We recently encountered a unique case of breast silicone implant-associated ALK-1 negative anaplastic large cell lymphoma (ALCL) in a female with a remote history of breast carcinoma, which presented as a sinusoidal infiltrate in an axillary lymph node (LN) and had a highly complex karyotype

Alobeid, Bachir

Sevilla, Deborah W.

El-Tamer, Mahmoud

Vundavalli, Murty V.

Savage, David G.

Bhagat, Govind

English

Columbia University Academic Commons

LETTER TO THE EDITORAggressive presentation of breast implant-associated ALK-1 negativeanaplastic large cell lymphoma with bilateral axillary lymph nodeinvolvementBACHIR ALOBEID1, DEBORAH W. SEVILLA1, MAHMOUD B. EL-TAMER2,VUNDAVALLI V. MURTY1, DAVID G. SAVAGE3, & GOVIND BHAGAT11Department of Pathology, Columbia University, New York, USA, 2Department of Surgery, Columbia University, New York,USA, and 3Division of Hematology and Medical Oncology, Department of Medicine, Columbia University, New York, USA(Received 18 November 2008; revised 5 January 2009; accepted 1 February 2009)We recently encountered a unique case of breastsilicone implant-associated ALK-1 negative anaplas-tic large cell lymphoma (ALCL) in a female with aremote history of breast carcinoma, which presentedas a sinusoidal infiltrate in an axillary lymph node(LN) and had a highly complex karyotype.A 68-year-old female had undergone right breastlumpectomy followed by right modified radicalmastectomy with axillary LN dissection in 1991 forinfiltrating moderately differentiated ductal carcino-ma. No lymphovascular invasion or LN involvementwas identified. She received six cycles of chemother-apy and 5 years of tamoxifen. In January of 1992, thepatient underwent right breast reconstruction with asilicone implant. Sixteen years later the patientdeveloped right axillary lymphadenopathy. Her pastmedical history was significant only for the priorbreast carcinoma and biliary cirrhosis. She had nohistory of non-Hodgkin or Hodgkin lymphoma. Rightaxillary LN biopsy showed a large cell neoplasminfiltrating and expanding the sinuses (Figure1A). Anexhaustive staining panel led to the diagnosis of anALK-1 negative ALCL (Figure1B). A staging bonemarrow biopsy showed no evidence of lymphoma.A subsequent FDG-PET/CT scan showed a hyper-metabolic focus (maximum SUV 7.4) posterior to thebreast implant. The grossly intact implantwas removed with capsulectomy. Histologic reviewof the fibrotic capsular tissue showed an infiltrate oflarge neoplastic cells as seen previously (Figure 2A),which had the following phenotype (Figure 2B):CD457/þ, CD30þ, CD15þ, EMAþ, MUM1þ,CD2þ and CD4þ. These cells did not express CD3,CD5, CD7, CD8, ALK-1, CD56, CD20, PAX5,CD79a, OCT2, CD138, p53, or cytotoxic T-cellgranule constituents (TIA-1, granzyme-B and perfor-in). In situ hybridisation for EBV mRNA was negative.The proliferation rate, as assessed with a stainfor Ki-67, was 490%. Cytogenetic analysis revealedhighly complex clonal chromosome abnormalities,penta-ploidy range metaphases and homogenouslystaining regions (hsr’s): 116–123,55N4,XX,71,add(1)(p36.3),i(1)(q10),hsr(1)(q21q25),þ2,þ362,þ6,hsr(7)(q32q35)62,i(8)(q10),þ9,þ10, inv(11)(p15.1q22.1)63,add(12)(q24.1),713,714,715,i(17)(q10),þ19,720,þ1*8mar[cp13]/46,XX,inv(11)(p15.1q22.1)[7]. FISH analysis using T-cellreceptor alpha/delta break-apart, ALK break-apartand D7S486/CEP7 probes showed no evidenceof rearrangement or deletion. PCR analysisshowed clonal T-cell receptor beta gene rearrange-ment.Four months after initial diagnosis, the patientdeveloped left-sided (contralateral) axillary lympha-denopathy, and a LN biopsy again disclosed sinu-soidal infiltrates of ALCL. After completion of sixCorrespondence: Dr. Govind Bhagat, 630 West 168th Street, Vanderbilt Clinic Rm. 14-228, New York, NY 10032. Tel: þ212-342-1323. Fax: þ212-305-2301.E-mail: gb96@columbia.eduLeukemia & Lymphoma, May 2009; 50(5): 831–833ISSN 1042-8194 print/ISSN 1029-2403 online  2009 Informa Healthcare USA, Inc.DOI: 10.1080/10428190902795527Leuk Lymphoma Downloaded from informahealthcare.com by Columbia University HHMI For personal use only.cycles of CHOP (cyclophosphamide, vincristine,doxorubicin, and prednisone) therapy, a repeatPET/CT scan showed a mildly hypermetabolic focusin the dome of the liver (SUV 2.8) and 2 minimallyhypermetabolic foci in the left breast (SUV 0.7),suspicious for residual disease. Of note, she had alsobeen under treatment for primary biliary cirrhosisand these lesions were not biopsied, therefore, itis unclear if the imaging findings representedlymphoma or a reactive condition.Our case represents an ALK-1 negative ALCLarising in a breast capsule, in association with asilicone implant and bilateral axillary LN involve-ment. This case thus adds to the growing literature ofbreast prosthesis-associated lymphomas, with 17cases published thus far [1–3], as well as a series ofsix unpublished cases [4].A recent case report by Wong et al. and theseven other ALK-1 negative ALCL cases reviewedin their article presented in the breast withoutnodal involvement [2]. Only one patient had arelapse, while all others were living free of disease.The four cases reported by Roden et al. were alsoALK-1 negative ALCL, which were described as‘therapy-resistant seroma’ adjacent to saline orsilicone implants; neoplastic cells being identifiedonly in the serous fluid without tissue invasion [1].Three of their patients were staged and showed noevidence of systemic disease. Three of the patientswere alive without evidence of disease after a meanfollow-up of 13 months (range of 9–20 months),suggesting that these lymphomas represent indolentT-cell lymphoproliferative disorders. Popplewellet al. described six cases of primary ALCL,including two ALK-1þ ALCL of the breastoccurring in patients 5–20 years after implantationof silicone breast prostheses. All of their patientshad lymphoma confined to the breast at the time ofdiagnosis; however, 2 suffered recurrences follow-ing initial therapy [4]. The latter underwentautologous stem cell transplantation, and showedno evidence of disease after a 2-year follow-up. Arecent study by de Jong et al. described fiveadditional cases of ALK-1 negative ALCLwith ‘dominant breast involvement’ occurring inthe fibrous capsules of saline breast implantsplaced 1–23 years before diagnosis [3]. Three oftheir cases had either bilateral breast involvementor nodal involvement at time of diagnosis andseemed to pursue a more aggressive clinicalcourse, similar to our case. However, it is unclearif all their cases represented true primary breastlymphomas.Although most lymphomas arising in the breast areof B-cell origin, the majority of those described inassociation with breast prostheses have a T-cellphenotype, and ALCL is the most common typedescribed. The neoplastic lymphocytes in all pub-lished studies were negative for ALK-1 expression[1–3].Interestingly, in our case, the lymphoma presentedinitially in a right axillary LN with a sinusoidalpattern of infiltration by large undifferentiatedmalignant cells, mimicking metastatic breast carci-noma. This represented a diagnostic challenge,especially given the remote history of breast carci-noma. The expression of CD15 was also unusual forALCL. In addition, the clinical behaviour of our casewas more aggressive than most cases describedpreviously.None of the previously published implant-associated ALK-1 negative ALCL have describedany cytogenetic or karyotypic aberrations. TheFigure 1. A: Lymph node biopsy showing anaplastic large cellswithin sinusoids (H&E, 6200), (B) the cells are CD30 positive(6400).Figure 2. A: Anaplastic cells infiltrating the fibrous capsule (H&E,6400), (B) the cells express CD4 (6400).832 Letter to the EditorLeuk Lymphoma Downloaded from informahealthcare.com by Columbia University HHMI For personal use only.chromosomal regions altered in our case differ fromthose reported in a recent study of systemic ALK-1negative ALCL [5]. Although cytogenetic aberrationsof chromosome 1, 6 and 13 were noted in our case,the affected loci differed from those previouslyreported.Despite the reported cases of implant associatedmalignancies and the intriguing overrepresentationof ALK-1 negative ALCL, the incidence of thesetypes of lymphomas remains extremely low giventhat breast prostheses have been widely used fordecades. However, oncologists and pathologistsshould be aware of this association and considerALCL in their differential diagnosis when examin-ing tissue removed during capsulectomy for failedor replacement breast prostheses, or when reviewof axillary LNs shows sinusoidal infiltrates of largecells, even if the patient had a prior history ofcarcinoma.References1. Roden AC, Macon WR, Keeney GL, Myers JL, Feldman AL,Dogan A. Seroma-associated primary anaplastic large-celllymphoma adjacent to breast implants: an indolent T-cell lympho-proliferative disorder. Mod Pathol 2008;214:455–463.2. Wong AK, Lopategui J, Clancy S, Kulber D, Bose S. Anaplasticlarge cell lymphoma associated with a breast implant capsule: acase report and review of the literature. Am J Surg Pathol2008;32:1265–1268.3. de Jong D, Vasmel WLE, de Boer JP, Verhave G, Barbe E,Casparie MK, et al. Anaplastic large-cell lymphoma inwomen with breast implants. J Am Med Assoc 2008;300:2030–2035.4. Popplewell L, Chang K, Olevsky O, Nademanee A, Forman S.Primary anaplastic large cell lymphoma of the breast occurringin patients with silicone breast implants. Blood 2004;104American Society of Hematology:Abstract 4563.5. Zetti A, Ru¨diger T, Konrad MA, Chott A, Simonitsch-Klupp I,Sonnen R, et al. Genomic Profiling of peripheral T-celllymphoma, unspecified, and anaplastic large T-cell lymphomadelineates novel recurrent chromosomal alterations. Am JPathol 2004;164:1837–1848.Letter to the Editor 833Leuk Lymphoma Downloaded from informahealthcare.com by Columbia University HHMI For personal use only.

Aggressive presentation of breast implant-associated ALK-1 negative anaplastic large cell lymphoma with bilateral axillary lymph node involvement

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Aggressive presentation of breast implant-associated ALK-1 negative anaplastic large cell lymphoma with bilateral axillary lymph node involvement

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