Giancarlo Zampi

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.

Expression of transforming growth factor β isoforms in osteosarcoma variants: association of tgfβ1 with high-grade osteosarcomas

Studies on osteosarcoma cell lines point to the potential importance of transforming growth factor β (TGFβ) as an autocrine factor which controls the growth of human osteosarcomas. To define further the role of TGFβ 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 TGFβ1, ‐2, and ‐3. The expression of TGFβ1 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 TGFβ2 and ‐3, only moderate or diffuse staining was observed. Low‐grade parosteal and periosteal osteosarcomas showed low or undetectable levels of TGFβ1, while TGFβ2 and ‐3 were moderately or diffusely expressed. Finally, three dedifferentiated parosteal osteosarcomas were diffusely positive for TGFβ1, ‐2, and ‐3 in the high‐grade component, while in the low‐grade component, available for analysis in two of these cases, TGFβ1 was demonstrated in a few neoplastic cells, and TGFβ2 and ‐3 maintained a diffuse distribution. Statistical analysis of these data showed that high‐grade osteosarcomas had a significantly higher expression of TGFβ1 than low‐grade osteosarcomas, while levels of TGFβ2 and ‐3 were comparable in the two groups (p<0·001; p=0·3; p=0·3, respectively; Fishers exact test). Similarly, mRNA levels of TGFβ1 detected by in situ hybridization were significantly higher (p=0·04, Fishers exact test) in high‐grade osteosarcoma variants, while no differences were found for TGFβ2 and ‐3 mRNA (p=1·0; p=0·2, respectively; Fishers 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 TGFβ1 in high‐grade osteosarcomas, while low‐grade tumours had low or absent mRNA expression. In conclusion, this positive association suggests that TGFβ1 may be involved in determining the aggressive clinical behaviour of high‐grade osteosarcomas.

Prognostic Significance of Accessory Cells and Lymphocytes in Nasopharyngeal Carcinoma

Forty-five consecutive biopsy specimens of nasopharyngeal carcinoma (NPC) and 10 biopsies of healthy nasopharyngeal mucosa obtained from non-cancer patients were investigated by immunohistochemical methods. Monoclonal (B2, T1) and policlonal antibodies (against S-100 protein and lysozyme) with reference to infiltrating lymphocytes and accessory cells (monocytic/macrophagic and dendritic cells) were used. Variable population densities of dendritic cells (S100+) were demonstrated in 22 out of the 45 cases (49%) of NPC; the distribution of these cells was typically within the cancer nests. Monocytic/macrophagic cells (Lys+) were found along the tumor margins and interspersed among the tumor cells in 14 out of 45 (31%) cases. No significant statistical correlation between density of accessory cells and histological type of NPC (classified according to Micheau criteria) was found. Cases with a moderate to marked density of dendritic and monocytic/macrophagic cells survived longer than those with a slight one (mean survival of 63%, 67% and 29%, 27% respectively). In NPC tissues T-lymphocyte infiltration was prevalent. In contrast, B cells were numerous and T cells rare in normal control tissues. The intensity of T-cell infiltration was significantly high in cases with a marked density of S-100+ cells, according to the ability of these cells to present antigens to sensitized T-cells. This study suggests a prognostic significance for reactive cells infiltrating NPC, which means longer survival for cases associated with marked infiltration density of accessory cells.

Prognostic value of proliferating cell nuclear antigen in lymph node—negative breast cancer patients

Background. The prognostic value of proliferating cell nuclear antigen (PCNA) has been demonstrated in recent studies of human tumors including breast cancer.

Gastric cancer in a high-risk area in Italy: histopathologic patterns according to Lauren's classification

Two thousand five hundred forty cases (1628 males and 912 females) of primary gastric cancer (GC) histologically diagnosed to gastroscopic biopsy or resected specimens, occurring from 1973 to 1982 in a high risk area in Italy (Florence), were reviewed. According to Laurens criteria, 1587 (62.5%) were classified as intestinal type, 624 (24.6%) as diffuse type and 329 (12.9%) as mixed unclassified. The intestinal type is more frequent in males and increases in both sexes with advancing age; conversely for the diffuse type. In the two 5‐year periods (1973–1977 and 1978–1982) the intestinal type shows a reduction over time more evident in females than in males, in contrast to the increasing trend for the diffuse type. In males, the distribution of Laurens histologic types is stable over time for resected specimens, whereas there is a significant reduction of intestinal type for biopsy specimens. In females, both for resected and biopsy specimens there is a reduction of the intestinal type and an increase of the diffuse type from the first to the second period. For a subgroup of 297 subjects two different specimens were available (gastroscopic biopsy and surgical); sensitivity and positive predictive value, for biopsy specimen as compared with the resected one, in the diagnosis for Laurens histologic types were calculated. An excess of diagnoses in the mixed/unclassified category for biopsy material was evident (positive predictive value = 44.3%). However, for the two main histologic types, the biopsy appears a quite reliable indicator of the final diagnosis on surgical material (intestinal: ppv = 88.6%; Diffuse: ppv = 87.0%). The study supports the hypothesis that the reduction in GC mortality in the Province of Florence in recent years may be associated with a moderate reduction in the frequency of the intestinal type.

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.

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 Crohns-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.

Osteogenic sarcoma of the breast. A case report.

A case of primary osteogenic sarcoma of the breast is reported. It should be distinguished from carcinoma with extensive osseous metaplasia. The results of light and electron microscopy including an immunohistochemical study are presented. Immunohistochemical and ultrastructural studies proved that the lesion, in the absence of epithelial differentiation, was a primary osteogenic sarcoma of the breast rather than a carcinoma with extensive osseous metaplasia. Diagnosis may be delayed because the tumor is confused clinically and mammographically with a calcific fibroadenoma.

Benign breast disease and cancer risk

IO. II. 12. 13. 14. 15. 16. Introduction BBD consensus statement Page’s histological classification 3.1. Non-proliferative BBD 3.2. Proliferative disease without atypia 3.3. Atypical hyperplasia 3.3. I. Atypical ductal hyperplasia (ADH) 3.3.2. Atypical lobular hyperplasia (ALH) A comparison of BBD histological classifications BBD and cancer risk: a review of epidemiological studies 5.1. Case-control studies 5.2. Cohort studies 5.3. Nested case-control studies 5.4. Gross cysts and BC risk Clinical significance of AH BBD and mammographic patterns BBDand cytologicexamination Reproducibility of histological diagnosis of proliferative disease Role of ancillary techniques to histological diagnosis Biological profile of AH Conclusions Acknowledgements Biographies Reviewer References 222 222 223 224 224 225 227 229 229 231 232 233 234 235 235 236 231 237 238 239 239 ‘40 240 240 240

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.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.