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Teaching Cases in Nuclear Oncology:Pediatric Cancers

Duccio Volterrani, Giulia Puccini, Sara Mazzarri, FedericaGuidoccio, and Lorenzo Biassoni

Contents

Neuroblastoma: Case No. 1 . . . . . . . . . . . . . . . . . . . . . . . . . 2Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2Follow-Up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Teaching Point . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3



Neuroblastoma: Case No. 4 . . . . . . . . . . . . . . . . . . . . . . . . . 7Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8Teaching Point . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Neuroblastoma: Case No. 5 . . . . . . . . . . . . . . . . . . . . . . . . . 9Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9Teaching Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Neuroblastoma: Case No. 6 . . . . . . . . . . . . . . . . . . . . . . . . . 13

Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13Teaching Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14



Lymphoma: Case No. 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18Follow-Up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19Teaching Point . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Ewing Sarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21Follow-Up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21Teaching Point . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Lymphoma: Case No. 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22Follow-Up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22Teaching Point . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

D. Volterrani (*) •G. Puccini • S. Mazzarri • F. GuidoccioRegional Center of Nuclear Medicine, University of Pisa,Pisa, Italye-mail: [email protected]

L. BiassoniNuclear Medicine Service, Great Ormond Street Hospital,London, UK

# Springer International Publishing AG 2016H.W. Strauss et al. (eds.), Nuclear Oncology,DOI 10.1007/978-3-319-26067-9_80-1

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mailto:[email protected]

Lymphoma: Case No. 3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24Teaching Point . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

Neuroblastoma: Case No. 9 . . . . . . . . . . . . . . . . . . . . . . . . . 24Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25Follow-Up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

KeywordsNeuroblastoma • [123I]MIBG •MRI • Contrastenhanced CT • 68Ga-DOTATATE • 177Lu-DOTATATE molecular radiotherapy •Ganglioneuroblastoma • Diffuse large B-celllymphoma • [18F]FDG PET/CT • Ewing sar-coma • Hodgkin’s lymphoma • Chemotherapy

Glossary[123I]MIBG [123I]-meta-

Iodobenzylguanidine[131I]MIBG [131I]-meta-

Iodobenzylguanidine[18F]FDG 2-Deoxy-2-[18F]fluoro-D-

glucose18F-DOPA 2-18F-Fluoro-L-3,4-

dihydroxyphenylalanineABVD Chemotherapy regimen based

on adriamycin, bleomycin, vin-blastine, and dacarbazine

ceCT Contrast-enhanced computedtomography

COJEC Chemotherapy regimen basedon cisplatin, vincristine,carboplatin, etoposide, andcyclophosphamide

CT X-ray computed tomographyDLBCL Diffuse large B-cell lymphomaDOTA 1,4,7,10-Tetra-

azacyclododecane-1,4,7,10-tetraacetic acid

DOTANOC DOTA-1-Nal3-octreotideDOTATATE DOTA-Tyr3-octreotateGy Gray unit (ionizing radiation

dose in the International Systemof Units, corresponding to theabsorption of one joule of radi-ation energy per kilogram ofmatter)

HASTE Half-Fourier acquisition singleshot turbo spine echo, a mag-netic resonance imagingtechnique

HVA Homovanillic acid, a dopaminemetabolite

IVC Inferior vena cavaMAP2 Microtubule-associated

protein-2

2 D. Volterrani et al.

MIBG meta-IodobenzylguanidineMIP Maximum intensity projectionMR Magnetic resonanceMRI Magnetic resonance imagingMYCN Gene encoding for the N-myc

proto-oncogene protein, alsoknown as N-Myc or basic helix-loop-helix protein 37(bHLHe37)

NCCN National Comprehensive Can-cer Network

NSE Neuron-specific enolasePET Positron emission tomographyPET/CT Positron emission tomography/

Computed tomographyRCHOP Chemotherapy regimen based

on rituximab, cyclophospha-mide, doxorubicin

SPECT Single-photon emission com-puted tomography

SPECT/CT Single-photon emission com-puted tomography/Computedtomography

STIR Short tau inversion recovery, amagnetic resonance imagingtechnique used for fat suppres-sion (also known as short T1inversion recovery)

SUV Standardized uptake valueSUVmax Standardized uptake value at

point of maximumSVC Superior vena cavaTVD Chemotherapy regimen based

on topotecan, vincristine, anddoxorubicin vincristine, andprednisone

VMA Vanyllilmandelic acid, a cate-cholamine metabolite

Neuroblastoma: Case No. 1

Presentation

A four-year-old girl with high-risk neuroblastoma(stage IV, MYCN amplified). Treated with induc-tion chemotherapy (modified N7 protocol), with

partial response (persisting 5–10% positive bonemarrow cells on bilateral trephines). Second-lineinduction chemotherapy with TVD, with someimprovement, but still about 5% positivity onbone marrow trephines. Further treatment withbevacizumab and temozolomide, with goodresponse. Surgery, with 80% tumor removal andleft nephrectomy (tumor invasion of the left renalhilum).

Findings

Persisting disease on reassessment [123I]MIBG(Fig. 1). The child has subsequently been treatedwith experimental therapies including monoclonalantibodies and modified T-cells. MRI scan afterfifth cycle of monoclonal antibody treatmentdisclosed a splenunculus (Fig. 2). A [123I]MIBGscan was performed 5 days after the MRI scan.There were two persisting foci of [123I]MIBGavid disease in the left side of the abdomen(Fig. 3). The intensity of uptake is significantlyreduced in comparison to the previous MIBGstudy after surgery. The SPECT/CT study raisesthe possibility that the splenunculus may beMIBG-avid (Fig. 3). Contrast-enhanced CT scan,performed the day after the [123I]MIBG scan,showed the splenunculus and a further soft tissuenodule just below it, corresponding to the [123I]MIBG avid nodule and compatible with residualdisease (Fig. 4). Moreover, residual disease in theretroperitoneum only minimally [123I]MIBG avidwas clearly seen on contrast-enhanced CT (Fig. 5).

Follow-Up

The child was discussed at the multidisciplinaryteam meeting, with the view to proceed to furthersurgery that seemed feasible based on the imagingstudies.

Teaching Point

The [123I]MIBG SPECT/CT study has been criti-cal in identifying the additional nodule of [123I]

Teaching Cases in Nuclear Oncology: Pediatric Cancers 3

MIBG avid disease below the splenunculus. Com-parison with contemporaneous cross-sectionalimaging has also been essential for a proper inter-pretation of the MIBG findings. Surgical planninghas included resection of that nodule, clearly sep-arate and different from the splenunculus.Withoutproper comparison with other imaging, the focalarea of abnormal [123I]MIBG uptake could havebeen interpreted as representing the splenunculus,with the possible risk of resecting an accidentalnormal finding and leaving in place a nodule of[123I]MIBG avid neuroblastoma.


Presentation

A five-year-old boy, diagnosed with stage IV neu-roblastoma (widespread skeletal disease) at the ageof 2.5 years (Fig. 6). Treated with induction che-motherapy (rapid COJEC) to complete remissionon MIBG and surgical resection of the primarytumor. Three months later, recurrent disease witha brain metastasis in the right parietal lobe; this wasresected, with subsequent radiotherapy and adju-vant chemotherapy. Subsequent relapse in the skel-eton (right tibia and femur) few months later,treated with second-line chemotherapy (TVD),topotecan, [131I]MIBG therapy, and high-dose che-motherapy, followed by antibody therapy. In com-plete remission on [123I]MIBG scintigraphy andX-ray as a result (Fig. 7). After 1 year, he presentswith acute onset of left knee pain.

Findings

The patient underwent aMRI of the left femur thatshowed a focal abnormality in the distal diaphy-sis, with abnormal signal and enhancement of theperiosteum and the bone marrow, highly

Fig. 1 Reassessment[123I]MIBG shortly aftersurgery (anterior andposterior planar images):two focal areas of [123I]MIBG avid disease in theleft side of the abdomenare seen

Fig. 2 MRI scan, T2 weight images, after fifth cycle ofmonoclonal antibody treatment and several months aftersurgery (axial view): there is a splenunculus


suspicious for recurrence (Fig. 8). One week later,[123I]MIBG scintigraphy resulted completely neg-ative with no evidence of abnormal uptake in theleft femur (Fig. 9). A subsequent 68Ga-DOTATATE whole body PET/CT scan found ahighly increased somatostatin analogue uptake inthe distal left femur, compatible with recurrentmalignant disease (Fig. 10).

Follow-Up

The child was treated with three courses of 177Lu-DOTATATE molecular radiotherapy, withimprovement in the left femoral metastasis.

Teaching Point

This case illustrates that previous [123I]MIBGavid neuroblastoma can relapse asMIBG negativedisease. Neuroblastoma, although detected with

Fig. 3 [123I]MIBG scan,performed 5 days after theMRI scan. Reassessmentafter five courses ofmonoclonal antibodytreatment. There are twopersisting foci of[123I]MIBG avid disease inthe left side of the abdomenon planar images (toppanel). The intensity ofuptake is significantlyreduced in comparison tothe previous [123I]MIBGstudy after surgery. TheSPECT CT study (axialviews) raise the possibilitythat the splenunculus maybe [123I]MIBG avid (middleand bottom panel).However, it is noted thatthere is no [123I]MIBGuptake in the spleen, andthis would be very unusual


high sensitivity by [123I]MIBG, is [123I]MIBGnegative in about 5% of cases. Also, [123I]MIBGpositive primary neuroblastoma can show clonesof [123I]MIBG negative cells. And a patient withmainly [123I]MIBG positive metastatic lesions canshow [123I]MIBG non-avid lesions. [123I]MIBG isa marker of the norepinephrine active uptake-1transport mechanism and is taken up by neuro-blastoma only if this mechanism is still functional.


Presentation

A five-year-old boy, with a diagnosis of high-riskneuroblastoma (poorly differentiated Schwannianstroma poor, stage IV, widespread skeletal

metastatic infiltration on [123I]MIBG) at the ageof 2 (Fig. 11).

Findings

He was treated with induction chemotherapy(rapid COJEC) with excellent response (resolu-tion of all skeletal metastatic lesions with theexception of a lesion in the sternum) (Fig. 12).He also received high-dose chemotherapy withbusulfan and melphalan and stem cell rescue,achieving complete remission on [123I]MIBG(Fig. 13). He had abdominal radiotherapy at thesite of the primary tumor, cis-retinoic acid, andimmunotherapy with anti-GD2 monoclonal anti-bodies. During immunotherapy he relapsed with afocal area of abnormal [123I]MIBG uptake in themanubrium of the sternum, exactly at the same

Fig. 4 Contrast-enhancedCT scan, performed the dayafter the [123I]MIBG scan.This shows thesplenunculus and a furthersoft tissue nodule just belowit, best seen on the coronalviews (bottom panel,arrow): this is likely tocorrespond to the[123I]MIBG avid noduleand is compatible withresidual disease


site of the previous disease (Fig. 14). This wastreated with cyclophosphamide and topotecan andexternal beam radiotherapy, with no significantchange on [123I]MIBG SPECT/CT scanning and68Ga-DOTATATE PET/CT (stable disease)(Fig. 15). An excision biopsy after 13 cycles ofchemotherapy showed ganglioneuroblastomawith extensive differentiated elements and no evi-dence of undifferentiated cells (Fig. 16).

Follow-Up

In view of the completely excised well-differentiated ganglioneuroblastoma and theabsence of undifferentiated cells, the cytotoxicchemotherapy based on cyclophosphamide andtopotecan has been withdrawn.

Teaching Point

This case illustrates the possible differentiation ofa highly malignant poorly differentiated neuro-blastoma into a much more benign well-differentiated ganglioneuroblastoma variant fol-lowing chemotherapy. [123I]MIBG scanningcould not differentiate between these histologicalvariants.


Presentation

A five-month-old baby girl diagnosed with apoorly differentiated neuroblastoma with veryelevated VMA/HVA urinary levels.

Fig. 5 [123I]MIBGSPECT/CT scan (top panel)and contrast-enhanced CT(bottom panel). Residualdisease in theretroperitoneum, onlyminimally [123I]MIBG avidon SPECT/CT and clearlyseen on contrast-enhanced CT


Findings

An MRI at diagnosis showed a large intra-abdominal mass lesion arising from the right adre-nal, with skin and liver metastases (Fig. 17). Her[123I]MIBG scan showed skeletal metastaticinvolvement (Fig. 18). However, her bone mar-row aspirate was negative for metastatic infiltra-tion. The molecular analysis from the biopsy ofher abdominal tumor did not show MYCN ampli-fication (and no segmental chromosomal abnor-mality). Consequently she was considered as

having intermediate rather than high-risk disease.The investigations of her disease at staging sug-gest a pattern of stage IV disease rather than IVs.

Management

On the basis of her stage (IV rather than IVs), thisgirl has been commenced on chemotherapy(carboplatin and etoposide), in line withEuropean guidelines.

Fig. 6 [123I]MIBG at diagnosis (aged 2.5 years): the pri-mary neuroblastoma in the right suprarenal region shows arim of [123I]MIBG avid disease surrounding a central area

with lower grade uptake. There are widespread [123I]MIBGavid skeletal deposits, consistent with bone and bone mar-row metastatic infiltration


Teaching Point

This is a very interesting and unusual case. Theage of the child (5 months) would raise the possi-bility of a IVs neuroblastoma; however, the natureof the primary tumor (crossing the midline,encasing vessels, extending to the retrocruralspace) and the pattern of metastatic infiltration(focal rather than diffuse hepatic metastatic infil-tration, no bone marrow disease, cortical bonemetastases) are consistent with stage IV disease.However, in view of the favorable tumor biology(MYCN non-amplified, no chromosomal abnor-malities) and of her age (<18 months), her neuro-blastoma can be classified as intermediate ratherthan high risk. On the other hand, as she has stageIV disease, she has been commenced on chemo-therapy. The [123I]MIBG scan successfully showsthe skeletal metastases but fails to distinguish

between bone and bone marrow disease (thebone marrow aspirate excluded bone marrowinvolvement). Also, the [123I]MIBG scan showedlow sensitivity for liver metastases, due to thenormal hepatic [123I]MIBG uptake.


Presentation

A two-month-old baby boy presenting with a3-day history of vomiting, diarrhea, and increas-ing abdominal distension.

Findings

His MRI scan at diagnosis showed a massivehepatomegaly with multiple nodules of disease.In addition, there was a right adrenal mass lesion,which on percutaneous biopsy was demonstratedto be a poorly differentiated neuroblastoma(Fig. 19). [123I]MIBG at diagnosis showed no

Fig. 7 X-ray of the left knee 2.5 years after diagnosis,when the child was in complete remission: there is a focalarea of sclerosis in the medial aspect of the distal left femur,very similar to a previous X-ray, possibly compatible witha healed metastasis

Fig. 8 MRI left femur 1 week later: focal abnormality inthe distal diaphysis of the left femur, with abnormal signaland enhancement of the periosteum and the bone marrow,highly suspicious for recurrence


evidence of significantly increased tracer uptake(Fig. 20).

Management

Clinically and radiologically, this baby boy hadIVs neuroblastoma. However, molecular analysison the biopsy specimen showed MYCN amplifi-cation. Therefore, in view of the unfavorable biol-ogy, he was upstaged to high risk and treated withrapid COJEC induction chemotherapy.

Teaching Points

A neuroblastoma can be [123I]MIBG entirely neg-ative in approximately 5% of cases. Therefore,[123I]MIBG cannot be used to follow up thesetumors. PET tracers, such as [18F]FDG, 18F-DOPA, 68Ga-DOTATATE, or DOTANOC can betried.

IVs neuroblastoma usually has a good progno-sis and is treated with mild chemotherapy. How-ever, in approximately 10% of cases, a IVsneuroblastoma can have amplification of theMYC oncogene; in this case it has a much worseprognosis and is treated with the aggressive form ofchemotherapy used for high-risk stage IV disease.

Fig. 9 [123I]MIBG 1 weekafter the MRI: no evidenceof abnormal uptake in theleft femur

Fig. 10 68Ga-DOTATATE whole body PET scan 1 weeklater: there is highly increased somatostatin analogueuptake in the distal left femur, compatible with recurrentmalignant disease (Image courtesy of Dr J. Bomanji, Insti-tute of Nuclear Medicine, University College LondonHospital)


Fig. 12 [123I]MIBG scan at the end of induction chemotherapy: there has been an excellent response, with resolution ofall the previously demonstrated metastatic lesions, with the exception of a lesion in the manubrium of the sternum

Fig. 11 [123I]MIBG scan at diagnosis: there is increased tracer uptake within in the primary neuroblastoma in the rightsuprarenal region, with widespread metastatic infiltration in the skeleton


Fig. 13 [123I]MIBG scan after high-dose chemotherapy: there is resolution of the previously seen metastatic lesion in themanubrium of the sternum; normal findings elsewhere. Complete remission

Fig. 14 [123I]MIBG at relapse: a focal area of intense [123I]MIBG uptake is seen in the manubrium of the sternum,exactly at the same site of the previously demonstrated disease


Fig. 15 68Ga-DOTATATEPET/CT scan showinghighly increased traceruptake in the manubrium ofthe sternum, correspondingto the abnormal [123I]MIBGuptake (Images courtesy ofDr J Bomanji, Institute ofNuclear Medicine,University College LondonHospital)

Fig. 16 [123I]MIBG scanwith SPECT/CT afterexcision biopsy: noevidence of residualabnormal [123I]MIBGuptake in the sternum orelsewhere. Completeremission



Presentation

A two-year-old girl, presenting with jaundice. Shewas found to have a large abdominal mass, whichon biopsy, following ultrasound and MRI, turnedout to be a poorly differentiated, Schwannianstroma poor, neuroblastoma.

Findings

MRI and [123I]MIBG showed localized disease inthe mid-upper abdomen (Figs. 21 and 22).

Management

Based on the bone marrow trephine result(Fig. 23), this is stage IV neuroblastoma, high

Fig. 17 MRI scan at diagnosis, STIR coronal (left panel)and T2 axial view (right panel): there is a large centralabdominal mass lesion, measuring 8 � 11 � 5 cm,

encasing the entire splanchnic circulation, extending intothe retrocrural space bilaterally, and displacing the rightkidney inferiorly. There are multiple liver metastases

Fig. 18 [123I]MIBG scan at diagnosis (planar images): theprimary neuroblastoma shows intense [123I]MIBG uptake.There are multiple skeletal metastases in the skull vault,left orbital region, base of the skull, both humeral shafts,

both femora and tibiae. Some of the metastatic liverdeposits show [123I]MIBG uptake. There are also numer-ous skin nodules in the lower limbs


risk (also considering the patient’s age and theunfavorable histopathology). The child was com-menced on induction chemotherapy based onrapid COJEC (no vincristine due to raisedbilirubin).

Teaching Points

The [123I]MIBG scan show localized disease;however, low-grade but definite bone marrowmetastatic infiltration was present, demonstratedon both right and left bone marrow trephines.Bone marrow infiltration cannot be excluded onan MIBG scan that shows localized disease. Bonemarrow trephines are always necessary as a stag-ing investigation.


Presentation

A two-year-old boy, presenting to the local hospitalwith a palpable abdominal mass, abdominal disten-sion, constipation, reduced appetite, and generallethargy. An abdominal ultrasound confirmed a12 � 6 cm mass, arising presumably from theright kidney, along with central abdominal

lymphadenopathy. Therefore a CT scan wasperformed: this showed a large partly calcifiedsuprarenal mass lesion which invaded the rightkidney and extended across the retroperitoneum.The aorta was encased by tumor. The massextended from the right suprarenal position to theaortic bifurcation, amounting to a craniocaudaldimension of at least 16 cm. There was a 2-cmleft supraclavicular calcified lump in keeping witha metastasis. Percutaneous biopsy result showed apoorly differentiated neuroblastoma with amplifi-cation of the MYCN oncogene and chromosomalabnormalities (high risk).

Findings

The [123I]MIBG scan disclosed a large masslesion with heterogeneous tracer uptake,extending from the right side of the abdomeninto the retroperitoneum medially and inferiorlyand crossing the midline. Moreover, a focal areaof increased tracer uptake, compatible with a met-astatic left supraclavicular lymphadenopathy, wasfound (Fig. 24). MRI showed a 11 � 8 � 8 cmheterogeneous right suprarenal mass invading theright kidney and encasing the upper abdominalvessels and both renal arteries and the involve-ment of multiple lymph nodes (Fig. 25).

Fig. 19 MRI scan at diagnosis, STIR coronal image, and T1 axial scan: there is a right adrenal mass lesion measuring4.4 � 4.7 � 6.1 cm. The liver is enlarged with multiple nodules of variable size scattered in both lobes, which showperipheral enhancement after i.v. contrast. No abdominal lymphadenopathy. No ascites. Appearances are suggestive of aright adrenal neuroblastoma with multiple liver metastatic deposits (likely stage IVs on MRI)


Following completion of dose-intensive induc-tion chemotherapy (rapid COJEC), MRI showed aresidual 6-cm mass lesion in the right suprarenalregion (Fig. 26). The [123I]MIBG scan resultednegative (Fig. 27).

Management

The residual right adrenal mass was surgicallyresected. No viable neuroblastoma was demon-strated within the right adrenal mass lesion,which showed necrosis and post-chemotherapy

changes. However, within a resected surroundinglymph node, there was a nodule of differentiatingand viable neuroblastoma; other nodules withpost-chemotherapy changes contained scattereddifferentiating neuroblastoma cells.

Teaching Point

An MIBG negative primary neuroblastoma fol-lowing induction chemotherapy cannot excluderesidual viable neuroblastoma cells.

Fig. 20 [123I]MIBG at diagnosis: the right adrenal pri-mary tumor is not [123I]MIBG avid. The liver is enlarged.However, it only shows background activity, with no evi-dence of significantly increased tracer uptake. The findings

are compatible with an [123I]MIBG negative neuroblas-toma; the metastatic lesions are also [123I]MIBG negative



Presentation

An eight-year-old boy, presenting to the localhospital with a 2-week history of right-sidedflank pain and constipation, associated with inter-mittent fevers. In addition, he experienced nightsweats, poor appetite, and increasing lethargy.

Findings

An ultrasound and an MRI at the local hospitaldemonstrated a right-sided abdominal mass(Fig. 28). Biopsy of the mass lesion showed adifferentiating neuroblastoma. Molecular biologyshowed a non-amplified MYCN and chromo-somal abnormalities. Staging was completedwith [123I]MIBG (Fig. 29).

Fig. 21 [123I]MIBG atdiagnosis: there is a highly[123I]MIBG avid masslesion in the mid-upperabdomen, with no evidenceof regional or distantmetastatic spread


Chemotherapy based on carboplatin andetoposide was started. At the end of chemother-apy, the tumor was resected, and histopathologyconfirmed a differentiating neuroblastoma. Cis-retinoic acid was then administered for 6 months.[123I]MIBG at the end of treatment showed a softtissue nodule on the retrocaval area and is suspi-cious for recurrent disease within a retrocavallymph node (Fig. 30). MRI confirmed the pres-ence of a retrocaval area of moderately restricteddiffusion and heterogeneous enhancement(Fig. 31).

Management

The nodule was surgically excised and it wasconfirmed to represent a retrocaval metastaticlymph node. In addition, the child was referredfor radiotherapy to the para-aortic lymph nodesand the original tumor bed.

Teaching Point

SPECT/CTwas critical in raising the suspicion ofa focal area of recurrence. The [123I]MIBG scan

Fig. 22 MRI scan at diagnosis: there is a retroperitoneal mass lesion in the upper abdomen measuring approximately8.3 � 8.7 � 9 cm. It is centered in the retroperitoneum and involves the head of the pancreas and the majority of the body.The common bile duct is compressed by the mass, and there is common bile duct and intrahepatic ductal dilatation. Thereis a retrocrural component extending to T9. A further component extends to the porta hepatis but does not infiltrate theliver. There is significant abdominal pelvic ascites and subcutaneous fluid. No discrete bony lesion demonstrated

Fig. 23 Bone marrow trephines: there are small scattered groups of abnormal cells, positive for MAP2, NSE, andsynaptophysin. These features are those of metastatic neuroblastoma


with SPECT/CT in neuroblastoma is now stan-dard of care, especially for lesions deep in theabdomen/pelvis.

Lymphoma: Case No. 1

Presentation

A 14-year-old boy with pain and tenderness in thedistal portion of the right femur. He underwent aMR scan of the right knee that showed an aggres-sive bone lesion with initial infiltration of soft

tissues and a popliteal lymphadenopathy, thatneeded a differential diagnosis between lym-phoma and sarcoma (Fig. 32).

Findings

A total body ceCT was performed which shows anot pathological enlargement of the thymus. Then[18F]FDG PET/CTwas performed that highlighteda focal hypermetabolism glucose within the lesionof the distal femur (SUVmax 8.5) and the right wingthymus (SUVmax 19.2) (Fig. 33).

Fig. 24 [123I]MIBG atdiagnosis: there is a largemass lesion withheterogeneous traceruptake, extending from theright side of the abdomeninto the retroperitoneummedially and inferiorly andcrossing the midline. Thereis a focal area of increasedtracer uptake in the leftsupraclavicular region,compatible with ametastaticlymphadenopathy. Noabnormal tracer uptakenoted in the skeleton


The reassessment of the ceCT stated the pres-ence of an anterior mediastinal mass cleaving tothe right portion of the thymus. Since bone mar-row biopsy resulted negative, an excisionalbiopsy of the lesion of the distal portion of theright femur was performed. Pathology reportedlymphoma derived from peripheral B lympho-cytes, large cells, and bone primitive.Chemotherapy based on according to the NCCNprotocol for the diffuse large B-cell lymphoma(DLBCL) at stage IV. At the interim reassessmentafter two cycles, PET/CT showed complete meta-bolic response of the anterior mediastinum lesion,almost complete resolution of the hypermetaboliclesion of the femur (Fig. 34).

Follow-Up

At the end of the treatment, MRI showed netreduction of the intraosseous extension of thelesion, normalization ofMR signal, and the reduc-tion of contrastographic enhancement (Fig. 35).

Fig. 25 MRI of the abdomen, coronal STIR (top), andaxial T2-weighted (middle) images. There is a 11 � 8 � 8cm heterogeneous right suprarenal mass invading the rightkidney and encasing the upper abdominal vessels and bothrenal arteries. The IVC is patent but displaced anteriorly.No intraspinal invasion. There is a left-sided conglomeratelymph node measuring 3.5 � 1.9 cm. There is evidence ofretrocrural disease. MRI of the neck (coronal STIR bottom)shows left supraclavicular lymphadenopathies

Fig. 26 Abdominal MRI after induction chemotherapy,T2-based sequence, coronal view: there is a residual masslesion in the right suprarenal region, measuring 6 cm inmaximum axial dimension


Teaching Point

PET/CT, by identifying the hypermetabolic masswithin the mediastinum, oriented the diagnosis tolymphoma and contributed to the disease staging.Moreover, the early response during chemother-apy showed by PET/CT predicted the response atthe end of treatment.

Ewing Sarcoma

Presentation

An eighteen-year-old patient with heaviness at theleft inguinal region and left sciatica during pro-longed sitting. After 3 months occasional finding

Fig. 27 [123I]MIBG afterinduction chemotherapy:there is no evidence ofabnormal tracer uptake. Inparticular, the residual masslesion demonstrated onMRI is MIBG negative


of left inguinal swelling, of hard consistence,painless nor dolorabile on palpation. On theadvice of the general practitioner, an abdominaland pelvic ceCTwas performed showing the pres-ence of a pelvic mass (17 � 10 � 15 cm) withparenchymatous structure, infiltrating the visceraand pelvic walls, with manifestation within theinguinal canal and the root of the left thigh. Itcoexisted also densification of the left pubicbone branch, probably reactive meaning. MRI

confirmed the large mass showing maximumdiameters in the pelvis and in the left thigh, witha global extension of about 24 cm. Biopsy of theleft inguinal mass drove to the diagnosis of anEwing sarcoma CD99 positive.

Findings

The mass presented inhomogeneous hyper-metabolic activity, as disclosed by [18F]FDGPET/CT (Fig. 36). Neoadjuvant chemotherapywas undertaken. PET/CT after chemotherapyshowed a net response of the mass confirmedalso by MRI. External beam radiotherapy of thepelvic mass (50 Gy) and other cycles of chemo-therapy were then performed. CT of the lungs andPET/CT became completely negative (Fig. 36).The patient underwent surgery with the exeresisof the pelvic mass along with the resection of theleft iliopubic and ischium-pubic branches. At thatlevel, postsurgery PET/CT showed an area ofhyperactivity with craniocaudal developmentand central hypoactivity, referred in the firsthypothesis to surgical outcomes. Moreover,some hypermetabolic lymphadenopathies wereseen in the groin and the right external iliac region(Fig. 37). Within the lungs PET/CT indicates thepresence of a paracardiac hypermetabolic nodulein the lingula. CT demonstrated other micro-nodules within the lungs consistent with second-ary lesions (Fig. 38).

Follow-Up

The patient underwent high-dose chemotherapywhich determined the disappearance of lung dis-ease. After 1 year the patient is still disease free.

Teaching Point

[18F]FDG PET/CT is an effective tool for moni-toring the efficacy of therapy. However, false-positive findings can be due to inflammatory or

Fig. 28 (a, b) MRI at diagnosis, coronal and axialHASTE T2-based images: there is a mass lesion in theaortocaval area displacing the IVC to the right. The massextends to the level of the porta hepatis, displacing andabutting the hepatic artery. The largest component of themass is at the right renal hilum, with the left renal vein andthe right renal artery encased by tumor. The infiltratingnature of this mass lesion favors a neuroblastic tumor


infectious processes, frequently occurring aftersurgery or radiotherapy. Since the lungs are afrequent site of metastasis of all sarcomas, [18F]FDG PET/CT must be performed along with adiagnostic CTwhich is more sensitive in detectingsecondary micronodules.


Case contributed by: F. Reyneke, M. Sathekge(Nuclear Medicine, University of Pretoria &Steve Biko Academic Hospital, Pretoria,South Africa).

Presentation

A 10-year-old male patient presented with a pain-less mass in the left side of his neck.

Findings

A biopsy taken from a left cervical lymph noderevealed classical Hodgkin’s lymphoma (mixedcellularity subtype).

[18F]FDG PET/CT for initial staging showed aconglomerate of lymph nodes in the left cervicalregion (involving all the lymph node groups)extending into the infraclavicular region –SUVmax 10.5 (Figs. 39 and 40).

Follow-Up

Following chemotherapy, [18F]FDG PET/CT wasrepeated to monitor response during therapy.Increased [18F]FDG uptake was still noted in cer-vical lymph nodes in levels II, III, and IV (SUVmax

8.16) with significant reduction in size demonstrat-ing a good response to therapy (Figs. 41 and 42).

Fig. 29 [123I]MIBG atdiagnosis: the mass lesiondemonstrated on MRIshows intense, [123I]MIBGuptake. No evidence ofregional or distantmetastatic spread. Thisfinding, together with theMRI and the molecularbiology, makes anintermediate-riskneuroblastoma


Fig. 30 (a, b) [123I]MIBGat the end of treatment. Theplanar images (a) show afocal area of moreprominent tracer uptake inthe region of the transversecolon on the midline. OnSPECT/CT (b), thislocalizes to a soft tissuenodule on the retrocavalarea and is suspicious forrecurrent disease within aretrocaval lymph node


Teaching Point

[18F]FDG PET/CT is highly sensitive in the detec-tion of Hodgkin’s lymphoma and can also accu-rately evaluate the effectiveness of therapy. Thisshould be done 6–8 weeks after therapy to mini-mize false-negative and false-positive results.


Case contributed by: T. Boshomane,M. Sathekge (Nuclear Medicine, University ofPretoria & Steve Biko Academic Hospital, Pre-toria, South Africa).

Presentation

A fifteen-year-old female with histologically con-firmed lymphoma (Hodgkin’s, clinical stage IIwith no other risk factors) and treated with che-motherapy (ABVD).

Fig. 32 MRI of the right knee showing a bone lesion withinitial infiltration of soft tissues and a popliteallymphadenopathy

Fig. 31 MRI followingsuspicion of relapse, axialSTIR image: there is a1.5 � 1.5 cm area ofmoderately restricteddiffusion andheterogeneousenhancement: thiscorresponds to the area ofabnormality demonstratedon [123I]MIBG SPECT/CT.The area of recurrence isinferior to the previouslylocated tumor and was notpresent previously


Fig. 33 On left top panel:ceCT showing the anteriormediastinal mass cleavingto the right portion of thethymus. In the left bottompanel: [18F]FDG PET/CTshowing thehypermetabolic activity ofthe anterior mediastinalmass. On the right: MIPimage of the PET/CTwholebody study demonstratingthe hyperactive lesion of theleft knee

Fig. 34 Interim PET/CT after two cycles of RCHOPdemonstrating the metabolic response of both the medias-tinal and femur lesions

Fig. 35 RM of the right knee showing the response at theend of six cycles of RCHOP


She presented to her oncologist >3 monthspost-chemotherapy complaining of unintentionalweight loss and increasing fatigue.

Findings

CT noted mediastinal lymphadenopathy(aortopulmonary, carinal, anterior to SVC, andparaoesophageal) with no skeletal changes. [Pre-viously only left cervical lymph nodes were seen].

Fused [18F]FDG PET showed metabolic activ-ity in the mediastinal lymph nodes SUV max(SUVmax: 9.9 aortopulmonary, 5.9 hilar, 10.0 inthe posterior mediastinum) and T2 vertebra(SUVmax 8.6) (Figs. 43 and 44).

Teaching Point

Given the high sensitivity of [18F]FDG PET/CTfor detecting bone marrow involvement, this casehighlights the importance of this modality whenavailable. An invasive procedure is averted asPET detects lymphomatous involvement of theskeleton therefore upstaging the disease. The indi-cation of the PET scan in this study was restagingafter chemotherapy.


Presentation

A 9-month-old girl presented with bilateral peri-orbital ecchymosis, right side exophthalmos, andabdominal distension.

Fig. 36 [18F]FDG PET/CT scans performed at staging(top panel), after chemotherapy (middle panel) and afterchemoradiotherapy (bottom panel), show the progressiveresponse of the left inguinal mass


Fig. 37 Postsurgery [18F]FDG PET/CT: area of hyperac-tivity and central hypoactivity in left iliopubic region con-sistent with surgical outcomes. Some hypermetabolic

lymphadenopathies are visible in the right groin and inthe right external iliac region


Fig. 38 [18F]FDG PET/CTparacardiac hypermetabolicnodule within the lingula.Basal CT shows severalmicronodules with noevidence of significant[18F]FDG uptake within thelungs, consistent withsecondary lesions


Fig. 39 [18F]FDG PET/CT coronal images demonstrate the conglomerate of lymph nodes on the left side of the neck


Fig. 40 [18F]FDG PET/CT MIP image (left). Sagittal and coronal images of the cervical mass (right)

Fig. 41 [18F]FDG PET/CTcoronal imagesdemonstrating residuallymph nodes in the cervicalregion (reduced SUVmax

and significant reduction insize compared to previousstudy)


Fig. 42 [18F]FDG PET/CTaxial images demonstratinga good metabolic responseto chemotherapy


Fig. 43 Top row: sagittal images of metabolic activity noted on [18F]FDG PET, which was not appreciated on the CTimages (middle row). Bottom row: fused PET/CT demonstrating the T2 lesion


Findings

CT revealed a renal mass (8 � 8 cm), retroperito-neal lymphadenopathy, as well as multiple hepaticand pulmonary lesions. CT of the head showedwidespread osseous metastases and right exoph-thalmus. Biopsy confirmed neuroblastoma (stageIV). [123I]MIBG planar and SPECT/CT images(Fig. 45) show a large partially calcified leftabdominal mass with pathological radiopharma-ceutical uptake, representing the site of primarytumor of adrenal origin. Abnormal foci of [123I]MIBG uptake are present in both lobes of theliver, corresponding to hepatic metastasis. Multi-ple foci of pathological uptake in the axial and theappendicular skeleton are also seen. Bilateral lungnodules do not show focal radiotraceraccumulation.

As a part of initial staging [18F]FDG PET/CTwas performed: images demonstrate low[18F]FDG uptake in the bone marrow of the pelvisand distal femurs and proximal tibiae (Fig. 46).The known abdominal mass and liver metastasesdo not show abnormal uptake. Bone marrowinvolvement was confirmed by bone marrowbiopsies that revealed the presence of neuroblas-toma without MYC-gene amplification.

Follow-Up

The patient was treated with neoadjuvant chemo-therapy and surgery (left adrenalectomy and ret-roperitoneal lymphadenectomy). Follow-upevaluation after adjuvant chemotherapy showedstable disease. [123I]MIBG scan demonstrates

Fig. 44 Axial images. Top row: metabolically activemediastinal lymph nodes demonstrated on [18F]FDGPET. Middle row: CT images showing the lung fields andmediastinum. Bottom row: fused PET/CT demonstrating

the mediastinal lymph nodes. The side image is the MIPimages showing the supradiaphragmatic disease butinvolving bone [adnexal activity was non-lymphomatous]


Fig. 45 [123I]MIBG scan. (a) Whole body image (anteriorand posterior view) shows increased radiotracer uptake inthe axial and appendicular skeleton. (b) Axial SPECT/CTimage (fused image in the left panel and CT image in the

right panel) of large partially calcified left abdominal mass.(c) Axial SPECT/CT image (fused image in the left panel,CT image in the right panel) of hepatic metastasis

Fig. 46 (a) [18F]FDG MIPimage demonstrates lowuptake in the bone marrowof the pelvis and distalfemurs and proximal tibiae.(b) [18F]FDG PET/CTfused coronal image: noabnormal uptake is seen inthe known abdominal tumoror in the liver


abnormal uptake in the axial and the appendicularskeleton and in the liver (Fig. 47). This case dem-onstrates that [18F]FDG PET/CT is not as

sensitive as [123I]MIBG imaging in many patientswith neuroblastoma.

Fig. 47 [123I]MIBG study(whole body image)performed afterchemotherapy shows thepersistence of pathologicaluptake in the skeleton andliver


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