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S J Diaz-Cano

Publications and source records attributed to S J Diaz-Cano.

At least 19 recordsLinked to original sources
PubMed2003

Malignant melanoma in an 8-year-old Caribbean girl: diagnostic criteria and utility of sentinel lymph node biopsy.

The incidence of malignant melanoma (MM) is continuing to rise, although childhood MM remains rare. We describe an 8-year-old Afro-Caribbean girl who developed a non pigmented lesion on the tip of her left thumb, which persisted despite treatment in primary care with cryotherapy. At biopsy she was found to have an acquired acral MM. She underwent amputation of the distal phalanx of her thumb, together with positive sentinel lymph node (SLN) biopsy and subsequent axillary lymph node clearance and adjuvant chemotherapy. MMs are very rare in this age and skin-type group, therefore requiring strict diagnostic criteria. These criteria include the distinction from MM mimics, especially Spitz tumours, and an appropriate use of staging techniques such as SLN biopsy to influence management.

Axilla↗
PubMed2002

Hashimoto's thyroiditis shares features with early papillary thyroid carcinoma.

Neoplastic transformation is a multistep process that results in a continuous spectrum from the normal (physiological) state to a fully established neoplasm. The gold standard for diagnosis of papillary thyroid carcinoma is conventional histology, the essential element being the characteristic nuclear features, regardless of whether papillary structures are present or not. However, other criteria are being used increasingly in the diagnosis of neoplasms, including immunohistochemical staining and molecular profile. The RET/PTC gene rearrangement is highly specific for papillary thyroid carcinoma and is associated with the characteristic nuclear features seen in papillary thyroid carcinoma. There is an overlap in the morphological features, immunohistochemical staining pattern, and most importantly, molecular profile between papillary thyroid carcinoma and Hashimoto's thyroiditis. Although considered a 'benign' condition, Hashimoto's thyroiditis almost always harbours a genetic rearrangement that is strongly associated with and is highly specific for papillary thyroid carcinoma. Submicroscopic foci of papillary thyroid carcinoma must be present in Hashimoto's thyroiditis, although the clinical behaviour is still benign. Further studies are required to predict which foci will progress to papillary thyroid carcinoma.

Carcinoma, Papillary↗
PubMed2001

Molecular and kinetic features of transitional cell carcinomas of the bladder: biological and clinical implications.

Molecular and kinetic analyses have contributed to our understanding of the biology of transitional cell carcinomas (TCC) of the bladder. The concordant pattern of X-chromosome inactivation of multiple TCCs appearing at different times and at different sites and concordant genetic abnormalities in a subset of muscle-invasive TCC strongly support a monoclonal origin and a homogeneous tumor cell selection throughout the neoplasm. However, topographic intratumor heterogeneity results from the accumulation of genetic lesions in tumor suppressor genes, predominantly neurofibromatosis (NF)-1-defective in the superficial compartment and tumor protein p53 (TP53)-defective in the deep one, with lower proliferation and down-regulation of apoptosis in the latter. TCCs follow the general concept of multistep carcinogenesis and proceed through two distinct genetic pathways responsible for generating different TCC morphologies. These are the inactivation of cyclin-dependent kinase inhibitors (p15, p16, and p21WAF/CIP1) in low-grade TCC and early TP53-mediated abnormalities in high-grade TCC. TCC progression correlates with genetic instability and accumulation of collaborative genetic lesions mainly involving TP53, retinoblastoma (RB)-1, and growth factors. Distinctive genetic (low incidence of RB-1 and NF-1 abnormalities) and kinetic (slower cell turnover) profiles also correlate with a "single-file" infiltration pattern and poor survival in muscle-invasive TCCs. The underlying molecular changes of carcinoma in situ involve multiple and more extensive deletions (normally TP53-defective) than coexistent invasive TCC, suggesting an independent genetic evolution, while low-grade dysplasia is mainly polyclonal and shows a low rate of gene deletions.

Carcinoma in Situ↗
PubMed2001

Contribution of the microvessel network to the clonal and kinetic profiles of adrenal cortical proliferative lesions.

Monoclonal adrenocortical lesions have been characterized by an inverse correlation between proliferation and apoptosis, and polyclonal lesions show a direct correlation. Their relationship with the vascular pattern remains unknown in adrenocortical nodular hyperplasias (ACNHs), adenomas (ACAs), and carcinomas (ACCs). We studied 20 ACNHs, 25 ACAs, and 10 ACCs (World Health Organization classification criteria) from 55 women. The analysis included X-chromosome inactivation assay (on microdissected samples), slide and flow cytometry, and in situ end labeling. Endothelial cells were stained with anti-CD31, and the blood vessel area and density were quantified by image analysis in the same areas. Appropriate tissue controls were run in every case. Regression analyses between kinetic and vascular features were performed in both polyclonal and monoclonal lesions. Polyclonal patterns were observed in 14 of 18 informative ACNHs and 3 of 22 informative ACAs, and monoclonal patterns were seen in 4 of 18 ACNHs, 19 of 22 ACAs, and 9 of 9 ACCs. A progressive increase in microvessel area was observed in the ACNH-ACA-ACC transition but was statistically significant between benign and malignant lesions only (191.36 +/- 168.32 v 958.07 +/- 1279.86 microm(2); P < .0001). In addition, case stratification by clonal pattern showed significant differences between polyclonal and monoclonal benign lesions; 6% of polyclonal and 57% of monoclonal lesions had microvessel area >186 microm(2) (P = .0000008). Monoclonal lesions showed parallel trends (but with opposite signs) for microvessel area and density in comparison with proliferation and apoptosis, whereas polyclonal lesions showed inverse trends. In conclusion, the kinetic advantage of monoclonal adrenal cortical lesions (increased proliferation, decreased apoptosis) is maintained by parallel increases in microvessel area and density.

Adrenal Cortex↗
PubMed2001

PCR techniques for clonality assays.

Clonal overgrowths represent the hallmark of neoplastic proliferations, and their demonstration has been proved useful clinically for the diagnosis of malignant lymphomas based on the detection of specific and dominant immunoglobulin and/or T-cell receptor gene rearrangements. Nonrandom genetic alterations can also be used to test clonal expansions and the clonal evolution of neoplasms, especially analyzing hypervariable deoxyribonucleic acid (DNA) regions from patients heterozygous for a given marker. These tests rely basically on the demonstration of loss of heterozygosity (LOH) resulting from either hemizygosity (nonrandom interstitial DNA deletions) or homozygosity of mutant alleles observed in neoplasms. LOH analyses identify clonal expansions of a tumor cell population, and point to monoclonal proliferation when multiple and consistent LOH are demonstrated. Based on the methylation-related inactivation of one X chromosome in female subjects, X-linked markers (e.g., androgen receptor gene) will provide clonality information using LOH analyses after DNA digestion with methylation-sensitive restriction endonucleases. Therefore, both non-X-linked and X-linked analyses give complementary information, related and not related to the malignant transformation pathway respectively. Applied appropriately, these tools can establish the clonal evolution of tumor cell populations (tumor heterogeneity), identify early relapses, distinguish recurrent tumors from other metachronic neoplasms, and differentiate field transformation from metastatic tumor growths in synchronic and histologically identical neoplasms.

Clone Cells↗
PubMed2001

Germline RET 634 mutation positive MEN 2A-related C-cell hyperplasias have genetic features consistent with intraepithelial neoplasia.

C-cell hyperplasias are normally multifocal in multiple endocrine neoplasia type 2A. We compared clonality, microsatellite pattern of tumor suppressor genes, and cellular kinetics of C-cell hyperplasia foci in each thyroid lobe. We selected 11 females from multiple endocrine neoplasia type 2A kindred treated with thyroidectomy due to hypercalcitoninemia. C-cell hyperplasia foci were microdissected for DNA extraction to analyze the methylation pattern of androgen receptor alleles and microsatellite regions (TP53, RB1, WT1, and NF1). Consecutive sections were selected for MIB-1, pRB1, p53, Mdm-2, and p21WAF1 immunostaining, DNA content analysis, and in situ end labeling. Appropriate tissue controls were run. Only two patients had medullary thyroid carcinoma foci. Nine informative C-cell hyperplasia patients showed germline point mutation in RET, eight of them with the same androgen receptor allele preferentially methylated in both lobes. C-cell hyperplasia foci showed heterogeneous DNA deletions revealed by loss of heterozygosity of TP53 (12 of 20), RB1 (6 of 14), and WT1 (4 of 20) and hypodiploid G0/G1 cells (14 of 20), low cellular turnover (MIB-1 index 4.5%, in situ end labeling index 0.03%), and significantly high nuclear area to DNA index ratio. MEN 2A (germline point mutation in RET codon 634) C-cell hyperplasias are monoclonal and genetically heterogeneous and show down-regulated apoptosis, findings consistent with an intraepithelial neoplasia. Concordant X-chromosome inactivation and interstitial gene deletions suggest clone expansions of precursors occurring at a point in embryonic development before divergence of each thyroid lobe and may represent a paradigm for other germline mutations.

Amino Acid Substitution↗
PubMed2001

Critical analysis of histologic criteria for grading atypical (dysplastic) melanocytic nevi.

Low concordance in grading atypical (dysplastic) melanocytic nevi (AMN) has been reported, and no systematic evaluation is available. We studied 123 AMN with architectural and cytologic atypia (40 associated with atypical-mole syndrome), classified according to standard criteria by 3 independent observers. Histologic variables included junctional and dermal symmetry, lateral extension, cohesion and migration of epidermal melanocytes, maturation, regression, nuclear features, nuclear grade, melanin, inflammatory infiltrate location, and fibroplasia. AMN (43 junctional and 80 compound) were graded mild (31), moderate (61), and severe (31). AMN-severe correlated with 3 or more nuclear abnormalities (especially pleomorphism, heterogeneous chromatin, and prominent nucleolus) and absence of regression, mixed junctional pattern, and suprabasilar melanocytes on top of lentiginous hyperplasia. AMN-severe diagnostic accuracy was 99.5% using these criteria, but only the absence of nuclear pleomorphism differentiated AMN-mild from AMN-moderate. No architectural features distinguishing AMN-mild from AMN-moderate were selected as significant by the discriminant analysis. AMN from atypical-mole syndrome revealed subtle architectural differences, but none were statistically significant in the discriminant analysis. Histologic criteria can reliably distinguish AMN-severe but fail to differentiate AMN-mild from AMN-moderate. AMN from atypical-mole syndrome cannot be diagnosed using pathologic criteria alone.

Adult↗
PubMed2000

Clonal patterns in phaeochromocytomas and MEN-2A adrenal medullary hyperplasias: histological and kinetic correlates.

The relationship among histological features, cell kinetics, and clonality has not been studied in adrenal medullary hyperplasias (AMHs) and phaeochromocytomas (PCCs). Thirty-four PCCs (23 sporadic and 11 MEN-2A (multiple endocrine neoplasia type 2A)-related tumours, the latter associated with AMH) from females were included in this study. Representative samples were histologically evaluated and microdissected to extract DNA and evaluate the methylation pattern of the androgen receptor alleles. At least two tissue samples (from the peripheral and internal zones in each tumour) were analysed with appropriate tissue controls run in every case. The same areas were selected for MIB-1 staining and in situ end labelling (ISEL). Malignant PCCs were defined by histologically confirmed distant metastases. All monoclonal AMH nodules from the same patient showed the same X-chromosome inactivated. Six sporadic PCCs revealed liver metastases (malignant PCC) and eight additional sporadic PCCs showed periadrenal infiltration (locally invasive PCC). All informative PCCs were monoclonal, except for five locally invasive PCCs and one benign PCC that revealed polyclonal patterns. Those cases also showed a fibroblastic stromal reaction with prominent blood vessels, focal smooth muscle differentiation, and significantly higher MIB-1 (126.8+/-29.9) and ISEL (50.9+/-12.8) indices. Concordant X-chromosome inactivation in nodules from a given patient suggests that MEN-2A AMH is a multifocal monoclonal condition. A subgroup of PCCs characterized by balanced methylation of androgen receptor alleles, high cellular turnover, and stromal proliferation also shows locally invasive features.

Adrenal Gland Neoplasms↗
PubMed2000

Kinetic profiles of intraepithelial and invasive prostatic neoplasias: the key role of down-regulated apoptosis in tumor progression.

The cell kinetic of prostatic intraepithelial neoplasia (PIN) is poorly understood. Herein we report the kinetic pattern of PIN, both not associated (primary) and associated (secondary) with coexistent invasive carcinoma (PCa). Surgical specimens collected in 20 cases of primary PIN, 20 of secondary PIN and 20 of PCa were studied by MIB-1 immunostaining, in situ end-labeling (ISEL) and DNA histogram analysis, and the cell density in each case was estimated using the formula N = (n pi/4)2. Fifty high-power fields (HPF), or the complete lesion if smaller, were screened in each lesion, and both mean and standard deviation were recorded. Statistical differences were studied by means of Fisher's exact test. ISEL indices were significantly (P < 0.0001) lower in PCa (0.1 +/- 0.3) than in primary PIN (0.5 +/- 0.3), while the MIB-I indices were similar in both conditions (P = 0.56). Statistically significant differences were also detected for both MIB-1 and ISEL indices when secondary PIN (MIB-1 1.9 +/- 0.7, ISEL 3.7 +/- 3.3) was compared with primary PIN (MIB-1 2.5 +/- 2.1, ISEL 0.5 +/- 0.3) and PCa (P < 0.0001). In terms of cellularity, primary PIN (26.3 +/- 7.1) revealed scores significantly lower (P < 0.0001) than those recorded in PCa (39.0 +/- 8.8) and secondary PIN (32.9 +/- 14.3). In conclusion, early prostatic tumor is mainly defined by down-regulated apoptosis rather than by increased proliferation. Secondary PIN displays unique kinetic features suggesting an evolved stage of primary PIN.

Aged↗
PubMed2000

Cell proliferation in skin tumors with ductal differentiation: patterns and diagnostic applications.

The kinetic features of skin tumors with ductal differentiation (TDD) remain mainly unknown. We selected 88 skin TDD (D-PAS-positive cuticles) classified according to Murphy and Elder's criteria. Tumors studied included 13 poromas, 12 nodular hidradenomas, 10 cylindromas, 6 spiradenomas, 9 syringomas, 9 chondroid syringomas, 7 porocarcinomas, 15 malignant nodular hidradenomas, and 7 not otherwise specified carcinomas. The same tumor areas were evaluated for mitotic figure counting (MFC) and proliferation rate (PR = MIB-1 index), screening 10 consecutive high-power fields (HPFs) in the most cellular areas. Results were recorded by HPF and tumor cellularity, considering both average and standard deviation. Differences were analyzed by Student's t-test and analysis of variance (ANOVA) and considered significant if p<0.05. PR was significantly higher in malignant (23.29 +/- 12.49) than in benign tumors (3.86 +/- 4.44) and in poromanodular hidradenoma (4.99 +/- 3.34) than in spiradenoma-cylindroma-syringoma (1.91 +/- 1.67), but not by malignant tumor type. MFC was significantly higher in malignant (25.52 +/- 4.10) than in benign tumors (1.57 +/- 0.38), showing porocarcinomas the biggest MFC/10 HPF and malignant nodular hidradenomas the highest MFC/1000 cells. PR and MFC are useful malignancy criteria in skin TDD and should be evaluated by tumor cellularity to avoid potential misinterpretations related with tumor heterogeneity.

Acrospiroma↗