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Prognostic histologic indicators of curatively resected hepatocellular carcinomas: a multi-institutional analysis of 425 patients with definition of a histologic prognostic index.

Despite growing information on the clinical behavior of hepatocellular carcinoma, the histologic features associated with survival are not well characterized. Clinical and pathologic data on 425 patients who underwent complete resection for hepatocellular carcinoma were reviewed. Six microscopic features, namely, microvascular invasion, nuclear pleomorphism, mitosis, tumor architecture, growth interface, and tumor necrosis, were examined. Independent predictors of survival were identified and combined into a simple prognostic index. By univariate analysis, microvascular invasion, seen in 51.3% of patients (p <0.001), nuclear grade 3, present in 42% of the cases (p <0.001), and mitosis (p <0.008) were significant predictors of poor survival. Hepatocellular carcinoma with a compact growth pattern had a better prognosis as compared with macrotrabecular (p = 0.014) and acinar (p = 0.051) patterns. By multiple regression analysis, only microvascular invasion (p <0.001) and nuclear grade 3 (p = 0.008) were independent predictors of poor survival. The predictive values of microvascular invasion and nuclear grade allowed the construction of a hepatocellular prognostic index (HPI) whereby HPI = (microvascular invasion status x 0.459) + (nuclear grade x 0.287), with microvascular invasion either absent (0) or present (1) and nuclear grade scored as 1, 2, or 3. Using a cut-off of 0.746 (corresponding to at least nuclear grade 2 with microvascular invasion), two groups could be segregated: fair prognosis (HPI < or = 0.746), with a 50% survival of 5.06 years, and poor prognosis (HPI >0.746) with a 50% survival of 2.71 years (p <0.001). HPI was more discriminating than Edmondson grade, with Edmondson II hepatocellular carcinomas dispersed in both fair and poor prognosis groups. Microvascular invasion and nuclear grade 3 emerge as strong prognostic indicators, and their combination provides adequate prognostic stratification. Practically, hepatocellular carcinoma can be stratified in two groups with regard to prognosis: 1) fair prognosis group (nuclear grade 1 with or without microvascular invasion and nuclear grade 2 without microvascular invasion), and 2) poor prognosis (nuclear grade 2 with microvascular invasion and nuclear grade 3 with or without microvascular invasion). The combination of these histologic parameters provides adequate prognostic stratification.

Adolescent↗

Clinical significance of serum hyaluronic acid as a fibrosis marker in chronic hepatitis C patients treated with interferon-alpha: histological evaluation by a modified histological activity index scoring system.

The aim of the present study was to investigate the histological changes effected by interferon (IFN) treatment and to evaluate the clinical significance of serum hyaluronic acid (HA) as a marker of fibrosis. Forty-nine patients with chronic hepatitis C treated with IFN-alpha were divided into three groups according to the existence of viraemia: sustained complete responders (CR), complete responders with relapse (PR) and non-responders (NR). Needle biopsy sections of the liver taken before and at the end of IFN treatment were assessed according to the modified histological activity index (HAI) scoring system. Serum fibrosis markers, including HA, were measured at needle biopsies. Biopsies of CR at the end of treatment showed a significant improvement in fibrosis and necroinflammatory scores. More significant correlation was observed between fibrosis scores and serum levels of HA before IFN treatment (r = 0.607, P < 0.0001) than those between fibrosis scores, on the one hand, and peptide of type III procollagen (PIIIP; r = 0.531, P = 0.0004) or type IV collagen 7S domain (type IV-C; r = 0.241, P = 0.1062) on the other. Moreover, serum HA levels fell significantly in patients in whom fibrosis improved (P = 0.011). This is the first paper describing the advantages of the modified HAI scoring system over others in estimating the effect of IFN-alpha; the results also indicate that serum HA can be useful in monitoring liver fibrosis in chronic hepatitis C patients treated with IFN-alpha.

Adult↗

Histological evaluation of prostatic cancer. (II): Reproducibility of a histological grading system.

The aim of this study was to evaluate the reproducibility, expressed by kappa coefficients, of the histological grading system of prostatic cancer as proposed by Schroeder, Hop, Blom and Mostofi in 1985. This grading system has five prognostic groups based on combinations of growth pattern, mitoses and nuclear anaplasia. All histological slides from 85 cases of prostatic carcinoma were blindly evaluated on two independent occasions by each of four pathologists. The overall INTER-observer agreement and mean INTRA-observer agreement regarding "prognostic group" were 0.55 and 0.69 respectively, whereas the kappa coefficients were 0.38 and 0.57 respectively. An acceptable level of INTER-observer reproducibility of prognostic group I (kappa = 0.70), of the parameter "growth pattern" (kappa = 0.60) and of "slight nuclear anaplasia" (kappa = 0.62) was found. A low overall kappa coefficient of "mitoses" and "nuclear anaplasia" was found. Based on the well reproducible parameters a simplified grading system is proposed.

Anaplasia↗

Ultrasound-guided, histological, fine-needle biopsy from suspect parathyroid tumours: success-rate and reliability of histological diagnosis.

Ultrasound-guided, fine-needle tissue biopsies were performed in 60 suspected parathyroid tumours in 55 consecutive patients with biochemically proven hyperparathyroidism. The specimens were randomly arranged and re-read "blind" by two pathologists. The interobserver agreement, corrected for chance agreement, was 0.92 (= kappa coefficient). Twenty-three of the 60 suspect parathyroid tumours were verified histologically following surgery. No diagnostic errors were seen but the percentage of insufficient biopsies from suspect parathyroid tumours or surgically verified parathyroid tumours was high (45 and 47%, respectively). We conclude that a reliable tissue diagnosis can be made by ultrasound-guided, fine-needle tissue biopsy. However, when the material is insufficient for histological diagnosis, we recommend the additional use of ultrasound-guided, fine-needle aspiration for cytology or parathyroid hormone determination.

Adult↗

Transvaginal ultrasound, endometrial cytology sampled by Gynoscann and histology obtained by Uterine Explora Curette compared to the histology of the uterine specimen. A prospective study in pre- and postmenopausal women undergoing elective hysterectomy.

BACKGROUND: The purpose of this study was to evaluate the diagnostic value of transvaginal ultrasound measurement of endometrial thickness, cytology obtained by Gynoscann, and histology of the endometrium sampled by Uterine Explora Curette compared with histology of the uterine specimen as the gold standard. METHODS: Consecutive patients admitted for hysterectomy had transvaginal ultrasound, sampling by Gynoscann, and Uterine Explora Curette done just before surgery, after informed consent. RESULTS: A total of 181 women entered the study. Sixteen had endometrial cancer, seven had atypical hyperplasia and nine had complex hyperplasia. A total of 168 patients had a transvaginal ultrasound done. At a cutoff limit of 4mm (endometrial thickness of 4mm or less indicating normal endometrium), the sensitivity was 90.3%, the specificity 24.8%, the positive predictive value 21.4% and the negative predictive value 91.9%. One endometrial cancer, one atypical and one complex hyperplasia were missed. The Gynoscann method showed a sensitivity of 62.5%, a specificity of 94.0%, a positive predictive value of 69.0% and a negative predictive value of 92.1%. Two cancers, three atypical and six complex hyperplasia were missed. The Uterine Explora Curette showed a sensitivity of 90.6%, a specificity of 100.0%, a positive predictive value of 100.0% and a negative predictive value of 98.0%. One endometrial cancer and two complex hyperplasia were missed. CONCLUSION: Transvaginal ultrasound is a reliable method in excluding endometrial pathology. The Uterine Explora Curette was superior to Gynoscann in diagnosing neoplasia of the endometrium. It was found to have the same diagnostic accuracy as conventional dilatation and curettage.

Adult↗

Influence of tumor stage, size, grade, vascular involvement, histological cell type and histological pattern on multifocality of renal cell carcinoma.

PURPOSE: We assessed the influence of clinical and pathological factors on multifocality of renal cell carcinoma. MATERIALS AND METHODS: Between June 1995 and September 1999 radical nephrectomy was performed in 71 men and 32 women with a mean age of 56.5 years. The 103 removed kidneys with renal cell carcinoma were sectioned at 3 mm. intervals and inspected microscopically for satellite carcinomas. We evaluated pathological stage, grade, cell type, histological pattern, vascular involvement, tumor size and the incidence of multifocality. To determine cell type we used several classification systems. RESULTS: The primary tumor was 2 to 20 cm. (mean plus or minus standard deviation 7.10 +/- 3.48). Overall satellite carcinomas were present in 22 of the 103 cases (21.4%). When the predominant lesion was 5 cm. or smaller, the incidence of multifocality was 19%. The incidence of multifocality was statistically higher in patients with stage pT3 than in those with stage pT1 or pT2 disease (p = 0.022). Multiple logistic regression analysis demonstrated that only primary tumor pathological stage was a significant predictor of renal cell carcinoma multifocality in stages T3 versus T1 and T3 versus T2 cancer (odds ratio 3.45, 95% confidence interval 1.15 to 10.39 and 5.75, 1.31 to 25.29, respectively). Other parameters, such as tumor size, grade, vascular invasion, cell type and histological pattern, did not correlate with multifocality. CONCLUSIONS: Our results imply that primary tumor stage is a significant factor for multifocal disease. Therefore, more precise preoperative staging of the primary lesion is required if nephron sparing surgery is indicated.

Adult↗

[Wilson's disease. A histological review of 7 patients and the value of histological copper positivity in relation to other hepatopathies].

BACKGROUND: Wilson's disease is an infrequent entity. Biopsy is essential for establishing its presence and degree of hepatopathy but it lacks diagnostic specificity. It is necessary to know the significance of positivity or negativity of histochemically demonstrated copper when faced with the diagnosis of Wilson's disease and cholestatic diseases. METHODS: Nine hepatic sample from 7 patients with clinical-biochemical Wilson's disease were reviewed. The rodanine histochemical technique was used for demonstration of copper in the samples aforementioned and in another 3 kinds of liver diseases: 16 biopsies of primary biliary cirrhosis, 86 biopsies of cholestatic hepatopathies (serum bilirubin greater than 68 mumol/l) and control biopsies with serum bilirubin less than 42.5 mumol/l. RESULTS: Among the 7 patients with Wilson's disease, 6 were diagnosed with cirrhosis and one chronic active hepatitis. The incidence of erosive necrosis (86%), Mallory hyaline (86%), macrovacuolar steatosis (71%), glucogenated nuclei (71%) and giant mitochondria (29%) was evaluated. Histologic copper deposit with Shikata orcein was objectified in 3 cases (43%) and with rodanine in 5 (83%). Positivity with rodanine was 69% among the series of primary biliary cirrhosis, 20% among the cholestatic hepatopathies and 0 in the control series. CONCLUSIONS: Histology of Wilson's disease remains without definitive diagnostic criteria. The disease is diagnosed in a late phase in Spain. The sensitivity of the histochemical demonstration of copper with rodanine is high (6/7) but its specificity is low, being positive in 68% of primary biliary cirrhosis and 19% of other cholestatic hepatopathies.

Biopsy, Needle↗

Computer-aided classification of malignancy in astrocytomas. II. The value of categorically evaluated histologic and non-histologic features for a numerical classifier.

The present study was carried out in order to obtain a numerical classifier for the assessment of the malignancy in astrocytomas including glioblastomas ('astrocytomas grade 4'). The attempt resulted in 'TESTAST 268', a classifier based on a reference sample of 268 tumours, 67 in each of four malignancy classes. TESTAST 268 aids the identification of astrocytomas with one of four malignancy classes by means of eight classification variables, five histologic and three non-histologic. Identification is achieved with the aid of linear discriminant functions, both according to Bayes' decision rule (BAYTEST) and by canonical discriminant analysis (CANTEST) using the squared Mahalanobis distance. The discriminant functions with the calibration of the reference sample of the 268 tumours may be implemented on personal and even small pocket computers for practical application.

Astrocytoma↗

[Reevaluation of the histological classification of breast cancer--a presentation of a new histological classification considering the relationship between scirrhous tendency and postoperative prognosis].

The present study was designed to evaluate the correlation between the histology and the prognosis of the patients with breast cancer. In this study, 1271 cases with breast cancer were retrospectively studied and an attempt of a new histological classification was presented, which was intended to reflect the prognosis more exactly than the ordinarily used classification by Japan Mammary Cancer Society. Japan Mammary Cancer Society classifies infiltrating carcinoma into 3 types; papillotubular, medullary tubular and scirrhous carcinoma. In this study, when scirrhous interstitial infiltration was observed in papillotubular or medullary tubular carcinoma, even if scirrhous tendency was observed only in small part, the patients' prognosis was as poor as scirrhous carcinoma. The prognosis of common type of infiltrating carcinoma with scirrhous tendency corresponded to that of one grade advanced stage without scirrhous tendency. Considering these results and clinical usefulness, common type of infiltrating carcinoma should be classified to 2 types, namely with or without scirrhous tendency in order to reflect the prognosis and to correspond to WHO classification.

Adenocarcinoma, Scirrhous↗

[Histologic grading of primary prostatic carcinoma--study of Gleason histologic grading].

Gleason histologic grading for prostatic carcinoma was evaluated in a retrospective analysis. The present study comprises 98 cases of prostatic adenocarcinoma followed from January, 1973 to December, 1985. Histological materials were obtained by needle biopsy, transurethral resection or by suprapubic prostatectomy. Such slides were examined by a pathologist without previous knowledge of the patients and were assigned according to the General Rules for Clinical and Pathological Studies on Prostatic Cancer (1985) or Gleason system. Most patients fell within a Gleason score of 6, 7 and 8, and had a correspondingly high stage tumors. The survival rate for the patients was analyzed according to Gleason score. Because of the small numbers of patients some scores were combined. There were no cancer deaths for the 15 patient with a Gleason score under 5. Patients with a higher score (9-10) had a poorer prognosis (32% of survival rate at 2,234 days), but there was no significant correlation between a Gleason score of 6, 7 or 8, or that of a higher score (9-10) and survival rate.

Adenocarcinoma↗

[Velofacial hypoplasia and submucous cleft palate: histologic analogies. A comparative histologic and histomorphometric study of velum musculature].

Velofacial hypoplasia (VFH) is particularly characterised by severe open nasalising with palate-throat insufficiency due to an abridged palatal velum. The cause of this disorder is unknown. Submucosal cleft palates (SMG), which may cause similar signs, are considered to be caused genetically, or acquired during pregnancy as an impedimental malformation. We compared histologically and histomorphometrically the palatal velums of patients with VFH and SMG, with normal specimens. In VFH and SMG, the muscle fibres of the palatal velums feature pathological variations of their diameters; moreover, these specimens contain more fibrous than muscle tissue compared with the controls. These changes do not indicate clearly either a neuropathogenic or a myopathogenic or other pathogenesis. However, the similarities of the clinical, histological and histomorphometric findings do indicate a common formal pathogenesis. Anamnestic examinations of the pregnancies (particularly of the first trimenon) of mothers of patients with VFH may reveal further findings supporting our assumption.

Child↗

Clinical and histological evaluation of synovial needle-biopsies in rheumatoid arthritis. II. Relationship between local clinical activity and histological pattern.

The histological pattern of synovial needle-biopsies of 50 patients suffering from classical or definitive rheumatoid arthritis has been compared with the clinical activity of the disease. Each histological change was evaluated in terms of its value in characterizing local clinical activity. It was shown that most changes of the synovial ground tissue are in a positive correlation with local clinical activity. Among the vascular changes of the synovial membrane, oedema of vascular walls, exudation of fresh fibrin, leukocyte infiltration and thickening of vascular walls were in negative correlation, while chronic fibrin, lymphocytic or plasma cell infiltration and hyalinosis were in positive correlation with local clinical activity.

Arthritis, Rheumatoid↗

[Histological classification and prognosis of mammary cancer-histological classification devised by the Japan Mammary Cancer Society and WHO classification].

Between 1966 and 1977, 427 patients with mammary cancer underwent surgery at the Shikoku Cancer Center Hospital. Using these subjects, the histological classification devised by the Japan Mammary Cancer Society was compared with the WHO classification. Since the WHO classification places 80.4% of all cases into the category of invasive duct carcinoma, the significance of the histological classification as a factor in predicting prognosis is reduced. Thus, some other subclassification is needed for practical application. We classified invasive duct carcinoma according to cellular atypism (CAT), structural atypism (SAT) and infiltration mode (INF), and examined their relationship to the 5-year survival rate; there was a positive correlation.

Breast Neoplasms↗

[Histological examination of lymphoid follicles in conjunctiva-associated lymphoid tissue in guinea pigs--Report 1. Histological characteristics of follicular dendritic cells].

We histologically examined the existence of follicular dendritic cells (FDCs) in the follicular area of conjunctiva-associated lymphoid tissue (CALT). Animals used in the experiment were Hartley guinea pigs sensitized with a topical application to the eyes of an emulsion of a mixture of ovalbumin and Freund's complete adjuvant in equal amounts. The animals were divided into 4 groups: a group with no eye drops administered (Group A), a group examined 1 week after administration of eye-drops (Group B-1), a group examined 2 weeks after administration (Group B-2), and a group given booster administration of eye-drops (Group C). These animals were examined by methyl green pyronine staining, alpha-naphthylacetate esterase staining, and enzyme-antibody methods against S-100 protein or major histocompatibility complex class II (MHC class II) antigen. Also peroxidase-anti-peroxidase (PAP) was applied to the eyes and the uptake of PAP in CALT was observed histologically. In each group, positive reticular stains to alpha-naphthyl-acetate esterase staining and S-100 protein were found in the CALT follicular area. The positive cells were found to be dendrite cells by immunoelectron microscopy. An uptake of PAP was seen in the CALT follicular area, suggesting the function of trapping and holding the antigen-antibody complex by FDCs. It was concluded that dendritic cells present in the follicular area of CALT were FDCs.

Animals↗

[Comparison between aspirates (cytology and histology) and biopsy (cytology and histology) in bone marrow evaluation in simple peripheral cytopenia].

UNLABELLED: In order to assess a "basic" comparison between needle biopsy (B) and aspirate (A) in terms of diagnostic efficacy two hundred consecutive samples of bone marrow from 180 patients with simple (non neoplastic) peripheral cytopenia were examined. Both B and A from the identical anatomical site (posterior superior iliac spine) were performed in every case. Histology (I) and cytology (C) were systematically prepared from B (IB and CB) and from A (IA and CA). The cases were subdivided in 7 groups according to the type of cytopenia (mono-bi-trilinear). From a nosologic point of view these corresponded to common hematological disorders. As far as myelodysplasia (MD) is concerned only refractory anemia (RA) and refractory anemia with ring sideroblasts (RARS) were included. MD represented 28.6% of anemias which in turn covered 63.0% of all the cases. The diagnostic significance of I and C referred to the final diagnosis (A + B). In each group were compared (vs) A (CA + IA) vs B (IB + CB), IB vs CA, CA vs IA,IB vs CB and IB vs IA. The results were expressed by putting each related case into one of the following three cathegories: equivalence, superiority, inferiority. Equivalence could be diagnostically significant or non significant. Combination I + C was diagnostic in 100% of cases for A + B and IB + CA, in 96.5% for CA + IA, in 92.5% for IB + CB. Combination IB + IA was significant in 99.5% of samples, similarly supported by IB and IA respectively accounting for 91.0% and 90.0 of diagnoses. Individually CA was diagnostic in 92.0% and CB in 80.5% of cases. In some istances uneffective CA was implemented by IA (4.5%) and analogously IB by CB (1.5%). Within A CA gave little more significance than IA (only +2.0%). The different rates of I + C coincident diagnostic significance were: 97.5% (A + B), 85.5% (CA + IA), 83.0% (IB + CA), 79.0% (IB + CB). In 25.0% of MD cases diagnosis was assured by A only. In case of diagnostic discrepancy the classical morphologic parameters as cellularity, linearity and cytological details were also comparatively analysed. CONCLUSIONS: 1) the data above mentioned measure the diagnostic efficacy of the various procedures, individually or in association, with reference to the examined area, but they can be "basically" significant in the perspective of other comparisons; 2) as a whole B and A showed diagnostic equivalence, but A was more contributory in RA and RARS; this methologically means that CA needs to be reappraised and that IA is very reliable; 3) association I + C seems to be the best procedural approach in order to provide complementary morphology and amplified availability of material for examination, diagnosis and further study; 4) the performance of histopathologist can be improved by simultaneous cytological evaluation.

Adult↗

Quantitative histology of the rat thyroid. Influence of histologic techniques on the morphometric data.

The influence of various histologic techniques on the results obtained by morphometric analysis of the rat thyroid gland was studied. The limits of thyroid follicles were more clearly defined in both silver-impregnated paraffin-embedded sections and resin-embedded semithin sections than in routinely stained paraffin-embedded sections, thus enabling more accurate measurements of thyroid structures. Due to its simplicity, the silver impregnation method is clearly useful for histomorphometric studies when large numbers of measurements are involved. C cells were easily identified in paraffin-embedded sections by immunohistochemical staining. The measurement of interstitial tissue in sections without immunostaining of C cells led to an overestimation of the volume fraction of interstitial tissue.

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↗

Correlation of DNA ploidy and histologic diagnosis from prostate core-needle biopsies: is DNA ploidy more sensitive than histology for the diagnosis of carcinoma in small specimens?

DNA ploidy has been shown to have prognostic value in adenocarcinoma of the prostate. While occasional benign lesions of the prostate may be associated with a DNA aneuploid status, most aneuploid epithelial proliferations of the prostate are carcinomas. Because of the relationship between aneuploidy and malignancy, DNA ploidy analysis might improve detection of adenocarcinoma in small core-needle biopsy specimens. In this study, DNA ploidy analysis was performed on 186 fresh core biopsies from 32 patients who had undergone transrectal, ultrasonographically directed core-needle biopsies. Ploidy level was determined by Feulgen staining and image analysis with a CAS 200 image analyzer (Becton Dickinson-Cellular Imaging Systems, San Jose, CA). The resultant DNA ploidy levels were compared with the initial histologic diagnosis and subsequent clinical and pathologic follow-up. Nondiploid DNA patterns correlated with a diagnosis of carcinoma on core biopsy in 11 of 16 nondiploid cases and with a final diagnosis of malignancy in 13 of 16 nondiploid cases. Two patients with biopsy proven carcinoma had DNA diploid tumor patterns. Ploidy analysis had a sensitivity of 86.6% and a specificity of 73.7% in predicting the final diagnosis of malignancy. One case interpreted as DNA tetraploid by image analysis revealed seminal vesicle tissue on both the cytologic preparations and the core biopsy. Two DNA aneuploid specimen associated with cores initially read as benign or atypical demonstrated adenocarcinoma either on review of the original core biopsy or the prostatectomy specimen. The final DNA aneuploid specimen revealed acute prostatitis in the core biopsy. DNA ploidy analysis of core biopsy specimens appears to have relatively good specificity and sensitivity for the detection of prostatic carcinoma. Sampling errors appear to be the major cause of false negative results. Inappropriate measurement of seminal vesicle tissue and acute prostatitis can result in false positive results.

Adenocarcinoma↗