Role of Sentinel Lymph Node Biopsy in Ductal Carcinoma-in-situ Treated by Mastectomy

Background Sentinel lymph node biopsy (SLNB) is a widely accepted alternative to axillary lymph node dissection in invasive breast cancer. Its role in ductal carcinoma-in-situ (DCIS) is unclear. The purpose of this study was to determine factors associated with the subsequent diagnosis of invasive disease and to determine the role of SLNB when performing a mastectomy for DCIS. Methods A retrospective study was conducted of all mastectomies performed on patients with a preoperative diagnosis of DCIS between 2000 and 2005 at a single tertiary-care institution. Results Ninety mastectomies for DCIS were included, 54 (60%) of which were performed with concurrent SLNB. Of 44 patients diagnosed preoperatively with DCIS by core biopsy only, 34 patients (63%) had a concurrent SLNB, while 10 patients (28%) were treated with mastectomy alone (P < .01). Overall, 30 patients (33%) had invasive disease, 22 of whom received concurrent SLNB. Seven SLNB patients (13%) had positive SLNs. On univariate analysis, multifocality (P = .03), multicentricity (P = .01), comedonecrosis (P = .01), and diagnosis by core biopsy (P < .001) were associated with invasive disease on pathology. On multivariate analysis, comedonecrosis (P = .04) and diagnosis by core biopsy (P < .01) were independent predictors for invasion. There was no statistically significant predictor for sentinel lymph node metastasis. Conclusions Approximately one-third of patients with DCIS treated with mastectomy at our institution later had invasive disease, and factors associated with invasion have been identified. On the basis of our results, routine SLNB is recommended in this patient population.     

Establishment of human T-cell leukemia virus type I T-cell lymphomas in severe combined immunodeficient mice

Human T-cell leukemia virus type I (HTLV-I) is recognized as the etiologic agent of adult T-cell leukemia (ATL), a disease endemic in certain regions of southeastern Japan, Africa, and the Caribbean basin. Although HTLV-I can immortalize T lymphocytes in culture, factors leading to tumor progression after HTLV-I infection remain elusive. Previous attempts to propagate the ATL tumor cells in animals have been unsuccessful. Severe combined immunodeficient (SCID) mice have previously been used to support the survival of human lymphoid cell populations when inoculated with human peripheral blood lymphocytes (PBL). SCID mice were injected intraperitoneally with PBL from patients diagnosed with ATL, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), or from asymptomatic HTLV-I-seropositive patients. Many of these mice become persistently infected with HTLV-I. Furthermore, after human reconstitution was established in these mice, HTLV-I-infected cells displayed a proliferative advantage over uninfected human cells. Lymphoblastic lymphomas of human origin developed in animals injected with PBL from two ATL patients. The tumor cells represented outgrowth of the original ATL leukemic clone in that they had monoclonal or oligoclonal integrations of the HTLV-I provirus identical to the leukemic clone and predominantly expressed the cell surface markers, CD4 and CD25. In contrast, cell lines derived by HTLV immortalization of T cells in vitro did not persist or form tumors when inoculated into SCID mice, indicating differences between in vitro immortalized cells and ATL leukemic cells. This system represents the first small animal model to study HTLV-I tumorigenesis in vivo.