Year : 2010 | Volume
: 53 | Issue : 1 | Page : 155--156
Extramedullary relapse of acute lymphoblastic leukemia in breast: A rare presentation
J Thanka1, K Krishnarathinam2, S Rajendiran1,
1 Department of Pathology, Sri Ramachandra University, Porur, Chennai - 600 116, India
2 Department of Hemato Oncology, Sri Ramachandra University, Porur, Chennai - 600 116, India
Department of Pathology, Sri Ramachandra Medical College & R.I, Sri Ramachandra University, Porur, Chennai - 600 116
Unusual sites of relapses following allogenic hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia (ALL) are rarely reported. Our report describes a thirty-two-year old female, who developed extramedullary (EM) breast relapse after allogenic HSCT for pre B cell Philadelphia chromosome negative ALL. She had no evidence of leukemia in her marrow demonstrating 100% full donor chimerism, while she had ALL relapse in her breast.
|How to cite this article:|
Thanka J, Krishnarathinam K, Rajendiran S. Extramedullary relapse of acute lymphoblastic leukemia in breast: A rare presentation.Indian J Pathol Microbiol 2010;53:155-156
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Thanka J, Krishnarathinam K, Rajendiran S. Extramedullary relapse of acute lymphoblastic leukemia in breast: A rare presentation. Indian J Pathol Microbiol [serial online] 2010 [cited 2021 Jan 26 ];53:155-156
Available from: https://www.ijpmonline.org/text.asp?2010/53/1/155/59212
Isolated extramedullary (EM) relapse of acute lymphoblastic leukemia (ALL) in breast with sparing of the marrow after allogenic hematopoietic stem cell transplantation (HSCT) is a rare occurrence. In adult patients, EM relapse after allogenic HSCT is associated with a better outcome than medullary relapse. We report an isolated breast relapse in a patient with ALL after allogenic HSCT.
Thirty-two-year-old female was admitted in the hemato oncology division for sudden onset of a painful lump in her left breast. She had Philadelphia chromosome negative ALL in the year 2005 and was treated with standard chemotherapy. She relapsed in January 2007, two years from the initial diagnosis. The flow cytometry performed with the peripheral blood showed 30% blasts. The cells expressed CD 10, CD 19, CD 22, CD 34, and HLA-DR. There was coexpression of CD 10 and CD 19 in 89% of these cells. T-lymphoid markers were absent. The findings were consistent with the diagnosis of precursor B acute lympholastic leukemia. BCR-ABL gene was not detected by fluorescent in situ hybridization (FISH) in the bone marrow specimen. The patient was treated with salvage chemotherapy. She was taken up for allogenic HSCT in second remission. The donor was her brother who was HLA identical. She was conditioned with injections of fludarabine and melphalan. Engraftment was rapid and she obtained complete donor chimerism on the 28 th day of poststem cell infusion, which was confirmed by FISH for sex chromosome. She had regular follow-up, which was uneventful except mild chronic graft verus host disease (GVHD) of the skin.
Six months after HSCT, the patient noticed a lump in her left breast which was sudden in onset and was admitted for evaluation. Fine needle aspiration cytology of the lump showed cells suggestive of leukemia [Figure 1]. A wide excision of the lump was done. Grossly, it was a grey white nodular mass measuring 3 cm in its greatest dimension [Figure 2]. Sections from the lesion showed tumor cells with increased nucleocytoplasmic ration, scant cytoplasm, and increased mitotic activity, suggestive of a high grade lymphoid neoplasm. An immunohistochemical workup was done and the tumor cells showed crisp membrane positivity for CD 20 [Figure 3] and negative for cytokeratin and CD3 antigens. The diagnosis of EM deposit of B cell leukemia was performed. Bone marrow and cerebrospinal fluid examination showed no evidence of relapse. At this time, the bone marrow cytogenetics confirmed 100% male karyotype.
EM relapse of hematological malignancies following allogenic HSCT is not uncommon in adults with the rate of involvement seen in 45-50% of the cases.  Central nervous system (CNS) is the most common site and involvement of breast is rare. Efficacy of HSCT is attributed to the cytotoxicity of the conditioning regimen and the graft versus leukemia (GVL) effect of the immunoreactive donor cells. Cytotoxicity is limited by the blast's spontaneous and therapy-dependent resistance to chemo and radiotherapy.  Selective involvement of EM site preceeding marrow relapse suggests either a high affinity of blasts to EM sites or due to specific biological features such as receptors or adhesion molecules. Our patient did not show any marrow relapse to date (18 months).
Another explanation would be a common predisposition to the affected organs to leukemic invasion in terms of immune privilege leading to a reduced GVL effect. They are called sanctuary sites which are well-described phenomena. These sites are protected form systemic chemotherapy by biological barrier, for example, CNS or distinct growth conditions such as lower temperature, as in testicles. In analogy to the sanctuary sites for chemotherapy, sanctuary sites for the GVL effect or immune privileged sites that are not sufficiently accessible to cytotoxic T-lymphocytes (CTLs) have been discussed by Goldberg et al. and Seo et al. in the context of EM relapse. , The term immune privileged site was originally used in the field of transplant immunology to describe sites, where allotransplants are protected from the effect of antigen-specific immune efforts. Various structures such as eye, CNS, testicles, ovaries, adrenal cortex, pregnant uterus, and hair follicles are considered to be immune privileged in that sense.
An EM disease after allogenic HSCT usually has a bad prognosis and presents mainly in individuals with high risk malignancies.  Due to low incidence of localized EM relapses, therapeutic strategies for these complications are not yet identified. With the preservation of donor's hematopoiesis in the recipients marrow, the use of intensive chemotherapy followed by donor lymphocyte infusion, is a promising option.  Our patient, after wide excision of the breast lump (isolated EM relapse), developed CNS relapse five months later and was treated successfully. She did not develop any bone marrow relapse. We are reporting this case for its rare presentation, the challenges for its diagnosis, therapeutic options, and also to highlight the possible mechanisms of isolated EM relapses.
|1||Lee KH, Lee JH, Kim S, Lee JS, Kim SH, Kim WK. High frequency of extramedullary relapse of acute leukemia after allogenic bone marrow transplantation. Bone marrow transplantation 2000;26:147-52.|
|2||Huck K, Laws HJ, Meisel R, Traeger A, Bernbeck B, SchönbergerS et al. Three cases of renal disease after allogenic hematopoietic stem cell transplantation for child hood acute lymphoblastic leukemia. Hematological 2006;91:20-5.|
|3||Goldberg SL, Mangan KF, Klumpp TR, Cropper TM, Schnall SF, Macdonald JS. Lack of a graft-versus-leukemia effect in an immunologically privileged sanctuary site. Bone marrow transplant 1994;14:180-1.|
|4||Seo S, Kami M, Honda H, Kashima T, Matsumura T, Moriya A et al. Extramedullary relapse in the so called sanctuary sites for chemotherapy after donor lymphocyte in fusion. Bone marrow transtplant 2000;25:226-7.|
|5||Ruiz-Argüelles GJ, Gomez-Almaguer D, Vela-ojeda J, Morales-Toquero A, Gomez-Rangel JD, Garcia - Ruiz - Esparza MA et al. Extraemdullary leukemic relapses following hematopoietic stem cell transplantation with non myeloablative conditioning. Int. J Hematol 2005;82:262-5.|
|6||Au WY, Kwong YL, Lie AKW, Ma SK, Liang R. Extramedullary relapse of leukemia following allogenic bone marrow transplantation. Hematological oncology 1999;17:45-52.|