Cytologic diagnosis of non-oxyphil follicular neoplasias of the thyroid. Multivariate classification procedure based on quantitative nucleolar features.

The study was done on cytologic material of 58 non-oxyphil follicular neoplasias of the thyroid, 32 of which were adenomas and 26 carcinomas. Three groups of nucleolar features were quantified using a routine microscope with an ocular micrometer: frequency-, size-, and margination-related features. Since value overlap was present between two categories for all the variables, stepwise discriminant analysis was applied. The following three features were selected by the computer for calculation of one canonical discriminant function: percentage of marginated nucleoli, percentage of nuclei with one nucleolus, mean major nucleolar diameter. The percentage of agreement between morphologic and computer classifications was 95%. Two follicular adenomas were allocated to the carcinoma category, whereas one follicular carcinoma was allocated to the adenoma category. Out of 58, 52 were diagnosed by the computer into one of the two diagnostic categories with a very high probability, i.e. P greater than 0.75, the remaining 6 being considered intermediate.     

Tannic acid-induced nucleolar changes in hepatocytes transplanted into syngeneic or xenogeneic host and in hepatocytes maintained in primary culture

In this study we have investigated the effect of a single dose of tannic acid, administered s.c., on the nucleolar ultrastructure of hepatocytes transplanted into a syngeneic or xenogeneic host in order to evaluate the validity of our hepatocyte transplantation system as an in vivo alternative to the use of whole animals to test for species and strain differences to the effects of hepatotoxins. Within 4-6 h following tannic acid injection, rat hepatocytes transplanted into the anterior chamber of eye and inguinal fat pads of rat and athymic nude mouse, showed changes of nucleolar components, with separation of ribonucleoprotein containing granules into discrete dark zones. These dark areas were surrounded by light areas consisting of granular and fibrillar components of the nucleolus. These changes were identical to tannic acid-induced nucleolar alterations in the homotopic liver. Hamster and rat hepatocytes xenotransplanted into athymic nude mice also displayed prominent nucleolar alterations in response to tannic acid. The similarity and extent of nucleolar alterations observed in transplanted hepatocytes and the in situ homotopic liver cells attest to the usefulness of the hepatocyte transplantation system for the evaluation of species differences in biological response to toxic/carcinogenic effects of xenobiotics.     

Enhanced lung maturation in cocaine-exposed rabbit fetuses

Because of cocaine's possible effect on the incidence of respiratory distress syndrome in offspring of cocaine-addicted mothers, we have studied the effects of maternal exposure to cocaine on the functional anatomy of fetal rabbit lungs. Pregnant dams were injected s.c. daily with either cocaine (18 mg/kg) or an equal volume of 0.9% NaCl at 24, 25, and 26 d gestation. Cocaine metabolites were confirmed both in urine of treated dams and in fetal amniotic fluid. Serum cortisol levels were higher in treated dams than in controls. Fetuses were delivered through hysterotomy at 27 d. Tracheas were cannulated and a volume-pressure diagram was obtained during initial lung inflation-deflation. Volume was measured for 2 min at each pressure (P) increment of 5 cm H2O. Body weights and dry lung weights were comparable between the two groups. In contrast, cocaine-exposed lungs differed from controls as follows: 1) wet lung weights were lower (0.79 versus 0.89 g, p less than 0.02); 2) opening pressure was lower (P25 versus P35); 3) volume (mL/kg) was higher in treated animals at each pressure step (p less than 0.05); 4) end-deflation volume at P0 was higher (30.4 versus 0.8 mL/kg, p less than 0.001); and 5) bubbles released from saccules by micropuncture, which were stable by Pattle's criteria, had estimated surface tension near zero (controls produced no stable bubbles). Light micrographs of cocaine-exposed fetuses revealed more secondary septa and thinner septal walls than controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of Periductal and Ductular Epithelial Cells of the Adult Rat Pancreas in Pancreatic Hepatocyte Lineage: A Change in the Differentiation Commitment

Development of pancreatic hepatocytes in adult rats maintained on copper deficient diet containing 0.6% trien (CuDT) has been reported recently. To elucidate the histogenesis of hepatocytes a sequential study was undertaken using morphologic, histochemical, immunochemical, in situ hybridization, and Northern blot analysis. Male F-344 rats weighing 80 to 90 g were fed CuDT for 8 weeks and returned to normal rat chow. Beginning from 4 weeks of copper depletion, there was a progressive loss of acinar cells and by 8 weeks more than 90% of the acinar tissue was lost. During this period, there was an increase in the number of adipocytes in the interstitium, and in the number of interstitial and ductular cells. Morphologic observations were confirmed by immunoblot and Northern blot analysis, in which the amount of pancreatic proteins and their mRNAs decreased between 5 and 8 weeks. During this period, a progressive increase in the level of albumin mRNA was observed. In situ hybridization, performed at 7 weeks of copper deficiency, showed localization of albumin mRNA over interstitial and ductular cells. Pancreatic hepatocytes were identified immediately after the rats were returned to a normal diet and gradually increased in number. The hepatocytes occupied almost 60% of the pancreatic volume by 8 weeks. During the early recovery phase, hepatocytes were identified in ductules as well as in the interstitium. Based on these studies, it is concluded that both the ductular cells and interstitial cells, which resemble oval cells of liver, are capable of transforming into pancreatic hepatocytes and these cells may be considered stem-cell equivalent.     

Basal cell hyperplasia and basal cell carcinoma of the prostate: a comprehensive review and discussion of a case with c-erbB-2 expression

Prostatic basal cell proliferations range from ordinary basal cell hyperplasia (BCH) to florid basal cell hyperplasia to basal cell carcinoma. The distinction between these forms of BCH, including the variant with prominent nucleoli (formerly called atypical BCH), and basal cell carcinoma depends on morphological and immunohistochemical criteria and, in particular, on the degree of cell proliferation. In florid BCH, the proliferation index is intermediate between ordinary BCH and basal cell carcinoma. Immunohistochemistry is also useful for identifying the cell composition of the basal cell proliferations, including the basal cell nature of the cells, their myoepithelial differentiation, and c-erbB-2 oncoprotein expression. Based on the information derived from the literature and on the appearance and follow up of the case presented here, florid BCH might represent a lesion with an intermediate position between ordinary BCH and basal cell carcinoma. However, criteria useful for the identification of those cases with a true precursor nature are not available. In general, basal cell carcinoma is seen as a low grade carcinoma. The immunohistochemical expression of the c-erbB-2 oncoprotein, similar to that seen in breast cancer, might have therapeutic importance.     

Human pancreatic adenocarcinoma line Capan-1 in tissue culture and the nude mouse: morphologic, biologic, and biochemical characteristics

Human pancreatic ductal adenocarcinoma line Capan-1 was studied in tissue culture and the nude mouse. In tissue culture, the neoplastic cells grew as large epithelial-like mucin-producing cells. Subcutaneous and intraperitoneal transplantation of neoplastic cells into nude mice resulted in tumor formation characterized by marked invasiveness and distant metastases. Histologically, the tumor appeared as a well-differentiated mucin-producing adenocarcinoma morphologically resembling the tumor of origin. Chromosomal analysis showed a human karyotype with a chromosome number between 51-61. Lactate dehydrogenase and beta 2-microglobulin used as tumor markers were present in both tissue culture and the serum of tumor-bearing mice. The neoplasm, which was characterized by an increased level of cAMP, had lost completely the ability to respond to secretin stimulation. The tumor grown in the nude mouse was resistant to treatment with 5-fluorouracil, behavior identical to that of the original tumor. Diphtheria toxin resulted in complete tumor destruction. Because Capan-1 tumor grown in the nude mouse shows morphologic, biologic, and biochemical characteristics similar to the tumor of origin, it may be an invaluable tool in furthering understanding of the biology of human pancreatic cancer.     

Narrative review of prostate cancer grading systems: will the Gleason scores be replaced by the Grade Groups?

The Gleason grading system, proposed by Dr. Donald F. Gleason in 1966, is one of the most important prognostic factors in men with prostate cancer (PCa). At consensus conferences held in 2005 and 2014, organized by the International Society of Urological Pathology (ISUP), the system was modified to reflect the current diagnostic and therapeutic approaches. In particular, in the 2014 Conference, it was recognized that there were weaknesses with the original and the 2005 ISUP modified Gleason systems. Based on the results of a research conducted by Prof. JI Epstein and his group, a new grading system was proposed by the ISUP in order to address some of such deficiencies: i.e., the five distinct Grade Groups (GGs). Since 2014, results of studies have been published by different groups and societies, including the Genitourinary Pathology Society (GUPS), giving additional support to the prognostic role of the architectural Gleason patterns and, in particular, of the GGs. A revised GG system, taking into account the percentage of Gleason pattern (GP) 4, cribriform and intraductal carcinoma, tertiary GP 5, and reactive stroma grade, has shown to have some advantages, however not ready for adoption in the current practice. The aim of this contribution was to review the major updates and recommendations regarding the GPs and GSs, as well as the GGs, trying to give an answer to the following questions: “How has the grade group system been used in the routine?” and “will the Gleason scoring system be replace by the grade groups?” We also discussed the potential implementation in the future of molecular pathology and artificial intelligence in grading to further define risk groups in patients with PCa.     

Towards a new WHO classification of renal cell tumor: what the clinician needs to know—a narrative review

In 1952, renal cell carcinomas had been divided into 2 categories—clear cell or granular cell—depending upon their cytoplasmic staining characteristics. In the following years, the inventory of renal epithelial tumors has expanded by the addition of tumors named by their architectural pattern (i.e., papillary RCC, tubulocystic RCC), anatomic location (i.e., collecting duct carcinoma, renal medullary carcinoma), associated diseases (i.e., acquired cystic disease-associated RCCs). With the extensive application of molecular diagnostic techniques, it becomes possible to detect genetic distinctions between various types of renal neoplasm and discover new entities, otherwise misdiagnosed or diagnosed as unclassified RCC. Some tumors such as ALK rearrangement-associated RCC, MiT family translocation renal carcinomas, SDH-deficient renal cancer or FH-deficient RCC, are defined by their molecular characteristics. The most recent World Health Organization (WHO) classification of renal neoplasms account for more than 50 entities and provisional entities. New entities might be included in the upcoming WHO classification. The aim of this review is to summarise and discuss the newly acquired data and evidence on the clinical, pathological, molecular features and on the prognosis of new RCC entities, which will hopefully increase the awareness and the acceptance of these entities among clinicians and improve prognostication for individual patients.     

Mass lesions of the frontal lobes in acute head injuries. A comparison with temporal lesions

Summary Contusions and lacerations of the frontal lobes are very frequent; 43.4% in the whole series of traumatic brain mass lesions. Clinical, ICP, CT scan data and neuropathological findings in patients with such lesions are analysed and correlated. Moreover, the clinical features and the outcome of frontal masses undergoing surgery are also compared with similar lesions located in the temporal lobes.Frontal lesions cannot be differentiated on purely clinical grounds and the factors governing the outcome in both locations are the same. On the whole, surgical indications nowadays seem to be rather rare; only lesions behaving truly as expanding lesions with obvious intracranial hypertension benefiting from surgery.Brain contusion-laceration syndromes in general can no longer be considered separate entities. Neither should they be included in the miscellaneous group of traumatic intracranial mass lesions, since the pathophysiological significance of purely extracerebral effusions is entirely different.Traumatic contusions and lacerations and/or intracerebral haematomas, whether frontal or located elsewhere, should, instead, be considered in the context of head injuries of a different degree of gravity, as having collateral features which, on occasion, may call for surgical management.