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

Abstract

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.

Cytoarchitectural and kinetic features in the histological evaluation of follicular thyroid neoplasms

“… Tissue reaction, either fibroblastic (homogeneous hyaline) or myxoid (basophilic loose) and its extension. Inflammation type (neutrophilic/lymphocytic/histiocytic) and grade (mild/severe), separately considered in both tumour and surrounding gland. Tumour capsule invasion, defined by tumour cell infiltration through the capsule. Vascular invasion (intravascular presence of atypical tumour cells adherent to the wall of endothelialized lumens located at the tumour periphery), type of vessels involved (with or without smooth muscle) and their location (capsular/extracapsular). Perineural invasion (presence of atypical tumour cells surrounding nerve fibres). Cytoplasmic features included staining (eosinophilic, basophilic and clear), appearance (homogeneous, foamy and granular) and the presence of sharp eosinophilic globules. The presence of cytoplasmic pigment (lipofuchsin/melanin) and special features (oncocytic differentiation, sarcomatoid features) were recorded. Nuclear features were independently analysed as reported, 11,12 including anisokaryosis (≥ 3 : 1), pleomorphism (in > 50% cells), chromatin distribution and presence of prominent nucleolus/i in > 50% of proliferating cells. N/C (nuclear–cytoplasmic) ratio (low/high) compared with that of follicular cells in the surrounding gland. Presence of bi‐ or multinucleated cells and nuclear pseudoinclusions. …”

“…Nuclear features were independently analysed as reported, 11,12 including anisokaryosis (≥ 3 : 1), pleomorphism (in > 50% cells), chromatin distribution and presence of prominent nucleolus/i in > 50% of proliferating cells.…”

“…10 Nuclear features were independently analysed as reported, 11,12 including anisokaryosis ( ‡ 3 : 1), pleomorphism (in > 50% cells), chromatin distribution and presence of prominent nucleolus ⁄ i in > 50% of proliferating cells. 11 N ⁄ C (nuclear-cytoplasmic) ratio (low ⁄ high) compared with that of follicular cells in the surrounding gland.…”

DNA and kinetic heterogeneity during the clonal evolution of adrenocortical proliferative lesions

“…In addition, there is no information about the relative timing of proliferation, DNA content abnormalities, and clonality profile. The reason for this disagreement is partly related with tissue heterogeneity, which affects both kinetic and genetic features [15,[20][21][22].…”

Microsatellite abnormalities and somatic down‐regulation of mismatch repair characterize nodular‐trabecular muscle‐invasive urothelial carcinoma of the bladder

“…The level of muscularis mucosa has also been useful in assessing topographical histological and molecular heterogeneity in bladder UroC 7,8 . This has resulted in distinctive microsatellite and clonal profiles leading to topographical segregation of proliferative and invasive tumour cells 9–13 . Therefore, topographical analysis of genetic and kinetic features will result in a better understanding of the molecular evolution of neoplasms 8 …”