fdg-pet in indolent lymphomas 2009/3/21 2009/3/21 新光醫院 核醫科 葉力豪

FDG-PET in Indolent FDG-PET in Indolent LymphomasLymphomas

2009/3/212009/3/21 新光醫院 核醫科 新光醫院 核醫科

葉力豪葉力豪

Case 1Case 1

66 y/o male66 y/o maleCC: progressive ptosis with poor CC: progressive ptosis with poor

visual acuity(os) for 2 years.visual acuity(os) for 2 years.Cranial CT for orbital study Cranial CT for orbital study

(2007/11/10): suspicious left orbital (2007/11/10): suspicious left orbital tumortumor

Cranial CT for orbital study (2007/11/10)Cranial CT for orbital study (2007/11/10)

FDG-PET (2007/12/7)FDG-PET (2007/12/7)

maxSUV:3.6

maxSUV:3.9maxSUV:3.3

maxSUV:1.7

Orbitl tumor

maxSUV:2.8 , Delayed maxSUV:4.5

maxSUV:1.8

FDG-PET (2007/12/7)FDG-PET (2007/12/7)

maxSUV:2.4

maxSUV:2.1

maxSUV:7.4

Left Orbital Lesion

maxSUV:2.8

Delayed maxSUV:4.5

Left cevical LN

1.0x0.7cm

maxSUV:2.4

Pretracheal LN

2.5x1.1 cm

maxSUV:3.3

Right axillary LN

1.2x0.8cmmaxSUV:1.7

Gastric wall

maxSUV:7.4

Gastric wall

Delayed image

Focal mild FDG uptake

maxSUV: 3.4

Right inguinal LN

1.5x0.8cm

maxSUV:1.8

PES PES (2007/11/11)(2007/11/11) Ulcers at fundusUlcers at fundus HP test (+) HP test (+)

PathologyPathology

1. Partial excision of Left Orbital tumor:1. Partial excision of Left Orbital tumor: Marginal zone lymphomaMarginal zone lymphoma, , most likelymost likely MALT lymphoma MALT lymphoma ((Extra-nodalExtra-nodal

Marginal Marginal zone lymphoma,zone lymphoma, Indolent lymphoma Indolent lymphoma))

2. Left inguinal LN biopsy:2. Left inguinal LN biopsy: lymphoid hyperplasia lymphoid hyperplasia

3. PES with biopsy : 3. PES with biopsy : ulcer at gastric antrumulcer at gastric antrum

Orbital MALT lymphomaOrbital MALT lymphoma

Orbital MALT lymphomaOrbital MALT lymphoma

Lymphoid Hyperplasia of Lymphoid Hyperplasia of inguinal LNinguinal LN

Lymphoid Hyperplasia of Lymphoid Hyperplasia of inguinal LNinguinal LN

Clinical Stage: IIIEBClinical Stage: IIIEB at leastat least

Orbital Lesion

Treatment & Follow-upTreatment & Follow-up

Chemotherapy as Chemotherapy as low grade low grade (indolent) lymphoma (indolent) lymphoma with with CyclophosphamideCyclophosphamide : 2008/1/11~4/18 : 2008/1/11~4/18

Partial RemissionPartial Remission

Follow-up Orbital CT (2008/5/19)Follow-up Orbital CT (2008/5/19)

Suspcious recurrenceSuspcious recurrence since 2008/8/8: since 2008/8/8:

A new nodule at left lower eyelid, a A new nodule at left lower eyelid, a LN at suboccipital areaLN at suboccipital area

Tx with Tx with Cyclophosphamide Cyclophosphamide

Partial RemissionPartial Remission

F/U FDG-PET on 2009/1/19F/U FDG-PET on 2009/1/19

2009/1/192009/1/192007/12/7

Left orbital lesion

maxSUV:2.8

lesion subsided

Left cevical LN

1.0x0.7cm

maxSUV:2.4

0.9x0.5cm

maxSUV:1.9

Pretracheal LN

2.5x1.1 cmmaxSUV:3.3

2.3x0.9 cmmaxSUV:3.1

Right axillary LN

1.2x0.8cm

maxSUV:1.7

0.9x0.5cm

maxSUV:1.0

Right inguinal LN

1.5x0.8cm

maxSUV:1.8

0.9x0.6cm

maxSUV:0.9

Case 2Case 2

56 y/o male56 y/o malePH:PH:

C-spine and L-spine DJDC-spine and L-spine DJD

GastritisGastritis

Smoking: (+) , socialSmoking: (+) , social

Drinking: rare Drinking: rare Underwent FDG-PET for physical Underwent FDG-PET for physical

check-upcheck-up

Left lingular lobe lesion

2005/12/31

maxSUV:2.4

2007/1/16

maxSUV:3.0

Underwent left lung surgery in NTUHUnderwent left lung surgery in NTUHPathology: Pathology: Pulmonary Extra-nodal Pulmonary Extra-nodal

marginal zone lymphoma (MALT marginal zone lymphoma (MALT lymphoma)lymphoma)

DiscussionDiscussion

Marginal zone B-cell Marginal zone B-cell lymphomalymphoma

The marginal zone lymphomas are so named The marginal zone lymphomas are so named because of their involvement of the because of their involvement of the marginal marginal zonezone surrounding normal lymphoid follicles surrounding normal lymphoid follicles..

IndolentIndolent lymphoma lymphoma Three subtypes:Three subtypes:

1. 1. ExtranodalExtranodal marginal zone B-cell lymphoma marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) of mucosa-associated lymphoid tissue (MALT) or or MALT lymphoma (or Maltoma) MALT lymphoma (or Maltoma) 2. 2. SplenicSplenic marginal zone B-cell lymphoma marginal zone B-cell lymphoma 3. 3. Nodal Nodal marginal zone B-cell lymphoma marginal zone B-cell lymphoma

MALT lymphomaMALT lymphoma

ExtranodalExtranodal marginal zone B-cell marginal zone B-cell lymphomalymphoma

May occur in the May occur in the stomach (most stomach (most often),often), orbitorbit, intestine, , intestine, lunglung, thyroid, , thyroid, salivary gland, skin, soft tissues, salivary gland, skin, soft tissues, bladder, kidney, and CNS.bladder, kidney, and CNS.

May present as May present as a new massa new mass, found , found on on routine imaging studiesroutine imaging studies, or be , or be associated with associated with local symptomslocal symptoms..

MALT lymphomaMALT lymphoma

Pathology pattern: infiltration of Pathology pattern: infiltration of small small lymphocytelymphocyte that are that are monoclonal B cellmonoclonal B cell and and CD5(-).CD5(-).

The majority present with The majority present with localized stage I localized stage I or IIor II extranodal disease, involving extranodal disease, involving glandular epithelial tissues of various sites. glandular epithelial tissues of various sites.

In some cases, transformation toIn some cases, transformation to diffuse diffuse large B cell lymphoma (aggressive large B cell lymphoma (aggressive lymphoma, worse prognosis)lymphoma, worse prognosis) occurs, and occurs, and both diagnoses may be made in the same both diagnoses may be made in the same biopsy. biopsy.

MALT lymphomaMALT lymphoma

These lymphomas can disseminate to These lymphomas can disseminate to other MALT sitesother MALT sites, lymph nodes, or marrow , lymph nodes, or marrow in about 30 percent of cases.in about 30 percent of cases.

In a series of 36 pts presenting with In a series of 36 pts presenting with non-GI non-GI MALT lymphomaMALT lymphoma, 12 , 12 (33%)(33%) were found to were found to have have gastric involvementgastric involvement at the time of at the time of initial workup.initial workup.

Some suggest that Some suggest that routine evaluation of routine evaluation of the stomachthe stomach should be a part of the initial should be a part of the initial staging workup, and at relapse, of non-GI staging workup, and at relapse, of non-GI MALT lymphomas MALT lymphomas

Clinical manifestations, pathologic features, and diagnosis of extranodal (MALT) and nodal marginal zone lymphomas. UpToDate

MALT lymphomaMALT lymphoma They often arise within tissues involved by They often arise within tissues involved by

chronic inflammatory disorderschronic inflammatory disorders of of autoimmune or infectious etiology:autoimmune or infectious etiology:1. Sjogren syndrome (salivary gland MALT)1. Sjogren syndrome (salivary gland MALT)2. Helicobacter gastritis (gastric MALT)2. Helicobacter gastritis (gastric MALT)3. Chlamydophila3. Chlamydophila psittaci conjunctivitis psittaci conjunctivitis (ocular (ocular

MALT)MALT)4. Borelia skin infection (cutaneous MALT)4. Borelia skin infection (cutaneous MALT)

★★ This neoplasm may lie on a continuum This neoplasm may lie on a continuum between between reactive lymphoid hyperplasiareactive lymphoid hyperplasia and and full-blown B-cell lymphomafull-blown B-cell lymphoma..

Treatment of MALT Treatment of MALT LymphomaLymphoma

Localized disease: Localized disease:

Local therapy such as radiation or Local therapy such as radiation or surgerysurgery

More extensive disease:More extensive disease:

Single-agent chemotherapySingle-agent chemotherapyCoexistent diffuse large B cell Coexistent diffuse large B cell

lymphoma:lymphoma:

Combination chemotherapyCombination chemotherapy

FDG Uptake Varies Among FDG Uptake Varies Among Different Types of LymphomaDifferent Types of Lymphoma

★ ★ Intensity of FDG uptakeIntensity of FDG uptake determined determined by:by:

HistologyHistology GradeGrade Viable tumor cell fractionViable tumor cell fraction Tumor cell proliferationTumor cell proliferation Up-regulation of glucose meyabolismUp-regulation of glucose meyabolism Local perfusionLocal perfusion Presence of hypoxiaPresence of hypoxia

PET Imaging for Response Assessment in Lymphoma: Potential and Limitation. Radio Clin N Am 46(2008) 225-241

FDG Uptake Varies Among FDG Uptake Varies Among Different Types of LymphomaDifferent Types of Lymphoma Indolent lymphomaIndolent lymphoma exhibit exhibit lower glucoselower glucose

metabolic activitymetabolic activity and hence FDG uptake and hence FDG uptake than the more aggressive ones.than the more aggressive ones.

Using an Using an SUV of 10SUV of 10 as a cutoff, FDG-PET as a cutoff, FDG-PET seperated aggressive from indolent seperated aggressive from indolent lymphoma with a sensitivity of 71% and a lymphoma with a sensitivity of 71% and a specificity of 81%.specificity of 81%.

There is (sometimes large)There is (sometimes large) heterogeneity heterogeneity between lesions of the same histologic between lesions of the same histologic entitiy and sometimes entitiy and sometimes overlapoverlap between between tumor grades.tumor grades. The Impact of Fluorodeoxyglucose-The Impact of Fluorodeoxyglucose-

Positron Emmision Tomography in Positron Emmision Tomography in Primary Staging and Patient Primary Staging and Patient management in Lymphoma Patients.management in Lymphoma Patients. Radiol Clin N Am 46(2008) 199-211Radiol Clin N Am 46(2008) 199-211

The Impact of Fluorodeoxyglucose-The Impact of Fluorodeoxyglucose-Positron Emmision Tomography in Positron Emmision Tomography in Primary Staging and Patient Primary Staging and Patient management in Lymphoma Patients.management in Lymphoma Patients. Radiol Clin N Am 46(2008) 199-211Radiol Clin N Am 46(2008) 199-211

FDG Uptake Varies Among Different Types of FDG Uptake Varies Among Different Types of LymphomaLymphoma

Indolent

Indolent

Indolent

Aggressive

Diagnostic accuracy of FDG-PET in Diagnostic accuracy of FDG-PET in patients with patients with MALT lymphomaMALT lymphoma

Overall disease detection Overall disease detection sensitivitysensitivity::In 5 studies (132 pts),In 5 studies (132 pts),54.4%(18/33) to 81%(21/26, 34/42) 54.4%(18/33) to 81%(21/26, 34/42)

Site dependentSite dependent::gastricgastric MALT : 38.9% MALT : 38.9%11 & 60% & 60%22

non-gastricnon-gastric MALT : 75% MALT : 75%11 & 88% & 88%22

Grade dependentGrade dependent::earlyearly stage disease (I-II): 42.3% stage disease (I-II): 42.3%11 & 79% & 79%22

advancedadvanced disease (stage III-IV): 100% disease (stage III-IV): 100% 1,2 1,2

1. Diagnostic accuracy of PET/CT in patients with extranodal marginal zone MALT lymphoma .Eur J Haematol. 2007 Sep; 79(3):205-9. Epub 2007 Jul 27

2. FDG-PET scanning for detection and staging of extranodal marginal zone lymphomas of the MALT type: a report of 42 cases. Annals of Oncology 16: 473–480, 2005

Diagnostic accuracy of FDG-PET in Diagnostic accuracy of FDG-PET in patients with patients with MALT lymphomaMALT lymphoma

Large cell transformationLarge cell transformation33::

Non-transformed SUV: 3.7 Non-transformed SUV: 3.7 (SD 1.4)

Transfromed SUV: 11.3 Transfromed SUV: 11.3 (SD 5.5)

3. Role of Fluorine-18 Fluoro-Deoxyglucose Positron Emission Tomography Scan in the Evaluation and Follow-Up of Patients With Low-Grade Lymphomas. CANCER July 1, 2006 / Volume 107 / Number 1

Usefulness of Usefulness of FDG-PET in FDG-PET in low low

grade grade lymphomaslymphomas

Role of Fluorine-18 Fluoro-Deoxyglucose Positron Emission Tomography Scan in the Evaluation and Follow-Up of Patients With Low-Grade Lymphomas. CANCER July 1, 2006 / Volume 107 / Number 1

Large cell transformation (LCT)

Some of indolent lymphomas (about 3% per year) will undergo large cell transformation (histologic transformation) during the course of the disease, an event that dictates a different management strategy and alters survival signicantly.

Although LCT can be suspected on clinical grounds alone, it may also go unnoticed or may be difficult to prove.

Role of Fluorine-18 Fluoro-Deoxyglucose Positron Emission Tomography Scan in the Evaluation and Follow-Up of Patients With Low-Grade Lymphomas. CANCER July 1, 2006 / Volume 107 / Number 1

Large cell transformation (LCT)

Significant difference between FDG uptake of nontransformed and transformed lymphomas.

When during the course of an otherwise indolent disease, there are FDG avid foci with much higher uptake than noted on the baseline study, suspicion should be raised regarding LCT.Role of Fluorine-18 Fluoro-Deoxyglucose Positron

Emission Tomography Scan in the Evaluation and Follow-Up of Patients With Low-Grade Lymphomas. CANCER July 1, 2006 / Volume 107 / Number 1

5 33 5 2 45

Low grade lymphomaHigh grade lymphoma

FDG-PET v.s. Bone Marrow FDG-PET v.s. Bone Marrow BiopsyBiopsy

Patients of Lymphoma in SKH

67y,M, Malignant lymphoma, small lymphocytic type, PET bone-

Conclusion

PET usefulness in staging low-grade(indolent) lymphomas varies depending on histology.

PET sensitivity is excellent in follicular lymphoma and moderate in marginal zone lymphoma.

Detectability of extra-nodal marginzal zone lymphoma (MALT lymphoma) is site and grade dependent:★Non-gastric > Gastric★Advanced > Early

Conclusion

PET is more specific than CT for follow-up in follicular lymphoma, marginal zone lymphoma, and B-cell small-cell lymphocytic lymphoma (SLL/CLL) .

PET has limited usefulness for B-cell small-cell lymphocytic lymphoma (SLL/CLL) staging.

Conclusion

In low-grade lymphomas, the emergence of foci of intense uptake should raise suspicion of conversion to high-grade disease.

FDG-PET scan may become the test FDG-PET scan may become the test of choice for of choice for early detectionearly detection of LCT of LCT and/or selection of the and/or selection of the optimal optimal biopsy sitebiopsy site when transformation is when transformation is suspected.suspected.

Conclusion

FDG-PET cannnot substitute for bone FDG-PET cannnot substitute for bone marrow biopsy, and is marrow biopsy, and is less sensitiveless sensitive in detecting bone marrow in detecting bone marrow involvement of involvement of low grade(indolent) low grade(indolent) lymphomalymphoma..

Thank You.Thank You.