This study was undertaken to develop an automated analytic system for recognition of atypical cells derived from dysplasia and carcinoma in situ of the cervix. Routine, cervical smears stained with Papanicolaou method were used. The cell samples were classified into two different cell patterns, i.e. parabasal dysplastic cells, one with finely granular chromatin and the other with coarsely granular chromatin. These cells were measured by means of Zeiss's SMP-05 connected on line to PDP 12 computer. A measuring spot of 1.0×1.0 micron was used and all measurements were carried out at a wavelength 550 nm. Digitized mirror images of individual cells were first printed out and paper punch tapes of absorbance data from each cell samples were concurrently prepared (paper tape data I). The analytic system for cell recognition developed by the research group of the Tokyo Metropolitan Detection Center of Cancer was composed of following three systems system of preanalysis for HITAC 10 II (A), system for contour line analysis (B) and system for graph analysis (C). System A is one which converts absorbance data measured with PDP 12 computer into paper tape data II for HITAC 10 II. Those converted data were introduced into system B. Area of the inside of LOOP, RATIO=length around LOOP (L) squared/area (5), INSUM=total of absorbance value within LOOP, INNO=number of spot within LOOP, MIN=minimum absorbance value within LOOP, MAX=maximum absorbance value within LOOP, XO, YO=barycentric co-ordinates of LOOP and SLOPE=average slope of absorbance value etc. are calculated and printed out as basic data. These basic data were also preserved in paper tape data III as original data prepared by contour line analysis. When these paper tape data were introduced into system C, graphs of AREA, SLOPE and RATIO were made, and selected data are further printed out. These data are easy to understand, because most important parameters of basic data mentioned above are only picked up. In case of decision and identification of cell pattern, area of the nucleus, width of the nuclear border and number of intranuclear granula were used as important parameters. On the basis of those parameters the indication graph for decision of cell pattern and histologic typing of lesions was drawn. As a result of this investigation the relation between both points was recognized, that there is an intimate relation between indication of cell pattern and histologic diagnosis of lesions. We intend to develop the study on complete automation of the analysis system, reduction of calculating times and printing out of indication graphs of the relation between cell pattern and histologic diagnosis of lesions.
Using the AUTO-CYTO-SCREENER, which has been developed in the Center for Adult Diseases, Osaka, the smears collected in mass examinations for cervical cancer by the self-collection have been screened automatically and experimentally. This apparatus, having a color TV camera as a sensor, can entirely automatically screen vaginal smears stained by the Feulgen reaction, and distinguish squamous cancer cells from benign cells by measuring nuclear size and stain concentration. However, this apparatus still cannot differentiate exactly a single cancer cell from a neutrophile and/or bacteria clump. To overcome this difficulty, a special method for the preparation of smears in which cells are dispersed and uniformly distributed was devised. Furthermore, it is desirable to get as many samples as possible which consist of dispersed squamous cells only, not including many leukocytes and/or bacteria. For this purpose, childbearing-age women were instructed to collect smears in the middle of the menstrual cycle, and postmenopausal women were requested to take Mestranol before collecting samples. Up to now, 2, 070 such specimens have been prepared and examined for suitability for automatic screening. Of these samples, 63.1% were found to be suitable or rather suitable specimens for automatic screening. Mestranol medication was found especially effective in making the specimens suitable for automatic screening. In addition, if it were possible to choose only the examinees without any subjective symptoms, about 3/4 of the samples given would be suitable specimens for automatic screening. In conclusion, for putting the automatic cytoscreening apparatus to practical use, monolayered and well-dispersed smears should be made. To this end, it is imperative that we adopt special methods for specimen preparation. And also, it seems necessary to get as many samples as possible, including dispersed squamous cells only by means of selecting examinees without any subjective symptoms, appointing the best time for sampling or controling the nature of samples of sex hormone medication.
Abnormalities of sex chromatin bodies such as multiplication or disappearance in cancerization have ever been reported. The present paper is to confirm the evidence and to investigate the entity of the abnormalities. For demonstration of sex chromatins, 0.1% thionin buffered solution (pH 5.7) after 1N HCL treatment was used. The positve rate of sex chromatin positive nuclei was 25.1±6.4% in normal cases, 22.7±4.7% in Dysplasia low degree, 18.1±4.5% in Dysplasia high degree, 15.9±6.1% in carcinoma in situ and 11.3±4.5% in invasive carcinoma. Although double or triple sex chromatins appeared in abnormal cells (1 to 2%). The incidence of double sex chromatin was 0% in normal cases, 2.7% in dysplasia, 12.2% in carcinoma in situ and 16.2% in invasive carcinoma. There was no relation between sex chromatin size and nuclear size, but a significant interrelation between the sex chromatin size and DNA content in normal cases.
A cytomorphological study of malignant cells in the ascites of ovarian cancer was made. Cytological specimens were obtained from the patients with ovarian carcinoma at the operation. The results of this study are as follows. 1. The shape and size of cellular clusters were helpful in identifying the histopathologic patterns to some degree. 2. In serous cystadenocarcinoma, isolated and scattered malignant cells or cellular clusters of various sizes were frequent, and cellular clusters mostly appeared like muscats. The presence of cilia or psamomma bodies in ascites strongly suggested that the primary site was serous cystadenocarcinoma of the ovary. 3. In Krukenberg tumors, malignant signet ring cells were found occasionally. Generally, cytoplasmas were scanty in Krukenberg tumors, but abundant in mucinous cystadenocarcinoma. 4. PAS staining was not helpful in identifying the tumor type.
A study of small cells with pyknosis-like nuclei in vaginal smears was made. Cytological specimens were obtained from the uterine cervix of patients (atrophic meno pause, severe dysplasia, carcinoma in situ and early in vasive carcinoma). In early invasive carcinoma, eosinophilic cells with pyknosis-like nuclei were found in all types of squamous epithel cells. But small cells (under 20μE in diameter) occupied the most part of eosinophilic cells with pyknosis-like nuclei in atrophic menopause. Polychromasia in small cells with pyknosis -like nuclei was most striking in early invasive carcinoma. Generally, few eosinophilic cells with pyknosis -like nuclei were found in severe dysplasia or carcinoma in situ
Renal carcinomas often metastasize to the endobronchial wall with no symptoms, so they are liable to be mistaken for primary lung tumors. Three cases of lung metastasis of renal carcinomas gave the following characteristic cytological indings: abundant cytoplasm with numerous vacuoles, eccentric but round nuclei and prominent nucleoli. Differentiation of lung metastasis of renal carcinoma from primary lung tumors especially “clear cell” carcinoma or benign clear cell tumor of the lung is discussed.
Cytological diagnoses on aspirated materials of lymph nodes were compared with histological diagnoses made on the excised nodes in 208 cases. Cytological diagnosis of malignant lymphoma was made in 40 of 62 finally diagnosed cases of malignant lymphoma, 2 of 79 cases of metastatic cancer, 2 of 12 cases of atypical hyperplasia or so-called reticulosis, and 1 of 55 cases of non-malignant diseases. There were some variations in accuracy of cytologic diagnosis of malignant lymphomas by the histologic types. The highest accuracy was found in lymphosarcoma, the second highest in reticulum cell sarcoma and Hodgkin's disease, and the lowest in follicular lymphoma. Lymphosarcoma and reticulum cell sarcoma were predominantly monocellular, but in occasional cases of reticulum cell sarcoma, sarcoma cells were not very dominant. In these cases the differential cell counts of lymph node aspirates may be useful for cytologic diagnosis. In reticulum cell sarcoma, cells resembling immunoblasts or immature reticulum cells accounted for more than 30% of all the cells. However, immature reticulum cells made up less than 30% of the cells in the other types of malignant lymphomas and other diseases. Follicular lymphoma was of mixed cell type, composed of lymphocytic cells and immature reticulum cells in variable proportions. In some cases lymphocytic cells had irregular nuclei and cleaved appearances. The cytologic pattern of Hodgkin's disease was pleomorphic, consisting of a variable number of lymphocytes, granulocytes, and plasma cells, in addition to the characteristic mononuclear Hodgkin's cells or multinucleated Sternberv-Reed cells.
Bile cytology has been performed in 38 cases (71 specimens) during the past 4 years. Most of the specimens (78.9%) were taken from PTC drainage. Cancer cells were cytologically positive in 13 (34.2%) of the 38 cases and 22 (31.0%) out of the 71 specimens. Twelve of the 13 cases were adenocarcinomas and a case, a squamous cell carcinoma. Six out of 9 cases of pancreatic head carcinoma, and 6 out of 9 cases of biliary tract carcinoma were diagnosed by cytologic examination. Bile cytology of PTC drainage is one of the useful diagnostic tools for detection of pancreatic, biliary tract and duodenal carcinoma.
Clinically, it is often difficult to distinguish between a mucous carcinoma and a benign lesion of the breast. We have performed cytologic examinations of 6 cases of mucous carcinoma by aspiration cytology and of 2 cases by the use of nipple secretion (Both materials were used in one case) Six out of 7 cases were cytologically positive, that is, cytologic examination was helpful in diagnosing these tumors. All 7 cases were resected and histologically confirmed as mucous carcinoma. Among them, 4 cases were pure mucous carcinoma and those remaining were mixed with other types of carcinoma. As the result of observation of cellular features of cytologic materials of these tumors, tumor cells most often appeared in solid clusters with clear evidence of distinct cell boundaries. The cytoplasm of tumor cells was abundant, anisokaryosis was slight, nuclei were usually small (8-10μ) and nuclear atypia was slight. A lesser degree of cellular atypism was generally found in pure mucous carcinoma compared with the mixed group. The periodic-acid-Schiff reaction was performed by the use of cytologic material of 4 out of 7 cases. The cytologic picture of tumor cells surrounded by amorphous mucin was characteristic in 3 cases. Futhermore, signet-ring type cells with PAS-positive substances were rarely observed.
Methyl-green (MG) has been used for histochemical and cytochemical demonstration of DNA; however, it has been reported that this staining reaction requires the presence of highly polymeric DNA. The following results of our study show that the polymerization of DNA is not always necessary for the reaction. 1) MG staining solution is easily influenced by the pH, and is very stable at around pH 4.0. Intensity of the reaction of MG goes with the ascent of pH when the starting solution is fresh. 2) In the DNase-enzymatic digestion test, MG stain has thesame effect as the Feulgen reaction. MG staining also stains not only pure DNA but RNA. 3) The cytoplasm of well preserved cells is stained with MG, and this result suggests that the MG staining reaction is not influenced by the degree of polymerization of DNA. 4) MG stain is available for measuring the DNA content of the nuclei under some conditions.
Adenosquamous carcinoma in situ (AIS +CIS) of the uterine cervix is a rare lesion. However, the lesion may be overlooked due to the well-established cytologic findings of CIS component, whereas AIS has not been studied thoroughly. The cyto- and histo-pathologies of our case have been described in comparison with those in the literature cases. Our cytologic observations include clusterizations of cells with occasional acinous or palisading arrangement, abundant lacy or vacuolized cytoplasm with pleomorphism and a small but marked nucleolus in a fine granular nucleus. When these findings are observed in addition to typical CIS cells, the possibility of AIS +CIS should be estimated. Literature review is also made concerning the incidence, relation to pregnancy, opinions for diagnostic criteria and the histogenesis of the tumor.
One case of clear cell adenocarcinoma of the uterine cervix is reported in this paper. Detailed analysis of cytologic specimens was performed, and we found somedifferent cytologic features from that of endocervical adenocarcinoma. Case Report. A forty-eight-year old woman, G. 7P.2, with complaints of vaginal bleeding and low abdominal tenderness, visited our clinic in 1974. This patient's case was diagnosed as myomata uteri and cervical erosion. Leukoplakia, punctation, and mosaic were found on colposcopic examination. Two different types of atypical cells were observed on cytologic examination, one suggesting adenocarcinoma and the other, carcinoma in situ of the uterine cervix. Histologic examination (punch biopsy, cone biopsy, and D & C) revealed early invasive squamous cell carcinoma, mesonephric adenocarcinoma of the uterine cervix, and clear cell adenocarcinoma of the endometrium. Radical hysterectomy, followed by chemotherapy and postoperative radiation, was performed, and the patient was followed up in the out-patient clinic. But she died of pulmonary metastasis and cancerous peritonitis 16 months after the operation. Histologic Findings The uterine corpus, child head sized, was elastic and hard. On the cross-section were found microcystic lesions, including bloody mucinous materials in the myometrium and cervical stroma. Bilateral ovaries were normal in appearance. Microscopically, early invasive squamous cell carcinoma was found in the uterine cervix, and tubular adenocarcinoma, suggesting hobnail pattern in some part, was also found in the deep cervical stroma which was situated at 10-12 o'clock and 2-7 o'clock positions of the cervix. Solid clear cell adenocarcinoma was also found in the myometrium penetrating in to the endometrium. These two types of adenocarcinoma had transitional parts in the upper cervical area. Right internal iliac, external iliac, and It parametral lymphnodes were involved by the solid clear cell adenocarcinoma. Staining reaction of these adenocarcinoma was weakly positive with P.A.S. and mucicarmin, but negative with.Sudan-III. Mitosis was rarely found. We thought that these tumors were mesonephric adenocarcinomas arising from the uterine cervix, involving the corpus and lymphnodes, and coexisting with early invasive squamous cell carcinoma of the uterine cervix. Cytologic Features Cervical swab smears and touch smears of the hysterectomized specimen were analysed. In the cervical swab smear, many glandular atypical cells were detected, arranged in sheet or isolated (70%). Tumor diathesis was seen. These cells had more abundant cytoplasm, finerchromatin pattern, and more macronucleoli than endocervical adenocarcinoma cells. In the touch smears, tumor diathesis was not seen, and polygonal cytoplasm and irregular chromatin pattern were predominant. Discussion Many mesonephric adenocarcinomas of the ovaries have been reported since the first description of Schiller's mesonephroma. Mesonephric remnant or cyst in several parts of the female genital tract were often found; therefore, the extraovarian mesonephric adenocarcinoma may be expected to be more often found. But mesonephric adenocarcinoma of the uterine cervix was rarely reported. Schiller pointed out the glomerulus-like structure as diagnostic criterion of mesonephroma. But Saphir, not agreeing to it, suggested clear cell patterns of the tumor as diagnostic criteria. Many authors used the term of clear cell adenocarcinoma and that of mesonephric adenocarcinoma synonymously. But some of adenocarcinomas and squamous cell carcinomas suggested the clear cell pattern; therefore, only the clear cell adenocarcinoma, suggesting hobnail pattern, peg-like pattern or glomerulus-like structure, should be diagnosed as mesonephric adenocarcinoma.
A seventy-one year old female complained of metrorrhagia, which was diagnosed as tuberculosis of the uterine cervix by cytological examination. Recently, tuberculosis of the cervix is rare, and thought to be a manifestation of the female genital tuberculosis. Since the report by Coleman in 1969 on cytological findings of cervical tuberculosis, there have been few reports in this field. In this report, we have described both cytological and histological findings in a case of cervical tuberculosis. In conclusion, the presence of epithelioid cells in the smear strongly suggests the possibility of tuberculosis regardless of the presence of Langhans' giant cells.
It is considered infrequent to detect cancer cells in the vaginal or cervical smear in a case of ovarian cancer. Cancer cells were detected in the cervical smear and endometrial aspiration smear from a 60-year-old woman, who had last menstrual period 12 years ago. She complained of lower abdominal pain occasionally for about 1 year. Ovarian origin was suspected from morphology of the cancer cells which were extremely large, had prominent nucleoli, and had partially vacuolated cytoplasm. Histopathological examination of the resected uterus, ovaries, and omentum showed the presence of papillary adenocarcinoma in bilateral ovaries, and metastasis was found in omentum and widespread in peritoneal surface and bowels, but not in the endometrium. Psammoma body which was not observed in the smear was proved in the histological section of the ovary. It was interpreted that the cancer cells in the cervical smear were carried through the tube and uterine cavity into the cervix from the ovary itself or peritoneal cavity. Cytohormonal study of this patient did not show a high estrogenic activity.
A case of multiple myeloma of the rib and thoracic vertebrae in a 75-year-old man is presented, together with the results of cytologic and light microscopic examinations. The specimens were obtained by needle aspiration biopsy from the bone marrow of the sternum and the lesion of the rib. The M-G stain of the specimen obtained from the bone marrow revealed that the tumor cells had the features of myeloma cells. The cytological findings of myeloma cells stained by the method of Papanicolaou have rarely been reported. The examination of the smears after Papanicolaou stain of the lesion of the rib in the present case revealed the following features ; the cells were round to oval; the cytoplasma was faintly stained by light green and had granules; the nuclei were all eccentric, and mostly had coarse granules and prominent nucleoli.
An autopsy case of bronchial carcinoid tumor is reported. The case terminated fatally after a rapid clinical course of four months since its onset. The carcinoid tumor was metastasized to many lymph snodes and many organs such as the liver, adrenals, vertebrae and so forth. One of the metastatic tumor nodes in the liver was ruptured into the peritoneal cavity. The tumor cells were first detected in the peritoneal fluid but not in the sputum. In cytologic preparations from the ascites both characteristics of oat cell carcinoma and typical carcinoid tumor were observed. Rosette formation and flat arrangement were the distinguishing findings. The N/C ratio of the tumor cells was slightly large, but was smaller than that of oat cell carcinoma. The nuclei were 8-20 (25) microns in diameter and ovoid or spindle in shape. Moderate atypism of the nuclei was noted, and the tumor was judged as malignant. The nuclear chromatin was increased, and showed fine to coarse granular patterns. A few small nucleolei were also observed. The tumor cannot be definitely diagnosed as an oat cell carcinoma from these cytological findings described above, but appears more malignant variant in carcinoid tumors which are potentially malignant. This tumor may then be considered to be an intermediate type or a transitional type between both tumors. The cytoplasm of the tumor cells is slightly positive by the Grimelius reaction. Most tumor cells are electromicroscopically found to have a few neurosecretory granules. These findings indicate that the tumor has originated from Kultschitzky cells of the bronchus, and there is an intimate relationship between carcinoid tumor and oat cell carcinoma.