Cervical intraepithelial neoplasia is common in young women, and invasive cervical cancer is one of the most common malignancies seen in pregnancy. Women with cervical cancer diagnosed at <20 to 24 weeks of gestation are typically treated immediately, whereas patients diagnosed later in pregnancy often defer treatment until after delivery. Women with early stage cervical cancer can be treated with either surgery or radiation, whereas those with advanced-stage disease are usually treated with radiation, often in combination with chemotherapy.
The aim of our study was to evaluate the validity of the quantitative analysis of nuclear features on aspiration smears in the distinction between follicular adenoma and follicular carcinoma. Karyometric and DNA features, including the nucleolar count, were evaluated on the cytologic material of 28 cases; the values were in general slightly higher in the carcinomas than in the adenomas, with overlap between the two diagnostic groups. By plotting the two most discriminant and least correlated parameters against each other and by drawing two straight lines (one perpendicular to the axis representing the mean of the major nuclear diameter at the 9-microns point, the other perpendicular to the axis of the percentage of nucleolated cells at the 75% point), we obtained two regions: a rectangle delimited by the two axes and the two lines containing 86% of adenomas, and the remaining part of the plane containing 79% of carcinomas. The validity of this approach was tested in 32 new cases not included in the original bivariate classification: accuracy 87%; sensitivity 86%; specificity 88%; predictive value of adenoma 88%; predictive value of carcinoma 85%. In conclusion, a simple cytometric method, i.e., the combined evaluation of the mean of the major nuclear diameter with the percentage of nucleolated nuclei, allows a substantial distinction to be made between follicular adenoma and carcinoma.
The influence of magnification on light microscopic morphometry was studied. Morphometry was performed on 34 hepatocytes by using a digitizer plate with micrographs of the nuclei, and with digitized image of the nuclei on a separate monitor. Intraobserver variation was smallest at objective magnifications of 40 and 100 X (CV of form factor, maximum diameter and nuclear perimeter under 1%, of nuclear area under 2%, when measured from the monitor). The results show that more reproducible measurements are possible with higher magnifications. The authors recommend objective magnifications of 40 and 100 X for morphometric measurements on nuclei. The results also suggest that morphometric grading should apply an intermediate third grade in dichotomous grading scales.
Out of a total of 200 patients with solitary thyroid nodules, 41 diagnosed by fine-needle aspiration biopsy (FNAB) (group A) and 159 by clinical and/or scintiscanning data (group B), 22 were found to have malignant neoplasias, 31 adenomas, 145 simple goiters and 2 thyroiditis. The use of the FNAB technique led to a percentage increase in the operations for malignant neoplasias, while it markedly reduced the number of surgical interventions for simple goiter. Statistical calculation of the sensitivity, specificity, negative predictive value and overall diagnostic accuracy of FNAB indexes demonstrated that FNAB is a simple, reliable, useful and cost-effective procedure.
DNA measurement represents a type of quantitative analysis which allows us to gain prognostic information on malignant tumors and to study the natural history of the epithelial neoplasia. However, there are sources of variation in evaluating the DNA content. These include variation due to field selection, variation between observers (interobserver variation), and variation between laboratories (interlaboratory variation). The influence of various variation sources was studied in 4 experiments. When DNA measurements were made from the same microscopic fields, the results did not differ remarkably. However, observer training proved to be important. Intra- and interobserver variation was lower among experienced morphometrists than among inexpert observers. Different laboratories and image analyzers may give different results when the same case is measured. To overcome at least part of the potential variation sources, undergraduates and postgraduates at the Departments of Pathology of Ancona and Kuopio Universities are specially trained in the use and application of morphometry. Special sampling rules should be applied and observers encouraged to follow the rules as uniformly as possible.
A peculiar case of renal oncocytoma was studied by clinical, light- and electron-microscopic examinations. The neoplasm, which was first discovered 21 years ago, at operation turned out to be very large, well-circumscribed and lacking any feature of aggressiveness. Histologically, it was composed totally of oncocytes without relevant atypia or necrosis. Ultrastructurally, a cytoplasmic filling by mitochondria with paucity of other organelles and filaments also supported the diagnosis. The authors also reviewed the literature and emphasized the diagnostic criteria of this type of tumor.
The reported incidence of cytokeratin and vimentin intermediate filament coexpression is rapidly expanding. An up-do-date list of the instances in which this occurs is presented and the implications of this event are discussed.
Morphological changes in lymph node biopsies of HIV-infected patients can be classified in four stages, based upon the degree of damage to follicular structures: (1) follicular hyperplasia, (2) follicular lysis, (3) follicular atrophy and (4) follicular and lymphocytic depletion. To define the relative usefulness of morphological, clinical and immunological findings for prognostic purposes, we followed the clinical evolution of 86 biopsied HIV+ patients for a period ranging from 1 to 56 months. A relatively good correlation between histological and clinical findings, at the time of biopsy, was observed. Statistical analysis confirmed the prognostic value of the histological features for clinical deterioration, progression to AIDS and survival. Moreover, histological findings gave more reliable prognostic information than clinical values. Our data suggest that lymph node biopsy can be utilized for prognostic purposes in the evaluation of the progression of the disease and effectiveness of antiviral therapeutic trials.
We report the unusual case of two distinct hamartomas in one of the breasts of a 20-year-old woman. Hamartoma (adenolipoma, fibroadenolipoma, lipofibroadenoma) of the breast, a rare benign lesion, occurs in females. It is unilateral and displays an organoid structure. It is composed of lactiferous ducts, mammary glands, and connective and fatty tissue, surrounded by a pseudocapsule. It causes enlargement of the breast, usually without localized lesion on palpation. Mammographic and intraoperative findings, however, are characteristic. As the microscopic features of hamartoma are similar to those of other related benign lesions of the breast, diagnosis may be difficult by histologic examination alone; in addition, knowledge of radiologic, surgical and clinical findings may be required.
In the light of recent findings concerning the importance of intermediate alpha 1-antitrypsin deficiency in the development of chronic liver disease and of hepatocellular carcinoma, we report the case of a 56-year-old woman affected by cirrhosis with significant features of liver cell dysplasia associated with intermediate alpha 1-antitrypsin deficiency (protease inhibitor SZ phenotype). In our paper we emphasize the importance of a precocious diagnosis and identification of individuals carrying the Z allele, also heterozygous.
Morphometric and morphological parameters have been evaluated in tumours of carotid body paraganglia and of aorticopulmonary and aorticosympathetic paraganglia. Paragangliomas are characterized by a higher cell density and rounder nuclei (roundness factor) than non-neoplastic carotid body paraganglia. The nuclear area has similar mean values in tumours and normal paraganglia; however, the former group shows higher standard deviation values and coefficients of variation, reflecting the fact that paragangliomas have nuclei of variable size; the variation is more pronounced in aorticopulmonary and aortico-sympathetic paragangliomas. However, subgroups on the basis of morphological features (architectural patterns and degree of intensity of argyrophilia), site of origin, and clinical behaviour (metastases and recurrences) show no morphometric differences.
An immunocytochemical study using a panel of commercially available antisera, has been performed to distinguish on the basis of their immunoreactivity a series of spindle cell sarcomas diagnosed solely on the histologic features: 11 malignant schwannomas (MS), 8 leiomyosarcomas (LMS) and 3 malignant fibrous histiocytomas (MFH). The results have been compared with those obtained in 12 benign and 8 malignant peripheral nerve sheath tumors (MPNST) in which the microscopic diagnosis was supported by their origin in a nerve trunk and/or in von Recklinghausen's (vR) disease. The following antisera were used: anti-S-100 protein, anti-Leu-7, anti-neuron specific enolase (NSE), anti-myelin basic protein (MBP), anti-glial fibrillary acidic protein (GFAP) and anti-actin. S-100 protein was present in 100% of benign and malignant peripheral nerve tumors and in 7/11 (63%) of MS diagnosed on histological basis only and in 3/8 (37%) LMS. MFH were negative. Leu-7 positivity was observed in 8/12 (66%) and 6/8 (75%), respectively, in benign and malignant PNS neoplasms, in 5/11 (45%) MS, 4/8 (50%) LMS and 2/3 (66%) MFH. NSE was present in 7/12 (58%) and 6/8 (75%), respectively, in benign and malignant PNS tumors, in 6/11 (54%) MS and in 1/8 (12%) LMS. MFH were negative. MBP resulted negative in peripheral nerve neoplasms and spindle cell sarcomas. GFAP positivity was observed in 2/12 (16%) and 1/8 (12%), respectively, in benign and malignant PNS neoplasms. All spindle cell sarcomas were negative. All cases of MPNST and spindle cell sarcomas showed actin immunoreactivity. These results indicate that: (1) MBP, Leu-7 and NSE do not represent markers of schwannian differentiation; (2) GFAP, although rarely expressed, may indicate schwannian differentiation, and (3) malignant peripheral nerve neoplasms and LMS share immunoreactivity for S-100, Leu-7, NSE and actin, therefore they cannot be differentiated on immunocytochemical basis using commercially available antisera.
To evaluate the possible transmural differences in the structure of left ventricular myocardium in patients with ischaemic heart disease, 45 human hearts were examined with morphometric methods. There were 10 control hearts, 10 hearts with coronary atherosclerosis but without myocardial infarction, 11 hearts with acute subendocardial infarction and 14 hearts with acute transmural infarction. The following histoquantitative parameters were separately estimated for both subendocardium and subepicardium in each heart: the volume fraction of diffuse connective tissue, the mean fiber diameter and the numerical density of arterioles. Diffuse myocardial fibrosis was more severe in subendocardium in all groups, the highest values were found in hearts with acute subendocardial infarction. In all groups the numerical density of arterioles was higher in subendocardium. The numerical density of arterioles was increased in respect to the controls in both subendocardium and subepicardium in hearts with coronary atherosclerosis without evidence of myocardial infarction and in hearts with acute subendocardial infarction. The possible pathophysiological implications for ischaemic heart disease are discussed on the basis of these results. The results suggest different pathophysiological mechanisms in subendocardial and transmural myocardial infarction. They also suggest that transmural differences should be considered when the findings of endomyocardial biopsies are evaluated.
Platelet factor 4 (PF 4), the low molecular weight polypeptide stored in the alpha granule, has been shown to be released from platelets during the process of activation. To examine the effects of known atherogenic food fats on platelet activation, as manifested in circulating PF 4 concentrations, groups of rhesus monkeys were fed diets enriched with varying quantities of different food fats. Plasma PF 4 levels were measured at set intervals during the experimental period. Platelet counts were performed and PF 4 values assayed using the radioligand binding technique. Animals given coconut-oil-enriched diets showed the greatest increase in PF 4 levels; while those fed corn, peanut and soybean-oil-containing rations showed small insignificant fluctuations of plasma PF 4 values. In this study the coconut oil effect on plasma PF 4 values increased with time; diluting the coconut oil with increasing quantities of corn oil led to progressive decreases in these values. These data indicate an increased incidence of platelet activation in animals fed coconut-oil-enriched diets, and suggest that corn oil counteracts this thromboactive effect of coconut oil.
Preparation of sections from undecalcified bone marrow biopsies embedded in glycol methacrylate (GMA, Technovit 7100) is reported. The beneficial effect of vacuum for a better penetration of resin into the hard tissue is assumed. Preserved details of 2- to 3-microns-thick sections of bone marrow specimens from various haematological malignancies yield a proper diagnosis and use of some histochemical methods on immature leukaemic cells is also possible. The use of embedding medium Technovit 7100 in the bone marrow histopathology is widely recommended for its simple, quick usage and non-toxic properties. An additional advantage is that blocks can be cut with ordinary steel knives (Histoknife H).
A Leydig cell tumor of testis was discovered during evaluation of infertility in a 36-year-old white man with azoospermia and high plasma estrogen level. Histological examination revealed multiple foci of calcification and massive adipose metaplasia. This is the first time that adipous metaplasia is observed in association with Leydig cell tumor of testis.
50 carcinoid tumors of different locations in the gastrointestinal and respiratory tracts were examined histochemically for mucin production. Isolated discrete aggregates of mucosubstances were identified in a large number of cases (46% of all carcinoid tumors, ranging from 53 to 36% in different organ locations). Acidity and composition of mucosubstances (sulfomucin vs. sialomucin contents) in carcinoids were not different from those described in their corresponding locations. These data support numerous other observations that point to a common stem cell precursor for both enterochromaffin and mucus-secreting epithelial cells in gastrointestinal and respiratory tract mucosal membranes. A shared endodermal derivation is favored over a separate neuroectodermal origin for the chromaffin cell system.
The utility of fine needle aspiration biopsy (FNAB) was checked in the diagnosis of 187 neoformations which arose in the same number of patients during follow-up after treatment for malignant neoplasia. FNAB diagnosis was 138 malignant lesions (9 primary and 129 secondary) and 49 benign lesions (8 neoplastic and 41 nonneoplastic). 157 of the 187 diagnoses (83.95%) were controlled: 124 histologically (78.98%) and 33 clinically (21.01%). Specificity was 100%, sensitivity 98.36%, predictive negative value 94.59% and total diagnostic efficiency 98.72%. The reliability of the method and the usefulness of the findings from the therapeutic point of view suggest the advisability of performing FNAB during the post-diagnostic phase of neoplastic disease.
A further case of xanthomatous endometritis, characterized by the presence of histiocytic cells in the endometrium, in the absence of carcinoma is described. This lesion seems to be a rare complication of hematometra with cervical occlusion. The foam cells would appear to be macrophages, components of a nonspecific inflammatory reaction, which have phagocytosed breakdown elements of retained endometrial hemorrhage.
Sixty-three bronchial tumours are described. Using the criteria of necrosis, a mitotic count of 5 or greater per 10 high-power fields, well marked nuclear pleomorphism, lymphatic and vascular invasion, either singly or in combination, 38% of cases were considered atypical or well-differentiated neuroendocrine carcinoma. If an undifferentiated growth pattern was added as a further criterion, 49% of bronchial carcinoids were atypical. Oncocytic change was common (59% of cases) but only one pure oncocytic carcinoid was present in the series. Bone was seen in 25% of cases. In some cases it arose from the bronchial cartilage but in others it was seen in the centre of the tumour. The range of histological patterns seen in carcinoids is described. Rare types of bronchial carcinoids showed a papillary pattern as well as spindle cell foci. Two cell types were noted--large cells with eosinophilic cytoplasm and cells with small hyperchromatic nuclei and little cytoplasm. These cells are apoptotic as shown ultrastructurally. The differential diagnosis of these tumours is discussed. In 35 cases a clinico-pathological correlation was possible. Bronchial carcinoids are biologically unpredictable tumours. The present study indicates that nearly half the cases could be classified as atypical or well-differentiated neuroendocrine carcinoma. However, there still remained some cases where the histology was typical but subsequent lymph node metastases developed.
