HBME-1 is the most sensitive marker for thyroid malignancy but the three markers may be useful in specific cases. This panel of markers is useful to differentiate the follicular patterned lesions, with special reference to the FVPC.

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BackgroundPrognostic factors in malignant melanoma are currently based on clinical data and morphologic examination. Other prognostic features, however, which are not yet used in daily practice, might add important information and thus improve prognosis, treatment, and survival. Therefore a search for new markers is desirable. Previous studies have demonstrated that fractal characteristics of nuclear chromatin are of prognostic importance in neoplasias. We have therefore investigated whether the fractal dimension of nuclear chromatin measured in routine histological preparations of malignant melanomas could be a prognostic factor for survival.MethodsWe examined 71 primary superficial spreading cutaneous melanoma specimens (thickness ≥ 1 mm) from patients with a minimum follow up of 5 years. Nuclear area, form factor and fractal dimension of chromatin texture were obtained from digitalized images of hematoxylin-eosin stained tissue micro array sections. Clark's level, tumor thickness and mitotic rate were also determined.ResultsThe median follow-up was 104 months. Tumor thickness, Clark's level, mitotic rate, nuclear area and fractal dimension were significant risk factors in univariate Cox regressions. In the multivariate Cox regression, stratified for the presence or absence of metastases at diagnosis, only the Clark level and fractal dimension of the nuclear chromatin were included as independent prognostic factors in the final regression model.ConclusionIn general, a more aggressive behaviour is usually found in genetically unstable neoplasias with a higher number of genetic or epigenetic changes, which on the other hand, provoke a more complex chromatin rearrangement. The increased nuclear fractal dimension found in the more aggressive melanomas is the mathematical equivalent of a higher complexity of the chromatin architecture. So, there is strong evidence that the fractal dimension of the nuclear chromatin texture is a new and promising variable in prognostic models of malignant melanomas.

Fractal characteristics of chromatin, revealed by light or electron microscopy, have been reported during the last 20 years. Fractal features can easily be estimated in digitalized microscopic images and are helpful for diagnosis and prognosis of neoplasias. During carcinogenesis and tumor progression, an increase of the fractal dimension (FD) of stained nuclei has been shown in intraepithelial lesions of the uterine cervix and the anus, oral squamous cell carcinomas or adenocarcinomas of the pancreas. Furthermore, an increased FD of chromatin is an unfavorable prognostic factor in squamous cell carcinomas of the oral cavity and the larynx, melanomas and multiple myelomas. High goodness-of-fit of the regression line of the FD is a favorable prognostic factor in acute leukemias and multiple myelomas. The nucleus has fractal and power-law organization in several different levels, which might in part be interrelated. Some possible relations between modifications of the chromatin organization during carcinogenesis and tumor progression and an increase of the FD of stained chromatin are suggested. Furthermore, increased complexity of the chromatin structure, loss of heterochromatin and a less-perfect self-organization of the nucleus in aggressive neoplasias are discussed.

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