- About this Journal
- Abstracting and Indexing
- Aims and Scope
- Article Processing Charges
- Articles in Press
- Author Guidelines
- Bibliographic Information
- Citations to this Journal
- Contact Information
- Editorial Board
- Editorial Workflow
- Free eTOC Alerts
- Publication Ethics
- Reviewers Acknowledgment
- Submit a Manuscript
- Subscription Information
- Table of Contents
Case Reports in Medicine
Volume 2013 (2013), Article ID 603614, 5 pages
Chronic Lymphocytic Leukemia Involving the Breast Parenchyma, Mimicker of Invasive Breast Cancer: Differentiation on Breast MRI
1Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
2Jefferson Radiology, Hartford, CT 06106, USA
3Department of Pathology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
Received 30 April 2013; Accepted 12 August 2013
Academic Editor: Stefan O. R. Pfleiderer
Copyright © 2013 Vandana Dialani et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Leukemic involvement of the breast is rare, particularly involvement by chronic lymphocytic leukemia (CLL). While concurrent invasive ductal carcinoma and CLL manifesting as a collision tumor in the breast is extremely rare, this association (CLL and carcinoma) has been described in other organs. We report here a case of a 58-year-old woman with concurrent invasive ductal carcinoma and CLL and describe the imaging features of CLL, particularly the differentiation on MRI.
1. Case History
A 58-year-old woman presented for screening breast MRI due to a high-risk history, specifically infiltrating breast carcinoma with ductal and lobular features involving the right breast in 1999, status after lumpectomy, tamoxifen therapy, and radiation therapy, without evidence of recurrence. Her medical history was also notable for chronic lymphocytic leukemia (CLL) diagnosed in 1998.
Breast MRI performed on a 1.5T (GE Healthcare, Milwaukee, WI, USA), showed a new 6 mm lesion with slightly irregular margins in the upper inner quadrant of the left breast. The lesion did not meet threshold criteria for enhancement (100% increase in signal within 90 seconds), and the curve demonstrated slow progressive uptake of contrast within the lesion (Figures 1(a)–1(c)). Given its appearance and the patient’s history of contralateral breast carcinoma, the enhancing lesion was categorized as a BIRADS 4B and biopsy was recommended. The lesion was mammographically occult. Focused ultrasound of the left breast demonstrated a hypoechoic, ovoid nodule at 10 o’clock, 4 cm from the nipple, oriented along the tissue planes, with slightly irregular margins. There was no abnormal vascularity (Figures 2(a) and 2(b)). A core biopsy under ultrasound guidance was performed, and an INRAD titanium clip was placed at the site of biopsy. An MRI of the breast was performed immediately after procedure and confirmed the clip placement within the enhancing lesion (Figures 3(a) and 3(b)).
Histologic examination of the core biopsy revealed multiple patchy foci of atypical lymphocytic infiltrates within the stroma and adipose tissue consisting of small mature monomorphic lymphocytes (Figures 4(a) and 4(b)). Immunohistochemistry displayed positive staining of these lymphocytes with CD20 and CD5. These cells were not reactive with CD3, CD23, or cyclin D1. These findings are consistent with involvement by the patient’s known CLL.
On further workup eighteen months later, in the left breast a new distinct irregular 8 mm lesion with early wash-in-wash-out kinetics was detected by MRI for which MR-guided biopsy was recommended and in addition adjacent 4 mm focus with benign kinetics, not meeting threshold criteria for enhancement, immediately adjacent to each other were noted (Figure 5). Core biopsy showed an 8 mm focus of invasive ductal carcinoma with adjacent foci of atypical lymphoid infiltrates, consistent with CLL, in the left breast parenchyma (Figure 6). The patient subsequently had bilateral mastectomies and sentinel lymph node biopsy on the left. Infiltration by CLL of the right breast and lymph nodes was also identified.
Leukemic involvement of the breast is extremely rare, particularly involvement by CLL [1, 2]. Though rare, one of the more familiar leukemias which involve the breast is acute myelogenous leukemia, which can present with granulocytic sarcomas (chloromas) . More rarely seen is acute lymphocytic leukemia, which can present as a diffuse bilateral breast process, an ill-defined mass, lymphadenopathy, or with a normal mammogram .
CLL can involve the breasts diffusely and bilaterally , include involvement of the overlying skin , present as an irregular breast nodule, be associated with microcalcifications , or be mammographically occult. In addition, CLL has been found synchronously in axillary lymph nodes ipsilateral to invasive breast cancer .
CLL manifesting in a collision tumor of the breast containing both invasive ductal carcinoma and foci of CLL is extremely rare [7, 8]. A postulated mechanism is that underlying etiology predisposes both tumor types (mutation of ATM gene or infection by Epstein-Barr virus) or that the CLL may express a B-cell receptor with affinity for an undefined breast cancer antigen . A few reports describe other collision tumors in the breast such as association of invasive ductal carcinoma and mucosa-associated lymphoid (MALT) lymphoma [9, 10]. Etkind et al. have postulated a possible involvement of the presence of MMTV-like (mouse mammary tumor virus-like) envelope gene in patients with both invasive ductal carcinoma and non-Hodgkin’s cell lymphomas .
CLL (chronic lymphocytic leukemia) and SLL (small lymphocytic lymphoma) are diagnosed primarily by morphology and secondarily by ancillary tools such as flow cytometry and immunohistochemistry. Confirmatory markers by flow cytometry include CD20 (dim), CD19, CD5 (aberrant coexpression), CD23, and light chain (dim). Immunohistochemistry performed in the tissue sections includes CD20 (dim), CD5 (dim), and CD23 . Once a diagnosis of CLL/SLL is made, then additional prognostic markers include a FISH panel (including 13q ), IgVH, ZAP70  is usually done on a case-by-case basis and the Rai-Binet score.
While MR imaging characteristics of breast primary and secondary lymphomas have been noted in the literature , to our knowledge, this report is the first in which CLL infiltration of the breast has been evaluated by MRI. The MRI findings were concordant with an indolent process; the enhancement within the small lesion did not meet threshold criteria and demonstrated progressive rather than wash-out kinetics, as against the invasive carcinoma which showed distinct early wash-in and wash-out kinetics. In addition, the lesion was neither palpable nor painful, and there were no associated overlying skin findings nor axillary lymphadenopathy. On ultrasound, the lesion was indeterminate with some irregularity of margins but respecting the tissue planes.
It is important to consider involvement of the breast by hematologic malignancies specifically in patients with known systemic involvement, when MRI shows indolent findings as described, so that appropriate followup can be provided for the patient.
- D. L. Seale, H. O. Riddervold, C. D. Teats, and D. D. Stone, “Roentgenographic appearance of chronic lymphatic leukemia involving the female breast. A case report,” The American Journal of Roentgenology, Radium Therapy, and Nuclear Medicine, vol. 115, no. 4, pp. 808–810, 1972.
- F. Famà, V. Barresi, G. Giuffrè et al., “An unusual presentation of secondary involvement of B-cell chronic lymphocytic leukemia. A case report,” Tumori, vol. 94, no. 4, pp. 617–620, 2008.
- T. J. Barloon, D. C. Young, and S. H. Bass, “Multicentric granulocytic sarcoma (chloroma) of the breast: mammographic findings,” American Journal of Roentgenology, vol. 161, no. 5, pp. 963–964, 1993.
- E. S. McCrea, C. Johnston, and P. J. Haney, “Metastases to the breast,” American Journal of Roentgenology, vol. 141, no. 4, pp. 685–690, 1983.
- P. K. Gogoi, I. D. Stewart, P. F. Keane, R. Scott, G. D. Dunn, and D. Catovsky, “Chronic lymphocytic leukaemia presenting with bilateral breast involvement,” Clinical and Laboratory Haematology, vol. 11, no. 1, pp. 57–60, 1989.
- M. Stierer, H. R. Rosen, R. Heinz, and H. Hanak, “Synchrony of malignant lymphoma and breast cancer,” Journal of the American Medical Association, vol. 263, no. 21, pp. 2922–2993, 1990.
- X. Catteau, M. F. Dehou, J. L. Dargent, M. Hackx, and J. C. Noël, “Chronic lymphocytic leukemia mimicking recurrent carcinoma of the breast: case report and review of the literature,” Pathology Research and Practice, vol. 207, no. 8, pp. 514–517, 2011.
- K. J. Cheung, W. Tam, E. Chuang, and M. P. Osborne, “Concurrent invasive ductal carcinoma and chronic lymphocytic leukemia manifesting as a collision tumor in breast,” Breast Journal, vol. 13, no. 4, pp. 413–417, 2007.
- P. H. Wiernik, X. Hu, H. Ratech et al., “Non-Hodgkin's lymphoma in women with breast cancer,” Cancer Journal, vol. 6, no. 5, pp. 336–342, 2000.
- J. M. Quilon, T. A. Gaskin, A. S. Ludwig, and C. Alley, “Collision tumor: invasive ductal carcinoma in association with mucosa-associated lymphoid tissue (MALT) lymphoma in the same breast,” Southern Medical Journal, vol. 99, no. 2, pp. 164–167, 2006.
- P. R. Etkind, A. F. R. Stewart, T. Dorai, D. J. Purcell, and P. H. Wiernik, “Clonal isolation of different strains of mouse mammary tumor virus-like DNA sequences from both the breast tumors and non-Hodgkin's lymphomas of individual patients diagnosed with both malignancies,” Clinical Cancer Research, vol. 10, no. 17, pp. 5656–5664, 2004.
- F. E. Craig, “Flow cytometric evaluation of B-cell lymphoid neoplasms,” Clinics in Laboratory Medicine, vol. 27, no. 3, pp. 487–512, 2007.
- D. L. Van Dyke, T. D. Shanafelt, T. G. Call et al., “A comprehensive evaluation of the prognostic significance of 13q deletions in patients with B-chronic lymphocytic leukaemia,” British Journal of Haematology, vol. 148, no. 4, pp. 544–550, 2010.
- Y. H. Wang, L. Fan, W. Xu, and J. Y. Li, “Detection methods of ZAP-70 in chronic lymphocytic leukemia,” Clinical and Experimental Medicine, vol. 12, no. 2, pp. 69–77.