is very accurate for the cytodiagnosis of lung cancer and becomes also rather specific once cytologic characteristics of the fresher samples obtained become familiar to the cytopathologist. Non-observance of the special characteristics of these better preserved cellular samples is the major pitfall as to diagnosing, cell typing and judging degree of differentiation of bronchogenic carcinoma in brush cytology specimens.     

The diagnostic reliability of cytologic typing in primary lung cancer with a review of the literature

To evaluate the growing tendency in recent years to attribute more diagnostic reliability to cytologic methods, we investigated the accuracy of cytologic typing in specimens obtained from bronchopulmonary material by five different clinical sampling methods, comparing the cytologic diagnoses with the known histologic diagnoses. The study consisted of 232 cytologic specimens from 157 cases of primary lung cancer. Of the 232 specimens, 173 (75%) were correctly typed and 59 (25%) incorrectly typed with respect to the appropriate histologic diagnoses. When all sampling methods were considered together, the study demonstrated that well-differentiated epidermoid carcinoma and "oat cell" and spindle-polygonal anaplastic carcinomas yielded high cytologic typing accuracies. In poorly differentiated tumors, bronchioloalveolar cell carcinoma and bronchogenic adenocarcinoma, the correct cytologic typing was much lower. The different tumor types and their degrees of differentiation seem to be the decisive factors in cytologic typing accuracy. The findings of this study were compared with those of others and were found to be consistent with the results of even larger series of cases. For some types the typing accuracy was higher than that reported in other series, whereas for other types, e.g., adenocarcinomas, it was lower.     

Ten years of respiratory cytopathology at Duke University Medical Center. II. The cytopathologic diagnosis of lung cancer during the years 1970 to 1974, with a comparison between cytopathology and histopathology in the typing of lung cancer

In 1975 Duke University Medical Center, a retrospective and prospective survey of respiratory cytopathologic specimens was undertaken for the ten-year period 1970 to 1979. The purpose of this study was to document the role of cytopathology in the diagnosis of lung cancer at this institution. This paper presents the results of the cytopathologic and histopathologic typing of cases of lung cancer seen at Duke University Medical Center from 1970 to 1974. During this period, 9,892 cytologic specimens from the lower respiratory tract were processed. Cytopathologic diagnoses of cancer with tissue confirmation were made on 483 specimens from 232 patients. Because original cytologic diagnoses, but not histopathologic diagnoses, had been made in conformity with a modified WHO classification of lung neoplasms, all histopathologic material was reviewed and reclassified when necessary. This was carried out by one of the authors (E.H.B.) as a blind review without benefit of knowledge of either preexisting cytopathologic or histopathologic diagnoses. Twenty-six patients were excluded from the current study because of lack of satisfactory histologic material. In 94 patients classified by histopathology as having squamous cell carcinoma, 76.4% of the positive cytologic specimens were also called squamous cell carcinoma; 18.6% were interpreted as large cell undifferentiated carcinoma. In 39 patients classified by tissue as having large cell undifferentiated carcinoma, the cytology agreed in 42.4% of the positive specimens. For the 29 patients thought histologically to have small cell undifferentiated carcinoma, the same diagnosis was rendered in 95.5% of the cytologically positive specimens from these patients. For the adenocarcinoma group of 43 patients, a cytopathologic diagnosis of adenocarcinoma was made in 67.8% of the positive specimens.     

Bronchial carcinoma and image analysis. Differentiation between poorly differentiated epidermoid carcinoma and small-cell carcinoma

The utility of automated image analysis in the distinction between poorly differentiated epidermoid carcinoma (eight cases) and small-cell carcinoma (ten cases) was studied. Material obtained using the bronchial brushing technique was prepared by a cytocentrifugation technique. In each case, a total of 100 bronchial cell nuclei were selected using the Leitz TAS, which measured eight parameters per cell in order to ascertain the homogeneity or the heterogeneity of the nuclear populations. Except for one sample exhibiting preparation artifacts, the method proved capable of differentiating between these two types of bronchial carcinoma, with heterogeneity of the malignant nuclei indicating an epidermoid carcinoma and homogeneity indicating a small-cell carcinoma. A correlation was observed to exist between the morphologic and the morphometric criteria.     

Antineoplastic antibiotics in the combined chemotherapy of squamous cell carcinoma

Sixty five patients with squamous cell carcinoma of various localization at stages III-IV or with severe relapses were subjected to chemotherapy according to 3 schemes: AMB (adriamycin + methotrexate + bleomycin or bleomycetin), 34 patients; AMBP (adriamycin + methotrexate + bleomycetin + platidiam), 17 patients and AMFP (adriamycin + methotrexate + fluorofur + platidiam), 14 patients. The efficacy of the schemes was 35, 17.7 and 43 per cent respectively. The AMB scheme in treatment of the patients with maxillofacial carcinoma resulted in remission in 8 out of 20 cases (40 per cent). Analysis of the adverse reactions to the chemotherapy showed that all the three schemes were relatively low toxic. The AMB and AMFP schemes may be recommended for treatment of patients with disseminated or inoperable forms of epidermoid tumors in oncological departments.     

Needle biopsy in diagnosis of prostatic cancer

Four methods available for the diagnosis of carcinoma of the prostate-digital rectal evaluation, prostatic smear, needle biopsy and open perineal or transurethral biopsy-were studied and correlated.One hundred ten patients with clinical indications of cancer of the prostate were subjected to needle biopsy and open perineal or transurethral biopsy. Seventy of the same patients had prostatic smear examination. Using the open perineal biopsy or the positive transurethral biopsy as the standard, the accuracy of prostatic palpation, prostatic smear and needle biopsy were obtained.A high degree of correlation (74 per cent) was demonstrated between digital rectal evaluation and positive surgical biopsies in both early and late cases. There were 17 false positive clinical diagnoses. The prostatic smear showed an overall correlation of 45 per cent when compared with the results of positive surgical biopsy. The overall accuracy of needle biopsy was 73 per cent. However, in the last 39 cases, including eight in which the carcinomas were of groups A and B (curable), the needle accuracy was 100 per cent. When there is clinical indication of malignant disease of the prostate, needle biopsy of the lesion is warranted and should be done before definitive or palliative treatment is undertaken.     

Specificity of epidermal chalone extracts for human epidermoid tumour cells in vitro: a preliminary report.

In order to test the mitosis-inhibiting effect and the tissue specificity of the epidermal G2 chalone for tumour cells, extracts from hairless mouse epidermis were tested in short-term tissue cultures of cells from human respiratory tract epidermoid carcinomas and adenocarcinomas. The chalone inhibited strongly the mitotic activity in two cases of histologically proven epidermoid carcinoma, and had no effect in two cases of adenocarcinoma. In one case of a supposed epidermoid carcinoma, the chalone had no effect. Revision of the histology, and the result of autopsy 11 months later, showed that in this case the lesion in the lung had been a poorly differentiated metastasis from an adenocarcinoma of the ovary. Liver extracts produced in the same way as the epidermal extracts showed no mitotic inhibition in any of the cultures. These results indicate that epidermal G2 chalone produced from mouse skin is tissue specific for human epidermoid tumour cells, and also indicate that a chalone test might be used as a diagnostic tool for poorly differentiated carcinomas to see whether they are of epidermoid origin or not.     

SPECIFICITY of EPIDERMAL CHALONE EXTRACTS FOR HUMAN EPIDERMOID TUMOUR CELLS IN VITRO: A PRELIMINARY REPORT

In order to test the mitosis-inhibiting effect and the tissue specificity of the epidermal G₂ chalone for tumour cells, extracts from hairless mouse epidermis were tested in short-term tissue cultures of cells from human respiratory tract epidermoid carcinomas and adenocarcinomas. the chalone inhibited strongly the mitotic activity in two cases of histologically proven epidermoid carcinoma, and had no effect in two cases of adenocarcinoma. In one case of a supposed epidermoid carcinoma, the chalone had no effect. Revision of the histology, and the result of autopsy 11 months later, showed that in this case the lesion in the lung had been a poorly differentiated metastasis from an adenocarcinoma of the ovary. Liver extracts produced in the same way as the epidermal extracts showed no mitotic inhibition in any of the cultures. These results indicate that epidermal G₂ chalone produced from mouse skin is tissue specific for human epidermoid tumour cells, and also indicate that a chalone test might be used as a diagnostic tool for poorly differentiated carcinomas to see whether they are of epidermoid origin or not.     

肺癌细胞多向分化与异质性的研究

探讨肺癌细胞多向分化与异质性。用光镜、免疫组化方法观察了87例肺癌手术标本组织切片,30例细胞涂片。（1）标本取材块数与病理分型种类多少里显著性正相关。（r=0．407,P＜0．01）;（2）作为单一类型的小细胞癌、鳞癌、腺癌、大细胞癌及类癌仅占27．6％、20％鳞癌、16．7％腺癌、23．3％大细胞癌KER、VIM双表达。66．7％有鳞、腺、神经内分泌三向分化;（3）在混合类型肺癌中,细胞学与组织学分型符合率为56．7％。肺癌细胞类型有明显异质性,其发生分子基础尚待进一步研究。     

Identification of types and primary sites of malignant tumors by examination of exfoliated tumor cells in serous fluids. Comparison with the diagnostic accuracy on small histologic biopsies

The accuracy of identification of tumor type and primary site of malignant tumors by examination of exfoliated tumor cells was cytologically studied in 448 malignant effusions from 366 patients for whom the primary tumor site had been confirmed by histology. Ninety-seven corresponding small biopsies from metastases were separately reviewed histopathologically. In four fluids, the cells were too scanty or too poorly preserved for tumor typing. The cytologic tumor typing was performed with nearly 100% accuracy in the remaining 444 fluids, except for those of intermediate-cell anaplastic carcinomas (0 of 3) and poorly differentiated squamous (epidermoid) carcinomas (1 of 5). Adenocarcinoma was correctly identified in 98% of 285 fluids, large-cell carcinoma in 97% of 108 fluids, oat-cell carcinoma in 94% of 16 fluids, well-differentiated (keratinizing) squamous carcinoma in 100% of 3 fluids, malignant lymphoma in 100% of 22 fluids and sarcoma in 100% of 2 fluids. The criteria and the failures are discussed at length. In the investigation of the accuracy of cytologic and histologic diagnoses with respect to the primary tumor site, tumors with variable sites of origin (sarcomas and lymphomas) and those with usually singular sites of origin (e.g., small-cell anaplastic carcinoma of the lung) were excluded, leaving 387 cytologic and 83 histologic specimens available for review. The breast as a primary site was correctly identified in 70% of both the cytologic and histologic specimens; the primary cytodiagnostic criteria included a uniform cell pattern, finely granular chromatin, dense cytoplasm and cell balls with smooth borders. Ovarian primaries were correctly identified in 70% of the fluids and 83% of the biopsy samples on the basis of very irregular clusters of large pleomorphic tumor cells, large nucleoli and psammoma bodies. Lung primaries, identified in 50% of the fluids and 29% of the biopsy samples, showed quite variable cell patterns, most often including large pleomorphic cells with or without mucus formation and prominent multinucleation. Gastric cancers of the diffuse type were accurately identified in 52% of the corresponding fluids, which showed mainly isolated cells with dense cytoplasmic rims, occasional signet-ring cells, "embryo-shaped" nuclei, marked hyperchromasia and densely granular chromatin.(ABSTRACT TRUNCATED AT 400 WORDS)     

Primary carcinoma of the gallbladder; review of 173 cases

One hundred seventy-three cases of primary carcinoma of the gallbladder were analyzed. In the group studied they made 2.11 per cent of all malignant tumors found at autopsy and were found in 1.89 per cent of all cases in which operation was done on the biliary tract. There was no appreciable change in the incidence of this tumor at autopsy during the period studied (1918-1948) at the Los Angeles County Hospital. Sixty-eight per cent of the cases were in females. A particularly high incidence was noted in Mexican females. Upper abdominal pain, loss of weight, nausea and vomiting, jaundice, and palpable mass or enlarged liver were the most common clinical features. Approximately one-third of the patients in whom the lesion was found at operation and one-fifth of all the patients whose records were studied had a history of chronic gallbladder disease. All but two of the 38 patients operated on were dead or had clinical recurrence within two years. One was alive and well 12 years after cholecystectomy. The most common gross appearance, particularly at autopsy, was a large tumor mass replacing the gallbladder and radiating to nearby organs, particularly the liver. In about one-third of the cases the tumor was grossly limited to the gallbladder. Polypoid tumors occurred in only about 10 per cent of the cases and most of the tumors were diffusely growing adenocarcinoma. Perforation appeared in nine cases, usually with fistula to the gastrointestinal tract. All of the tumors were histologically adenocarcinoma, usually of simple glandular structure. No purely squamous cell growth occurred. Gallstones were found in 79.8 per cent of the cases.     

Cytopathologic diagnosis of xanthogranulomatous cholecystitis and coexistent lesions. A prospective study of 31 cases

OBJECTIVE: To evaluate the diagnostic accuracy and reliability of preoperative ultrasound (US)-guided fine needle aspiration cytology (FNAC) in the diagnosis of xanthogranulomatous cholecystitis (XGC) and coexistent lesions (carcinoma) and also to evaluate the possibility ofmissing either carcinoma or XGC on cytology. STUDY DESIGN: The cytologic diagnoses of XGC and coexistent lesions were made according to standard criteria. In a prospective, 5-year study, preoperative US-guided FNAC from 42 cases of XGC was compared with follow-up histologic diagnoses, which were available in 31 cases. When FNAC after the first aspiration showed the aspirate to be nondiagnostic, FNAC was repeated under US guidance. RESULTS: Preoperative US-guided FNAC diagnoses of XGC were made in 31 cases, for which follow-up histology was available in all cases. US-guided FNAC diagnosis ofXGC only was made in 30 cases and coexistent lesions in 1 case. Followup histology revealed 26 cases of XGC, 4 of a coexistent lesion and 1 of squamous cell carcinoma only. The overall diagnostic accuracy of preoperative US-guided FNAC was 96.77%. The overall possibility of missing XGC was 3.33% and that of carcinoma, 12.01%. CONCLUSION: Preoperative US-guided FNAC is safe, rapid, reliable, cost-effective and accurate in diagnosing XGC. However, the possibility ofcoexistent carcinoma cannot be definitely ruled out. It is therefore recommended that FNAC be performed from multiple suspicious sites under radiologic guidance. Thus, preoperative US-guided FNAC diagnosis would help in determining the urgency of treatment and also in planning the surgical procedure for gallbladder lesions.     

Advanced primary clear cell carcinoma of the vagina not associated with diethylstilbestrol

BACKGROUND: Primary vaginal clear cell carcinoma occurs in young women exposed to diethylstilbestrol (DES) in utero. Primary vaginal clear cell carcinoma not associated with DES is very rare. We report the clinicopathologic and cytopathologic features of a patient with advanced, sporadic primary vaginal clear cell carcinoma with metastases to liver, lung and paraaortic lymph nodes. CASE: A postmenopausal, 63-year-old woman presented to our department with genital bleeding. A hemorrhagic tumor found in the vagina was diagnosed as a clear cell carcinoma by cytopathologic examination of the tumor smear and by histopathologic examination of a biopsy specimen. A chest radiograph revealed multiple lung metastases, and metastases to the liver and paraaortic lymph nodes were noted on computed tomography and magnetic resonance imaging. The tumor was diagnosed as primary clear cell carcinoma of the vagina, stage IVb (FIGO) based on a normal cytopathologic examination of the cervix, endometrium and ascites; normal appearance of the uterus, ovaries and kidneys on magnetic resonance imaging; and absence of detectable tumor in the urinary tract. The patient died of respiratory failure 31 days after hospitalization. The tumor demonstrated overexpression of p53 protein and did not show microsatellite instability. CONCLUSION: This patient was the second reported Japanese woman with advanced primary vaginal clear cell carcinoma not associated with DES.     

The usefulness of a panel of immunostains in the diagnosis and differentiation of metastatic malignancies in pericardial effusions

Pericardial effusions are not uncommon in patients with an advanced malignancy Rarely malignancies may present initially with a pericardial effusion. Cytological examination of pericardial fluid may be valuable in differentiation of these cases. However, a metastatic tumour in serous effusion may not always show the functional differentiation of the primary tumour. In such a situation, although a wide range of special studies have been suggested for the diagnosis of malignancy we have found the use of a panel of a few common immunostains to be useful in confirming or suggesting the site of a primary tumour. The material for this study consisted of 76 pericardial fluids obtained between January 1991 and October 1998 from 46 males (mean age 59 years) and 30 females (mean age 52 years). Metastatic malignancy was diagnosed in 22 of the 76 patients and in 7/22 cases pericardial effusions were the initial presentation. The subsequent follow-up in the seven cases revealed adenocarcinoma of lung (n = 2), small cell anaplastic carcinoma of lung (n = 1), squamous cell carcinoma lung (n = 1), melanoma leg (n = 1), non-Hodgkin's lymphoma retroperitoneal lymph nodes (n = 1) and carcinoma of the breast (n = 1). Of the remaining 15 cases with a known history of malignancy, eight had cancers (three adeno; two small cell; one poorly differentiated, and two squamous cell types) of the lung; breast (n = 3); colon (n = 1); melanoma (n = 2) and non Hodgkin's lymphoma (n = 1). Immunostains which were useful in the diagnosis were EMA, CEA, cytokeratin, B72.3, HMB45, vimentin, S100, LCA, L26 and kappa and lambda light chains.     

PRIMARY CARCINOMA OF THE GALLBLADDER—Review of 173 Cases

One hundred seventy-three cases of primary carcinoma of the gallbladder were analyzed. In the group studied they made 2.11 per cent of all malignant tumors found at autopsy and were found in 1.89 per cent of all cases in which operation was done on the biliary tract. There was no appreciable change in the incidence of this tumor at autopsy during the period studied (1918-1948) at the Los Angeles County Hospital. Sixty-eight per cent of the cases were in females. A particularly high incidence was noted in Mexican females.Upper abdominal pain, loss of weight, nausea and vomiting, jaundice, and palpable mass or enlarged liver were the most common clinical features. Approximately one-third of the patients in whom the lesion was found at operation and one-fifth of all the patients whose records were studied had a history of chronic gallbladder disease.All but two of the 38 patients operated on were dead or had clinical recurrence within two years. One was alive and well 12 years after cholecystectomy.The most common gross appearance, particularly at autopsy, was a large tumor mass replacing the gallbladder and radiating to nearby organs, particularly the liver. In about one-third of the cases the tumor was grossly limited to the gallbladder. Polypoid tumors occurred in only about 10 per cent of the cases and most of the tumors were diffusely growing adenocarcinoma. Perforation appeared in nine cases, usually with fistula to the gastrointestinal tract. All of the tumors were histologically adenocarcinoma, usually of simple glandular structure. No purely squamous cell growth occurred.Gallstones were found in 79.8 per cent of the cases.     

Negative predictive value of pulmonary fine needle aspiration cytology.

Percutaneous fine needle aspiration (FNA) for cytologic examination is an accepted and reliable technique for diagnosing neoplasia. It is less useful, however, in excluding that diagnosis. We performed a retrospective analysis of a consecutive series of pulmonary FNA specimens at Memorial Sloan-Kettering Cancer Center to determine the negative predictive value (NPV) of this technique in the setting of a large cancer hospital. Fifty-seven cases were studied. Six cases (10.5%) were initially diagnosed as negative but acellular and were not further analyzed, and another 6 were lost to follow-up; 24 cases (42.1%) were subsequently confirmed negative by tissue or clinical follow-up, and 21 of the cases (36.8%) were proven positive for malignancy by repeat aspiration, tissue diagnosis or clinical means. Of these 21 cases, 1 was misdiagnosed as negative, and review demonstrated malignant cells on the slide; 3 of the 21 cases should have been initially rejected as unsatisfactory, and 18 of the 21 contained material sufficient for a cytologic diagnosis but not representative of the lesion. On follow-up the false-negative cases showed primary adenocarcinoma, epidermoid carcinoma, lymphoma, metastatic breast carcinoma and metastatic sarcoma. Specific benign diagnoses were made on the initial cytologic preparation in three cases. No benign tumors were found. The NPV in our series was 53.3%, comparable to values in previous reports. The single largest factor contributing to false-negative diagnoses is sampling error, and we recommend repeat aspiration when no specific benign diagnosis is made. In addition, we suggest that the diagnoses of negative for malignant cells and insufficient for diagnosis or acellular be considered separate categories.     

Carcinoembryonic antigen content in fine needle aspirates of the lung. A diagnostic adjunct to cytology.

Carcinoembryonic Antigen (CEA) was measured in 59 consecutive fine needle aspirates (FNAs) of the lung from 58 patients to determine if the CEA content would enhance the sensitivity of the cytologic diagnosis. Twenty-eight males and 30 females with tumors 1-40 cm in diameter were studied. Final diagnoses were correlated with the clinical history, radiologic studies, tissue (when available) and follow-up. Image-guided FNAs were performed by radiologists using a 22-gauge Chiba needle and 20-mL syringe with one to four passes per specimen. Cytologic examination included rapid assessment in the radiology suite and a final diagnosis in 24 hours. CEA was measured by enzyme immunoassay using monoclonal antibody. Nine benign aspirates and 50 malignant aspirates were diagnosed. The sensitivity of cytology was 86% and specificity, 100%. Using 5 ng/mL as the cutoff, the sensitivity of CEA for malignant aspirates was 50% and specificity, 90%. The combined sensitivity of CEA and cytology was 95%. The mean CEA in malignant aspirates was 131 ng/mL and in benign aspirates, 2.41. The highest mean CEA was seen in adenocarcinoma, 402.6 ng/mL. Lower CEA content was seen in epidermoid carcinoma (58.6 ng/mL), large cell carcinoma (8.09), oat cell carcinoma, metastatic carcinoma of the kidney and breast, thymoma and lymphoma (each less than 1 ng/mL). Elevated CEA alone was diagnostic in two aspirates of bronchioloalveolar carcinoma; carcinoma with an unknown primary source, three; and large cell carcinoma, one. The adjunctive use of CEA in FNAs of the lung enhances the sensitivity of the cytologic diagnosis.     

Combined carcinoembryonic antigen and cytopathologic examination in ascites

OBJECTIVE: To investigate use of the combined carcinoembryonic antigen (CEA) test and cytopathologic examination to improve the diagnosis of neoplastic vs. nonneoplastic ascites. STUDY DESIGN: The tests were performed prospectively on 130 patients with ascites whose effusions were submitted for cytologic examination. RESULTS: Sixty-seven patients had epithelial tumors, and the cytologic examination was positive in 39 (58.2%). The CEA level was > or = 11.0 ng/mL in 36 patients (53.73%). CEA was helpful in the diagnosis in 18 cases, increasing to 57 (85.07%) the number of positive diagnoses. Eight samples of nonepithelial tumors had low levels of CEA. In 55 patients with nonneoplasic ascites the cytopathologic examination was negative, but the CEA assay was > 11.0 ng/mL in 3 patients. CONCLUSION: The cytopathologic examination should be performed in all cases, and the CEA assay should be done in suspected cases of epithelial neoplasia in which the cytologic examination was negative, there was uncertainty about the histologic type of neoplasia, or a diagnosis of nonepithelial neoplasia was made. When ascitic leukocytosis or hepatic failure is present, one should be cautious in interpreting the CEA assay because false positivity can occur.     

Flow cytometric analysis of human lung cancer. Correlation with histologic type and stage

DNA ploidy and cell-cycle characteristics of 65 operable lung cancers (41 adenocarcinomas, 19 epidermoid carcinomas, 3 large-cell carcinomas and 2 small-cell carcinomas) were analyzed using flow cytometry. Eighty percent of the tumors were aneuploid. The mean DNA index was lower in epidermoid than in adenocarcinoma. In adenocarcinoma, a low DNA index was correlated with early-stage disease; no correlation between DNA index and stage was observed in the other cell types. The %S-phase cells was highest in two cases of undifferentiated large-cell carcinoma and lowest in adenocarcinoma. The RNA index was increased approximately two-fold in all cell types. Longer follow-ups will be required to establish any correlation between the cell kinetic measurements reported here and survival times.     

Neurophysins as markers of vasopressin and oxytocin release. A study in carcinoma of the lung

Vasopressin-neurophysin (hNpI), oxytocin-neurophysin (hNpII) and blood osmolality were assayed before any treatment in basal conditions in 35 patients suffering from lung carcinoma (20 oat cell, 6 undifferentiated and 9 well-differentiated epidermoid cell carcinomas). Plasma vasopressin (antidiuretic hormone, ADH) was also assayed in 7 of the 20 patients suffering from oat cell carcinoma. We found a close correlation (r = 0.98) between plasma ADH and hNpI levels in the 7 patients. Further, hNpI was elevated in 13 out of the 20 oat cell carcinoma patients and in none of the epidermoid-cell carcinoma group; however, searching for an abnormality of ADH secretion as reflected by a detectable plasma hNpI level together with subnormal plasma osmolality revealed 2 additional positive results in the oat cell carcinoma group, and 2 out of the 6 in the undifferentiated-cell carcinoma group. hNpII was increased together with an increase in hNpI in 6 oat cell carcinoma patients; it was specifically increased without hNpI increment in 2 additional oat cell carcinoma patients and in 2 patients of the undifferentiated-cell carcinoma group (different from the 2 positive for the hNpI-osmolality ratio). hNpI and hNpII were normal in the majority of undifferentiated and all of the differentiated epidermoid-cell carcinoma group. Hence, our results show that simultaneous measurements of hNpI, hNpII, and blood osmolality could detect abnormalities in 17 out of 20 oat cell carcinoma patients, in 4 of the 9 undifferentiated-cell carcinoma patients, but in none of the differentiated epidermoid-cell carcinoma patients, suggesting that the neurophysin assay can be used for the early detection of oat cell- and possibly other neuroendocrine-derived carcinomas.