Posterior wall as atypical localization of left atrial myxoma : Diagnosis and management.

Atrial myxomas are the most common benign cardiac neoplasms. Although the majority occur in the left atrium (LA) and are attached to the interatrial septum (75-80 % of cases), they can arise from any part of the LA and the cardiac chambers. We report the case of a 65-year-old woman who presented with features of worsening dyspnea and persistent headache. During transthoracic echocardiography, a suspected cardiac myxoma was found arising from the posterior wall of the LA.

Metastatic liposarcoma of the heart. Case series and brief literature review.

Secondary cardiac tumors are 20-40 times more frequent than primary lesions. Primary cardiac lesions are represented by myxomas when related to benign tumors, and by sarcomas in terms of malignant disease. Metastases to the heart from liposarcomas are very rare. We present three cases of secondary liposarcomas involving the left atrium, the right atrium, and the pericardium.

Gastric ciliated metaplasia. A study of 3406 gastrectomy specimens from dwellers of the Atlantic and the Pacific basins.

BACKGROUND: Ciliated cells in gastrectomies from patients dwelling in the Pacific and Atlantic basins have been reported previously. AIM: To compare all the results in an attempt to explain the findings. METHODS: Sections from 3406 gastrectomies were reviewed: 1966 and 1440 from the Atlantic and Pacific basins, respectively. Ciliated cells and intestinal metaplasia (IM) were recorded; IM was classified into focal or extensive IM. The total number of sections/gastrectomy was noted. RESULTS: In the Atlantic basin, 5% of specimens had ciliated metaplasia (CM); it was more frequent in intestinal carcinoma (IC; 9%) than diffuse carcinoma (DC; 3%) or miscellaneous gastric diseases (MGD; 3%). In the Pacific basin, the frequency of specimens with CM was 29%: it was more frequent in IC (43%) than in DC (16%) or MGD (10%). The difference between the frequency of CM in specimens with IC or with DC/MGD in the Atlantic and the Pacific basins was significant (p < or = 0.05). The presence of CM was influenced by age and the extent of IM in both basins, but not by sex or the number of sections investigated. CONCLUSIONS: CM-apparently an independent microscopic marker-was significantly higher in the Pacific than in the Atlantic basin. Environmental carcinogens involved in the evolution of IM and IC seem to be implicated in gastric ciliogenesis. Carcinogens that differ in nature and/or in strength in both basins might activate the latent natural genes encoding ciliated processes in gastric cells in patients subsequently developing gastric carcinoma, more notably of intestinal type.

Serrated and microtubular colorectal adenomas in Italian patients. A 5-year survey.

Colorectal adenomas from 1552 Italian patients were histologically classified into tubular (TAs), tubulo-villous (TVAs), villous (VAs), serrated (SAs) and microtubular (MTAs). The purpose was to compare the results to those in 3135 colorectal adenomas from Swedish patients. Of the 1552 adenomas, 827 (53%) were TAs, 352 (23%) TVAs, 196 (12%) VAs, 102 (7%), SAs and 14 (0.9%) MTAs. The remaining 61 (4%) were of combined phenotypes (COMBAs). The percentage of VA (considered as the most important dysplastic precursor of colorectal cancer) was higher in Florence than in Stockholm. Notably, the incidence of colorectal cancer in males was also higher in Florence (78.6/10(5)) than in Stockholm (57.2/10(5)). Notwithstanding, the highest rate of submucosal invasion (7%) was found among SAs. The diameter of the largest section was used to define the size of the largest adenoma in individual patients. Of the 1380 neoplasias measuring < or =12 mm, only 0.9% (n=13) had invasive carcinomas, but as many as 8.1% (n=14) of the 172 neoplasias measuring > or =13 mm. SAs and MTAs are special adenoma phenotypes with particular morphological and cell proliferative attributes at variance from those of TAs, VAs or TVAs. In the light of the present results, it is proposed that SAs and MTAs are included in future reports of colorectal adenomas in order to compare their frequency worldwide.

Ultrastructural features of solid/trabecular areas in differentiated thyroid carcinoma.

The presence of areas exhibiting a solid/trabecular pattern of growth within an otherwise differentiated thyroid carcinoma represents a source of controversy as regards its proper classification and biologic and prognostic significance. The aim of the current study was to investigate the ultrastructural features of solid/trabecular areas in differentiated thyroid carcinoma and to compare those features with the submicroscopic profile of differentiated, poorly differentiated (insular), and undifferentiated (anaplastic) variants of thyroid cancer. The study series included differentiated carcinoma with solid/trabecular areas (3 cases), conventional papillary carcinoma (4 cases), follicular variant of papillary carcinoma (4 cases), poorly differentiated (insular) carcinoma (3 cases), and undifferentiated (anaplastic) carcinoma (3 cases). It was found that the solid/trabecular areas in differentiated carcinoma and poorly differentiated (insular) carcinoma share similar ultrastructural features and overall retain, even if attenuated, many of the submicroscopic attributes of differentiated carcinomas. In particular, nests of neoplastic cells were observed showing a highly developed cytosecretory apparatus and the presence of numerous abortive/rudimentary follicles, and intercellular and intracellular (intracytoplasmic) lumina/canaliculi of variable morphology. The study supports the hypothesis that the solid/trabecular areas do not merely represent an architectural pattern but rather should be regarded as the expression of a process of reduced differentiation similar to that of poorly differentiated (insular) carcinoma.

Gastric carcinomas of intestinal type concur with distant changes in the gastric mucosa. A multicenter study in the Atlantic basin.

Population studies in the Pacific Basin showed that gastric carcinomas of intestinal type often concur with distant mucosal changes (DMCs). In the present work, the presence of DMCs was investigated in populations dwelling in the Atlantic Basin. A total of 1737 gastrectomy specimens were reviewed: 627 in New York, 435 in Reykjavik, 198 in Buenos Aires, 186 in Florence, 174 in London and the remaining 117 in Stockholm. A total of 17,282 sections were carefully scrutinized. The following DMCs were investigated: intramucosal glandular cysts, gastric cells with ciliated metaplasia, with large or small mucus negative vacuoles, and extensive intestinal metaplasia (IM). The highest frequencies of DMCs were found in Florence for specimens with intestinal type carcinoma: 41.3% had intramucosal cysts, 22.4% had cells with ciliated metaplasia, 12.9% cells with large vacuoles, and 50.9% had high IM. The highest frequency of gastric cells with small vacuoles was recorded in New York (9.1%), also in specimens with intestinal type carcinoma. Significantly lower DMCs percentages were found in specimens with carcinomas of diffuse type, and miscellaneous gastric diseases. The occurrence of DMCs was not influenced to a significant degree by the number of sections available per gastrectomy. Since environmental factors trigger the evolution of intestinal type carcinomas and as DMCs also occurred in specimens without carcinoma-although at a significantly lower rate--it is conceivable that DMCs are also evoked by environmental factors (before a gastric carcinoma ensues). DMCs were found in specimens having intestinal carcinomas either in the cardia, the corpus or the antrum. Thus, DMCs seem to provide the adequate "soil" for the development of gastric carcinomas of intestinal type, independently of the future localization of that tumor in the stomach.

Prognostic significance of microsatellite instability in sporadic mucinous colorectal cancers.

We investigated the prognostic significance of microsatellite instability (MI) in 50 consecutive patients with sporadic mucinous colorectal cancer who had undergone only surgery. We evaluated MI and the pathological features with a possible prognostic value for each tumor, and the effect of the examined parameters on patients' outcome was statistically analyzed (univariate and multivariate analysis). All patients were followed-up for a minimum of 72 months or until death; in evaluating survival, only deaths of colorectal cancer were considered. DNA extracted from tumor sections and the corresponding normal tissue was analyzed by polymerase chain reaction at six microsatellite loci: D2S123, D3S1611, D3S49, D5S107, BAT26, BAT40. Alterations at two or more loci were detected in 36% of cases (MI+ tumors). MI+ and MI- cancers differed significantly in the pattern of growth, and most MI+ tumors showed an expanding type of growth (72.2%, P = .005). At univariate analysis, improved survival rate was significantly associated with MI, as well as with the following parameters: expanding cancer growth, Dukes stage, and absence of venous invasion. Nevertheless, at multivariate analysis, only the pattern of cancer growth and Dukes stage were independent prognostic factors, whereas the effect on survival of MI and venous invasion was found to be negligible. In our study, MI+ and MI- cancers differ only on the pattern of growth; therefore, our data suggest that the better survival rate in mucinous cancers with genomic instability is strictly related to their less aggressive type of growth.

Expression of transforming growth factor beta isoforms in osteosarcoma variants: association of TGF beta 1 with high-grade osteosarcomas.

Studies on osteosarcoma cell lines point to the potential importance of transforming growth factor beta (TGF beta) as an autocrine factor which controls the growth of human osteosarcomas. To define further the role of TGF beta isoforms in these neoplasms, a series of 27 osteosarcomas was studied using immunohistochemical, mRNA in situ hybridization, and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. All 14 central high-grade osteosarcomas, two telangiectatic osteosarcomas, and one high-grade surface osteosarcoma showed cytoplasmic immunoreactivity for TGF beta 1, -2, and -3. The expression of TGF beta 1 was moderate or diffuse in 14 cases (82.3 per cent), while low expression was detected in only three cases (17.7 per cent). For TGF beta 2 and -3, only moderate or diffuse staining was observed. Low-grade parosteal and periosteal osteosarcomas showed low or undetectable levels of TGF beta 1, while TGF beta 2 and -3 were moderately or diffusely expressed. Finally, three dedifferentiated parosteal osteosarcomas were diffusely positive for TGF beta 1, -2, and -3 in the high-grade component, while in the low-grade component, available for analysis in two of these cases, TGF beta 1 was demonstrated in a few neoplastic cells, and TGF beta 2 and -3 maintained a diffuse distribution. Statistical analysis of these data showed that high-grade osteosarcomas had a significantly higher expression of TGF beta 1 than low-grade osteosarcomas, while levels of TGF beta 2 and -3 were comparable in the two groups (p < 0.001; p = 0.3; p = 0.3, respectively; Fisher's exact test). Similarly, mRNA levels of TGF beta 1 detected by in situ hybridization were significantly higher (p = 0.04, Fisher's exact test) in high-grade osteosarcoma variants, while no differences were found for TGF beta 2 and -3 mRNA (p = 1.0; p = 0.2, respectively; Fisher's exact test). In addition, mRNA analysis performed by RT-PCR in seven cases (five high-grade and two low-grade osteosarcomas) confirmed the presence of high levels of TGF beta 1 in high-grade osteosarcomas, while low-grade tumours had low or absent mRNA expression. In conclusion, this positive association suggests that TGF beta 1 may be involved in determining the aggressive clinical behaviour of high-grade osteosarcomas.

Immunohistochemical detection of c-fos and c-jun expression in osseous and cartilaginous tumours of the skeleton.

The products of c-fos and c-jun proto-oncogenes form the heterodimeric complex AP-1 (activator protein 1), which play an important part in the control of bone cell proliferation and differentiation and in the development of bone tumours. We examined the expression of c-fos and c-jun in a series of 52 primary skeletal neoplasms, using an immunohistochemical method on formalin-fixed, paraffin-embedded sections. The expression of c-fos and c-jun was restricted to bone-forming lesions, while cartilaginous tumours were devoid of immunoreactivity. In benign osteoblastic lesions moderate c-fos and c-jun expression was found in 2 cases (18.1%). The highest levels of c-fos and c-jun expression were detected in high-grade central osteosarcomas (7 of 15 cases with moderate/diffuse expression) while 1 telangiectatic osteosarcoma, 2 low-grade central osteosarcomas, 1 low-grade periosteal osteosarcoma and 7 low-grade parosteal osteosarcomas were either negative or had low expression. The high-grade component of a dedifferentiated parosteal osteosarcoma showed diffuse immunoreactivity for both oncoproteins. Comparison of c-fos and c-jun expression by histological grade showed that high-grade osteosarcomas had a significantly higher expression of both oncoproteins than did low-grade osteosarcomas (P = 0.01, Fisher's exact test). Thus, c-fos and c-jun overexpression may be implicated in the development of high-grade osteosarcomas, but they appear to have little or no relevance for the development of low-grade osteosarcomas and cartilaginous skeletal neoplasms.

Lack of prognostic value of p53 protein expression in node-negative breast cancer.

AIMS AND BACKGROUND: The association of p53 protein accumulation and prognosis in node-negative breast cancer patients has been alternately demonstrated and denied in literature reports, and opinions on the use of p53 expression as an indicator of high risk of recurrence and as a guide for adjuvant therapy are controversial. STUDY DESIGN: The association of p53 protein accumulation with prognosis was retrospectively evaluated in a series of 221 node-negative breast cancer patients treated with surgery alone and followed up for a minimum of 10 years. p53 accumulation was determined by immunohistochemistry on archive material, and classified into four grades of increasing immunostaining. RESULTS: No association was observed between p53 and age or pT category, whereas a significant association with nuclear grade was found (P = 0.0014). Univariate and multivariate analysis of 10-yr disease-free and overall survival showed a significant and independent prognostic association for tumor size (pT category) and nuclear grading but not for p53 expression, whatever grade grouping was used. CONCLUSIONS: We did not find any evidence supporting the use of p53 immunostaining in current practice as an independent prognostic indicator or as a discriminant factor for adjuvant treatment of node-negative breast cancer patients.

Effects of tumor necrosis factor-alpha and interleukin-6 on fluid-phase permeability and ammonia diffusion in CNS-derived endothelial cells.

BACKGROUND: Proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) play an important role in the blood-brain barrier breakdown present in several neurological diseases including multiple sclerosis and AIDS. However, the specific effects of these cytokines on central nervous system-derived endothelial cells (CNS-EC) is not fully understood. In this study the effects of TNF-alpha and IL-6 were tested on different permeability mechanisms of CNS-EC. METHODS: Central nervous system endothelial cells were isolated from human brain and retina and cultured in vitro in a transwell system. Fluid-phase endocytosis and transcytosis, absorptive-mediated endocytosis, and ammonia diffusion were measured with specific methods. Endothelial cells were studied with electron microscopy for the ultrastructural effects of cytokine stimulation. RESULTS: Fluid-phase endocytosis and transcytosis were significantly increased by TNF-alpha and IL-6. This effect was dose dependent and reversible. The ammonia diffusion rate was also significantly increased by TNF-alpha. Absorptive-mediated endocytosis was not enhanced by TNF-alpha. Ultrastructural analysis of cytokine-treated CNS-EC confirmed the alterations in permeability showing an increase in endocytotic activity and a decrease in tight junctions. CONCLUSIONS: The proinflammatory cytokines IL-6 and TNF-alpha induce specific changes in the morphology and permeability of CNS-EC. These alterations can be important in many diseases characterized by increased cytokine production.

Pathologic features of hereditary non-polyposis colorectal cancer.

In hereditary non-polyposis colorectal cancer (HNPCC) patients, the cancer frequently arises in the proximal colon and is often multiple (synchronous or metachronous). Pathologic differences seem to exist between hereditary and sporadic large bowel cancer, but the data are not uniform. Many authors reported that the following histologic features are often present in HNPCC: 1) mucinous histotype, 2) poorly differentiated tumors, 3) presence of peritumoral lymphocytic infiltrate, with Crohn's-like lymphoid reaction. Such features have also been found in apparently sporadic colorectal cancer with, but not in sporadic colorectal cancer without DNA replication errors. Many studies have suggested that adenoma plays a main role in HNPCC carcinogenesis, and that the "adenoma-carcinoma sequence" may be the pathway to cancer in HNPCC as in sporadic colorectal cancer. Moreover, HNPCC adenomas show an early onset, villous component, high-grade dysplasia, and positivity for DNA replication errors more frequently than sporadic adenomas. Such data suggest that the adenoma-carcinoma sequence is accelerated in- HNPCC and that surveillance in these patients should therefore be strict to avoid cancer development.

Primary signet-ring cell carcinoma of the colon and rectum.

PURPOSE: Colorectal signet-ring cell carcinoma (SRCC) is uncommon; discordant data have been previously reported about clinicopathologic features. Thirty-four cases of primary colorectal SRCC were retrospectively reviewed to clarify controversies. METHODS: Primary colorectal SRCC was diagnosed when the following criteria were satisfied: 1) the tumor was primary; 2) histologic material was adequate; 3) signet-ring cell represented more than 50 percent of the cancer. RESULTS: We identified 34 cases (1.1 percent) of 2,995 consecutive large bowel cancers collected at the Institute of Anatomic Pathology of Florence between 1985 and 1993. Patients ranged in age from 31 to 89 (mean, 63.5; median, 65) years; 19 were male, and 15 were female (male:female = 1.3:1). Fifteen tumors were located in the proximal colon, 11 in the rectum, and 8 in the distal colon. The gross shape was infiltrative in 24 cases and exophytic in 10; only 6 cases (17.6 percent) showed features of linitis plastica. Most cancers (61.8 percent) were Stage C, 29.4 percent were Stage B, and distant metastases were present in only three cases (8.8 percent). No Stage A case was found. Prognosis was extremely poor, and overall five-year survival rate was 9.1 percent. Survival was influenced significantly by tumor stage (P < 0.01). CONCLUSIONS: Comparison of our data with the literature showed many differences that could be related to different applied diagnostic criteria. We underlined the importance of histology as reproducible criterion for diagnosis of primary colorectal SRCC.

Mesothelioma as a risk indicator of asbestos exposure: the role of the pathologist.

Malignant mesothelioma is an uncommon tumour, which has become an important epidemiological marker for exposure to asbestos. This tumour is characterised by a wide range of microscopic features which may be classified in three histologic patterns: epithelial, mesenchimal and mixed or biphasic. Histochemical staining is often necessary to distinguish mesothelioma from carcinoma. As regards immunohistochemistry, only the use of a combination of antibodies significantly decreases the risk of false-negative results. Analytic electron microscopy techniques may also be useful, permitting the evaluation of the cumulative fiber burden in the target organ.

Accuracy and reliability of frozen section diagnosis in a series of 672 nonpalpable breast lesions.

Frozen section (FS) diagnosis was routinely performed in a large series of nonpalpable breast lesions from 1977 through 1991. The original FS diagnoses of 672 patients were classified in four categories (1 = benign lesion, 2 = in situ carcinoma, 3 = invasive carcinoma, 4 = deferred diagnosis) and compared with the diagnoses obtained at review of the permanent paraffin sections to estimate the accuracy of FS. A review of the mammographic pattern of the lesion was also performed. Frozen section diagnostic conclusion was deferred to permanent paraffin sections in only 22 cases (3.3%). Benign or malignant (grouping in situ and invasive carcinomas) FS diagnoses were accurate in 623 of 650 cases (95.8%). Overall, the prevalence of malignant lesions was 44.8% with a benign/malignant ratio of 1.2. The diagnosis was modified on the basis of permanent sections in 27 cases (4.2%) with three false positives and 24 false negatives. Sensitivity and specificity of FS diagnoses were 91.7 and 99.2%, respectively. When the comparison between FS and histologic diagnoses was analyzed according to the mammographic pattern, sensitivity among patients with microcalcifications as the only alteration was lower (88.8%) than among patients with opacities (94.9%). On the basis of these results, FS is to be considered a feasible and reliable diagnostic procedure in nonpalpable breast lesions, particularly in cases excised because of a mammographic opacity that is identifiable on gross examination of the surgical specimen.

[Intraoperative histological study of nonpalpable lesions of the breast]. / L'esame istologico intra-operatorio nelle lesioni non palpabili della mammella.

The intraoperative frozen section technique has proven to be valid and accurate in the diagnosis of palpable breast lesions, while its use in non-palpable lesions of the breast has been recently discussed. In order to estimate the accuracy of frozen section technique in non-palpable breast lesions we reviewed our series of 672 cases of non-palpable lesions examined intraoperatively between January 1977 and December 1991. Frozen section diagnoses were compared with diagnoses obtained at review of the permanent paraffin sections. A review of the mammographic pattern of each lesion was also carried out. Frozen section diagnosis was replaced by permanent paraffin sections in 22 cases (3.3%). Benign or malignant (in situ and invasive carcinomas) frozen section diagnoses were accurate in 623 of 650 cases (95.8%). Frozen section diagnosis was modified on the basis of permanent sections in 27 cases (4.2%), with 3 false positives and 24 false negatives. Sensitivity and specificity of frozen section technique were 91.7% and 99.2%, respectively. Comparing frozen section and definitive diagnosis according to the mammographic pattern, sensitivity was lower in patients with microcalcifications as the only alteration (88.8%) compared with patients with opacities (94.9%). On the basis of our results the frozen section technique in non-palpable breast lesions is to be considered a valid and reliable diagnostic procedure, particularly in lesions detectable at mammography as an opacity and identifiable on gross examination of the surgical specimen.

Expression of retinoblastoma protein in human breast cancer: an immunohistochemical study.

The product of the human retinoblastoma gene (pRb) is a nuclear phosphoprotein that is thought to function as a tumor suppressor. Heterogeneous expression of the Rb gene product contributes to the genesis of a diverse group of human neoplasma such as breast, prostate, small cell lung, bladder carcinomas and leukemia. The clinical importance of Rb function demands a reproducible Rb immunohistochemical assay to distinguish Rb+ from Rb- tumor cells. We report an immunohistochemical study to detect Rb protein in a series of 50 invasive breast cancers. Our results support the hypothesis that the Rb gene functions as both a cell growth factor and a tumor suppressor.

[Thyroid cancer: anatomy and pathologic histology]. / Il cancro della tiroide: anatomia e istologia patologica.

Current pathological classifications of thyroid carcinoma only partially reflect the radical changes in our knowledge of these tumors, due to a large series of clinicopathological studies carried out over the past few years. Based on a critical review of this growing body of information concerning malignant thyroid neoplasms, a working formulation for clinical usage is proposed. This scheme has been adopted to classify 1339 consecutive cases of thyroid carcinoma observed at the Pathology Institute of the University of Florence between June 1966 and December 1993. The clinical implications of newer classification systems with regard to diagnosis, treatment and outcome of thyroid carcinoma are also discussed.