Cell Cycle Checkpoints p16 and p21-Strong Predictors of Clinicopathologic Outcomes in High-Grade Osteosarcoma.

PURPOSE: In this study, we used a series of immunohistochemical measurements of 2 cell cycle regulators, p16 and p21, to evaluate their prognostic value, separately and in combination, for the disease outcomes. METHOD: A total of 101 patients with high-grade osteosarcoma were included in this study. Clinicopathologic data were collected, and immunohistochemistry for p16 and p21 was performed and interpreted by 3 independent pathologists. Statistical analysis was performed to assess the strength of each of these markers relative to disease outcome. RESULTS: Our results indicate that more than 90% expression (high) of p16 by immunohistochemistry on the initial biopsy has a strong predictive value for good histologic response to chemotherapy. The patients are also more likely to survive the past 5 years and less likely to develop metastasis than patients with less than 90% p16 (low) expression. The results for p21, on the other hand, show a unique pattern of relationship to the clinicopathologic outcomes of the disease. Patients with less than 1% (low) or more than 50% (high) expression of p21 by immunohistochemistry show a higher chance of metastasis, poor necrotic response to chemotherapy, and an overall decreased survival rate when compared with p21 expression between 1% and 50% (moderate). Our results also showed that the expression of p16 and combined p16 and p21 demonstrates a stronger predictive relationship to 5-year survival than tumor histologic necrosis and p21 alone. DISCUSSION: The results of this study, once proven to be reproducible by a larger number of patients, will be valuable in the initial assessment and risk stratification of the patients for treatment and possibly the clinical trials.

Misinterpreted Myoepithelial Carcinoma of Salivary Gland: A Challenging and Potentially Significant Pitfall.

Myoepithelial carcinoma (MECA) is an underrecognized challenging entity with a broad morphologic spectrum. Misinterpreting MECA is not uncommon as distinguishing it from its mimics, especially cellular myoepithelial-rich pleomorphic adenoma (PA), can be difficult. We described 21 histologically challenging cases of MECAs (16 MECA ex-PA and 5 MECA de novo). All MECAs ex-PA were intracapsular or minimally invasive except for 3 cases. Eighteen (86%) were initially misinterpreted as benign neoplasms, including PA (10), atypical PA (5), and myoepithelioma (3). The remaining 3 were initially diagnosed as malignant (MECA ex-PA) but were histologically challenging. Histologic features that were found most helpful in recognizing the malignant nature of MECA included: uniformly cellular myoepithelial proliferation with an expansile nodular lobulated pattern (all cases) and alternate hypocellular and hypercellular zonal distribution (76% of cases). Among the 16 MECA patients with follow-up, 14 (87.5%) progressed: 10 developed local recurrence and 5 distant metastases. In contrast, only one of 33 patients with cellular PA (control group) recurred locally. Ten of the 14 MECAs that progressed were MECA ex-PA, and 12 (85%) had an initial benign diagnosis. Two patients with MECA ex-PA died of their disease; one had an initial diagnosis of PA. MECA is a histologically challenging entity that closely mimics PA and seems to carry a significant risk of recurrence. Areas of clonal appearing cellular myoepithelial growth with an expansile nodular lobulated pattern and zonal cellular distribution distinguish the majority of MECAs and may serve as useful diagnostic histologic features to differentiate MECA from its benign mimics.