Paragangliomas. Static cytometric studies of nuclear DNA patterns

Abstract

Background. The biologic behavior of most paragangliomas cannot be predicted from their histologic appearance. Recently, cytometric studies have found an association between an aggressive clinical behavior and the presence of a hyperdiploid or tetraploid range in the DNA nuclear content. Methods. The authors have studied morphometric (nuclear area and nuclear form factor) and DNA densitometric (integral optical density and DNA ploidy) features of 23 cases of paraganglioma by means of slide cytophotometry with the micro TICAS system (University of Chicago, Chicago, IL). The samples were selected from paraffin‐embedded tissue, and representative sections were stained with the Feulgen technique. The differences between groups (cervical versus extracervical paragangliomes) were investigated with the Mann‐Whitney test and Fisher discriminant linear function. Results. The densitometric study showed aneuploid cell lines in 15 of 16 noncervical paragangliomas (with a DNA index within the tetraploid range), whereas 3 of 7 cervical paragangliomas were aneuploid and only 1 case did not have not a diploid cell line (with a DNA index within the peridiploid range). Mean ploidy (4.33 arbitrary units [AU] and 2.72 AU, respectively), nuclear area (58.74 μm2 and 32.08 μm2, respectively), the minor and major DNA indices (1.09–1.24 and 1.83–1.96, respectively), and DNA content variability (2c deviation indices [2cDI] of 8.62 and 1.88 AU, respectively) were higher in noncervical paragangliomas. With Fisher linear discriminant function, mean nuclear area (P = 0.0008), 2cDI (P = 0.0030), and the minor DNA index of each cell proliferation were correlated with location. None of the variables established statistically significant differences in comparisons of malignant and benign paragangliomas. Conclusions. Karyometric and DNA densitometric parameters have limited value in determining the prognosis of paragangliomas, although they are correlated with tumoral location, which is still an indicator in establishing the prognosis of these neoplasms.

Estimation of growth rate in patients with head and neck paragangliomas influences the treatment proposal

“…However, paragangliomas are extremely well vascularized and central hypovascularity or necrosis seldom is observed. To our knowledge DNA ploidy studies and immunohistochemistry of paragangliomas to date have shown that these tumors are heterogeneous in DNA ploidy and expression of different proliferation markers 19–21. This heterogeneity could reflect differences in growth rate, but to our knowledge this has yet to be investigated.…”

Differential kinetic features by tumour topography in cutaneous small‐cell neuroendocrine (Merkel cell) carcinomas

“…External diploid controls were used to determine DNA indices (complete rat hepatocytes and lymphocytes from reactive lymph nodes) and to standardize the nuclear area/DNA content analysis (basal keratinocytes from normal areas) 23,24 . The internal controls were used for setting the G 0 /G 1 cell limits and calculating the DNA index of each G 0 /G 1 peak (> 10% of measured cells with evidence of G 2 + M cells) 25–27 .…”

Prognostic Value of Immunohistochemical Expression of Topoisomerase Alpha II, MIB-1, p53, E-Cadherin, Retinoblastoma Gene Protein Product, and HER-2/neu in Adrenal and Extra-adrenal Pheochromocytomas

“…The utility of DNA ploidy analysis in the assessment of prognosis is limited because of the presence of aneuploid or tetraploid DNA patterns in more than 50% of clinically benign lesions and the inability of a diploid pattern to exclude malignant behavior (6,7). Clearly reliable prognostic markers for the prediction of clinical outcome in PHEOs are needed to assign optimal treatment for malignant tumors.…”