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Phase contrast x-ray imaging is a powerful technique for the detection of low-contrast details in weakly absorbing objects. This method is of possible relevance in the field of diagnostic radiology. In fact, imaging low-contrast details within soft tissue does not give satisfactory results in conventional x-ray absorption radiology, mammography being a typical example. Nevertheless, up to now all applications of the phase contrast technique, carried out on thin samples, have required radiation doses substantially higher than those delivered in conventional radiological examinations. To demonstrate the applicability of the method to mammography we produced phase contrast images of objects a few centimetres thick while delivering radiation doses lower than or comparable to doses needed in standard mammographic examinations (typically approximately 1 mGy mean glandular dose (MGD)). We show images of a custom mammographic phantom and of two specimens of human breast tissue obtained at the SYRMEP bending magnet beamline at Elettra, the Trieste synchrotron radiation facility. The introduction of an intensifier screen enabled us to obtain phase contrast images of these thick samples with radiation doses comparable to those used in mammography. Low absorbing details such as 50 microm thick nylon wires or thin calcium deposits (approximately 50 microm) within breast tissue, invisible with conventional techniques, are detected by means of the proposed method. We also find that the use of a bending magnet radiation source relaxes the previously reported requirements on source size for phase contrast imaging. Finally, the consistency of the results has been checked by theoretical simulations carried out for the purposes of this experiment.

Aim of the Study: To evaluate the indications for open surgical biopsy of breast lesions resulting in a benign histologic report., Methods: A consecutive series of 754 benign breast biopsies was collected from six Italian centers previously participating in a multicenter study on the benign/malignant biopsy ratio. Histologic diagnosis, diagnostic tests performed, final clinical diagnosis and the indication for surgical biopsy were compared., Results: Fibrocystic alterations represented the most frequent histologic type (43.2%), followed by fibroadenomas (34.5%). Atypical hyperplasia, phyllode tumors and cancer-like lesions (radial scar, sclerosing adenosis) accounted for a minority of cases. The diagnostic approach was different among centers, with mammography, ultrasonography or cytology being underused in some of them. Suspicion of cancer was an indication for surgical biopsy in 66.7% of cases. In the remaining cases the final report was negative or benign, but biopsy was advised for growing lesions (11.3%) or for cosmetic (3%) or psychological reasons (8.2%). In 4% of cases surgical biopsy was presumably advised for the concurrent influence of high-risk conditions such as previous breast cancer (0.7%), family history of breast cancer (2%) or contralateral synchronous breast cancer (1.3%). In 6.8% of the cases biopsy was advised elsewhere for unknown reasons. The indications for biopsy differed among centers, with one center having a low rate of suspicious cases (37%) and a high rate of reported "cosmetic" or "psychological" reasons (47%)., Conclusions: Leaving aside differences in diagnostic approach and aggressiveness, two thirds of all lesions were biopsied in order to exclude cancer. The routine use of a more complete diagnostic protocol and/or alternative methods to obtain a histologic diagnosis (e.g. core biopsy) might substantially reduce the need for open surgical biopsy.

The expression of nuclear proteins high mobility group (HMG) I and HMGY was investigated in intraepithelial and invasive lesions of the uterine cervix. Human carcinoma cell lines C-41, ME-180, and CaSki were used for testing protein expression in neoplastic cells from the cervix. Morphological grading of the dysplasias (CIN 1, CIN 2, and CIN 3) and invasive carcinomas from formalin-fixed paraffin-embedded samples parallels the degree of nuclear immunostaining obtained using a polyclonal antibody raised against the amino-terminal region of HMGI(Y) proteins. The immunostaining obtained with HMGI(Y) antibody was compared with that observed using the antibody Ki-67, and the results were similar. We suggest the use of HMGI(Y) antibody in clinical oncology as a useful marker of intraepithelial lesions and invasive carcinomas.

We present the clinical, light microscopic, and immunohistochemical features of two new cases of leiomyosarcoma of the female breast. Both the patients were old (83 and 86 years) and were referred with a history of a long-standing breast lump. The results of the physical examination and the preoperative radiologic investigations suggested a phyllodes tumor. The patients were treated with mastectomy. The tumors measured 6 and 6.5 cm in the largest dimension, respectively, and were composed of fascicles of atypical, actively proliferating spindle cells, often intersecting at right angles. The axillary lymph nodes were free of tumor. Immunohistochemically, the tumor cells were positive for desmin, muscle-specific actin, and vimentin and negative for other markers, including keratins and hormone receptors. Focal rhabdomyoblastic differentiation was noted in one case. Follow up at 1 year is negative for metastases or local recurrences. Our study confirms that leiomyosarcoma of the breast is a locally invasive neoplasm and that it could represent a peculiar anatomic entity among mesenchymal tumors of the breast.

We report two cases of squamous carcinoma of the breast detected during the gestational period. One woman was post-partum and lactating; one was in the first trimester of pregnancy. The lesions were clinically palpable, multifocal, and measured more than 5 cm in their largest dimension; both had a cystic appearance. They were treated with radical mastectomy. One patient received pre-operatory chemotherapy. Histologically, the tumors were poorly differentiated squamous cell carcinomas. No areas of ordinary duct differentiation were seen. Lymph nodes contained metastatic squamous carcinoma in both cases. Tumor cells were negative for estrogen and progesterone receptors. Also, they expressed a high proliferative index and several markers of tumor progression, including cErb-B2, p53 protein, bcl-2, and epidermal growth factor receptor. One patient died of tumor 5 months following breast surgery and had extensive metastases proven at autopsy. The other patient had evidence of pulmonary metastases: following cisplatin therapy, she underwent clinical remission. This study shows that squamous carcinoma of the breast may occur in pregnant or lactating women: it appears clinically distinguishable from the non-gestational type that is usually associated with a better prognosis and occurs in peri- or postmenopausal women.

In our study we analyzed a file of 756 males with lung cancer and an equal number of controls matched by sex, age and year of death. All the subjects were resident in the Trieste area, died between 1979-81 and 1985-86 and underwent autopsy at the Istitute of Pathological Anatomy of the University of Trieste. The aim of the research was to analyze and quantify the risk to develop lung cancer in those exposed to asbestos, and well-recognized carcinogens (list A of I.A.R.C.) or suspected (list B). We have also analyzed the relative risk (R.R.) for lung cancer among those subjects with environmental exposure to air pollution in industrial and urban areas. The study was set up in the Trieste province, a geographic area which is particularly suitable for epidemiological studies. We have demonstrated on excess of risk for males exposed to asbestos (R.R. = 1.99) and to other well known carcinogens (R.R. = 2.28). The capability in differentiating the relative risk of smoking and professional exposure to oncogenetic substances allowed us to detect an excess of risk for people living in industrial and urban areas, when compared to those living in rural and peripheral areas.

We report three cases of an unusual primary carcinoma of the liver composed of small cells. The patients were adult males (56 to 89 years) who presented with jaundice, weight loss and abdominal discomfort. Surgery was attempted in one case. Clinical evolution was rapid, with death ensuing between 1 and 5 months after diagnosis. Surgical (1 case) and autopsy (2) tissues were available for review. All three tumours arose in non-cirrhotic livers. They were composed of broad nests of small epithelial cells with little supporting tissue. They were positive for low-molecular weight keratins and alpha-fetoprotein. One case was immunoreactive for erythropoietin antigen. Expression of neuroendocrine markers was focal and erratic. No immunostaining was observed for carcinoembryonic antigen or S-100 protein. In one case ultrastructural investigation disclosed canaliculi surrounded by microvilli and junctional complexes. In the light of these features, it appears that small cell carcinoma represents a rare, but definite variant of hepatocellular carcinoma. Although it does not segregate in a peculiar clinical setting, it should be distinguished from metastatic pulmonary small cell carcinoma as well as from other malignancies featuring small cells.

In the last few years percutaneous cryoablation surgery of the prostate has been re-introduced as an alternative means to treat prostatic carcinoma. Advantages of the technique include local effectiveness in eradicating tumors, minimal morbidity rate and lower costs when compared to radical surgery. We report a study documenting the histopathological changes seen in 317 biopsy specimens obtained from 30 patients (age range 59-83 years, median 73 years) treated with cryosurgical ablation for prostate cancer. Pre- and postoperatory assessment was inclusive of plain clinical, laboratory and instrumental data (digital rectal examination, transrectal ultrasound scan, serum prostatic specific antigen concentration) and systematic biopsies obtained from conventional and modified prostate sextants. Fifteen patients had tumors extending through the prostate capsule (pT3 and pT4). Six patients had stage PT1 tumors and 9 had stage pT2. Tissues were sampled at 3, 6 and between 12-18 months postoperatively. The histologic findings, in decreasing order of frequency, were: full core fibrosis, necrosis, granulation tissue, basal cell hyperplasia, cell swelling, hemosiderin deposits, chronic inflammation, thick nerves and prostatic hyperplasia. Necrosis was of the coagulative type, sometimes associated with nuclear debris, and seen at relatively short interval from cryotherapy. Fibrosis with hyaline qualities was seen especially at 12-18 month interval. The presence of necrosis, as well as granulation tissue, hemosiderin deposits and cell swelling, strongly correlate to intervals from cryosurgical ablation. Residual tumor tissue was focal (0.5-1 mm) and recognizable in 9 cores from 4 patients (13.3%) sampled especially from the prostatic apex. Incipient tumor necrosis was seen in 11 cores, without particular distribution. These findings indicate that cryosurgery results in distinctive changes in both tumoral and non-tumoral prostate tissue. Knowledge of the histopathologic patterns is important since it provides the clinicians with information on treatment efficacy or failure, and could assist in the selection of larger groups of patients eligible to cryosurgical ablation.

We report a case of inflammatory fibrosarcoma occurring in a 49 year-old man, that manifested with distinct multinodular masses in the mesentery. Histologically, the lesion was characterized by spindle fibroblast-like cells, histiocytes, pool of lymphocytes and eosinophils, abundant fibrous to hyaline stroma, and numerous "ganglion" cells. Of special interest was the presence of large multinucleated tumor cells which displayed optically clear nuclei and prominent nucleoli, bearing a deceitful resemblance to the diagnostic Reed Sternberg cells of Hodgkin's disease. The differential diagnosis between the two conditions rests on the evaluation of the appropriate clinical background, as well as on an in-depth assessment of the basic pathologic features. Immunohistochemical reactivity of spindle and ganglion cells for actin along to complementary negativity for CD15, and CD30 further assists in separating the two conditions.

Four cases of small cell carcinoma characterized by a striking involvement of the pleural sheets were investigated. The patients, four adult males with a long history of cigarette smoking, presented with symptoms common to pleural tumors, including cough and chest pain. Malignant cells were identified in pleural effusions of all cases and in the bronchial aspirate of one patient. Antitumoral treatments included chemo- and/or radiotherapy. Survival ranged from three to 17 months. At autopsy, the serosal sheets resulted to be extensively involved by thick tumor rinds, associated with massive hilar metastases. Histologically, the tumors were composed of small epithelial cells, expressing carcinoembryonic antigen and keratins and occasionally neuroendocrine markers. Our findings indicate that small cell carcinoma should be added to the group of pseudomesotheliomatous lung carcinomas and, above all, that it deserves distinction from ordinary mesothelioma, especially the small cell variant, because of its medico-legal implications and possible antitumoral treatment.

Objective: To evaluate effusion cytology on routine smears in patients with hepatocellular carcinoma., Study Design: Filed smears from 106 patients with autopsy-proven hepatocellular carcinoma were retrospectively reviewed for the presence of malignant cells. Morphologic patterns, as well as immunochemical reactivity for a panel of antibodies, were analyzed when feasible., Results: Malignant cells were identified in 10 cases of ascites and 1 of pleural fluid. Positive smears were variably cellular, with paucicellular, round or linear aggregates of polygonal cells. The cytoplasm was usually evident and very stainable. The nuclei were hyperchromatic or vesicular, with inconspicuous nucleoli. Reactive changes were frequent. Malignant cells were positive for keratins (7/8) and erythropoietin (4/8) and negative for carcinoembryonic antigen (0/8). Concomitant cirrhosis was present in 103 cases (97.1%); all the noncirrhotic cases had malignant cells identifiable in the effusion. Antemortem clinical diagnosis of malignancy was made in 59 cases (55.7%); cytology was the only source of the morphologic diagnosis in most of them., Conclusion: These results indicate that although the yield of hepatocellular carcinoma in effusion cytology is limited, it may be important in the initial assessment of the disease, given the ineligibility of most patients for invasive procedures and the equivocal features of instrumental investigations. Immunocytochemistry may further assist in differentiating doubtful cases.

A sample of 2,563 cases of liver cirrhosis diagnosed among 26,879 autopsies performed consecutively in the years 1976/85 was considered in order to study the morphologic feature of the liver cirrhosis and their relationship with primary liver cancer (PLC) outbreak. The study showed that age of patients affected by cirrhosis is a significant risk factor for PLC. In fact, in the 10 years considered, the observed mean annual increase of age at death of the cirrhotic patients was associated with an increase in PLC cases. This may be explained as a well known consequence of the conversion of micronodular type of cirrhosis to mixed and macronodular ones (for which cancer complication is more frequent) but also as a statistically significant higher risk of PLC in the older group of patients affected by micronodular cirrhosis. The older age of cirrhotic patients at death observed in the last few years in the Trieste area is probably correlated to a general European trend: our results, although relative to a restricted geographic area, seem to be of interest in order to identify better the patients at risk of PLC among those affected by cirrhosis.

A positive association between alcohol consumption and stroke incidence has been clearly established. The present study evaluated the frequency of stroke in a sample of 500 autopsied patients affected by liver cirrhosis mainly due to chronic alcohol abuse as confirmed by the histologic pattern mostly of mixed and micronodular types. Frequency of stroke was compared to that of 4,741 non-cirrhotic patients autopsied in the same period. Our findings demonstrate that stroke frequency, especially when due to thromboembolism, decreased significantly in cirrhotics. Therefore, hepatopathy is a crucial event in alcoholic patients. Nevertheless the concomitant presence of liver cirrhosis, in studies dealing with this subject, is not being currently evaluated.

This study, aimed at elucidating the epidemiological features of primary liver carcinoma developing in non-cirrhotic livers, was based on 25,103 autopsies performed between 1975 and 1984 in Trieste, Italy. These autopsies correspond to approximately 70% of all deaths that occurred in this area. Various factors allegedly related to carcinomas were analysed in reference to our previous study on cirrhotic livers and in comparison with 5,603 autopsies in Kurume, Japan. There were 28 cases of hepatocellular carcinoma (HCC), 16 of cholangiocellular carcinoma (CCC) not associated with cirrhosis in Trieste, and 48 HCC and 19 CCC in Kurume. On the basis of our findings, it was concluded that cirrhosis, regardless of its cause, is the main pathogenetic factor in HCC; it is responsible for a much higher frequency (14.2:1) than in non-cirrhotic livers, as well as for early occurrence of tumours (an average of 6 years earlier in cirrhotic liver) in Trieste. Patients in Trieste were older than those in Japan, and the frequency of HCC among all autopsies was much greater in the latter. By contrast, the influence of cirrhosis on cholangiocellular carcinoma (CCC) was negligible, as such association appeared purely coincidental or absent. The incidence of CCC among autopsies was greater in Japan. Our data on CCC were not sufficient to demonstrate any clear aetiopathogenetic association between this tumour and alcohol abuse and hepatitis B virus (HBV) infection, except for a possible aetiological role of gallstones. The frequency of CCC relative to HCC was greater in Trieste than in Japan; the incidence of HCC was much less in Trieste, whereas CCC was more frequent in Japan.

The authors report their data on epidemiology of liver cancer (LC) in Trieste. Because of the high autopsy rate in the Province (the ratio autopsies/deaths is about 70%), the findings allow to draw some conclusions which could be regarded as a paradigm, at least in Northern Italy: 1) At autopsy LC prevalence is about 1.8% and the value has been increasing over the last few years; 2) 95.4% of LC are hepatocellular (HCC) and 92.9% of the latter occur in cirrhotic livers. Patients with HCC and cirrhosis are 6 years younger than those affected by HCC alone. On the basis of the above reported conclusions, the role of liver cirrhosis as preneoplastic condition is discussed.