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A 14-month-old infant had a classical Wilms' tumor of the left kidney and subsequently developed a tumor showing predominantly mature mesenchymal elements and lack of cellular atypia in the right kidney. His father had classical Wilms' tumor of the left kidney. The various possibilities regarding the precise nature and mechanism of the development of the tumor in the right kidney are discussed. The similarities and the differences between this tumor and congenital mesoblastic nephroma are noted. The possible relation of chemotherapy to mesenchymal differentiation and maturation in Wilms' tumor is considered. The possibility of an unusual, histologically benign, mesenchymal variant in the spectrum of infantile nephroblastic neoplasia is also suggested.

Tumors of smooth muscle cell origin of the upper respiratory tract are extremely rare, especially of the larynx, and less than twenty cases have been reported in literature. Survey of literature also revealed that there was no case of laryngeal leiomyoma reported in Japan.A 47-year-old, otherwise healthy man visited our clinic with complaint of slight laryngeal discomfort. Indirect laryngoscopr showed a semiglobular tumor-like swelling of the right false cord. Direct laryngoscopy was performed under general anethesia and the tumor, lying in the submucotic region of the false cord, was enucleated totally. It was a firm, smooth and round tumor with a diameter of 8mm. Microscopic examination revealed that the tumor was a vascular leiomyoma most likely arising from the smooth muscle of the submucous small blood vessels of the right false cord. No cellular atypia or mitosis was observed. The patient is well without recurrence eleven months after operation.

Dysplastic changes in the mucosa of stomach or of colo-rectum are defined as those having following histological features: 1) cellular atypia, 2) abnormal differentiation and 3) disorganised mucosal architecture: and the changes are graded into mild-, moderate- and severe dysplasia, according to agreements done at W.H.O.-Meeting in London in 1978.

In a prevalence study of oral mucosal lesions carried out 1973–1974, 20,333 individuals, aged 15 years or above were examined. Chronic lip fissures were found in 110 people, corresponding to a prevalence rate of 0.57%. The fissures were more prevalent among males (0.92%) than females (0.20%) and more prevalent in the age groups below 45 years than in those above. In 1976 – 1978, 7 patients with annoying, chronic lip fissures were treated by excision. The mean observation time was 26 months (range 17–33 months). No recurrences of the fissures were observed. Histologic examination revealed a chronic inflammatory non-specific infiltrate and no dysplasia or cellular atypia was seen.

62 cases of adenoid cystic carcinoma (ACC) arising in major and minor salivary glands were studied. Factors which appeared to influence the clinical course included: 1) histologic pattern, 2) presence or absence of tumor on the surgical lines of excision, 3) site, 4) size of primary lesion, 5) presence or absence of tumor in lymph nodes, and 6) degree of cellular atypia. On histologic examination, these neoplasms were classified according to their predominant histologic pattern (tubular, cribriform or solid). Recurrences have been seen in 59% of patients with ACC demonstrating a predominantly “tubular” pattern, as compared to 89% for the “cribriform” lesions and 100% for the “solid” neoplasms. Of patients who eventually died of tumor, those having “tubular” predominant lesions had the longest course (average 9 years before death, in contrast to 8 years for the “cribriform” and 5 years for the “solid” tumors). Our findings suggest that the “tubular” predominant pattern has the best prognosis and represents the best differentiated histologic form of ACC. In contrast, the “solid” pattern is the least differentiated and is associated with the worst prognosis. The predominantly “cribriform” lesions appear to lie between the other two forms both clinically and histologically.

In 585 cases with primary cutaneous stage I malignant melanoma (294 disease-free for at least 5 yr, 291 with later metastases) prognostic parameters were examined. The most effective proved to be tumor thickness and mitotic activity, particularly when combined as a prognostic index. Furthermore, vascular invasion, ulceration in thick tumors (thickness greater than or equal to 3.0 mm), severe cellular atypia, the small, lymphocytic-like cell type and the absence of an inflammatory reaction were closely associated with a high rate of metastatic cases. Less relevant prognostic factors were the level of invasion, sex, site, tumor breadth, clinical diameters and infiltrative growth. Tumor type, age, duration and an adjacent nevocellular nevus were not significantly associated with the occurrence of later metastases. Furthermore, the growth-type (exo- or endophytic) did not have a bearing on the prognosis.

A series of 112 children with nephroblastoma were analyzed with respect to clinical factors, structure, tumor size, and treatment. The statistical method employed was a multivariate analysis. Histologically, the tumors were classified according to their degree of tissue differentiation and cellular atypia as three different types. Histologic type, stage, and irradiation had a positive correlation to prognosis. Age of the patient, tumor size, method of treatment, and year of admission did not influence the prognosis significantly.

The cytologic and histologic diagnoses have been compared in 83 non-treated bladder tumours and 26 recurrent tumours after surgical treatment, involving a total of 99 patients. A histologic grading into five groups, based on the cellular characteristics of the tumour, has been used. A further 96 cases with no tumour of the urinary tract have been examined cytologically. Generally speaking the conformity is good. It should be possible to reduce the number of unsatisfactory smears and of indecisive cytologic diagnoses through increased experience and improved techniques. The cytologic diagnosis is useful in the prognostic evaluation of individual cases, particularly respecting tumours with histologically moderate cellular atypia (grade II), which appear to constitute a biologically heterogenous group.The material does not yet permit an appraisal of the accuracy of cytology in the follow-up after radiation treatment. It is quite evident, however, that a recurrence can be detected cytologically long before it...

One hundred cervical cone biopsies and the subsequent hysterectomized uteri were studied. In each case the diagnosis of carcinoma in situ (CIS) was established on the cone biopsy. The lesions were classified by 4 criteria: the degree of cellular atypia, linear, circumferential and glandular extension. The patient's age and the presence or absence of residual tumor in the hysterectomy specimen were recorded. In about half of the cases the lesions were fairly well differentiated and were located at the squamocolumnar area without extension beyond 2 cervical quadrants and the superficial endocervical glands. The other half presented highly anaplastic and extensive in situ carcinomas. These patients were older and all 17 cases of residual tumor in this series occurred in this group. The most important factors in determining the presence of residual tumor are the degree of linear and circumferential extension. The grading of CIS on cone biopsy according to this method may effect a re-evaluation of the indications for hysterectomy in which the cone biopsy itself may constitute final therapy.

Introduction: The grading of transitional cell cancer of the bladder as proposed by Bergkvist et al. 1963, is based on the grade of cellular atypia in tissue specimens. To get more information on the cytological parameters of this grading the correlation of the data obtained from cytophotometric measurements of tumor cell nuclei with the results of histological grading was studied. Material and Methods: Imprint preparations from biopsy specimens of 21 bladder tumors were fixed immediately in 96% ethanol; after Feulgen staining according to Swift (1955), the DNA content of tumor cell nuclei was determined by an integrating microdensitometer (GN 2, Barr & Stroud, Glasgow, Scotland). The DNA distribution pattern of the tumor cell population as obtained by cytophotometry was analyzed, regarding the DNA stem line ( Seidel and Sandritter , 1963) and the scattering of individual DNA values. Furthermore the mean DNA content, standard deviation and variation coefficient of the populations were calculated and a χ 2 -test performed. The data obtained from this procedure were compared with the results of the histological grading as described above.

The radiation therapy of keratoacanthomas in fifty-five patients treated between 1976 and 1986 using orthovoltage X rays (contact and soft X ray therapy) is reported. The total dose delivered was 40 Gy by means of twice weekly fractions of 4 Gy each in 52 cases, and 60 Gy by twice weekly fractions of 5 Gy each in 3 cases with notable cellular atypia. In all cases we obtained complete regression of the lesions irradiated within 1 month after the termination of radiotherapy. So far we have not had any recurrences. The cosmetic result was always satisfactory. We should like to point out the association between keratoacanthomas and a second malignancy in two cases. The role of radiotherapy in the treatment of keratoacanthomas is discussed and re-confirmed, in relation to the literature data.

A special modification of the double-contrast method of colon examination has been used routinely in Malmo for the past 13 years, and more than 36,000 examinations have been made. The method has been extremely valuable in the early diagnosis of ulcerative colitis, regional colitis, and polyps. Polypoid tumors were found in 3,101 (12.5%) of 24,783 patients. This figure correlated with the incidence of polypoid tumors found at autopsy. Certain characteristics are useful in determining the malignancy of a polyp and criteria for operative intervention. On the basis of x-ray findings, 1,062 patients were operated upon. In 204 cases, polyps were definitely malignant, and 855 showed a more or less marked cellular atypia. The importance of the diagnosis of so-called sentinel polyps and of the routine follow-up examinations after surgery is stressed.

Instillation of refined formaldehyde solution in the bladders of 11 patients with massive life-threatening hematuria secondary to cyclophosphamide therapy and radiation cystitis has been effective in hemostasis. Cystitis has been induced in mice by the use of cyclophosphamide. Histologic changes in the bladder were cellular atypia, telangiectasia, and fibrosis of the detrusor muscle. No histologic changes resulted from the instillation of refined formaldehyde solution in the bladders of these mice. These experiments indicate that instillation of refined formaldehyde solution in the bladder is a simple, safe, and, when properly used, life-saving method of bladder hemostasis.

Hypophyses of four groups of 50 female rats (F0—nulliparous, F0—multiparous, F1—standard diet, and F1—low protein) were examined by light microscopy and immunocytochemistry by the avidin-biotin complex method. In pituitary glands of rats fed a low protein diet, the incidence of neoplasms of the pars distalis, the number of multifocal tumors, and the degree of neoplastic cellular atypia were significantly reduced. Pituitary adenomata in rats fed a low protein diet also caused significantly less brain compression at the time of necropsy than in rats fed a standard diet. All but two neoplastic foci from the 83 tumors stained for prolactin, and 14 of these also stained for growth hormone. No differences were found in the frequency of hemorrhagic or solid patterns of tumor. These findings may reflect a reduction in pituitary tumor initiation, promotion, and/or progression in rats fed a low protein diet.

A patient was seen with a pigmented plaque of malignant melanoma and multiple surrounding skin-colored dermal and subcutaneous nodules. Histologic examination showed that the pigmented lesion represented the balloon cell variant of malignant melanoma and that the adjacent nodules were local metastasic lesions. This case, along with a review of the literature, illustrates that many balloon cell melanomas show only mild cellular atypia and minimal mitotic figures, although the tumor has a malignant course, with local or distant metastasis. A careful examination of all the sections of the balloon cell tumor is important.

Two cases of carcinoid tumours of the larynx are described. One was histologically a typical carcinoid whilst the other showed cellular atypia, numerous mitoses and invasion of the surrounding tissues. Both were argyrophilic but not argentaffin positive whilst electron microscopy demonstrated the presence of neurosecretory granules and amyloid. The previous literature on these rare tumours of the larynx is reviewed.

The histopathological appearance of proliferative squamous lesions removed from the skin of iatrogenically immunosuppressed patients differs subtly from that of classical malignant and premalignant epidermal lesions. The majority of cases show 'Bowenoid' changes with a marked degree of cellular atypia including characteristic multinucleate cells.

A case of polypoid endobronchial fibroma which led to subsegmental atelectasis in a 45-year-old male is reported. The diagnosis was made preoperatively by roentgenograp hic examination, bronchoscopy and biopsy. A lobectomy of the right middle lobe was performed. The polypoid tumor occupied the lumen of the subsegmental bronchus of the right middle lobe and had a stalk. Histologically, the tumor was composed mostly of collagen bundles with scant spindle-shaped fibroblastic cells and a myxomatous component. There was neither cellular atypia nor mitotic figures nor infiltration of small round cells. The diagnosis was pulmonary fibroma of the endobronchial type. To date, 66 cases of pulmonary fibroma have been reported in the English literature since 1880; 21 of these were polypoid endobronchial fibroma. Only five cases of polypoid endobronchial fibroma including this case have been reported in the Japanese literature.

A woman is presented in whom cellular atypia and signs of abnormal fibrinolysis in a jet washing caused persistent suspicion of malignancy after a benign curettage. Nearly 3 years later a fallopian tube carcinoma was diagnosed. The value of determination of biological markers of neoplasia in addition to the cytologic interpretation of uterine fluid is emphasized.

The Arias-Stella reaction (hyperplastic changes of the endometrial epithelium associated with cellular atypia) may be seen in uterine or extra-uterine pregnancies. I found a modified Arias-Stella reaction in paratubal epithelial cells. The fallopian tube studied was removed because of ruptured ectopic pregnancy. Although this phenomenon has not been previously reported, it is not really remarkable because of the embryological similarity of paratubal and endometrial epithelium.

A case of a busulfan-induced hemorrhage cystitis is reported. Spontaneous resolution occurred following cessation of the drug. The similarity between the histologic appearances of busulfan cystitis and both radiation and cyclophosphamide-induced cystitis is discussed and the world literature reviewed. In view of the known tendency of busulfan to induce cellular atypia and carcinoma in other sites, periodic urinary cytology is suggested in patients on long-term therapy.

Two adult patients who had synovial chondromatosis occurring within bursae formed around osteochondromas are described. In spite of marked cellular atypia of the cartilage cells, the clinical course was unremarkable, pointing out the discrepancy between histologic changes and subsequent behavior in this condition. Histologic features, in addition, are not always helpful in distinguishing primary from secondary chondrometaplasia.

A non-invasive example of hidroacanthoma simplex that contained focal cellular atypia and abnormal mitoses occurred on the leg of an 80-year-old man. Ultrastructural features included abundant glycogen, peripheral tonofilaments and sparse short desmosomes. Nuclear profiles were smooth and nucleoli were dense and round. Thus, tumor cells were easily distinguished from the surrounding keratinocytes with which they formed short desmosomal junctions.

We report seven cases of atypical cutaneous fibrous histiocytoma, which appears to be a variant of cutaneous fibrous histiocytoma (dermatofibroma). These patients are all middle-aged women (mean, 39 years old) with small nodules occurring on the trunk and limbs. The lesions are characterized by marked focal cellular atypia, the absence of mitoses, and xanthomatous changes in both mononuclear and giant cells--all found within a small dermal nodule (approximately 1 cm) separated from an acanthotic epidermis by a Grenz zone. Their benign nature is demonstrated by the absence of recurrence, even after 9 years follow-up time.

One hundred and twelve melanocytic naevi measuring less than 5 cm in largest diameter were excised from 85 patients referred because of minor concern about possible growth or malignant potential of these naevi. Sections from all 112 naevi were examined histologically, without access to the clinical history, and the following features noted: type of melanocytic proliferation in the basal layer area, contiguity of epidermal and dermal components, total width and depth of naevus, involvement of subcutaneous fat and of skin appendages, the presence or absence of an ‘Indian file’ type of naevus cell infiltration, cellular atypia and evidence of maturation of these cells. On the basis of these features, naevi were assigned to either a ‘congenital type’ or ‘acquired type’ classification, and their distribution in these two classifications then compared with the clinical history. It was found that in 107 of 112 lesions correct assignation had been made on histological grounds alone, 43 as congenital and 64 as acquired. A histological pattern not previously reported to be associated with congenital naevi was seen in 17 (34%) of the congenital lesions. This study suggests that it is possible to differentiate the majority of small congenital naevi from acquired naevi on histopathological grounds alone. This observation could be of considerable value in the examination of excised primary malignant melanomas for evidence of a pre-existing naevus of either type.

Transrectal aspiration biopsy is useful as an alternative method to examine the prostate. As a means to improve the sensitivity of this method we investigated the significance of cellular atypia. Transrectal aspiration biopsy revealed highly atypical cells in 30 of 225 patients and in 17 patients slightly atypical cells were found. Biopsy was repeated in 22 patients with highly atypical cells and cancer was confirmed in 17 (77 per cent). In the group with only slight atypia 2 of 6 patients had cancer upon repeat prostatic biopsy. When transrectal aspiration biopsy contains highly atypical cells biopsy should be repeated to avoid a false negative diagnosis. These results suggest that atypia is an abnormal finding that must be followed clearly to maintain a high sensitivity with this biopsy method. (J. Urol., 140: 766-768, 1988)

The histogenesis of papillary and nonpapillary transitional cell carcinomas were studied morphologically and autoradiographically in 177 female Wistar rats after oral application of N-butyl-N-(4-hydroxybutyl)-nitrosamine with varying exposure and induction times. By far the largest proportion of carcinomas developed by a malignant transformation of preexisting papillomas or their precursors, the papillary hyperplasias. The transition into a focally malignant growth did not take place abruptly, but occurred stepwise through different successive stages of transformation, each having its own distinct morphological character. The first stage consisted of a focal, sharpely defined cellular atypia. In a further stage carcinomata in situ developed out of the atypical foci and progressed finally in a last stage of transformation into a circumscript infiltrative growth. The successive development of each stage occurred independent of any further carcinogen application after transformation was initiated at the molecular level. The number of papillomas with transformation stages increased with a lengthening of the exposure and induction time. 74.4% of all the registered papillomas had been transformed. Consequently papillomas must be considered potentially highly malignant. The 3H-TdR index was 4.2 times higher in atypical urothelial areas (7.6%) and 7.5 times higher in carcinomata in situ (14.3%) than in the surrounding papillomatous structures which appeared light microscopically benign. The latter demonstrated a rather constant 3H-TdR index, whether they bordered on atypical foci (1.8%) or carcinomata in situ (1.9%). The length of exposure and induction time exercised no significant influence on the degree of proliferative activity. The development of transitional cell carcinomas from a primary carcinoma in situ (intraurothelial carcinoma) played a much less significant role.

Leiomyomas of the renal pelvis are rare tumors. To date only 4 cases have been reported. We present a unique case with cellular atypia in which ultrastructural and immunohistochemical findings are described.

The cytologic findings in 355 patients with symptoms of genito-urinary disorders were compared with the clinical and histologic diagnoses. Neoplasm was histologically verified in 140 cases. The tumours were graded according to the degree of cellular atypia in histologic specimens as papilloma (grades 0–1) or carcinoma (grades II-IV). Papilloma was found in 23 per cent of the tumour cases.The cytologic diagnosis was based on analyses of sediment from urine and bladder washings. No false positive cytologic diagnosis of malignancy was made in the 195 patients without neoplasm. No definite cytologic report of malignancy was made in the 32 cases of papilloma. Of the 108 cases histologically classified as carcinoma, 71 per cent (58 per cent of grade II and 85 per cent of grades III-IV tumours) were cytologically recognized as malignant from the first sample of urine and bladder washings.The importance of uniform concepts of histologic grading of bladder tumours for evaluating the accuracy of exfoliative cytolog...

Carcinoma of the prostate is defined as latent when it is detected at autopsy or in surgical specimens from patients in whom carcinoma was clinically not suspected. When symptoms and/or signs have aroused suspicion of prostatic malignancy, the term clinically manifest carcinoma of the prostate is used.

The more problematic the evaluation of a histological diagnosis, the longer the pathologist’s comment on it. This seems to be necessary in order to demonstrate the perplexing matter to the clinician. It remains, however, often doubtful whether a certain understanding is established or not. Everybody expects a “useful” diagnosis from his pathologist making room for therapeutic consequences and prognostic aspects. From the pathological anatomist’s point of view, this is impossible in borderline cases; that is why we have to claim an accurately adjusted nomenclature. I am talking about alterations which are qualified by us as “proliferation of the glandular neck with cellular atypia”, by others as “cell atypia” or “proliferative intestinal metaplasia”. In simple words this would mean a diagnosis corresponding to Papanicolaou III in cytology. It depends on clinical findings what further diagnostic procedures or follow-up studies will be indicated.

The European Organization for Research on Treatment of Cancer (EORTC) Thyroid Cancer Cooperative Group presented a prognostic index in 1979 that included all histologic groups of thyroid carcinomas, and was based on a multivariate analysis of 507 patients with a median follow-up of 40 months. The current report not only uses a multivariate analysis to study the clinical validity and reproducibility of this index on case material consisting of 226 differentiated thyroid carcinomas with a considerably long follow-up (11 years), but also it investigates possible prognostic factors, other than those proposed by the EORTC. Three EORTC variables could be reproduced as important: age at diagnosis, locally advanced disease, and distant metastases. Of the additional histopathologic variables tested, microscopic tumor invasion beyond thyroid capsule (pT4) and marked cellular atypia (MCA) proved to be significant. When the effect of the age-correlated tumor factors pT4 and MCA of differentiated thyroid carcinomas were taken into consideration, age alone lost its prognostic importance as a guide for treatment.

Lipoblastoma, a relatively rare benign adipose neoplasm, predominantly affects children younger than 3 years of age. We herein report the case of a 7-month-old girl with an unusual myxomatous histology of lipoblastoma. A rapidly growing mass was detected in the subcutaneous area of the left buttock. Histologically, the tumor consisted of abundant myxoid stroma exhibiting cellular atypia and a high mitotic activity. Although the histological findings were unusual, the tumor was diagnosed as a lipoblastoma according to both PLAG1 immunohistochemistry and the presence of PLAG1 rearrangement on fluorescence in situ hybridization.

Cellular atypia in stromal cells of nasal polyps is a peculiar response in fibroblasts or fibrohistiocytes to increased intercellular fluid and/or vascular compromise. Adherence to established histologic criteria will eliminate misjudging these cytologic changes as sarcomas.

The complex detection system leading to the discovery and treatment of precancerous lesions and early cancer of the uterine cervix is described in detail and discussed. By far the most difficult and underestimated component of this system is the screening and interpretation of cervical (Papanicolaou) smears. Cytologic case finding may fail because of inadequate samples, insufficient time devoted to screening, or human fatigue. Other weak points of the system, such as an inadequate clinical component, inadequate patient compliance, poor reproducibility of diagnoses, and ineffective aftercare, are also described. For example, obtaining a second smear to confirm or refute a diagnosis of cellular atypia is often a misleading practice. Although this cancer detection system has been shown to be effective in reducing the rate of morbidity and mortality from invasive cervical cancer in appropriately screened populations, there is no evidence that the Papanicolaou test has succeeded anywhere in complete eradication of this theoretically preventable disease. It is important to inform the public about the potential failures of the system and the reasons for them. (JAMA1989;261:737-743)

A group of 1760 women aged 14-35 years were examined for the concurrent presence of Chlamydia trachomatis and cellular atypia of cervical smears. Positive tests for C trachomatis were found in 126 women (7.2%). Cell changes were found in 85 women (4.8%), and 25 of these were C trachomatis-positive. Slight cellular atypia was the major finding in the smears from 22 of the C trachomatis-positive women, whereas three patients had more pronounced cell changes. Smears reverted to normal in 18 of the 23 patients who returned for tetracycline treatment and follow-up cytology. All 18 patients had smears showing slight cellular atypia prior to therapy. In five patients who also had cellular changes suggesting a human papillomavirus infection, the smears did not revert to normal after antibiotic therapy during the observation period. These findings suggest that patients with C trachomatis and mild cellular atypia should have antibiotic therapy and repeat smears taken before further treatment is considered. More advanced cellular atypia is unlikely to be caused by C trachomatis.

• We report on a patient with preinvasive malignant change in an oncocytoma of the right parotid gland. Histologic transition from benign morphology to malignant cellular atypia, to our knowledge described only once previously in the literature, was present. Satisfactory results from wide surgical resection and postoperative radiotherapy in our patient serve as additional experience in the treatment of this rare malignancy. ( Arch Surg 113:318-319, 1978)

• A patient has been observed with a distinct form of disseminated porokeratosis. During the course of his disease, he developed changes in the porokeratosis lesions that included cellular atypia, dysplasia, and invasive squamous cell carcinoma. One of the squamous cell carcinomas produced regional and disseminated metastases, resulting in the death of the patient. Although malignancy has been previously described in the various types of porokeratosis, this is the first report of disseminated metastases and death in any form of this disease. ( Arch Dermatol 1987;123:1521-1526)

• A 30-year-old woman had a nontender subcutaneous mass over the left temple that histologically demonstrated a mixed pattern of mature lipocytes and spindle cells, many in a palisading and fascicular pattern, separated by fibrous trabeculations. No cellular atypia or increased mitotic activity was seen, and a predominance of mast cells was noted. This case illustrates the spindle cell lipoma, a benign variant of lipoma that has been confused in the past with both malignant spindle cell and lipocytic tumors. Our case, although atypical in sex, age, and location, serves to identify this entity in the dermatologic literature. ( Arch Dermatol 114:1065-1066, 1978)