Ricardo González-Cámpora

Ki-67 MIB1 labelling index and the prognosis of primary TaT1 urothelial cell carcinoma of the bladder

Aims: To evaluate whether ki-67 labelling index (LI) has independent prognostic value for survival of patients with bladder urothelial tumours graded according to the 2004 World Health Organisation classification. Methods: Ki-67 LI was evaluated in 164 cases using the grid counting method. Non-invasive (stage Ta) tumours were: papilloma (n = 5), papillary urothelial neoplasia of low malignant potential (PUNLMP; n = 26), and low (LG; n = 34) or high grade (HG; n = 15) papillary urothelial carcinoma. Early invasive (stage T1) tumours were: LG (n = 58) and HG (n = 26) carcinoma. Statistical analysis included Fisher and χ2 tests, and mean comparisons by ANOVA and t test. Univariate and multivariate survival analyses were performed according to the Kaplan–Meier method with log rank test and Cox’s proportional hazard method. Results: Mean ki-67 LI increased from papilloma to PUNLMP, LG, and HG in stage Ta (p<0.0001) and from LG to HG in stage T1 (p = 0.013) tumours. High tumour proliferation (>13%) was related to greater tumour size (p = 0.036), recurrence (p = 0.036), progression (p = 0.035), survival (p = 0.054), and high p53 accumulation (p = 0.015). Ki-67 LI and tumour size were independent predictors of disease free survival (DFS), but only ki-67 LI was related to progression free survival (PFS). Cancer specific overall survival (OS) was related to ki-67 LI, tumour size, and p27kip1 downregulation. Ki-67 LI was the main independent predictor of DFS (p = 0.0005), PFS (p = 0.0162), and cancer specific OS (p = 00195). Conclusion: Tumour proliferation measured by Ki-67 LI is related to tumour recurrence, stage progression, and is an independent predictor of DFS, PFS, and cancer specific OS in TaT1 bladder urothelial cell carcinoma.

Hürthle cell and mitochondrion‐rich cell tumors. A clinicopathologic study

Hürthle cells are large eosinophilic thyroid cells that contain a large number of mitochondria with a high content of oxidative enzymes. In the last 10 years several reports have emphasized the disagreement over the morphologic features, biologic behavior and treatment of Hürthle cell tumors. The authors reviewed the clinical and pathologic features of 28 patients with Hürthle cell and mitochondrion‐rich cell tumors (16 adenomas, 10 follicular carcinomas, and 2 papillary carcinomas) and present electron microscopic, immunohistochemical, and morphometric data. The results suggest that there is a correlation between biologic behavior and pathologic findings, that tumor size should not be considered a special conditioning factor in order to assign a biologic behavior, that nuclear size and anisokaryosis are not an absolute criteria for diagnosing malignancy, and finally, that electron microscopic examination is not useful in separating benign from malignant Hürthle cell tumors.

Genetic and expression profiles of cerebellar liponeurocytomas

Cerebellar liponeurocytoma, a rare, newly identified CNS neoplasm of adults, is characterized by advanced neuronal/neurocytic and focal lipomatous differentiation, low proliferative potential and a favorable clinical prognosis. Despite the different age distribution and benign biological behavior, the cerebellar liponeurocytoma shares several features with the cerebellar medulloblastoma, which may include an origin from the periventricular matrix of the fourth ventricle or the external granular layer of the cerebellum. To establish the genetic profile of cerebellar liponeurocytomas, we have formed an international consortium and collected tumor samples from 20 patients. DNA sequencing revealed TP53 missense mutations in 4 (20%) of 20 cerebellar liponeurocytomas, a frequency higher than in medulloblastomas. There was no case with PTCH, APC, or β‐catenin mutations, each of which may be present in subsets of medulloblastomas. Isochromosome 17q, a genetic hallmark of classic medulloblastomas, was not observed in any of the cases investigated by FISH analysis. cDNA array analyses were carried out on 4 cerebellar liponeurocytomas, 4 central neurocytomas, and 4 classic medulloblastomas. Cluster analysis of the cDNA expression data of 1176 genes grouped cerebellar liponeurocytomas close to central neurocytomas, but distinct from medulloblastomas. These results suggest cerebellar liponeurocytoma as a distinct tumor entity that is genetically different from medulloblastoma. Furthermore, the cDNA expression array data suggest a relationship to central neurocytomas, but the presence of TP53 mutations, which are absent in central neurocytomas, suggests that their genetic pathways are different.

Concurrence of a symptomatic encapsulated follicular carcinoma, an occult papillary carcinoma and a medullary carcinoma in the same patient

6. markers in the histopathological diagnosis of medullary (C cell) thyroid carcinoma. Pathof. Res. Pract. 1992: 188; 123-1 30. Albores-Saavedra J, LiVolsi VA, Williams ED. Medullary carcinoma. Semin. Diagn. Pathof. 1985: 2: 137-146. Mendelsohn G, Bigner SH. Eggleston JC, Baylin SB, Wells Jr SA. Anaplastic variants of medullary thyroid carcinoma. A. lightmicroscopic and immunohistochemical study. Am. 1. Surg. Pathol.

Granular cell atypical fibroxanthoma: report of two cases.

Two cases of an uncommon histopathological variant of atypical fibroxanthoma (AFX) are described. Even though both lesions presented as clinically conventional atypical fibroxanthoma, histopathology disclosed a neoplasm composed of cells with granular change that was negative for S100 staining, and showed prominent pleomorphism, severe nuclear atypia, and a high mitotic index. Degenerative change may explain the granular phenotype in these two cases of AFX. The differential diagnosis with primitive nonneural granular cell tumor is discussed.

HYALINIZING TRABECULAR CARCINOMA OF THE THYROID GLAND : REPORT OF TWO CASES OF FOLLICULAR CELL THYROID CARCINOMA WITH HYALINIZING TRABECULAR PATTERN

Recently tumors have been reported that have an architectural pattern and cellularity similar to hyalinizing trabecular adenoma and show either parafollicular differentiation or histological findings suggestive of malignant neoplasm of the follicular cells. This study describes two cases of thyroid carcinoma of follicular cells that displayed a hylinizing trabecular pattern. The first case was a 25-year-old euthyroid woman with a cold thyroid nodule in the right lobe. On fine needle aspiration a diagnosis of papillary carcinoma was rendered. The thyroidectomy disclosed a 2-cm, firm, brown, encapsulated tumor in the right lobe. The tumor had a growth pattern and cytologic features similar to those described in hyalinizing trabecular adenoma. The differences between these neoplasms were the presence of mitotic figures, prominence of the nucleolus, capsular blood vessel invasion, and microtubule groups in the endoplasmic reticulum. The second case was a 19-year-old euthyroid woman with a cold thyroid nodule in the left lobe. A cytologic diagnosis of follicular proliferation was rendered. A 4-cm, firm, whitish, encapsulated nodule was found in the left lobectomy. The tumor cells were arranged in two clear-cut patterns: a trabecular hyalinizing pattern with a small focus of papillary growth, and a follicular pattern. These findings confirm the existence of malignant thyroid tumors with a hyalinizing trabecular pattern and illustrate the nonspecificity of this peculiar pattern, since it may also be seen in papillary carcinomas of the thyroid. The relationship between hyalinizing trabecular adenoma and papillary carcinoma of the thyroid is commented on.

Apoptosis in breast carcinoma.

Apoptosis may play a major role in determining tumor growth and aggressiveness. The aim of this study was to examine the relationship between apoptosis, expression of bcl-2 and p53 proteins, proliferation index, and other clinicopathological features of breast carcinoma. Sixty-five formalin-fixed paraffin-embedded tissue sections from invasive ductal breast carcinomas were studied for the presence of apoptosis by the terminaldeoxynucleotidyl-transferase-mediated dUTP-FITC nick end-labeling (TUNEL) method. Immunohistochemical methods were also used to determine the expression of estrogen receptor, Ki67, bcl-2 and p53 proteins. The number of apoptotic cells ranged from 2.0 to 236.0/10HPF (mean 36.26, median 28.0). The observation of 30 apoptotic cells/10HPF was more common in tumors > 3 cm, of histological grade III, with a high mitotic index, Ki67 index > or = 300, and p53 positivity; however, statistical significance was found only for the histological grade. Grade I and III tumors displayed an inverse association between the apoptotic index and bcl-2 and p53 protein expressions; grade I tumors frequently expressed bcl-2 (19/28), lacked p53 (20/28), and presented a low number of apoptotic cells (18/28), whereas grade III tumors tended to express p53 (12/17), lacked bcl-2 (13/17), and displayed a high number of apoptotic cells/10HPF (12/17). Multivariate analysis for survival revealed that estrogen receptors and apoptosis were independent variables. These data suggest that apoptosis, rather than proliferation index or expression of bcl-2 or p53 proteins, is an independent factor for the prognosis of survival.

Nuclear DNA in anaplastic thyroid carcinoma with a differentiated component

Fifteen cases of anaplastic thyroid carcinoma, including eight cases with a differentiated component, were studied by DNA analysis. All areas of anaplastic carcinoma showed an aneuploid DNA content. The eight cases of anaplastic carcinoma with differentiated component (two follicular carcinomas, two papillary carcinomas, one Hürthle cell carcinoma and three poorly differentiated carcinomas) exhibited aneuploid DNA content in the differentiated area of the tumour. Karyometric parameters allowed a fairly clear separation between giant cell, spindle cell and differentiated components. The results support the hypothesis that patients with aneuploid differentiated carcinoma represent a higher risk group and are probably more prone to developing anaplastic carcinoma.

Recurrent Pyogenic Granuloma with Multiple Satellites

The condition wherein multiple satellite angiomatous lesions develop around the scar of a recently treated pyogenic granuloma is a rare occurrence. To date 30 such cases have been reported. One additi

Loss of heterozygosity at 9q32-33 (DBC1 locus) in primary non-invasive papillary urothelial neoplasm of low malignant potential and low-grade urothelial carcinoma of the bladder and their associated normal urothelium

Tumour recurrence has a major impact on patients with non‐invasive papillary urothelial tumours of the bladder. To explore the role of DBC1 (deleted in bladder cancer 1 locus), a candidate tumour suppressor gene located at 9q32–33, as prognostic marker we have performed loss of heterozygosity (LOH) testing in 49 patients with primary papillary urothelial tumours and associated normal urothelium. Data from the 38 tumours and 11 specimens of normal urothelium that were informative in the LOH study (D9S195 marker) showed that LOH in urothelium (45.4%) but not in non‐invasive tumours (60.5%) was associated with tumour recurrence (p = 0.026) but not to grade or progression. Also, tumours whose normal urothelium had LOH were larger (p = 0.020) and showed cyclin D1 over‐expression (p = 0.032). Non‐significant increased expression of p53, p21Waf1, apoptotic index and tumour proliferation, and decreased expression of p27Kip1 or cyclin D3 also characterized tumours whose normal urothelium had LOH. The expression of these G1–S modulators, apoptotic index and tumour proliferation was more heterogeneous in papillary urothelial tumours, irrespective of having retained heterozygosity or LOH. Also, Bax expression decreased in papillary urothelial tumours having LOH (p = 0.0473), but Bcl‐2 was unrelated to LOH status. In addition, FGFR3 protein expression decreased in LOH tumours (p = 0.036) and in those having LOH in their normal urothelium (p = 0.022). FGFR3 immunohistochemical expression was validated by western blot in selected cases. The survival analysis selected LOH in normal urothelium as a marker of disease‐free survival (log‐rank 5.32, p = 0.021), progression‐free survival (log‐rank 3.97, p = 0.046) and overall survival (log‐rank 4.26, p = 0.038); LOH in tumours was significant in progression‐free survival (log‐rank 3.83, p = 0.042). It is concluded that LOH at the DBC1 locus in normal urothelium seems to be relevant in the prognosis of non‐invasive papillary tumours of the bladder via selecting cases with increased proliferation, frequent alterations of the G1–S phase modulators, and decreased FGFR3 protein expression. Copyright