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Phosphorylated histone H3, Ki-67, p21, fatty acid synthase, and cleaved caspase-3 expression in benign and atypical granular cell tumors.

Kapur P,Rakheja D,Balani JP,Roy LC,Amirkhan RH,Hoang MP

Abstract

Granular cell tumors (GCTs) are classified as benign when none of the following features is present: spindling of the tumor cells, necrosis, diffuse pleomorphism, prominent nucleoli, high nuclear-cytoplasmic ratio, and mitotic rate >2 per 10 high-power fields. It has been suggested that a GCT be classified as atypical when 1 or 2 of these features are seen and as malignant when 3 or more of these are present. In our practice, we do not classify GCTs as malignant in the absence of metastasis.
To compare immunohistochemical staining for phosphorylated histone H3 (PHH3), Ki-67 (MIB-1), p21, fatty acid synthase, and cleaved caspase-3 in histologically classified benign and atypical GCTs.
We reviewed 25 cases of GCT from our archives and classified 14 as atypical based on histologic features. Immunohistochemical staining for PHH3, Ki-67, p21, fatty acid synthase, and cleaved caspase-3 was performed using standard methods. The number of positive cells for Ki-67, p21, and PHH3 was calculated in 10 consecutive high-power fields in a hot spot. Fatty acid synthase and cleaved caspase-3 cytoplasmic expression was graded from 1 to 3.
Ki-67 and PHH3 scores were significantly higher in atypical GCTs. The expression of p21, fatty acid synthase, and cleaved caspase-3 was not significantly different between atypical and benign GCTs.
This study shows that histologic features are reliable in identifying GCTs that have a higher proliferative potential as shown by higher immunoreactivity for Ki-67 and PHH3. These immunostains may help in classifying GCTs in cases where a thorough histologic evaluation is precluded by the small size of a biopsy specimen.

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