Case report/Kazuistyka
Extraneural relapse of medulloblastoma mimicking acute leukemia: A diagnostic challenge in adult patient
Monika Joks
1,a,*, Maciej Machaczka
2,3,a, Anna Czyż
1, Jolanta Parulska
1, Maciej Majcherek
1,4, Jan Bręborowicz
5, Grzegorz Dworacki
4,
Mieczysław Komarnicki
11DepartmentofHematology andBone MarrowTransplantation, PoznańUniversityof MedicalSciences, Poznań, Poland
2MedicalFaculty,UniversityofRzeszów,Rzeszów,Poland
3Hematology Center Karolinska and Department of Medicine at Huddinge, Karolinska Institutet, Karolinska UniversityHospitalHuddinge,Stockholm,Sweden
4ChairofClinicalImmunology,PoznańUniversityofMedicalSciences,Poznań,Poland
5DepartmentofTumorPathology,WielkopolskaCenterofOncology,Poznań,Poland
Introduction
Medulloblastoma, an invasiveembryonic tumor of cerebel- lum, is an infrequent primary malignancy of the central
nervoussystem(CNS)inadults[1,2].Whilenoclearetiology has been identified, a link may exist with maternal diet and blood or immune disorders during pregnancy, early JohnCunninghampolyomavirus infectionsinchildhood,or human cytomegalovirus. The most common cytogenetic actahaematologicapolonica 48(2017) 217–219
article info
Articlehistory:
Received:14.06.2017 Accepted:07.08.2017 Availableonline:12.08.2017
Keywords:
Medulloblastoma
Acuteleukemia
Relapse
Extraneural
Terminaldeoxynucleotidyl transferase
abstract
Medulloblastomais themostfrequent malignanttumor ofthecentral nervous system (CNS)inchildren,butitcanrarelyoccurinadults. Extraneuralrelapseofmedulloblas- tomaoccursveryrarelyanditisusuallyassociatedwithdismalprognosis.Wepresent acaseofyoungadultwithrelapsedmedulloblastomawithextraneuralmetastasesinthe bone marrow and expression of terminal deoxynucleotidyl transferase (TdT) on the malignantcellsmimickingacuteleukemia.Tothebestofourknowledge,thisisthefirst reportofmedulloblastomaexhibiting expressionoftheTdTinadult.Wewouldliketo emphasizethatincaseslikethis,differentialdiagnosisofanemiaandthrombocytopenia inadultsshouldincludeaconsiderationofprimaryorsecondarybonemarrowinvolve- mentbymedulloblastomaorotherraremalignancy.
©2017PolskieTowarzystwoHematologówiTransfuzjologów,InstytutHematologiii Transfuzjologii.PublishedbyElsevierSp.zo.o.Allrightsreserved.
*Corresponding author at: Department of Hematology and Bone Marrow Transplantation, Poznań University ofMedical Sciences, SzamarzewskiegoStreet82/84,60-569Poznań,Poland.
E-mailaddress:monikajoks@tlen.pl(M.Joks).
a M.JoksandM.Machaczkahavecontributedequallytowritingofthispaper.
ContentslistsavailableatScienceDirect
Acta Haematologica Polonica
journalhomepage:www.elsevier.com/locate/achaem
http://dx.doi.org/10.1016/j.achaem.2017.08.002
0001-5814/©2017PolskieTowarzystwoHematologówiTransfuzjologów,InstytutHematologiiiTransfuzjologii.PublishedbyElsevierSp.
zo.o.Allrightsreserved.
abnormality in medulloblastoma is i17q (isochromosome 17q),whereintheshortarm(p)isabsent,andthereisagain of genetic material from the long arm (q). The search for putativetumorsuppressorgenesonchromosome17pinthe contextofmedulloblastomaisongoing[2].
Medulloblastoma presents with high invasive growth with spread of tumor cells into the leptomeningeal space alongtheneuroaxisearlyinthecourseofthedisease[1].It constitutes approximately 3% of primary CNS tumors [2].
Extraneural relapse of medulloblastoma occurs in 3–5% of patientsanditisusuallyassociatedwithdismalprognosis.
Here, we describe a case of young adult with relapsed medulloblastoma with extraneural metastases and expres- sion of the terminal deoxynucleotidyl transferase (TdT)on themalignantcellsmimickingacuteleukemia.
Case presentation
A 19-year-old man was presented with headache and dizzinessforonemonth.Magneticresonanceimaging (MRI) of the brain displayed a tumor in the right hemisphereof
the cerebellum. The patient underwent surgical resection and histopathological diagnosis of medulloblastoma (WHO grade IV) was established. He then received adjuvant cra- niospinal radiation therapy with a boost to the posterior fossa.
Oneyearlaterthepatientcomplainedofintensegeneral- ized bone pain. A positron emission tomography scanning showed a disseminated bone marrow and bone 18F-FDG uptakewithSUVmaxrangingfrom3to8.BrainMRIrevealed nosignsofcancerrelapse.Thepatientunderwentpreventive chemotherapyincludingcarboplatinandetoposide.
Afterwards he developedprolonged anemia and throm- bocytopenia. Bonemarrowexaminationwasperformedand bone marrowcytologyshowed infiltrateswithblast-resem- bling cells, mimicking morphologically low-differentiated acute leukemia and accounting for 92% of nucleated bone marrowcells(Fig.1A).
However, flow cytometry of bone marrow showed that immunophenotype of the pathological cells was CD45( ), CD56(+),CD33( ),CD13( ),CD117( ),CD14( ),MPO( ),CD10 ( ), CD7( ), cytCD79a( ), and TdT(+) (Fig. 1B). Trephine biopsy revealedan extensivemass of cellspositive for the
Fig.1–Medulloblastomainthebonemarrow:(A)bonemarrowcytology.Largecellsmimickingblastswithahighnuclear/
cytoplasmicratio,nucleuswithadispersedchromatinstructureandprominentnucleoli(MGGstain,magnification2000T);
(B)flowcytometryresultshowingTdT(+)/CD45(S)cells(markedarea);(C)trephinebiopsydisclosingcellsfocallypositivefor GFAPstain(magnification400T);(D)trephinebiopsyshowingcellsstronglypositiveforCD56stain(magnification400T)
acta haematologicapolonica 48 (2017) 217–219
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expression of vimentin, glialfibrillary acidicprotein (GFAP) (Fig.1C),neuralcelladhesionmolecule(CD56)(Fig.1D),and neurone-specific enolase. These cells were negative with regard to myeloid and lymphoid antigens, cytokeratin, synaptophysinandchromogranin.
Metastasesofmedulloblastomatothebonemarrowwere confirmed andthe patientreceiveda palliativechemother- apy with 3 courses of ICE (ifosfamide, carboplatin, etopo- side). Unfortunately, he developed further metastases to lymph nodes, spleen and liver. The patient died 3 years afterinitialdiagnosisofmedulloblastoma.
Discussion
MedulloblastomaisthemostcommonCNStumorinchildren (15–30%ofall primaryCNStumorsinchildhood), whileitis extremely rare in adults [3]. The cerebellum and brain are commonsites of metastases.The main sites of extraneural relapse are bones, bone marrow, lymph nodes, lungs, and liver(84%,27%,15%,6%,6%ofcases,respectively).Inadults, atypicalmetastaticsitesarebones(80%)andlungs[2,3].
Primitive neuroectodermal tumor can morphologically mimic acute leukemia [4]. In our patient, bone marrow cytologyandhistologyrevealedmorphologicallyatypicalcells resembling leukemic blasts. However, both immunopheno- typeandimmunohistochemicalexaminationwereconsistent withbonemarrowinvolvementofrelapsedmedulloblastoma.
Inthepresentreport,themedulloblastomacellsshowed expression of the precursor lymphoid antigen TdT inflow cytometry in the absence of other lymphoid and myeloid antigens. In the literature cases of medulloblastoma have been described that mimic acute leukemia and show the expression of myeloid antigens [4]. Theexpression of TdT hasbeendescribedinnon-hematopoieticmalignanciessuch asMerkelcarcinomaorpulmonary smallcellcarcinoma[5]
and medulloblastoma in children [6]. To the best of our knowledge, this is the first report of medulloblastoma expressingtheTdTinadult.
In cases like this, differential diagnosis of anemia and thrombocytopeniainadults shouldinclude aconsideration of primary or secondary bone marrow involvement by medulloblastoma or other rare malignancy [4, 7]. Never- theless,secondaryacuteleukemiaorparallel occurrenceof acute leukemia and medulloblastoma has also been reported[8–10].Insuchcases,theresultsofflowcytometry, immunohistochemicalstaining,andsometimesgeneticana- lyses are crucial in the process of establishing adequate diagnosisandtreatment.
Authors’ contributions/Wkład autorów
Accordingtoorder.
Conflict of interest/Konflikt interesu
Nonedeclared.
Financial support/Finansowanie
Nonedeclared.
Ethics/Etyka
The work described in this articlehas been carried out in accordance with The Code of Ethics of the World Medical Association (Declarationof Helsinki)for experiments invol- ving humans; EU Directive 2010/63/EU for animal experi- ments;UniformRequirementsformanuscriptssubmittedto Biomedicaljournals.
Acknowledgements/Podziękowania
The authors thank Nick Bolton, PhD, and JanJaroszewski, MD,PhD,forlinguisticexpertise.
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