Myeloid sarcoma of the breast: a pathology that should not be forgotten

Luca Nicosia1, Antuono Latronico1, Mariagiorgia Farina1, Anna Carla Bozzini1, Paola Baratella2, Viviana Enrica Galimberti2, Stefano Fiori3, Marta Montesano4 and Enrico Cassano1

1Department of Breast Radiology, European Institute of , 20141 Milan, Italy 2Division of Breast , IEO, European Institute of Oncology, 20141 Milan, Italy 3Division of Pathology and Laboratory Medicine, IEO, European Institute of Oncology, 20141 Milan, Italy 4Department of Radiological Sciences, Oncology and Pathology, I.C.O.T. Hospital, ‘Sapienza’ University of Rome, 04100 Latina, Italy

Abstract

Myeloid sarcoma (MS) is a rare , represented by a tumoural mass composed of myeloid blasts, occurring at any anatomical site other than the . MS is considered the tissue-based equivalent of acute myeloid leukaemia (AML), requiring the same therapeutic specification, independently from the association with previous or coexisting myeloid . Isolated breast involvement by MS is exceedingly rare, with only exceptional cases reported in the literature. This work aims to provide a pic- torial essay of the main features of breast involvement by MS. Even though it is a rare condition, we should not forget this neoplasm, and its possibility of being disguised by the Image Report Image AML, as it requires prompt treatment.

Keywords: myeloid sarcoma, breast, , breast cancer

Introduction

Myeloid sarcoma (MS) was first described by Burns in 1811 and subsequently linked to Correspondence to: Luca Nicosia myeloid neoplasms in 1893, by Dock [1]. MS is defined in the latest World Heath Orga- Email: [email protected] nization (WHO) Classification of Tumours of Haematopoietic and Lymphoid Tissues as ecancer 2020, 14:1160 a tumour mass, with tissue effacement, composed of myeloid blasts, occurring at any https://doi.org/10.3332/ecancer.2020.1160 anatomical site other than the bone marrow [2–4]. Published: 21/12/2020 Received: 30/08/2020 MS can variably precede or coincide with acute myeloid leukaemia (AML), represent relapse of a previous AML, or blastic transformation of , myelo- Publication costs for this article were supported by ecancer (UK Charity number 1176307). dysplastic/myeloproliferative neoplasm or myeloproliferative neoplasm. A diagnosis of MS is hence considered equivalent to AML [5–7]. In the largest published series, MS Copyright: © the authors; licensee occurring independently from AML or myeloid neoplasm is reported in about a quarter ecancermedicalscience. This is an Open Access article distributed under the terms of the of the cases [6]. Creative Commons Attribution License (http:// creativecommons.org/licenses/by/3.0), which The most common sites involved are skin, lymph nodes, intestinal tract, bone and cen- permits unrestricted use, distribution, and tral nervous system; on the contrary, isolated breast involvement is exceedingly rare, reproduction in any medium, provided the original with only exceptional cases reported in the literature. Histologically, MS is composed of work is properly cited.

ecancer 2020, 14:1160; www.ecancer.org; DOI: https://doi.org/10.3332/ecancer.2020.1160 1 tissue samplingtosubmitfor cytogenetic andmolecular analyses). initially consider such infrequent diagnosis, in order to startthecorrect diagnostic-therapeutic approach ina timely manner (includingfresh This work’sis to purpose provide apictorial essayfeaturesmain onthe of breast MS.For theaggressiveness of thisdisease,itisimportant to molecular procedures. bone marrowwithout involvement,analysissuch may beproblematic andrequire afresh tissuesampleto besubmitted for cytogenetic or Recognisingalterations such for iscrucial theassessment of stratified riskandthesubsequent therapeutic approach [8].In isolated MScases, NPM1 mutation, are linked to MSandextramedullary presentation of AML [7–9]. Specificgenetic alterations, ast(8;21)(q22;q22.1) such RUNX1-RUNXT1, inv (16)(p13.1q22) or t(16;16)(p13.1;q22) and CBFB-MYH11, B-cell (DLBCL)inthe widest series assessment,an immunohistochemical for adiagnosisofRemarkably, MS. of 10out 25isolated MSs have beenmisdiagnosedasdiffuselarge ferential in diagnosis is mainly related toand smallround lymphoma cell tumours, evenbut with poorly differentiated carcinoma ismandatory erythroid of megakaryoblasticfeatures are uncommonand associated with transformation from myeloproliferative neoplasm. The major dif myeloid blasts presencewith the orabsence the of neutrophilicor granulocytic maturation. Monocytic differentiation isquite common, while ecancer 2020, 14:1160; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1160 caudal and(b): mediolateral obliqueprojection, showing anoncalcifiedill-defined radiopaquemass withpoorly defined ‘feathery’ margins (arrow). Figure 1.Left sidefull-fielddigitalmammography of a70-year-old patient presenting aunilateral breastmasssubsequently identified asa MS. (a): Cranio ‘feathery’’ margins [10,11],asshown inFigures. 1and2 Themammogram typical manifestation of granulocyticsarcoma is thepresence of alarge, non-calcifiedirregular mass with poorly defined Radiological andhistopathological appearance bilateral massandoften canbeindistinguishablefrom benigntumours or lymphoma. The most common feature ofis the presenceMS of a rapidly growing mass: clinically, MS involving the breast can present as a unilateral or Clinical appearance andpresentation [6]. 2 -

Image Report ecancer 2020, 14:1160; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1160 low attenuation are appreciated, withill-defined margins (arrows). Figure 4. A 60-year-old patient presenting aright unilateral breast mass subsequently identified asa MS. The heterogeneous echo patternsand marked low attenuation, withill-defined margins (arrow). (b): Thebiopsy ofthelesion withtheneedleinsidelesion (arrowhead). Figure 3. A 55-year-old patient presenting aright unilateral breast masssubsequently identified asaMS. (a): The heterogeneous echo patternsand marked and (b): mediolateral obliqueprojection, showing anoncalcifiedill-defined radiopaquemass withpoorly defined ‘feathery’ margins (arrow). Figure 2.Right sidefull-fieldmammography of a40-year-old patient presenting aunilateral breastmasssubsequently identified asa MS. (a): Craniocaudal defined margins, are thetypicalultrasound features asshown inFigures 3and4. Frequently thediagnosisisperformed ultrasoundwith biopsy [12,13]:heterogenous echopatterns andmarked low attenuation, with ill- 3

Image Report tion andrestricted diffusion( relative to breast parenchyma,and hypointense on T1 images (Figure 5),inhomogeneous enhancement (F Magneticresonance imagingusing T2-weighted images may show granulocytic sarcoma asill-defined, heterogeneous, hyperintense masses ecancer 2020, 14:1160; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1160 (arrow) and(b): therestricted diffusion of thesamemass (arrow) intheapparent diffusion coefficient (ADC)mass. Figure 7. The samepatient of Figure 6,showing right unilateral breast mass,subsequently identified asaMS. (a): Diffusion imaging with hyperintense mass administration (arrow) and(b): theappearance of themassenhancement (arrow) inthemaximumintensity projection. Figure 6. A 63-year-old patient presenting aright unilateral breast masssubsequently identified asaMS. (a) Inhomogeneous enhancement ongadolinium masses relative to breast parenchyma on T2images (arrow) and(b): hypointense on T1images (arrow). Figure 5. A 70-year-old patient presenting aright unilateral breast masssubsequently identified asaMS. (a): Ill-defined, heterogeneous, hyperintense Figure 7). igure administra 6)ongadolinium - 4

Image Report ecancer 2020, 14:1160; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1160 right breast, andasecond needlebiopsy was required to assesscytogenetic andmolecular features. associated with eosinophils(a, haematoxylin-eosin) andexpress CD34(b) andmyeloperoxidase (c). In thiscase,thediseaseinvolvement was limited to the Figure 10.Histologic features of breast MS.(a–c): Breast involvement by MS with inv(16) (p13.1q22) ina21-year-old female patient. Myeloid blasts are Figure 9.Same patient of Figure 8,showing irregular contrast-enhancing soft tissuemass (arrow), resultinginthelocalisation ofMS. (arrow). mass onthecomputed tomography exam, showing inhomogeneous contrast enhancement (arrow). (b):The abnormal glucose uptake inPET examination Figure 8. A 50-year-old patient presenting aright unilateral, incidental finding of breastmasssubsequently demonstrated tobeaMS. (a): Irregular breast especially for thedifficultiesencountered distinguishingMSfrom lymphoma(Figures 10–12). ofMS with breast the presentcan other softlocalisation,tissue asthekidneysuch (Figure 9).The histopathological diagnosisischallenging Theappearance typical isof anirregular breastmass inhomogeneouswith contrast enhancement andglucose uptake. On occasion, patients MS canalsobefound fortuitously duringCT or PET examination inoncologic patients ([14–16];F igure 8). 5

Image Report ecancer 2020, 14:1160; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1160 This research didnot receive any specificgrant from fundingagencies commercial inthepublic, or not-for-profitsectors. Funding All authors declare that they have noconflict of interest. Conflict of interest The MS Conclusion B-cell lineage of theneoplasm,butextensive immunohistochemical analyses are mandatory to differentiate MS from aggressive . cells (a, haematoxylin-eosin), quite similar to themyeloid blastsshown inFigures 10aand11a.Diffuse positivity for CD20 (b) and PAX5 (c) proves the Figure 12.(a–c): A caseof DLBCL,asanisolated left breast lesionina57-year-old woman. The lesionismadeup of solidsheets of large lymphoidblastic acute myeloid leukaemia without maturation, with extramedullary involvement/MS was made. infiltration) wasthendiscovered. Cytogenetic andmolecular analyses, performed onmarrow aspirate, did not show any alterations, andadiagnosis of disseminated involvement (mammary, central nervous system, renal, cardiac, uterine, skeletal andnodalPET-positive lesions,massive bonemarrow maturation (a, haematoxylin-eosin), positive for CD34 (b) and (c). Inthiscase,thedisease arose withbilateral breast masses,but Figure 11.(a–c): Breast involvement by MSina76-year-old female patient. The neoplasmismadeup of solidsheets of large blastic cells without other neoplasms; itis,therefore, important to beaware of thispathology anditsmainradiological andanatomopathological characteristics. confrontationthe diagnosis ofand the particular this andextremely rare typeof neoplasm.Besides beingrare, thistumour closely mimics useful. This pictorial review’sis to purpose provide ashowcaseof someof themostimportant imagingandpathologic features that allow reason, andfor theobjectivecomplexity diagnostic inisolatedcases, theidentification MS of characteristic imagingfeatures could be very of and istreatedAML, accordingly, eventually requiringallogeneic bonemarrow transplantation to achieve complete remission. For this breast pathology team,to asitiscrucial decidethebesttherapeutic approach. MSisanaggressive disease,for itisthesolidcounterpart

ofbreast the tissue, no signsofwith is extremely leukaemia, rare [17,18]:providing acorrectdiagnosis canbechallengingfor the 6

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