Immunophenotypic Transformation in CLL/SLL Patients
Xiaojun Wu, Ashwin Kishtagari, Nicole Lamanna, Maria Arcila, Julie Feldstein. Memorial Sloan-Kettering Cancer Center, New York, NY
Background: About 2 to 9% of CLL/SLL patients undergo Richter's transformation (RT) and suffer a poor prognosis with a median survival time of 5-8 months. Typically, morphologic transformation is needed to establish the diagnosis. Cases with equivocal histomorphologic features but increased Ki-67 expression, known as Immunophenotypic Transformation (IPT), are not very well studied. Hence, a vague pathologic diagnosis might be rendered, which compromises the clinical decision of personalized patient care. The aim of this study is to explore the histomorphologic, molecular and clinical features of CLL/SLL patients with IPT and to better understand the impact of IPT on prognosis.
Design: Pathology reports from a total of 1,721 consecutive cases of CLL/SLL collected at MSKCC between 5/1998 and 2/2012 were reviewed under an approved IRB waiver. Twenty cases were identified with morphologic features suggestive of but not diagnostic of RT. Histologic features, immunohistochemistry studies on p53 and Ki-67, molecular or cytogenetic analyses and clinical information were collected in 14 cases. Data were analyzed using the t test and the Fisher's Exact Test as statistically appropriate. A p value of less than 0.05 was considered statistically significant.
Results: CLL/SLL Patients with IPT were mostly male (M/F: 12/2) with a mean age of 57 (ranged from 45 to 74) at the time of diagnosis. All fourteen cases showed a diffuse infiltrate of small to intermediate size lymphoid cells with effacement of pseudo-follicles. Scattered large cells were increased but did not grow in sheets. Ki-67 positivity was diffuse with a mean of 54%. Despite of histologic similarity, these patients had heterogeneous clinical outcomes. Eight of them had aggressive disease progression, i.e. refractory and resistant to multiagent chemotherapy regimens and/or died of their disease. The remaining 6 responded to chemotherapy. These two groups did not differ significantly in age, selection of chemotherapy regimen, the length of follow up, or molecular or cytogenetic studies. However, the Ki-67 expression is significantly associated with worse outcome (p< 0.05) as it was noted that four patients with Ki-67 fraction above 60% had aggressive clinical course. Moreover, 62.5% of patients with worse outcome had p53 overexpression while only 17% of those with better outcome had so.
Conclusions: Compared with de novo CLL/SLL patient, patients with IPT have heterogeneous clinical outcome with a subgroup showing poor prognosis. A high Ki-67 and p53 overexpression can help identify this population and may play an important role in the prognostic stratification of such patients and clinical decision making in the future.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 243, Monday Morning