Neuroblastomas of suprarenal glands and Wilms'tumors are relatively common malignant tumorsin children. These tumors often grow into largeretroperitoneal tumors and their clinical diagnosticdifferentiation is rather difficult. Diagnostic cytologymay be effective for differential diagnosis on thesecases. The cytological examinations of aspirationbiopsy smears and tuch smears prepared from 3patients with neuroblastomas and 2 Wilms' tumorswere performed, and the following results fordifferential cytodiagnosis were obtained. 1. Epithelial cell clusters were much more frequently found in Wilms' tumors than in neuroblastomas. 2. Cytoplasms of some Wilms' tumor cells withepithelial arrangement were stained deep blue bythe may-Giemsa's method. 3. Neuroblastoma cells had marked anisocytosisand were smaller in size than Wilmis' tumor cells. 4. Nuclei of neuroblastoma cells were most frequently composed of densely distributed chromatinwith fine or coarse granular structure, and those of Wilms' tumor cells were composed of moderatelyincreased chromatin with fine reticular or granularpattern. 5. Nucleoli of neurolastoma cells were inrregularin shape, small in size and 2 to 4 in number. Tooseof Wilms' tumor cells were round, small and 1 or2 in namber, or hardly observable. By the cytological findings described above, it was possible to distinguisn neuroblastomas from Wilms'tumors in diagnostic cytology.
The purpose of this paper is to examine whetherthe cytological fine needle aspiration biopsy is useful, or not, to make settled diagnosis of diseasewith goiter. To study this possibility, both histological and cytological examinations were made onthe same case. A new instrument for the aspiration biopsy wasused in this study. The instrument is devised soas to be fitted, without any aseptic precaution, witha 10ml syringe, which is usually used in a clinic. Afine needle, 6 cm in length and 0.7mm in outerdiameter, is attached to the syringe. Using the instrument, the aspiration biopsy wasapplied to 123 patients with goiters, the histologicalclassification of which consisted of 25 carcinomas, 42 adenomas, 10 simple cysts, 25 Graves' diseases, 15 Hashimoto's diseases, 5 adenomatous goiters andone subacute thyroiditis. The conclusions of this study are as follow: 1. In 121 of 123 examined cases, aspirated cellswere sufficient for diagnosis. Both the remainingcases histologically showed “adenocarcinoma withmassive fibrosis and scant tumor cells”. 2. No complication of hemorrhage, infection ortumor cell spreading was accompanied by this procedure. 3. The smear from thyroid carcinoma was usually abundant in cancer cells. Frequently, they ga- thered to form characteristic clusters of cells, which were large in size and showed irregular anddense crowding of cells. Although the cancer cellsaspirated from the thyroid also showed the generalfeatures of malignant cells, it was peculiar to theformers that many of their nuclei had rather finegranuloreticular patterns of chromatin structure. 4. Adenoma cells considerably differed in morphology from cancer cells, and cytological diagnosisof benign adenoma was not so difficult. 5. The diagnosis of cyst was determined byaspiration of massive fluid and observation of characteristic foamy cells. 6. There were medium-sized to small clustersin the aspiration smears of Graves' diseases, all ofwhich had fallen into euthyroidism with treatments.The epithelial cells, of which the clusters consisted, were slight in atipism, large in size and regular in arrangement. 7. Cytological diagnosis of Hashimoto's diseasewas based upon a large number of lymphocytes anda few degenerative epithelial cells. 8. Some characteristic, multinucleated giantcells were aspirated from a goiter of subacute thyroiditis. 9. Based upon such cytological features of aspiration smears from various kinds of goiters asmentioned above, cyto-diagnosis was retrospectivelytried again on the blind specimens of 123 examinedcases. In 21 out of 25 thyroid cancers, cyto-diagnosis of cancer was settled, in one case cancerwas suspected, in one a diagnosis of benign adenoma was made, and in 2 the cells were too insufficiently aspirated to an exact cyto-diagnosis. In addition, there was one false-positive
It was discussed last year about “cytologicalcriteria of breast cancer for the purpose of massscreening” in the paper vol.10.1. pp.9-22 of thisJournal. Main points of previous paper were as follows; 1) Over 20μ of nuclear diameter. 2) Over 5μ of nucleolar diameter. 3) Over 5 nucleoli in onenucleus. 4) The largest nuclear diameter have 2times as the smallest one in one cell cluster. (Marked anisokaryosis.) These 4 findings mean positivecytology. In this report, it is discussed that how many casescome under these criterias. 50 cases of breast cancer (Papillo-tubular carcinoma 28 cases, Medullary tubular carcinoma 11 cases, Scirrhous carcinoma 10 cases and 1 case of adenoidcystic carcinoma.) are examined. Aspiration smear preparations are stained by MayGiemsa method, and tissue preparation of operationmaterials are stained by H.E. method. Results are as follows. 1) Smear preparation which keep the cells ofover 20μ nuclear diameter are found in 41cases of all cases. (80%) 2) Smear preparation which keep the cells ofover 5μ nucleolar diameter are found in 25cases. (50%) 3) Smear preparation which keep the cells ofnumerous (over 5) nucleoli found in 18 cases. (36%) 4) Anisokaryosis over 2 times in one cell clusterwhich keep the clear chromatin structure found in 34 cases. (68%) So it may be clear that the first criteria for massscreening is large nucleus (over 20μ). 80% of allcases of breast cancer may be checked by this finding. Another cases (20%) may be diagnosed by otherfindines. But a few cases of non-malignant disease havelarge nucleus (over 20μ)., Benign cells with largenucleus have well stained wide cytoplasma and scattered solitary not clumped.
Origin of so-called “Foam cell” of mammarygland are studied cytologically: Papanicolaou staining, May-Giemsa staining, Peroxydase reaction, Berline blue reaction, Test of phagocitic activity bycarbon particle method. Results are as follows: (1) 57.1% of foam cells are positive for Peroxydase reaction. (2) 56.8% of foam cells include leucocytes asdegenerated shape in their cytoplasma. (3) Almost all foam cells are positive for Berlinblue reaction. (4) 79.0% of foam cells have distinct phagocitic activity by means of carbon particle method. Peroxydase granule in cytoplasma of foam cellare recognized accompanied with degenerated leucocytes nuclei. If, Peroxydase granules are only recognized incytoplasma without leucocytes nucleus, degeneratednuclei of leucocytes are found attached to the cyto-plasmic borders. Carbon particles are found scattered by belongto the reticular structure of cytoplasma. It may be said that the almost foam cells are origina ted by histiocytes.
Studies on the automated cytoscreening by therole-plastic film taking the place of the hithertoused conventional glass slide, especially on thegraphing system, were carried out. In this experimental study, there were two kindsof problem. The first investigation was about thesurface analysis of synthetic polymers, and thesecond was about the fluid cytological specimens. The results of studies are following 1. The polyester-tape which is a specially prepared and optically transparent plastic tape wasused as a role-film. 2. Improvements on the surface of film were forthe film to be coated with one of the synthetic polymers among the silicon groups as thesurface modifire. Improvements (1) It could wet the surface of film much better to be down the surface-tension. (2) It gave the good spread of cells on theobservation through a microscope to givethe wettability on the film. (3) The perfect cell-fixing on the surface offilm was gotten by the wettability. 3. In a 100% cell-fixing on the surface of film, we used a fluid adhesive (C.M.C) and a surface active agents (N-310). 4. In the cellular material of the cytology, wefound that the most concentrated suspensionof cells is 5-10volum-percent under thebasic experiment of the AH-13 and Y-S cells. 5. On the cellular material of the self-irrigationsmear, especially Tenjin-type, you should usethe sediments of continer which let alonestanding more than two hours to get themost concentrated suspension. 6. In such sediments, there are almost fully cancer cells for diagnosis.
1. A cervical cone biopsy was carried out with Masubuchi type cervical Cone Cutter on 403 casesand its result was compared with that of punchbiopsy, removed material, and cytology, in orderto asses diagnostic value of cone biopsy. 2. A more advanced malignant process wasrecognized in 32.8% of 403 cone biopsy materialsafter punch biopsy and in 5.8% of the removedmaterial after cone biopsy. 3. There was a high incidence of residual cervical lesion after cone biopsy and residual carcinoma in situ was present in 61.0%. 4. There were 59 patients in these 403 caseswho showed suspicious or positive punch biopsy.Of these 59, 24 were reported as showing carcinoma in situ and 10 as early invasive carcinoma in theircone biopsy specimens. 5. Cone biopsy of the cervix is the most reliabletechnique for the dlagnosis of cervica lesion. Therewere on complications from cone biopsy by thetrachelotom.
Papanicolaou's classification in prevalent use asthe criteria of cytologic diagnosis for female genitalorgans is ambiguous enough to pose many problems.In an attempt to find differences between cells withdifferent types of lesion, i.e. benign change, dysplasiaand carcinoma, cytologic findings were dividedinto features of cell group, cytoplasm and nucleususing cytologic maps and slides worked out by someof the leading investigators in this field, to examineaccording to the descriptions for the maps or ourprivate plan of criteria for the slides whether therewas any difference in the number of features betweendifferent types of lesion. 1. According to the descriptions for the cytologicmaps, there was no substantial different types oflesion with respect to features of cytoplasm. As tonuclear features, nowever, 2 or less factors werefound described for benign lesion, 3 factors for amajority of dysplastic cells and 3 or more factorsfor a majority of carcinomatous cells. 2. In studying the slides, our private plan of criteria was relied on, which was worked out withreference to existing books on cytologic diagnosisand which embraced 4 factors for cell group features, 4 factors for cytoplastic features and 20 factorsfor nuclear features. 3. In the slides there was no substantial difference both as to cell group and cytoplasmic features.A difinite difference was noted, in the number ofnuclear features:2 or less factors for benign lesionand mild dysplasia, 3 factors for a majority ofseverely dysplastic cells and 4 or more factors forcarcinomatous cells. 4. From these results, specimens with one or morefactors for cell group and cytoplasmic features wereregarded as abnormal, on the assumption that normal nucleus denotes 1 or less, abnormal nucleus 2or more, atypical nucleus 3 or more and malignantnucleus 4 or more factors for nuclear features. 5. Baced on this assumption, our tentative planof definition of Papanicolaou's classification wasworked out taking into consideration the relativenumber of abnormal cells to be examined.
In an attempt to improve the diagnostic accuracyfor uterine cancer, especially endometrial carcinoma, an apparatus was developed to facilitate desquamation of endometrial cells by ultrasonic waves. Experimental results thereby obtained wereas follows: 1) As a basic experiment, this apparatus wasused on 15 cases of removed uterus, under thecondition of 40W, 28kHz, and oscillator amplitudeof 10μm. This was found to give satisfactory collection of the cells and no untoward effect on theuterine wall. 2) This method was applied as clinical diagnosison 30 cases and anticipated result was obtained, there being no discomfort of pain, hemorrhage, orother side effects.
With a view to improving the diagnosis of thoracicdiseasis, the author has devised a new-developedneedle of percutaneous aspiration biopsy, and usedit in 230 cases of thoracic disease, thus testing itsvalue as a diagnostic tool for especially, pulmonarycarcinoma. Our needle is finer than Silverman's.The outer cylinder is 1mm in diameter, and theinner cylinder 0.8mm, at the tip of which hasseveral fine protrusions. These were found tosample cells successfully. Among of 230 casesdiagnosis was established by operation or biopsy in145 cases, including 96 cases of pulmonary carcinoma.Malignant cells were noted in 99 (48.6%) of 117 malignant thoracic lesions. The rate of diagnosisin 96 cases of pulmonary carcinoma studiedby puncture was 48.9% by sputum smears, 47.6% by TV-brushing, whereas as high as 48.4% by ourmethod, when applied to small tumors 2cm or less, our method has given a much higher positive rateof 75%. Complications have included hemoptysis in 2.4%, and pneumothorax in 4.0%. In all 17 cases (6.9%) they have been slight. Since our puncturemethod is relative safe, the author believes that itshould be wedely used in dignosing peripheralpulmonary lesions. Finally, morphological comparison has been made between free cancer cells insputum and those collected by the puncture methodThe author has found that the former, being detachedfree cells, have been subject to degeneration in theprocess of expectoration, whereas the latter, collecteddirect from the tumor, are fresh cells showing littledegeneration. Especially, marked differences havebeen noted between them in intranuclear structure.
Tumor ce llswere detected in stained smears with May-Grünwald-Giemsa of aspiration materials of bonemarrow in one hundred and seventy-six patientswith various malignancies other than leukemias.Specimens from primary or metastatic tumors werediagnosed histologically as adenocarcinoma in 37, anaplastic carcinoma in 13 and squamous cell carcinomain 1, respectively. Characteristics of scattering of tumor cells onmarrow smears were observed as entirely diffuse inleukemia and other hematopoietic malignancies, diffuse with pair cell or smaller clumps of cells inanaplastic carcinoma as well as that in neuroblastoma, retinoblastoma, keratotic type of squamouscell carcinoma or mucocellular type of adenocarcinomatubulare, ca. clumping like in common typeof adenocarcinoma tubulare, that with irregular arranged, mostly firmly connected cell accumulationespecially in scirrhus type of adenocarcinoma tubulare, and that with sheet like double or triple cell layers in non-keratotic type of squamous cell carcinoma, respectively. Cells of anaplastic carcinoma, neuroblastoma or retinoblastoma were shown as homogeneous, strong or weak basophilic cytoplasm, unif ormlydistributed chromatin net-works with veryfine cr relatively fine reticular appearances, hardly visible or very smallnucleoli and increased N-Cratio such as in leukemic cells. Differential cytodiagnosis not only between anaplastic carcinoma andneuroblastoma, retinoblastoma, but hematopoieticmalignancies is infrequently difficult without close careful cytological observations, Cytomorphologicalfindings of mucocellular type of adenocarcinoma tubulare were characterized by abundant cytoplasmawith unhomogeneous basophility by various sized unstained vesicles, deformed or irregular shaped nucleuswith condensed coarse chromatin net-works and invisible nucleoli. Cells of scirrhus type of adenocarcinoma tubularewere observed in irregular, not smoothly discriminated cell margin, increased N-C ratio, and finereticular chromatin net-works of thicker appearancesof nucleus, but less than that of anaplastic carcinoma and more than that of adenocarcinoma tubulare. Of non-keratotic type of squamous cell carcinoma, they were seen in short or long spindle or ellipsoid shaped cytoplasm with unhomogeneous weakbasophilic appearances, slightly ellipsoidal nucleuswith relatively fine, uniformly reticular chromatinnet-works and with hardly visible nucleoli. On contrary to non-keratotic type of squamous cell carcinoma, cytomorphological characteristics of its keratotic type which was obtained from metastatic bonylesion, were seen in very irregular shaped cytoplasmwith pale light blue colared and homogenous appearances like painting, irregular shaped nucleus withmarkedly condensed chromatin net-works. For theadvances in clinical practice and research in cancerproblem, cytodiagnosis must be more and more togo into details.
Aspiration smear of lymph node has been an important method to study of lymphadenopathies. Theprocedure is simpl and of great value for diagnosisof metastatic cancer and sarcoma in lymph node, malignant lymphoma, inflammation of lymph nodeand reticulosis etc. The technique of aspiration smear is used theapparatus consisting of an 22 gauge needle attachedto a 10ml record syringe (Franzén's method modification). No anesthesia is used. Smear are stained May-Grünwald-Giemsa, PAS and Papanicolaou's method. The cytological findings in lymph node smear arepresented. Cytological comparisons between primarylesion and lymph node metastasis in cancer casesare studied. A lymph node aspiration may bl repeated at interval furnishing a guide to the effect of treatment, and used rapid diagnosis during operation and diagnosis of primary lesion in malignant tumor.
Cytologic examination on 1715 cases (52 cases ofcancer and 1663 cases of non-cancer) was executedin Miyagiken Seijinbyo Center (Adult Disease Center of Miyagi Prefecture). Cytologic examination of nipple discharge wascarried out on 1099 cases. The results were positivein 2 cases, suspicious in 1 case and negative in 11 cases of all 14 cases of cancer. Of all 1085 cases ofnon-cancer were 1084 cases negative, one case suspicious and no positive. The results of aspiration smear cytology on 740 cases were positive in 35 cases, suspicious in 3 casesand negative in 7 cases of 45 cases of cancer andnegative 693 cases, suspicious in 2 cases and nopositive of 695 cases of non-cancer. The causes of the “false negative” in aspirationsmear cytology are chiefly due to the unsuited sitefor puncture and secondly due to the misjudgementof cytology. The “false positive” is evidently dueto misjudged cytology. Careful regard should be paid to following fiveitems as the diagnostic criteria for the malignantcells in aspiration smear cytology. 1. decrease of intercellular connection. 2. excessively and asymmetrically piled figureof cells and nuclei. 3. fusion of cells, the cellular inclusion andnuclear deformation. 4. enlarged cells (especially with the increasednuclear cytoplasmic ratio). 5. some dense distribution of distinctly granulated chromatin.
Aspiration smears of the prostate obtained by Franzén needle, as we already reported, providemore reliable diagnosis of prostatic cancer thanhistological biopsy specimens. Successful results require some care in operatingaspiration procedures and reading cells on the slide. To obtain good specimens, negative pressure on theaspiration syringe must be continued for at least 30 seconds. And 2 or 3 slides must be made, untillwhite granules are found on it. In the microscopicexamination, attention should be payed not to individual cells, but to clustered cells, since it is oneof the particular findings of prostatic cancer thatmany clustered cells, which, indeed, have diagnosticproperties, can be aspirated. Nevertheless, one should observe specimens obtained from cancer patients treated with estrogens with particular care, because they show similar cytological trends to benign features. Discrimination of prostatic cancer from other metastatic malignancies can be delivered more easily byexamination of acid phosphatase activity in the aspirate.
Sixty-three cases of Lung Cancer were studied by brushing smears. We found a much higher frequencyof metaplasia in Squamous cell Ca. than inother types. The frequency of metaplasia in thecytologic groups of Squamous cell Ca. was 80% Metaplastic cells exhibit a round or rarely polygonaloutline. The Cytoplasma is eosinophillic, and the Nucleus is round and regular with. fine chromatinnetwork. These findings makee asy to distinguish itfrom Cancer cell, but it's very difficult to establichthe differential diagnosis between atypical metaplastic cell and Squamous cell Carcinoma. It mayprove possible to diagnose a pulmonary Cancer bymeans of a careful follow-up with cytologic examination. The radiation effect on the Cancer can be recognized in smears. But definite classification ofirradiated benign cells and malignant ones is occasionally impossible.
Metaplasia of the respiratory epithelium mayoccur in two forms: squamous metaplasia of thebronchial epithelium and adenomatous metaplasia of the alveolar epithelium. Squamous metaplasia is the replacement of thebronchial mucosa by squamous epithelium, and theresult of abnormal multiplication of basal cells. Adenomatous metaplasia is the replacement of thealveolar lining by cuboidal cells, and the result ofabnormal proliferation of type B alveolar epithelialcells. Differentiation of small anaplastic cancer cellsfrom basal cells of the bronchial epithelium issummarized in Table 1. Differentiation of squamous cancer cells fromsquamous cells originating in squamous metaplasiais summarized in Table 2. Differentiation of adenocarcinoma cells from adenomatous cells originating in adenomatous metaplasia is summarized in Table 3.
Regeneration is the common plenomenon for restoring of ulcer and erosion on the superficial layer of the polyp or the chronic gastritis. These cells on the regeneration epithelium showsometimes very active figurs which are sometimesdifficult of differentiate from cancer cells. During last 4 years, cytological false positive caseswere 12 among 569 of gastric ulcer and 3 out of 60 in cases of gasting benign polyp. They comprised of 2.1% in gastric ulcer casesand 5% in gastric benign polyp. I compared these cells of fals epositive cases withearly gastric cytologically. In conclusioin, incidence of abnormal shape ofnucleus like as identations etc. under 15μ, a in diameter is higher in cancer cellsthan that of regenrative epithelial cells, and cells with many round or ovaln uclei without so remarkable abnormality of shape are seen rather in benign cases. Cells with increased nuclear-cytoplasmic ratio, hyperchromasia of nucleus with fine granular chromatin over 15μ in diameter is seen in rather malignant cases. And also remarkable abnormality ofnucleus with granularly dotted chromatin is malignant. These findings are different with Papanicolaou and May-Grünwald-Giemsa staining in details, so carefulobservation based on characteristics of these staining is necessary. On the other hand, cells exfoliated from atypicalepithelium of the stomach called as border line lesion show slender cytoplasm with slender nucleus, slightly increased nuclear-cytoplasmic ratio, and slight atypism of nucleus with close superimposition. But some cases in this group show cytologicalpositive result. Among them, small early gastriccancer is seen in some cases. So the cytological examinaton is important forthe clinical analysis of atypical epithelium of thestomach.
The process of squamous metaplasia in the uterinecervix might be discussed more properly in contextwith inflammation, regeneration or repair for itsinitiation may be related to the inflammatory process. On the other hand, squamous metaplasia maybe initiated by non-inflammatory stimuli such aschronic irritation of a physical nature or by chemicalirritants. Althorgh the process of squamous metaplasia is extremely common in the uterine cervix, itis not usually regarded as a change which necessarilyantedates development of cancer. However, some of the chemical stimuli which initiate squamous metaplasia are also capable of inducing cancer in theuterine cervix of the experimental animals. Squamous metaplasia can be arbitrarily subdividedinto: 1. reserve cell hyperplasia, 2. immature squamous metaplasia, 3. premature squamous metaplasia and 4. mature squamous metaplasia. The cellularchanges which can be related to each of them havebeen presented.
To clarify a process of regeneration in the cervicalepithelia, special attention was accorded to thenature of mitotic cells. The regenerative process ofthe squamous epithelium was followed after chemicalor mechanical injuries to the cervix. The mechanism of regeneration and metaplasia of the columnar epithelium was studied by means of cryotherapy. Regeneration of both epithelia was performedby active proliferation of their epithelial cells. Priorto proliferation, these well differentiated cells undergo dedifferentiation from functional phase to proliferative phase. The morphological characteristics ofthe dedfferentiated cells were shown as those of regenerative cells. Some problems on proliferation anddifferentiation of the epithelial cells were discussedin connection with subepithelial connective tissue. Mitotic form of the columnar cells and the originof the reserve cells were also discussed.
An autopsy case of malignant hemangioendothe-lioma arising from the right atrium of the heart ispresented.The patient is 30-year-old house-wife. Final coursewas about 7 months. Clinical symptoms were painalong lumbar verteburae, ascites, and hemopericar-dium. Hematologically severe anemia, marked leuko-erythroid reaction, severe thrombocytopenia and hypofibrinogenemia were proved. About one month before death, non-epithelial tumor cells were detected in left pleural fluid. Theirnuclei are oval or round and have fine granularchromatin, one or several nucleoli and thin nuclearmembranes. Cytoplasm stains thin, greensh-blue. Their shape is polymorphous but in most partsspindle-shaped. Occasionaly, several tumor cells formrosette-like arrangement. Surgically tumor of theright atrium was resected but she died from pulmonary complication. Autopsy diagnosis was malignant hemangioendothelioma with hematopoiesis intra tumori of the heart. Metastasis were found onthe pericardium, pleurae, in lungs, bone marrows, spleen, liver, kidneys, ovaries, right adrenal, duramata, thymus and lymphnodes. Cytological diagnosis is very useful for diagnosisof malignant tumors arising from hearts.
1. A case of fimbrial carcinoma of right fallopiantube in a 65 year old patient is reported. 2. Only 42 Cares of tubular carcinoma have beenreported in Japan up to 1969. 3. The present case demonstrated papillary adenocarcinomahistologically and no mucin productionis present. 4. Premortem cytology of pleural effusion demonstratedclusters of markedly atypical, vacuolatedcells and diagnosed as class V. The cells reveald nomucin. 5. Morphorogy of tumor cells observed in thepleural effusion and in the tisue appears slightlydifferent. It is considered that mucin production istubular carcinoma is very little in histological aswell as in cytological preparation. 6. In case of adeno-carcinoma demonstrated inpleural effusion and ascites cytology, possibility offallopian tube carcinoma should be considered infemale patients.