Scanning electron microscopic observations were performed to study the ultrastructure of the surface of precancerous lesions and invasive cancers of the uterine cervix.Specimens were collected from patients who visited the Gynecologic Cancer Clinic of Keio University Hospital. 1.Normal squamous epithelium: Thin polygonal cells were arranged regularly in the shape of pavement and the nuclear excrescences were observed in the center of the cells.Numerous, short and irregular villous processes were seen on the surface, and irregular runs of small grooves on the back side of the cells.The surface of the underlying cells was covered by a network of cytoplasmic microridges. 2.Metaplastic epithelium: It was composed of round to elipsoid shaped cells varying slightly in size.The surface was covered by short, rounded, villiform proje ctions.The intercellular spaces were dilated, and well developed intercellular bridges noted. 3.Dysplasia: Cells with increased nucleocytoplasmic ratio were arranged irregularly and the overlapping of cells was noted.The villiform projections of most cells were shorter, and had rounded tips, as compared with those of normal squamous epithelium. 4.Carcinoma in situ: Relatively uniform and round cells were packed together, exhibiting a somewhat monotonous picture.However, the arrangement of the cells was irregular, and the overlapping of the cells was apparent.The microvilli on the surface of the cells were much shorter in size and rounder in shape, and were almost granular. 5.Early invasive carcinoma: It was mainly composed of round cells as seen in carcinoma in situ, but mixed with those cells were differentiated malignant cells having slender cytoplasmic processes. 6.Invasive carcinoma: Cells of markedly irregular sizes and irregular shapes were seen overlapping in the way of house tiles.Various kinds of bizarreshaped cells were observed on the surface of the tumor. The surface of most cells was rather granular.
The ultrastructures of the surfaces of normal and neoplastic cells of the ectocervix were observed with a scanning electron microscope. Specimens were obtained by wedge biopsy from the ectocervical area which had been carefully examined by colposcopy, then fixed in 2.5% glutaraldehyde and 1% osmium tetraoxide solution, dehydrated with etha nol series, and dried by the critical point drying method using CO2.A part of the specimens was used for optical microscopic observation. The surfaces of normal squamous epithelial cells were covered with microvilli, such as those described by Shinglton et al.in their transmission electron microscopic studies. Cells of carcinoma in situ, and early invasive cancer differed significantly from normal cells.The indivi dual cells were rounded and irregularly arranged.The surfaces of cancer cells were covered closely and packed with a soft microvillus-like structure. The area of epithelium that corresponded to the colposcopic“Leukoplakia”was covered with large flat cells, which had neither microvilli nor microridges on the surface. No qualitative differences in the surface structure between“basement”and“field”have been recognized.
The following conclusions were drawn from the microspectrophotometric studies of DNA contents of various lesions of the uterine cervix.Measurements were made of the DNA contents of the specimens as follows: normal squamous epithelium (two cases);low high and equivocal dysplasias (eight cases);carcinoma in situ (three cases);invasive cancer that had carcinoma in situ lesions just above the cancer nestles (three cases). 1.In the cases of normal squamous epithelium, the predominance of diploid DNA value was characteristic of its mode, and its distribution was confined between diploid and tetraploid levels. 2.The cases of low dysplasia gave different histog rams of the layers.At the basal layer, 8 n or greater DNA values were recognized, while such irregularities were diminished as the layers went up, and finally in the fourth layer the whole histogram was confined mostly between diploid and tetraploid range. 3.In the cases of high dysplasia, the distribution of DNA was ranged further wider, spreading beyond 8n. The gradual narrowing of histograms as observed in the upper layers of the cases of mild dysplasia was absent here.However, in the case where modes were recognizable, they tended towards the lower value as the layer went up. 4.In the cases of equivocal dysplasia, histograms showed a broader range of DNA distribution, some including as much as 10n or even larger values.There was no discrepancy between the respective layers.The mode, if any, stayed on a single definite value, regar dless of layers. 5.The cases of carcinoma in situ tended to show a wider range of DNA distribution than the cases of equivocal dysplasia did.The second or the third layer gave a broader histogram than the basal layer and sometimes the fourth layer had the widest DNA distribution.And such a trend was also recognized that the values of DNA became higher as the layers went up. 6.Comparison made between the histograms of carcinoma in situ lesions that had cancer nestles developed underneath and those of carcinoma in situ lesions without invasive cancer nestles demonstrated that there was no significant difference between them. 7.From these data the following conclusions were drawn: high dysplasia and equivocal dysplasia were precancerous lesions, and carcinoma in situ, malignant lesions. 8.Comparison between the histograms of carcinoma in situ lesions and cancer nestles taken from one tissue demonstrated a clear difference in their patterns: in other words, the histograms of the invasive cancer tend to have the mode in hyperdiploid or hypertetra ploid.It appears that this may be attributed to the possible presence of stem cells in cancer of the uterine cervix as suggested by Makino.
Vaginal and endometrial cytologic examinations were done in Women who were on one of two kinds of oralcontraceptives. 1) No malignant changes were found by these cytologic examinations. 2) Endocrinologically, the vaginal smears resembled those of early pregnant women, and the endometrial smears resembled those of the early secetory phase of normal endometriums.The mean eosinophilic cell index of these vaginal smears was 15%, and the standard deviation, 17%.The mean karyopyknotic index of these vaginal smears was 13%, and the standard devia tion, 22%. 3) The method of simple endometrial smear test which I routinely use is also described.
From the results of scraping smear cytology perfor med with a total of 366 cases of either neoplastic or nonneoplastic ovaries, the cytological pictures of various types of ovarian malignancies are presented herewith. The author is of the opinion that prior to perform resection in a doubtful case of ovarian tumor, either frozen section histology or scraping smear cytology should be carried. At the same time, the author presents his“5-class-classification”of the ovarian scraping smear.
The presence of neutrophilic leukocytes with thin thread-like nuclear excrescences was studied by use of peripheral blood smears from 80 patients of gastric cancer and 40 of gastric ulcer. The rate of leukocytes with thin nuclear excrescen ces was significantly higher in patients of gastric cancer than in patients of gastric ulcer.This finding was noted even in patients of early cancer, and more striking in patients of advanced cancer.These leuko cytes were decreased after curative resection of gastric cancer.Patients of gastric cancer who had many such leukocytes survived shorter than those who fewer such leukocytes.
During the 9 years from 1963 to 1971, 5, 296 times of gastric cytology and 1, 972 times of endoscopic biopsy were carried out at National Cancer Center Hospital. Techniques empolied for the collection of cells were gastric lavage, abrasive balloon, endoscopic lavage, imprint smears of biopsy or surgical materials. Results of cytology and biopsy were reported by 5 classes and classes III to V were calculated as positive. In malignant cases, its diagnosis was confirmed by surgery or autopsy or made by biopsy and the patients had died without autopsy.However, in to two thirds of benign cases their diagnosis was based only on biopsy or clinical follow-up by radiology and endoscopy. Positive rate for malignant cases was 71.1% in lavage method, 75.0% in imprint smear and 87.3% in biopsy. Falsepositive reports were encountered in 2.8%, 5.7% and 0.1% of benign cases respectively. Very low rate of fals-epositives is the most charact eristic feature of biopsy. The positive rate in early cancers was 56.4% in lavage methad, 74.8% in imprint smear and 92.9% in biopsy.The lavage method, which may collect cells from all parts of gastric lining, is an ideal way for cytologic diagnosis of gastric cancer.However its accuracy decreases considerably when the size of a cancerous lesion becomes smaller than 3 cm.By radiology or endoscopy, detection of a focus smaller than 3 cm is not so difficult.Accordingly lavage cytology for screening of gastric malignancy was discarded gradually.In imprint smear and biopsy, on the contrary, small size of a lesion scarcely affect their accuracy.Somewhat unfavourable results in imprint smears and biopsy for cancers located at the proximal part of the stomach were caused by technical difficulty of endoscopy.However, this difficulty had been eliminated recently by the improvement of instruments.For cancer of this part, positive rate was relatively high in lavage method. Comparatively high rate of false-positives in imprint smear was considered to have been resulted partly by our poor knowledge about fresh cells excised by biopsy.Imprint smear cytology was performed as an adjuvant to biopsy.Both of them were positive in 76.8%, only imprint cytology in 3.7% and both were negative in 7.6% of malignant cases.In cytology, positive rate was somewhat low in the signet-ring cell type cancer and in biopsy it was slightly low in the tubulary adenocarcinoma. In malignant lymphoma the result of cytology and biopsy was lower than that in carcinoma, and in leiomyosarcoma both were negative except one case of positive biopsy.In cases of borderline atypical epithelium, lavage method was usually negative, but imprint smear was positive in 33.3% and biopsy in 3.3%.In biopsy, 90.0% of them were reported as borderline cases. Much criticism was centered to the Papanicolou's classification for expression of cytologic diagnosis. We have adoptted 5 classes to indicate our confidence about malignant neature of cells on a specimen.By lavage method, for example, the percentage of malig nant cases among those which were reported as class I was 8.4%, 19.5% among class II, 67.9% among class III, 88.4% among class IV and 99.2% among class V. We believe that a report by 5 classes is a suitable way to inform an impression of a cytologist to the clinicians concerned. Usefullness of cytology or biopsy for diagnosis of gastric cancer was investigated by a comparison of their results to clinical diagnosis when the examination was indicated.The number of malignant case which were detected among those who were diagnosed as bengin by barium meal and/or endoscopy were 24 by lavage method, 34 by imprint smear and 50 by biopsy during these 9 years.In conclusion, superiority of biopsy for the diagnosis of gastric malignancy was unquestionable.However cytologic examination by imprint smear is indispensable as an adjuvant to it.
The cytologic morphology was studied with the patients of pancreatic, duodenal and biliary cancer and the histopathologic bases of the cancer cells were analysed. Duodenal-drainage smears of the patients were found to contain two different types of cancer cells or cancer cell groups;One is characteristic with crowded cancer cell groups consisting of mutnal included cancer cell group, mucus producing cancer cells, less prominent nucleoli, and granular agglutinations of chromatins.These cancer cells are chiefly exfoliated from papillary cancer proliferating in the intraductal space of the pancreaticoduodenal biliary tracts.The other is an anaplastic cancer cell freely separated or a small cancer cell group showing loose cohesion.In most cases, enlarged nucleoli, increased chromatin contents and stiffened nuclear membrane were observed. Thesespecimens of anaplastic cancer cells were obtained from anaplastic tubular or medullar types of the cancer proliferating mainly into the surrounding tissues around the ducts.
Aspiration cytology was performed in ten patientsof renal tumors, consisting of seven patients of renalcell carcinoma and three of pelvic transitional cellcarcinoma. Specimens from8of them (80%) were adequate forcytological diagnosis. Because these two tumor groupshad specific cytological features, respectively, therenal tumors were easily differentiated. Cytologicalspecimens obtained by open aspiration biopsy and bydirect stamping of the tumors further verified thesefindings. Urinary sediments were examined cytologically in13patients of renal tumors, comprising nine patientsof renal cell carcinoma and four of pelvic transitionalcell carcinoma. Atypical cells were detected only in6of them (46%). In this study, percutaneous aspiration cytodiagnosiswas proved to be a valuable method to differentiaterenal malignancies preoperatively. Fat stain with Oil Red-O was applied to the cytological specimens obtained by aspiration biopsy andurinary sediments. Oil Red-O positive cytoplasmicgranules were observed in 10 of 17 specimens fromthe patients of renal cell carcinoma and 1 of 11 specimens from the patients of pelvic transitional cellcarcinoma. The positive specimen from the lattergroup was a smear of urinary sediment from a patient of renal pelvic tumor. This fact suggests that thefat stain is not specific for renal cell carcinoma only.
In cases of testicular tumor, seminoma and embryonal carcinoma were seen more frequently than othertypes.But seminoma and embryonal carcinoma differed significantly in clinical findings. Specimens forthe cytological study were obtained by imprintingand aspiration of tumorous testis or metastatic lymphnodes from 7 patients with seminoma and 4 patients with embryonal carcinoma. Cytological findings onseminoma and embryonal carcinoma are as follows: Seminoma: Tumor cells are monotonous and noncohesive. The cells are polygonal, and their cytoplasmic rims are distinct. Nuclei are oval or round, with thin and smooth rims as well as delicate chromatin networks. Prominent round nucleoli are locatedin the center. Cytoplasm is clear and stained lightgreen in perinuclear region by the Pap. method, whileit either is homogeneously light blue or shows marginal vacuolization by the M-G method. Embryonal Carcinoma: Tumor cells are in closeclumps. Shapes of cells are irregular, they are fibrous, spindleshaped or tadpoleshaped at times. The cytoplasmic rims are indistinct.Nuclei are irregular in shape or oval with thin rims and fine granular chromatins. Nucleoli are irregularly shaped or round.Cytoplasms are foamy and stained light green by the Pap. method, and light blue or amphophilic by the M-Gmethod. They are in many cases vacuolated.
1. A forty-two year old woman showed chronic inflammatory process and Michaelis-Gutmann bodiesunder the urinary sediment cytology, thus a diagnosisof malakoplakia of urinary bladder was made. Laterthis diagnosis was confirmed by the histologicalsection. 2. This paper presents the case of urinary tractmalakoplakia diagnosed by the urinary sediment cytology, which is the third evidence available in thebibliography already published.
Diagnostic courses of two cases of carcinomas of thegallbladder which were preoperatiively diagnosed mainly by exfoliative cytology as primary keratinizedsquamous cell carcinoma of the gallbladder are brieflydescribed. One of the two cases was diagnosed on thebasis of cytologic features of a specimen obtainedfrom the gallbladder by aspiration biopsy under thedirectvision control with laparoscope, and the othercase on the same features of a specimen biopsiedfrom the duodenum under duodenoscopic direct vision. The cytologic findings of smears of the two casesclosely resembled each other. The detailed examination of smears revealed that in both cases atypicalepithelial cells had the following features characteristic of keratinized squamous cell carcinoma: variouscell shapes from oval or polygonal to quite irregularand bizarre forms, various cell sizes ranging betweenthe sizes of parabasal type and superficial type ofnormal squamous cell, dense opaque orangeophiliccytoplasma very frequently showing a laminar structure and/or perinuclear halo, nuclear pyknosis andkaryorrhexis or karyolysis and so forth.
Three cases of cancer of extra-genital origin werediagnosed by gynecologic smear tests during 1973, while 3, 753 materials were examined at Kitasato universityhospital. The occurrence rate of this diagnosis wasone in every 1, 251 cases. Case 1. A sixty-two y. o. female complained of hema-turia and dysuria. The corpus uteri was the size ofsmall fist, including the bladder. The cytology out of the uterine cavity revealed a group of cells which hada large amount of greenish cytoplasm with cornersand placed their nucleus on one side. Those roundnuclei appeared hyperchromatic with one or more marked nucleoli. Bizarre solitary cells including the snakeshaped ones with enlarged eccentric nuclei were alsoscattered. Adenomatous cell clusters were sporadi-cally seen. The findings led to a diagnosis of high-graded transitional cell carcinoma. Case 2. A thirty-one y. o. patient was admitted with c. c. of palpitation, and noted to have anemia as well asa dark red spot on the posterior fornix and an irregularhard tumor beneath the normal uterus.Smear of the fornix showed a thick cluster of highcolumnar cells withpalisade-like arrangement. The abundant cytoplasmspreserved vacuoles. Their malignant nuclei retainedthe thickened membrane and a large nucleolus. Thiscase was diagnosed as adenocarcinoma tubulare of thecaecum in addition to the detection of G-I series.Case 3. A 41 y. o. patient with c. c. of metrorrhagiahad a history of gastrectomy due to stomach cancer 2 years previously. The uterine corpus was the sizeof small fist, and movable. The right ovary was enlar-ged and of small hen-egg size. All smears from theuterine cavity and cervix revealed scattered malignantsignet-ring cells. Surgical specimen showed infiltratingadenocarcinoma mucocellurare onto the ovary, and theuterine cervix and corpus. The significance of cancer of extra-genital originwhich emerged out of routine gynecologic smear sampleshas been discussed and the literature reviewed bothcytologically and statistically.
Two cases of clear cell carcinoma, namely, a metastasis of hypernephroma to the vagina in a 51 year oldwoman and a clear cell carcinoma of the cervix in a 69 year old woman, are presented, together with theresults of cytologic and light microscopic examinations. Metastasis of hypernephroma to the vagina is extremely rare and has seldom been reported. Clear cell carcinoma of the vagina and the cervix isalso rare, but recent reports have indicated that thistumor has been increasing in association with intrauterine exposure to diethylstilbestrol. Histologically, ithas been occasionally reported that there was a closeresemblance between a focus of hypernephroma andthat of primary clear cell carcinoma of the femalegenital tracts, which could be distinguished only byelectron microscopic study. In the two cases presentedherein, however, no such close resemblance was found. There has been no successful attempt to make aspecific diagnosis of clear cell carcinoma as opposedto other types of adenocarcinoma by exfoliated cytology. We could neither find any cytological characteristics of clear cell carcinoma in both of the twocases.