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Histological grading of transitional cell tumours of the bladder. Value of histological grading (WHO) in prognosis.

Mortality among 139 patients with transitional cell tumour of the bladder was studied. Tumours were reevaluated according to the grading system recommended by WHO. The absolute 5-year survival of histologically benign papilloma cases was 68%, of grade I carcinoma cases 64%, of grade II carcinoma cases 42% and of grade III carcinoma patients 34%. Clinical staging (UICC), however, would have been more effective than histological grading (WHO) for prognostic purposes. 3 of the 14 patients with histologically benign papilloma in this study developed grade I carcinoma during follow-up periods of between 4.5 and 24 years. Following radical treatment all recurrences were papillomas. The study suggests that histological grading should be used to complement clinical staging in prognosis and that with half-yearly check-ups and elimination of any tumours thus detected, patients with papilloma rarely develop carcinomas of higher grade than grade I.

Aged

Structural patterns and histological behaviour of experimental sarcomas. I. General considerations, histology and histochemistry.

Methylcholanthrene-induced rat sarcomas were used as a model for the examination of morphological and cytological differentiations in tumours of the connective tissue. Particular attention was paid to the question how far these sarcomas are comparable to human connective tissue tumours. The histological examination yields a broad spectrum of mesenchymal differentiations ranging from undifferentiated anaplastic sarcomas over less differentiated fibrosarcomas and malignant fibrous histocytomas to well-differentiated fibrosarcomas, myosarcomas and haemangiopericytomas. It is worth mentioning that different histological structures can be encountered with one and the same tumour.

Animals

[Use of automatic devices for histological processing and staining of the tissues and certain characteristics of preparation of histological specimens].

The experience in using automatic devices AT-2, AT-3, AT-4 and in this connection some peculiar features of making histological preparations are discussed. Some modifications of treatment and paraffin embedding of pieces of the tissue are suggested. Recommendations concerning economizing reagents used in the automatic apparatus referred to above without lowering the quality of preparations are given. The technique described makes it possible to prepare specimens and to carry out investigations of bioptic materials in the course of 2-3 days (including the fixation period).

Autopsy

A retrosepctive histological study of 669 cases of primary cutaneous malignant melanoma in clinical stage I. 6. The relation of dermal solar elastosis to sex, age and survival of the patient and to localization, histological type and level of invasion of the tumour.

A selected series of primary malignant melanoma of the skin, clinical stage I, was studied. The series includes 37 lentigo maligna melanomas, 301 superficial spreading malignant melanomas, 194 nodular malignant melanomas and 137 unclassifiable malignant melanomas. Dermal solar elastosis was graded. The most common finding was lack of solar elastosis which together with slight elastosis was mostly found on the trunks of young men and on the legs of young women in cases of superficial spreading malignant melanoma. Marked and moderate elastosis was found almost exclusively on the head, especially in old women with lentigo maligna melanoma. Nodular malignant melanoma was related neither to any special grade of solar elastosis, nor to localization, but showed some relation to the male sex after 50 years of age. The present study does not permit any conclusions to be made about a possible causal relationship between the three types of malignant melanoma and previous sun-exposure, because of lack of clinical information and a control series concerning solar elastosis in the normal population. Level of invasion and prognosis of the patient did not show any covariation with grade of solar elastosis.

Adult

Significance of abnormal rabbit ileal histology in the pathogenesis of diarrhea.

In spite of several macroscopic criteria for predicting the presence of histological abnormalities in rabbit ileum, microscopic ileal abnormalities still can escape detection. The effect of histologically abnormal rabbit ileum was evaluated on basal intestinal absorption, on basal absorption, on basal adenylate cyclase activity, and on cholera toxin-induced secretion and cholera toxin-induced stimulation of adenylate cyclase activity. Compared to histologically normal rabbit ileum, the presence of histological abnormalities was associated with decreased basal intestinal water, Na, Cl, and glucose absorption, absent glucose-dependent water absorption, and elevated basal adenylate cyclase activities. However, histologically abnormal rabbit ileum responded to inoculation of purified cholera toxin with stimulation of intestinal water secretion and adenylate cyclase activity similar to that in histologically normal ileum. These data have implications concerning the design of experiments that attempt to study the pathogenesis of diarrheal diseases by correlating changes in ileal transport with changes in ileal mucosal adenylate cyclase activity. In spite of abnormal ileal histology, studies of intestinal secretory states which attempt to define the role of adenylate cyclase in secretory processes can be performed provided animals are used as their own controls. However, when groups of animals are compared, the presence of an histologically abnormal ileum can cause changes in basal and intestinal secretagogue-stimulated ileal water and electrolyte transport and in basal and intestinal secretagogue-stimulated mucosal adenylate cyclase activity which can lead to erroneous conclusions if the presence of the abnormal ileal histology is not considered.

Adenylyl Cyclases

Clinical course of cystosarcoma phyllodes related to histologic appearance.

A series of 17 females having cystosarcoma phyllodes underwent surgical treatment. The subsequent clinical course was observed periodically. Twelve patients had originally histologically benign tumors. Six patients had a recurrence, and of these, malignant characteristics developed in four instances. Five patients had originally histologically malignant tumors. Recurrences were encountered in four. Five patients died from a generalized spread of the tumor. Three of these patients had originally histologically benign tumors, in which malignant features of the recurrent tumor subsequently developed. The surgical treatment ranged from local excision to simple mastectomy with additional roentgenotherapy in three. Neither procedure prevented a recurrence from the original tumor, whether benign or malignant. Poor correlation exists between biologic behavior and histologic appearance of cystosarcoma phyllodes, independent of the surgical procedure. Wide local excision in histologically benign and mastectomy in histologically malignant tumors are advised, but no final decision could be reached. It is proposed to restrict ther term cystosarcoma phyllodes to histologically malignant tumors and use the term fibroadenoma phyllodes in instances of histologically benign tumors.

Breast Neoplasms

Endoscopic, histological and ultrastructural correlations in chronic gastritis.

Thirty-three patients presenting with dyspepsia were examined with the Olympus Fiber-gastroscope. An endoscopic diagnosis was made in each case and multiple gastric biopsies were obtained for histological and ultrastructural assessment. The endoscopic, histological and ultrastructural findings were compared with each other. Of 33 patients endoscoped, 29 were found to have endoscopic evidence of various types of gastritis and all of these latter had histological evidence of some form of gastritis. Histological confirmation of specific types of endoscopically diagnosed gastritis, however, was only found in 3/9 cases of chronic atrophic gastritis (CAG), 10/14 cases of chronic (superficial) gastritis (CG) and in none of six cases of acute gastritis (AG), indicating that endoscopic diagnosis of specific types of gastritis is relatively inaccurate. Endoscopic diagnosis should thus be restricted to presence or absence of gastritis, leaving the specific typing to histological assessment of the gastric biopsies. Multiple gastric biopsies should be obtained even though the gastric mucosa appears normal endoscopically, since histological evidence of gastritis was found in three out of four cases with endoscopically normal gastric mucosa. Comparison of histological diagnosis with electron microscopy showed that generally there is good correlation between the severity of the histological changes and the ultrastructural grade of damage as defined in this study. It would appear that E.M. examination of the gastric biopsies will not significantly increase the diagnostic accuracy of light microscopy, although it has elucidated the various cellular changes which characterize chronic gastritis. The rough surface contours, the large gastric pit and the increasing number of surface microvilli, seen by scanning E.M., aid the grading of the disease process. Some of these changes are reflected in observations made by transmission E.M. where in addition the basal intercellular edema of the mucosal layer and the appearance of electron-dense mucosal lining cells are observed. The latter, which are the counterpart of "intestinal metaplasia", possess mucus granules which resemble those of gastric mucosal lining cells or intestinal goblet cells, or both.

Adult

Integration of Gene Expression and Digital Histology to Predict Treatment-Specific Responses in Breast Cancer.

Deep learning models applied to digital histology can predict gene expression signatures (GES) and offer a low-cost, rapidly available alternative to molecular testing at the time of diagnosis. We optimized transformer-based models to infer GES results and applied this approach to pre-treatment H&E-stained biopsies from 1,940 breast cancer patients treated with neoadjuvant chemotherapy in clinical trial and real-world cohorts. The most predictive histology-derived GES for pathologic complete response (pCR) in the I-SPY2 trial was validated in four external cohorts: CALGB 40601, CALGB 40603, a trial of durvalumab plus CT, and standard-of-care CT-treated patients from the University of Chicago. Among HER2-negative patients, a transformer-based model trained using a signature composed of estrogen-regulated genes, proliferation, apoptosis, and interferon response genes predicted pCR with an AUC of 0.794, outperforming models based on clinical features alone (AUC 0.704, p = 0.001), pathologist TIL assessment, and a model trained directly to predict response from I-SPY2 cases. Tertiles of this signature stratify patients into clinically relevant groups with increasing likelihood of complete response, with pCR rates ≥50% in the top tertile regardless of treatment or hormone receptor status. Additional transformer-based signature models predicted response to specific therapies (but not chemotherapy alone), including a HER2 signaling signature in IO-treated patients, and a claudin-low signature in bevacizumab treated patients. In HER2- cohorts with available gene expression data and histology, models trained on expression data performed similarly to digital histology predictions, but the combination of gene expression and histology outperformed histology alone. These findings suggest that histology-based GES provides additive information to RNA sequencing data and can inform precision treatment selection across breast cancer subtypes.

Journal Article

Stage shift, histological differentiation, and survival patterns of lung squamous cell carcinoma versus adenocarcinoma in low-dose CT screening.

BACKGROUND: Whether LDCT-associated stage shift translates into similar survival patterns across lung cancer histologies remains uncertain. We compared stage shift, histological differentiation, tumor characteristics, and survival between lung squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD) in the National Lung Screening Trial. METHODS: Among participants diagnosed with LUSC or LUAD, stage distribution and histological differentiation were compared between LDCT and chest X-ray (CXR) arms. Survival among diagnosed cases was measured from randomization. Multivariable models tested screening arm-by-histology interactions. Screen-detected LDCT tumors were compared by histology. RESULTS: During 6.5 years of median follow-up, 498 LUAD and 249 LUSC cases were diagnosed in the LDCT arm, and 374 and 212, respectively, were diagnosed in the CXR arm. LDCT was associated with higher odds of stage I disease for LUAD (adjusted odds ratio [aOR], 2.48; 95% CI 1.88-3.28) and LUSC (aOR, 1.71; 95% CI 1.17-2.48), without significant interaction (P&#x202f;=&#x202f;0.116). LDCT was associated with lower hazard of lung cancer-specific death among diagnosed LUAD cases (adjusted hazard ratio [aHR], 0.54; 95% CI 0.43-0.66), but not among diagnosed LUSC cases (aHR, 1.04; 95% CI 0.78-1.39; P for interaction<0.001). LUSC had lower screening sensitivity, more frequent detection in annual screening rounds, greater prediagnostic tumor size increase, and fewer well-differentiated stage I tumors than LUAD. CONCLUSION: LDCT was associated with stage shift for both subtypes, but favorable survival patterns among diagnosed cases were mainly observed for LUAD. Lower screening sensitivity, greater prediagnostic tumor size increase, and poorer histological differentiation may help explain why stage shift did not translate into similar survival patterns for LUSC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00047385.

Humans

Clinical utility of lymphocyte surface markers combined with the Lukes-Collins histologic classification in adult lymphoma.

To determine whether analysis of lymphocyte surface markers adds clinically useful information to the Lukes-Collins classification of lymphomas, tumors from 107 adults were histologically classified and studied for surface markers. Ninety-six cases were histologically classified as Lukes-Collins B-cell lymphomas; 87 showed B and one showed T surface markers, whereas eight had neither marker. Eleven lymphomas were histologically T-cell tumors; four of the 11 showed T surface markers, and seven had neither marker. Both the Lukes-Collins classification and surface markers identified patient groups with different clinical characteristics, chemotherapeutic responsiveness and survival. However, by combining surface markers and histologic features, additional important therapeutic and prognostic information was obtained. In each histologic class, patients whose lymphomas failed to express immunologically the histologically predicted marker had fewer responses to chemotherapy and shorter survivals than patients whose lymphomas expressed the predicted marker. Our data suggest that the analysis of surface markers in combination with the Lukes-Collins classification identifies many patients who respond poorly to current therapy and who thus require new therapeutic approaches.

Aged

Cytologic, histologic and electron microscopic correlations in poorly differentiated primary lung carcinoma. A study of 43 cases.

For 43 poorly differentiated lung carcinomas we compared cytopathologic diagnoses made on specimens obtained prior to biopsy with histologic and electron microscopic diagnoses. Tissues were obtained by transbronchial biopsy, mediastinoscopy o pulmonary resection. Cytologies, tissues and electron micrographs were reviewed independently and blindly by five pathologists and one cytotechnologist. The cytologic, histologic and electron microscopic diagnoses agreed in 27 cases (62.7%), including adenocarcinoma (12), squamous carcinoma (five), oat cell carcinoma (six), mesothelioma (two) and adenosquamous carcinoma (two). In 14 cases the cytopathologic diagnoses had more accurately reflected the cell type ultimately diagnosed by electron microscopy than had the histologic diagnoses. Of ten poorly differentiated adenocarcinomas, eight had been interpreted as large-cell undifferentiated carcinomas, one as squamous carcinoma and one as poorly differentiated carcinoma histologically. Four poorly differentiated squamous carcinomas had been histologically diagnosed as giant cell, oat cell, undifferentiated carcinoma and adenocarcinoma. In these cases the previous cytologic diagnoses had been in agreement with the ultimate electron microscopic interpretation. The accuracy of cytodiagnoses may exceed that of histologic diagnoses in poorly differentiated lung cancer.

Adenocarcinoma

Correlative study of regional left ventricular histology and contractile function.

In 110 patients with documented coronary artery disease, transmural biopsy of the anteroapical region of the left ventricle was performed during aortocoronary bypass grafting. Biopsy specimens were semiquantitatively graded microscopically for myocardial fibrosis as an indicator of chronic ischemic damage. Preoperatively, systolic wall motion of the region from which the biopsy specimen was taken was semiquantitatively graded as showing normal motion, hypokinesia, akinesia or dyskinesia on ventriculography. Wall motion-histologic correlations, taking into account both electrocardiographic evidence of anterior infarction and ST-T abnormalities, were then established. Overall, there was fair agreement (72 percent) between functional and histologic assessment of the left ventricular region evaluated, both qualitatively (normal versus abnormal, 72 percent agreement) and quantitatively (degree of abnormality, correlation coefficient 0.66, P = 0.005). The 22 patients with electrocardiographic evidence of anterior infarction had various degrees of abnormal regional motion and myocardial fibrosis. Discordance between wall motion and histologic findings was most common (50 percent of instances) in the 34 patients with anterior ST-T changes without infarction and generally was manifest as abnormal motion with normal histologic features. By contrast, normal motion and abnormal histologic features represented the most common type of discordance (22 percent of instances) in the 54 patients without either anterior infarction or ST-T deviation. These data provide a basis for inference of myocardial morphologic features (fibrosis) from assessment of ventriculographic wall motion and the electrocardiogram. They may thus be useful in predicting the potential functional benefits of bypass grafting of coronary arteries supplying abnormally contractile segments of the left ventricle.

Adult

Liver damage after paracetamol overdose. Comparison of liver-function tests, fasting serum bile acids, and liver histology.

54 patients have been studied after paracetamol (acetaminophen) overdose. Liver-function tests and fasting serum bile-acids were measured daily; liver biopsy was done in all cases, and slides were examined "blind" to assess liver damage. The plasma-paracetamol was measured on one occasion. A histological abnormality was present in the livers of 53 of the 54 patients, and was minor in 23, moderate in 16, and severe in 14. In 6 patients with moderate and 18 with mild histological abnormality liver-function tests were normal. A serum-aspartate-aminotransferase above 400 units/1 was always associated with severe histological liver damage. Fasting serum bile-acids were raised in 51 of the patients with abnormal liver histology; the serum-bile-acid seemed to be a more sensitive indicator of mild liver-cell damage than was the transaminase level. There was, however, little correlation between increase in bile-acid concentration and the degree of histological abnormality. As a result of these investigations empirically determined levels of plasma-paracetamol have been drawn which give a guide to the likelihood of liver damage after paracetamol overdose.

Acetaminophen

Nephroblastoma in the rat: histology of a spontaneous tumor, identity with respect to renal mesenchymal neoplasms, and a review of previously recorded cases.

The histology of a spontaneously occurring neoplasm of the rat kidney conforming to a classification of nephroblastoma is described and compared with that of N-nitrosodimethylamine-induced renal mesenchymal tumors. This rat nephroblastoma was an encapsulated epitheloid neoplasm with a uniform histologic pattern. Clumps of densely crowded, hyperchromatic cells frequently associated with central, well-differentiated ducts were supported by a less cellular, interconnecting stroma of loose areolar or mature fibrous connective tissue. Neoplastic cells were organized into primitive, ill-defined tubular formations. The neoplastic cell component strongly resembled metanephrogenic blastema. In contrast, the renal mesenchymal tumor was nonencapsulated and consisted of a heterogeneous mixture of connective tissue elements including fibroblast-like spindle cells, smooth muscle, and embryonic mesenchyme that engulfed and sequestered preexisting renal tubules and glomeruli. The separate morphologic identities and apparently unrelated existence of rat nephroblastoma and renal mesenchymal tumor were stressed. The rat nephroblastoma morphologically resembled the malignant epithelial component of human Wilms' tumor, whereas rat renal mesenchymal tumor appeared to have counter-parts in the mesenchymal component of Wilms' tumor and in congenital mesoblastic nephroma (leiomyomatous hamartoma) of infancy. The histologic descriptions of previously recorded occurrences of spontaneous and experimentally induced rat neoplasma classified as nephroblastoma or its synonyms were reevaluated in comparison to the present case. In all but four instances, in which sufficient histologic detail was provided in previous reports, a consistent histologic pattern emerged for this neoplasm in the rat.

9,10-Dimethyl-1,2-benzanthracene

The deoxyribonucleic acid (DNA) skin test in systemic lupus erythematosus. 2. Histological findings.

A total of fifty-five biopsies from fifty-two intradermal DNA skin tests were studied. The biopsies were taken, 6, 8-10, 24 or 48 h after the injection of the DNA material. Necrosis of the vessel wall was taken to be the main characteristic of a specific reaction. In forty of the fifty-two tests the results of the histological evaluation closely matched the clinical results. In five of the fifteen cases with discrepancies, the histological evaluation ruled out clinically false positive test results. In three cases of SLE on corticosteroid treatment, the histological examination gave a positive result despite a clinically negative result. In seven of the fifteen cases the discrepancies occurred in borderline cases with reactions of 5 to 6 mm diameter. The amount of inflammatory cells in positive as well as in negative reactions was also recorded. The number of polymorphonuclear cells in positive reactions increased with the age of the reaction. The number of lymphocytes was not found to increase in the positive reactions, thus differing from the delayed hypersensitivity type of reactions. Rather, the reaction was characterized by an Arthus type of hypersensitivity. On the basis of the present study it may be concluded that clinically positive tests at 6 or 8 h may merely be expressions of nonspecific vascular alterations. On the other hand, in late reactions, even in patients on systemic treatment, histological examination revealed clinically negative results to be positive. By using the histological picture of hypersensitivity angiitis as the main diagnostic criterion the specificity of the clinical reactions may be established.

Adult

[Case studies of the histological characterization of primary tumors of the testis].

One hundred-ninety nine cases of testicular tumours, of which 189 (94,9%) germ cell tumours, have been studied by histological methods. Seminoma with its two subtypes (anaplastic and spermatocytic) is the most frequent tumour (110 cases i.e. 55,2%), followed by embryonal carcinoma (30 cases: 15,3%), teratocarcinoma (25 cases: 13,2%), teratoma (12 cases: 6,3%) and choriocarcinoma (5 cases: 2,6%). Tumours showing more than one histologic pattern are frequent. The distinctive histologic features have studied, with emphasis of those useful for diagnostic and prognostic purposes. The ages mostly involved by various tumours are stressed. The rarest tumours are briefly described. Histologic data suggest that germinal tumours are originated by the same primordial germ cell which is able to develop various degrees of differentiation. Histologic and histogenetic features of limphomas and tumours of specialized gonadal stroma are also discussed.

Adult

Gross and histological abnormalities of the talus in congenital club foot.

Gross and histological abnormalities were demonstrated in a club-foot talus from a boy with multiple congenital anomalies who died when he was nine days old. Both tali were studied, the one from the club foot and the one from the normal foot. The gross anomalies involved the smaller size of the club-foot talus and the increased medial deviation of a stunted, misshapen head and neck region. Serial histological sections of both tali allowed for a three-dimensional geometric appreciation of both bones and an assessment of the nature and extent of histological and cytological features. The ossification center of the club-foot talus was absolutely and relatively smaller than that of the normal talus. It was eccentrically positioned, being more lateral and anterior than that of the normal talus. The marked histological abnormalities seen in the head and neck region of the club-foot talus involved extensive breaching of the endochondral sequence by vessels. The posterior aspect of the endochondral sequence and ossification center was normal. The extra-osseous and intra-osseous blood supply of the two tali was normal with the exception of the increased and irregular breaching of the endochondral sequence in the club-foot talus. This study demonstrates histological abnormalities in the head and neck region of the club-foot talus, which was most abnormal grossly. The eccentric position of the secondary ossification center as well as its related vascular abnormalities do not support a theory of developmental arrest of the talus but appear sufficiently abnormal to support the theory of a primary defect in the cartilage anlage. Clinically, one must bear in mind that early open reduction of the talocalcaneal navicular joint in a foot such as this would have served to reposition the navicular onto a talus that still was structurally abnormal.

Clubfoot