Expression of PU.1 in Histiocytic and Dendritic Cell Neoplasms and Histologic Mimics
MB Ruzinova, JL Hornick. Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Background: Histiocytic sarcoma (HS) is a rare malignant neoplasm of monocyte/macrophage lineage. The hematopoietic nature of HS can sometimes be difficult to establish, and HS can therefore be difficult to distinguish from other epithelioid and spindle cell neoplasms. PU.1 is an Ets transcription factor that plays a critical role in the development of the B-lymphoid and myeloid lineages, particularly monocytes and histiocytes, but is not expressed in non-hematopoietic cells. The purpose of this study was to evaluate expression of PU.1 in large cell, spindle cell, histiocytic, and dendritic cell neoplasms in order to establish the utility of this marker in the diagnosis of HS.
Design: In total, 112 tumors were studied: 9 HS; 9 Langerhans cell histiocytosis (LCH); 7 sinus histiocytosis with massive lymphadenopathy (SHML); 4 interdigitating dendritic cell (IDC) sarcomas; 12 follicular dendritic cell (FDC) sarcomas; 9 metastatic melanomas; 10 cases each of malignant peripheral nerve sheath tumor (MPNST), inflammatory myofibroblastic tumor (IMT), anaplastic large cell lymphoma (ALCL), and metastatic poorly differentiated carcinoma; and 22 diffuse large B-cell lymphomas (DLBCL). Immunohistochemistry was performed following pressure cooker antigen retrieval using an anti-PU.1 monoclonal antibody (G148-74, BD Biosciences, 1:100) and the EnVision+ detection system (Dako). The extent of immunoreactivity was graded according to the percentage of tumor cells showing nuclear staining: 0, no staining; 1+, <5%; 2+, 5-25%; 3+, 26-50%; 4+, 51-75%; and 5+, 76-100%.
Results: Diffuse staining for PU.1 was observed in all cases of LCH (5+ ) and SHML (5+ , 4+ ). Most histiocytic sarcomas (77%) were also positive for PU.1 (5+ , 3+ , 2+ ). As expected, expression of PU.1 was seen in all cases of DLBCL; however, the extent was variable (5+ , 4+ , 3+ , 2+ ). Only a minority of IDC sarcomas (25%), FDC sarcomas (8%), and IMT (10%) were positive for PU.1. All cases of metastatic melanoma, MPNST, and metastatic carcinoma were completely negative for PU.1. Surprisingly, 30% of ALCL cases (all cutaneous) exhibited strong staining for PU.1.
Conclusions: PU.1 is expressed in the majority of histiocytic sarcomas and in LCH and SHML, but is rarely expressed in non-hematopoietic mimics. Thus, PU.1 may be useful in a panel for the diagnosis of histiocytic and dendritic cell tumors. In addition, reactivity for PU.1 was seen in cutaneous but not systemic ALCL, suggesting that aberrant expression may be useful in distinguishing between these ALCL variants.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 220, Tuesday Morning