𝛾𝛿t-cell acute lymphoblastic leukemia/lymphoma: discussion of … · 2019. 7. 30. ·...

Case Report120574120575 T-Cell Acute Lymphoblastic LeukemiaLymphomaDiscussion of Two Pediatric Cases and Its Distinction fromOther Mature 120574120575 T-Cell Malignancies

Eric X Wei1 Vasiliki Leventaki2 John K Choi2 Susana C Raimondi2

Elizabeth M Azzato2 Sheila A Shurtleff2 Menchu G Ong1 Diana M Veillon1

James D Cotelingam1 and Rodney E Shackelford1

1Department of Pathology and Translational Pathobiology LSU Health Shreveport Shreveport LA USA2Department of Pathology St Jude Childrenrsquos Research Hospital Memphis TN USA

Correspondence should be addressed to Eric X Wei ericxweiyahoocom

Received 9 June 2017 Revised 31 July 2017 Accepted 14 August 2017 Published 24 September 2017

Academic Editor Marie-Christine Kyrtsonis

Copyright copy 2017 Eric X Wei et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Gamma delta (120574120575) T-cell antigen receptor (TCR) expression and its related T-cell differentiation are not commonly reported inT-cell acute lymphoblastic leukemialymphoma (T-ALL) Here we report two pediatric T-ALL cases and present their clinicalfeatures histology immunophenotypes cytogenetics andmolecular diagnostic findingsThe first patient is a two-year-old girl withleukocytosis circulating lymphoblasts and a cryptic insertion of a short-arm segment at 10p12 into the long-arm segment of 11q23resulting in an MLL and AF10 fusion transcript which may be the first reported in 120574120575 T-ALL She responded to the chemotherapyprotocol poorly and had persistent diseases Following an allogeneic bone marrow transplant she went into remissionThe secondpatient is an eleven-year-old boy with a normal white cell count circulating blasts and a normal karyotype but without anyimmature cellular markers by flow cytometric analysis He responded to the chemotherapy well and achieved a complete remissionThese cases demonstrate the diverse phenotypic cytogenetic and molecular aspects of 120574120575 T-ALL Early T-precursor- (ETP-) ALLand their differential diagnosis from other mature 120574120575 T-cell leukemialymphomas are also discussed

1 Introduction

Gamma delta (120574120575) T-cell neoplasms are characterized by theexpression of the 120574120575 T-cell antigen receptors (TCRs) arerare and include a variety of clinicopathologic entities T-cell acute lymphoblastic leukemia (T-ALL) with expressionof alpha beta (120572120573) or 120574120575 TCR has been previously describedin about 35 T-ALL cases while 120574120575 T-ALL cases repre-sented 9ndash12 of T-ALL including children and adults [1]Mature T-cell neoplasms with TCR 120574120575 expression includehepatosplenic T-cell lymphoma skin and mucosal 120574120575 T-celllymphoma and 120574120575T-cell large granular lymphocytic (T-LGL)leukemia [2 3] The 2016 revision of the WHO classificationof lymphoid neoplasms emphasizes the primary cutaneous120574120575 T-cell lymphoma [4] 120574120575 T-cell lymphomas other thanhepatosplenic T-cell lymphoma and primary cutaneous 120574120575

T-cell lymphoma are often classified within subcategories ofT-cell lymphomas 120574120575 T-ALL is uncommon with only 2of all acute lymphoblastic leukemia (ALL) cases showingexpression of the 120574120575 TCR [1] 120574120575 TCR expression and T-celldifferentiation are not frequently reported in T-ALL [1 5]Wereport clinicopathological features of twopediatric cases of 120574120575T-ALL and discuss the differential diagnosis of other types of120574120575 T-cell leukemialymphoma

2 Case Presentation

The first case is a 2-year-old Caucasian girl previously ingood health who suddenly presented at the LSU hospi-tal with fever shortness of breath rhinorrhea cyanosisand hepatosplenomegaly by chest X-ray She had anemia

HindawiCase Reports in HematologyVolume 2017 Article ID 5873015 7 pageshttpsdoiorg10115520175873015

2 Case Reports in Hematology

Figure 1 Bone marrow aspirate smear from patient 1 Wright-Giemsa 1000x

and thrombocytopenia with a white cell count (WBC) at1188 thousand120583L and 73 lymphoid cells Flow cytometry ofperipheral blood showed a 120574120575 T-cell proliferation Molecularstudies revealed clonal TCR 120574- and 120573-chain gene rearrange-ments by PCR The patient was started on intravenousfluids and antibiotics She did not undergo a liver or spleenbiopsy Her white cell count decreased to 568 thousand120583Lthe next day and she was transferred to St Jude ChildrenrsquosResearchHospital (SJCRH) Bonemarrow evaluation showed90 lymphoblasts exhibiting slightly open chromatin andirregular nuclear contours (Figure 1) Flow cytometry ofbonemarrow showedT lymphoblasts expressing surfaceCD3(variable) and cytoplasmic CD3 CD5 CD7 (bright) CD34CD45 (dim) and TCR 120574120575 The blasts were negative for CD1aCD2 CD4 CD8 CD10 CD56 HLA-DR TCR 120572120573 TdT andMPO (Figure 2) Cytogenetic studies of the bone marrowshowed that 90 of the metaphases had an abnormal kary-otype 47 XX 119905(410)(q28p12) cryp ins(1110)(q23p12p12)+17 (Figure 3(a)) FISH assays using the BCR-ABL1 andTLX3 probes were normal FISH was also performed usingthe break-apart AF10 (10p12) probe (research use only) onsequential G-banded to FISH metaphases and it was foundthat the probe was rearranged where the telomeric 31015840 AF10moved to the 4q confirming 119905(410) Of interest the cen-tromeric 51015840 AF10 signal is inserted into the 11q23 region (Fig-ure 3(b)) By FISH MLL was not rearranged (Figure 3(c))The reason MLL was not rearranged or separated becausethe insertion was very tiny and did not separate enoughthe 51015840 from the 31015840 signal Overall FISH results indicate acryptic insertion that is a segment of 10p12 had been donatedto the recipient 11q23 Molecular studies by real-time RT-PCR assay confirmed an MLLMLLT10 (MLLAF10) fusiontranscript (Figure 4)The patient received treatment per TotalXVI (TOTXVI) protocol

At day 15 following induction flow cytometry revealedresidual disease with 35 blasts in bone marrow Follow-ing reintensification I therapy the patient had significantlydecreased blast percentages but remained persistently pos-itive for minimal residual disease (MRD) with the lastMRD before bone marrow transplant (BMT) at 0018 byflow cytometry She eventually underwent allogeneic BMTShe had been on day +126 after transplant remained MRDnegative and had been followed up at the LSU hospital

The second case is an 11-year-old African American boywith an asthma history who complained of cough chesttightness and one-week back pain His chest X-ray did notshow a mediastinal mass CBC showed a normal white cellcount mild thrombocytopenia and increased circulatingblasts which appeared to be lymphoblasts morphologicallyFlow cytometry revealed approximately 32 circulating 120574120575T-cell lymphoblasts After maintenance on intravenous fluidand allopurinol therapy he was transferred to SJCRH forchemotherapyHis bonemarrow showed 89blasts that weresmall to medium in size with a high nuclear to cytoplasmicratio fine chromatin round to slightly irregular nuclei andscant cytoplasm (Figure 5) Flow cytometric analysis of thebone marrow confirmed the presence of T lymphoblaststhat were positive for surface CD3 (variable) cytoplasmicCD3 CD5 (dim) CD7 CD45 (dim) CD79a and TCR 120574120575They were negative for CD1a CD2 CD4 CD8 CD10 CD34TdT MPO and TCR 120572120573 (Figure 6) Cytogenetic studiesperformed on the bone marrow showed normal a malekaryotypewithout numerical or structural abnormalitiesThepatient received treatment per Total XVI (TOTXVI) protocoland achieved MRD negativity after induction on day 42Following remission subsequent to chemotherapy the patienthad been followed up at the LSU hospital

3 Discussion

Thedifferential diagnosis of these twopediatric cases includesskin and mucosal 120574120575 T-cell lymphoma in leukemic phasehepatosplenic T-cell lymphoma 120574120575 T-cell large granularlymphocytic (T-LGL) leukemia and 120574120575 T-ALL [2 4 6]Peripheral 120574120575 T-cell lymphoma is a subtype of peripheralT-cell lymphoma occurring mainly in skin and mucosalregions often harboring cytotoxic activity In the skin 120574120575 T-cell lymphoma can be divided into mycosis fungoides-likeand primary cutaneous 120574120575 T-cell lymphoma presenting withSezary syndrome in blood involvement [2 4 7] Mucosal120574120575 T-cell lymphoma may occur in the nasopharynx lunggastrointestinal tracts and other organs with intestinal 120574120575 T-cell lymphoma being type II enteropathy associated [2 6 89]

Hepatosplenic T-cell lymphoma is a type of 120574120575 T-celllymphoma with extranodal and systemic involvement [2

Case Reports in Hematology 3

Normal T lymphocytesT lymphoblasts

Myeloid cells and B lymphocytes

102

103

104

1050

103

104

105

0

cyCD

3 Pe

rCP-

A

CD3 V450 BV1-A

CD3 V450 BV1-A

minus199

103

104

105

0

CD34

PE-

A

minus206

minus13210

210

310

410

50

103

104

105

0

cyCD

3 Pe

rCP-

A

TCR GD PE-A

minus199

minus173

TCR

GD

PE-

A

CD2 FITC-A10

310

410

50

102

103

104

105

0

TCR

GD

PE-

A

minus199

minus137010

210

310

410

50

102

103

104

105

0minus173

minus132

CD45 V500 BV2-A10

310

410

50minus2831

103

104

105

0

CD34

PE-

A

minus206

CD5 PE-Cy7-A10

310

410

50minus242

103

104

105

0

CD34

PE-

A

minus206

CD7 FITC-A10

310

210

410

50minus208

102

103

104

105

102

103

104

105

TCRa

b FI

TC-A

CD3 (BL) PerCP-A

103

104

1050

102

103

104

105

0

cyCD

3 Pe

rCP-

A

CD5 PE-Cy7-A

minus173

minus280

Figure 2 Representative flow cytometric histograms of bone marrow aspirate from patient 1

3 6 10 11] It tends to occur in younger patients withhepatosplenomegaly systemic symptoms and cytopeniaTheneoplastic cells involve the cords and sinuses of spleenliver and bone marrow [12] The tumor cells are interme-diate in size with condensed chromatin indistinct nucleoliand absence of azurophilic granules [11 12] Phenotypicallythe lymphoma cells are usually positive for CD2 CD3CD7 CD56 and TCR 120574120575 and negative for CD4 CD5CD8 and TCR 120572120573 Although the first patient showed hep-atosplenomegaly with a 120574120575 T-cell phenotype she hadmarkedleukocytosis at the beginning of her disease course withlymphoblastic appearing neoplastic cells positive for CD5and CD34 and negative for CD2 Thus the diagnosis ofhepatosplenic T-cell lymphoma is not supported

In spite of the fact that the majority of T-LGL leukemiacases are of 120572120573 type there are rare cases of 120574120575 T-LGLleukemia [2 13] In comparison to its 120572120573 counterpart 120574120575T-LGL leukemia patients are prone to having rheumatoid

arthritis lower absolute neutrophil counts more severethrombocytopenia and a higher probability of CD4 andCD8double negativity However both groups of T-LGL leukemiafrequently have anemia an indolent clinical course and asimilar overall survival [2 13]

T-ALL comprises approximately 20 of all ALL cases[1 2 14] Overall 120574120575 T-ALL is similar to 120572120573 T-ALL in themajority of clinical and hematological aspects [4 14] T-ALLis more common in children and younger adults with amale preponderance The bone marrow is affected in almostall T-ALL cases and mediastinal or thymic involvement iscommon They tend to have a high leukocyte count lym-phadenopathy and hepatosplenomegaly Morphologicallythe lymphoblasts are intermediate in size and have delicatechromatin inconspicuous nucleoli and scant cytoplasmImmunophenotypically they are often positive for CD1aCD2 surface andor cytoplasmic CD3 CD5 CD7 CD10CD34 CD45 and TdT but are negative for B cell andmyeloid


1

6 7 8 9 10 11 12

13

19 20 21 22 X Y

14 15 16 17 18

2 3 4 5

(a)

10

der(11)

der(4)

(b)

11

(c)

Figure 3 Cytogenetic and FISH results from patient 1 (a) Conventional karyotype with 47 XX 119905(410)(q28p12) +17 (b) Break-apart AF-10probe on sequential G-banded to FISH metaphases shows that telomeric 31015840 AF10 moves to the 4q28 and the centromeric 51015840 AF10 signalinserts into the 11q23 region (c) The MLL FISH is not rearranged In (a) the arrows to 4p28 and 10p12 are for indication of 119905(410)(q28p12)the arrow to chromosome 17 is for indication of +17

markers They may be CD4 and CD8 double negativedouble positive or only positive for CD4 or CD8 Withcytoplasmic CD3 as themost specific T-cell marker expressedin all maturation stages there are pro-T (CD7+) pre-T(CD2+ andor CD5+ andor CD8+) cortical T (CD1a+)

and medullary T (surface CD3+ CD1aminus) subtypes of T-ALL based on progressive stages of differentiation [14] Theexpression levels of TCR 120572120573 or TCR 120574120575 in association withdifferent differentiating stages are rarely reported [1] T-ALLalmost always shows clonal TCR gene rearrangements and


1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39

1000

0100

0010

0001

Cycle number

Delt

a Rn

Delta Rn vs Cycle

Figure 4 Real-time RT-PCR showing the MLLMLLT10 fusion transcripts from patient 1 Delta Rn = normalized fluorescence reportersignal minus baseline cycle number = cycle of PCR purple is the positive control green is the patient red is no-template control blue is thenegative control (HL60 cell line)


often carries an abnormal karyotype and an unfavorableprognosis Early T-precursor- (ETP-) ALL expressing stemcell or myeloid markers has a much poorer clinical outcomecompared to other T-ALL [14] Numerous genes have beenimplicated for the pathogenesis and prognosis for T-ALLincluding NOTCH1 TAL1 and HOX1 [5 14] 120574120575 T-ALL is arare variant of T lineage lymphoblastic leukemialymphomaCompared to 120572120573 T-ALL 120574120575 T-ALL tends to present withlower hemoglobin concentrations in children more frequentsplenomegaly and higher WBC in adults and higher per-centages of the CD45RAminusCD45RO+ phenotype in bothchildren and adults [1] Although 120574120575 T-ALL usually showsTCR gamma and TCR delta chain gene rearrangements TCRbeta chain and biclonal rearrangements involving both V1205751and V1205752 segments have also been reported [5] Both of thesetwo pediatric 120574120575 T-ALL patients were likely in medullary(mature) T-ALL stage at presentation with variable surfaceCD3 expression Neither of our patients has ETP-ALL due

to the strong CD5 expression in the first patient and lackof immature or myeloid markers in the second patient Thecryptic insertion involving MLL and AF10 resulting in theexpression of the fusion transcript has rarely been reportedin T-ALL [15] To our knowledge such cryptic insertion withMLLMLLT10 fusion may be the first reported in 120574120575 T-ALLPrevious studies have shown a higher percentage of 120574120575 T-ALL at 9sim12 in comparison with the very low proportionof 120574120575 T-cells in the normal thymus which is at 1 [1] Thereason for this phenomenon is unclear It is possible that 120574120575T-cells have a higher chance of progression to malignancycompared to 120572120573 T-cells or a subset of 120574120575T-ALLmay originatefrom extrathymic tissues [1] Even though normal 120574120575 T-cells are more commonly double negative for CD4 andCD8 a significant percentage of 120574120575 T-ALL may exhibit CD4CD8 or both CD4 and CD8 which may be due to antigenevolution during malignant transformation [1] 120574120575 T-ALLmay represent a subcategory of acute lymphoblastic leukemia


TCRg

d P

E-A

102

103

104

105

0minus153

CD45 V500 BV2-A10

310

410

50minus2423

CD3 V450 BV1-A10

2

TCRg

d P

E-A

102

103

104

105

0minus153

103

104

1050

minus129

105

103

104

0CD

34 P

E-A

minus318

CD7 FITC-A10

310

210

410

50minus231

103

104

1050

cyCD

3 Pe

rCP-

A

TCRgd PE-Aminus153

minus78

103

104

105

010

2

102

103

104

105

CD3 (BL) PerCP-A

TCRa

b FI

TC-A

103

104

105

102

cyCD

3 Pe

rCP-

A

CD3 V450 BV1-A10

210

210

310

410

50minus129

minus78

102

103

104

105

0

TCRg

d P

E-A

102

103

104

105

0minus153

minus527CD2 FITC-A10

310

410

50

103

104

105

0

CD34

PE-

A

minus318

CD5 PE-Cy7-A10

310

410

50minus452

CD34

PE-

A

103

104

105

0

minus318

CD45 V500 BV2-A10

310

410

50minus1597




with slightly distinctive clinical and laboratory featuresMorestudies are needed to further investigate such subtypes ofT-ALL including their pathological diagnosis and clinicalmanagement

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publication of this paper

References

[1] DMMatos E G Rizzatti M Fernandes V Buccheri and R PFalcao ldquoGammadelta and alphabeta T-cell acute lymphoblasticleukemia comparison of their clinical and immunophenotypicfeaturesrdquo Haematologica vol 90 pp 264ndash266 2005

[2] P Gaulard K Belhadj and F Reyes ldquo120574120575 T-cell lymphomasrdquoSeminars in Hematology vol 40 no 3 pp 233ndash243 2003

[3] C Tripodo E Iannitto A M Florena et al ldquoGamma-delta T-cell lymphomasrdquo Nature Reviews Clinical Oncology vol 6 no12 pp 707ndash717 2009

[4] S H Swerdlow E Campo S A Pileri et al ldquoThe 2016 revisionof the World Health Organization classification of lymphoidneoplasmsrdquo Blood vol 127 no 20 pp 2375ndash2390 2016

[5] H Zheng X Wang Y Ma et al ldquoThe TCR 120574120575 repertoire andrelative gene expression characteristics of T-ALL cases withbiclonal malignant v1205751 and V1205752 T cellsrdquo DNA and Cell Biologyvol 33 no 1 pp 49ndash56 2014

[6] FVega L JMedeiros andPGaulard ldquoHepatosplenic and other120574120575 T-cell lymphomasrdquo American Journal of Clinical Pathologyvol 127 no 6 pp 869ndash880 2007

[7] EDMerrill R Agbay RNMiranda et al ldquoPrimary cutaneousT-cell lymphomas showing gamma-delta (120574120575) phenotype andpredominantly epidermotropic pattern are clinicopathologi-cally distinct from classic primary cutaneous 120574120575 T-cell lym-phomasrdquo American Journal of Surgical Pathology vol 41 no 2pp 204ndash215 2017


[8] A L Wilson S H Swerdlow G K Przybylski et al ldquoIntestinal120574120575T-cell lymphomas aremost frequently of type II enteropathy-associatedT-cell typerdquoHumanPathology vol 44 no 6 pp 1131ndash1145 2013

[9] T TanakaHYamamotoAA Elsayed et al ldquoClinicopathologicspectrum of gastrointestinal T-cell lymphoma reappraisal basedon T-cell receptor immunophenotypesrdquo American Journal ofSurgical Pathology vol 40 no 6 pp 777ndash785 2016

[10] A J M Ferreri S Govi and S A Pileri ldquoHepatosplenicgamma-delta T-cell lymphomardquo Critical Reviews in Oncol-ogyHematology vol 83 no 2 pp 283ndash292 2012

[11] M Yabe L J Medeiros G Tang et al ldquoPrognostic factors ofhepatosplenic T-cell lymphoma clinicopathologic study of 28casesrdquoAmerican Journal of Surgical Pathology vol 40 no 5 pp676ndash688 2016

[12] M Yabe L J Medeiros S A Wang et al ldquoDistinguishingbetween hepatosplenic T-cell lymphoma and 120574120575 T-cell largegranular lymphocytic leukemiardquo American Journal of SurgicalPathology vol 41 no 1 pp 82ndash93 2017

[13] M Yabe L J Medeiros S A Wang et al ldquoClinicopathologicimmunophenotypic cytogenetic and molecular features of T-cell large granular lymphocytic leukemia an analysis of 14patients suggests biologic differences with T-cell large granularlymphocytic leukemiardquo American Journal of Clinical Pathologyvol 144 no 4 pp 607ndash619 2015

[14] M J You L J Medeiros and E D Hsi ldquoT-lymphoblasticleukemialymphomardquo American Journal of Clinical Pathologyvol 144 no 3 pp 411ndash422 2015

[15] K Matlawska-Wasowska H Kang M Devidas et al ldquoMLLrearrangements impact outcome in HOXA-deregulated T-lineage acute lymphoblastic leukemia A Childrenrsquos OncologyGroup Studyrdquo Leukemia vol 30 no 9 pp 1909ndash1912 2016

Submit your manuscripts athttpswwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom



and thrombocytopenia with a white cell count (WBC) at1188 thousand120583L and 73 lymphoid cells Flow cytometry ofperipheral blood showed a 120574120575 T-cell proliferation Molecularstudies revealed clonal TCR 120574- and 120573-chain gene rearrange-ments by PCR The patient was started on intravenousfluids and antibiotics She did not undergo a liver or spleenbiopsy Her white cell count decreased to 568 thousand120583Lthe next day and she was transferred to St Jude ChildrenrsquosResearchHospital (SJCRH) Bonemarrow evaluation showed90 lymphoblasts exhibiting slightly open chromatin andirregular nuclear contours (Figure 1) Flow cytometry ofbonemarrow showedT lymphoblasts expressing surfaceCD3(variable) and cytoplasmic CD3 CD5 CD7 (bright) CD34CD45 (dim) and TCR 120574120575 The blasts were negative for CD1aCD2 CD4 CD8 CD10 CD56 HLA-DR TCR 120572120573 TdT andMPO (Figure 2) Cytogenetic studies of the bone marrowshowed that 90 of the metaphases had an abnormal kary-otype 47 XX 119905(410)(q28p12) cryp ins(1110)(q23p12p12)+17 (Figure 3(a)) FISH assays using the BCR-ABL1 andTLX3 probes were normal FISH was also performed usingthe break-apart AF10 (10p12) probe (research use only) onsequential G-banded to FISH metaphases and it was foundthat the probe was rearranged where the telomeric 31015840 AF10moved to the 4q confirming 119905(410) Of interest the cen-tromeric 51015840 AF10 signal is inserted into the 11q23 region (Fig-ure 3(b)) By FISH MLL was not rearranged (Figure 3(c))The reason MLL was not rearranged or separated becausethe insertion was very tiny and did not separate enoughthe 51015840 from the 31015840 signal Overall FISH results indicate acryptic insertion that is a segment of 10p12 had been donatedto the recipient 11q23 Molecular studies by real-time RT-PCR assay confirmed an MLLMLLT10 (MLLAF10) fusiontranscript (Figure 4)The patient received treatment per TotalXVI (TOTXVI) protocol

At day 15 following induction flow cytometry revealedresidual disease with 35 blasts in bone marrow Follow-ing reintensification I therapy the patient had significantlydecreased blast percentages but remained persistently pos-itive for minimal residual disease (MRD) with the lastMRD before bone marrow transplant (BMT) at 0018 byflow cytometry She eventually underwent allogeneic BMTShe had been on day +126 after transplant remained MRDnegative and had been followed up at the LSU hospital

The second case is an 11-year-old African American boywith an asthma history who complained of cough chesttightness and one-week back pain His chest X-ray did notshow a mediastinal mass CBC showed a normal white cellcount mild thrombocytopenia and increased circulatingblasts which appeared to be lymphoblasts morphologicallyFlow cytometry revealed approximately 32 circulating 120574120575T-cell lymphoblasts After maintenance on intravenous fluidand allopurinol therapy he was transferred to SJCRH forchemotherapyHis bonemarrow showed 89blasts that weresmall to medium in size with a high nuclear to cytoplasmicratio fine chromatin round to slightly irregular nuclei andscant cytoplasm (Figure 5) Flow cytometric analysis of thebone marrow confirmed the presence of T lymphoblaststhat were positive for surface CD3 (variable) cytoplasmicCD3 CD5 (dim) CD7 CD45 (dim) CD79a and TCR 120574120575They were negative for CD1a CD2 CD4 CD8 CD10 CD34TdT MPO and TCR 120572120573 (Figure 6) Cytogenetic studiesperformed on the bone marrow showed normal a malekaryotypewithout numerical or structural abnormalitiesThepatient received treatment per Total XVI (TOTXVI) protocoland achieved MRD negativity after induction on day 42Following remission subsequent to chemotherapy the patienthad been followed up at the LSU hospital

3 Discussion

Thedifferential diagnosis of these twopediatric cases includesskin and mucosal 120574120575 T-cell lymphoma in leukemic phasehepatosplenic T-cell lymphoma 120574120575 T-cell large granularlymphocytic (T-LGL) leukemia and 120574120575 T-ALL [2 4 6]Peripheral 120574120575 T-cell lymphoma is a subtype of peripheralT-cell lymphoma occurring mainly in skin and mucosalregions often harboring cytotoxic activity In the skin 120574120575 T-cell lymphoma can be divided into mycosis fungoides-likeand primary cutaneous 120574120575 T-cell lymphoma presenting withSezary syndrome in blood involvement [2 4 7] Mucosal120574120575 T-cell lymphoma may occur in the nasopharynx lunggastrointestinal tracts and other organs with intestinal 120574120575 T-cell lymphoma being type II enteropathy associated [2 6 89]

Hepatosplenic T-cell lymphoma is a type of 120574120575 T-celllymphoma with extranodal and systemic involvement [2




102

103

104

1050

103

104

105

0

cyCD

3 Pe

rCP-

A

CD3 V450 BV1-A

CD3 V450 BV1-A

minus199

103

104

105

0

CD34

PE-

A

minus206

minus13210

210

310

410

50

103

104

105

0

cyCD

3 Pe

rCP-

A

TCR GD PE-A

minus199

minus173

TCR

GD

PE-

A

CD2 FITC-A10

310

410

50

102

103

104

105

0

TCR

GD

PE-

A

minus199

minus137010

210

310

410

50

102

103

104

105

0minus173

minus132

CD45 V500 BV2-A10

310

410

50minus2831

103

104

105

0

CD34

PE-

A

minus206

CD5 PE-Cy7-A10

310

410

50minus242

103

104

105

0

CD34

PE-

A

minus206

CD7 FITC-A10

310

210

410

50minus208

102

103

104

105

102

103

104

105

TCRa

b FI

TC-A

CD3 (BL) PerCP-A

103

104

1050

102

103

104

105

0

cyCD

3 Pe

rCP-

A

CD5 PE-Cy7-A

minus173

minus280







1

6 7 8 9 10 11 12

13

19 20 21 22 X Y

14 15 16 17 18

2 3 4 5

(a)

10

der(11)

der(4)

(b)

11

(c)





1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39

1000

0100

0010

0001

Cycle number

Delt

a Rn

Delta Rn vs Cycle






TCRg

d P

E-A

102

103

104

105

0minus153

CD45 V500 BV2-A10

310

410

50minus2423

CD3 V450 BV1-A10

2

TCRg

d P

E-A

102

103

104

105

0minus153

103

104

1050

minus129

105

103

104

0CD

34 P

E-A

minus318

CD7 FITC-A10

310

210

410

50minus231

103

104

1050

cyCD

3 Pe

rCP-

A

TCRgd PE-Aminus153

minus78

103

104

105

010

2

102

103

104

105

CD3 (BL) PerCP-A

TCRa

b FI

TC-A

103

104

105

102

cyCD

3 Pe

rCP-

A

CD3 V450 BV1-A10

210

210

310

410

50minus129

minus78

102

103

104

105

0

TCRg

d P

E-A

102

103

104

105

0minus153


310

410

50

103

104

105

0

CD34

PE-

A

minus318

CD5 PE-Cy7-A10

310

410

50minus452

CD34

PE-

A

103

104

105

0

minus318

CD45 V500 BV2-A10

310

410

50minus1597







References






















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















102

103

104

1050

103

104

105

0

cyCD

3 Pe

rCP-

A

CD3 V450 BV1-A

CD3 V450 BV1-A

minus199

103

104

105

0

CD34

PE-

A

minus206

minus13210

210

310

410

50

103

104

105

0

cyCD

3 Pe

rCP-

A

TCR GD PE-A

minus199

minus173

TCR

GD

PE-

A

CD2 FITC-A10

310

410

50

102

103

104

105

0

TCR

GD

PE-

A

minus199

minus137010

210

310

410

50

102

103

104

105

0minus173

minus132

CD45 V500 BV2-A10

310

410

50minus2831

103

104

105

0

CD34

PE-

A

minus206

CD5 PE-Cy7-A10

310

410

50minus242

103

104

105

0

CD34

PE-

A

minus206

CD7 FITC-A10

310

210

410

50minus208

102

103

104

105

102

103

104

105

TCRa

b FI

TC-A

CD3 (BL) PerCP-A

103

104

1050

102

103

104

105

0

cyCD

3 Pe

rCP-

A

CD5 PE-Cy7-A

minus173

minus280







1

6 7 8 9 10 11 12

13

19 20 21 22 X Y

14 15 16 17 18

2 3 4 5

(a)

10

der(11)

der(4)

(b)

11

(c)





1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39

1000

0100

0010

0001

Cycle number

Delt

a Rn

Delta Rn vs Cycle






TCRg

d P

E-A

102

103

104

105

0minus153

CD45 V500 BV2-A10

310

410

50minus2423

CD3 V450 BV1-A10

2

TCRg

d P

E-A

102

103

104

105

0minus153

103

104

1050

minus129

105

103

104

0CD

34 P

E-A

minus318

CD7 FITC-A10

310

210

410

50minus231

103

104

1050

cyCD

3 Pe

rCP-

A

TCRgd PE-Aminus153

minus78

103

104

105

010

2

102

103

104

105

CD3 (BL) PerCP-A

TCRa

b FI

TC-A

103

104

105

102

cyCD

3 Pe

rCP-

A

CD3 V450 BV1-A10

210

210

310

410

50minus129

minus78

102

103

104

105

0

TCRg

d P

E-A

102

103

104

105

0minus153


310

410

50

103

104

105

0

CD34

PE-

A

minus318

CD5 PE-Cy7-A10

310

410

50minus452

CD34

PE-

A

103

104

105

0

minus318

CD45 V500 BV2-A10

310

410

50minus1597







References






















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















1

6 7 8 9 10 11 12

13

19 20 21 22 X Y

14 15 16 17 18

2 3 4 5

(a)

10

der(11)

der(4)

(b)

11

(c)





1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39

1000

0100

0010

0001

Cycle number

Delt

a Rn

Delta Rn vs Cycle






TCRg

d P

E-A

102

103

104

105

0minus153

CD45 V500 BV2-A10

310

410

50minus2423

CD3 V450 BV1-A10

2

TCRg

d P

E-A

102

103

104

105

0minus153

103

104

1050

minus129

105

103

104

0CD

34 P

E-A

minus318

CD7 FITC-A10

310

210

410

50minus231

103

104

1050

cyCD

3 Pe

rCP-

A

TCRgd PE-Aminus153

minus78

103

104

105

010

2

102

103

104

105

CD3 (BL) PerCP-A

TCRa

b FI

TC-A

103

104

105

102

cyCD

3 Pe

rCP-

A

CD3 V450 BV1-A10

210

210

310

410

50minus129

minus78

102

103

104

105

0

TCRg

d P

E-A

102

103

104

105

0minus153


310

410

50

103

104

105

0

CD34

PE-

A

minus318

CD5 PE-Cy7-A10

310

410

50minus452

CD34

PE-

A

103

104

105

0

minus318

CD45 V500 BV2-A10

310

410

50minus1597







References






















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39

1000

0100

0010

0001

Cycle number

Delt

a Rn

Delta Rn vs Cycle






TCRg

d P

E-A

102

103

104

105

0minus153

CD45 V500 BV2-A10

310

410

50minus2423

CD3 V450 BV1-A10

2

TCRg

d P

E-A

102

103

104

105

0minus153

103

104

1050

minus129

105

103

104

0CD

34 P

E-A

minus318

CD7 FITC-A10

310

210

410

50minus231

103

104

1050

cyCD

3 Pe

rCP-

A

TCRgd PE-Aminus153

minus78

103

104

105

010

2

102

103

104

105

CD3 (BL) PerCP-A

TCRa

b FI

TC-A

103

104

105

102

cyCD

3 Pe

rCP-

A

CD3 V450 BV1-A10

210

210

310

410

50minus129

minus78

102

103

104

105

0

TCRg

d P

E-A

102

103

104

105

0minus153


310

410

50

103

104

105

0

CD34

PE-

A

minus318

CD5 PE-Cy7-A10

310

410

50minus452

CD34

PE-

A

103

104

105

0

minus318

CD45 V500 BV2-A10

310

410

50minus1597







References






















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















TCRg

d P

E-A

102

103

104

105

0minus153

CD45 V500 BV2-A10

310

410

50minus2423

CD3 V450 BV1-A10

2

TCRg

d P

E-A

102

103

104

105

0minus153

103

104

1050

minus129

105

103

104

0CD

34 P

E-A

minus318

CD7 FITC-A10

310

210

410

50minus231

103

104

1050

cyCD

3 Pe

rCP-

A

TCRgd PE-Aminus153

minus78

103

104

105

010

2

102

103

104

105

CD3 (BL) PerCP-A

TCRa

b FI

TC-A

103

104

105

102

cyCD

3 Pe

rCP-

A

CD3 V450 BV1-A10

210

210

310

410

50minus129

minus78

102

103

104

105

0

TCRg

d P

E-A

102

103

104

105

0minus153


310

410

50

103

104

105

0

CD34

PE-

A

minus318

CD5 PE-Cy7-A10

310

410

50minus452

CD34

PE-

A

103

104

105

0

minus318

CD45 V500 BV2-A10

310

410

50minus1597







References






















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of






























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















𝛾𝛿t-cell acute lymphoblastic leukemia/lymphoma: discussion of … · 2019. 7. 30. ·...

Documents