1. FDG-PET in Indolent Lymphomas
2009/3/21
新光醫院 核醫科
葉力豪

2. Case 1
66 y/o male
CC: progressive ptosis with poor visual acuity(os) for 2 years.
Cranial CT for orbital study (2007/11/10): suspicious left orbital tumor

3. Cranial CT for orbital study (2007/11/10)
眼科 hematology. Bilateral inguinal LAP noted. Pt said bil. Inguinal mass for 2 years.
 Chest and abd CT: axillary, mediastinal, inguinal LAP, gastric lesion

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

5. FDG-PET (2007/12/7) Orbitl tumor maxSUV:2.8 , Delayed maxSUV:4.5

6. Left Orbital Lesion
maxSUV:2.8
Delayed maxSUV:4.5

7. Left cevical LN
1.0x0.7cm
maxSUV:2.4

8. Pretracheal LN
2.5x1.1 cm
maxSUV:3.3
Right axillary LN
1.2x0.8cm
maxSUV:1.7

9. Gastric wall
maxSUV:7.4

10. Gastric wall
Delayed image
Focal mild FDG uptake
maxSUV: 3.4

11. Right inguinal LN
1.5x0.8cm
maxSUV:1.8

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

13. Pathology 1. Partial excision of Left Orbital tumor:
Marginal zone lymphoma, most likely
MALT lymphoma (Extra-nodal Marginal
zone lymphoma, Indolent lymphoma)
2. Left inguinal LN biopsy:
lymphoid hyperplasia
3. PES with biopsy :
ulcer at gastric antrum

15. Orbital MALT lymphoma

16. Orbital MALT lymphoma

17. Lymphoid Hyperplasia of inguinal LN

18. Lymphoid Hyperplasia of inguinal LN

19. Clinical Stage: IIIEB at least
Orbital Lesion

20. Treatment & Follow-up
Chemotherapy as low grade (indolent) lymphoma with Cyclophosphamide : 2008/1/11~4/18
Partial Remission
Left vision improves, Neck and axillary LN become not palpable. But bilateral inguinal LNs palpable

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

22. Suspcious recurrence since 2008/8/8:
A new nodule at left lower eyelid, a LN at suboccipital area
Tx with Cyclophosphamide
Partial Remission
F/U FDG-PET on 2009/1/19

23. 2009/1/19
2007/12/7

24. Left orbital lesion
maxSUV:2.8
lesion subsided

25. Left cevical LN
1.0x0.7cm
maxSUV:2.4
0.9x0.5cm
maxSUV:1.9

26. Pretracheal LN
2.5x1.1 cm
maxSUV:3.3
2.3x0.9 cm
maxSUV:3.1

27. Right axillary LN
1.2x0.8cm
maxSUV:1.7
0.9x0.5cm
maxSUV:1.0

28. Right inguinal LN
1.5x0.8cm
maxSUV:1.8
0.9x0.6cm
maxSUV:0.9

29. Case 2 56 y/o male PH: C-spine and L-spine DJD Gastritis
Smoking: (+) , social
Drinking: rare
Underwent FDG-PET for physical check-up

30. Left lingular lobe lesion

32. 2005/12/31
maxSUV:2.4
2007/1/16
maxSUV:3.0

33. Underwent left lung surgery in NTUH
Pathology: Pulmonary Extra-nodal marginal zone lymphoma (MALT lymphoma)

34. Discussion

35. Marginal zone B-cell lymphoma
The marginal zone lymphomas are so named because of their involvement of the marginal zone surrounding normal lymphoid follicles.
Indolent lymphoma
Three subtypes:
1. Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) or MALT lymphoma (or Maltoma)
2. Splenic marginal zone B-cell lymphoma
3. Nodal marginal zone B-cell lymphoma

36. MALT lymphoma Extranodal marginal zone B-cell lymphoma
May occur in the stomach (most often), orbit, intestine, lung, thyroid, salivary gland, skin, soft tissues, bladder, kidney, and CNS.
May present as a new mass, found on routine imaging studies, or be associated with local symptoms.

37. MALT lymphoma
Pathology pattern: infiltration of small lymphocyte that are monoclonal B cell and CD5(-).
The majority present with localized stage I or II extranodal disease, involving glandular epithelial tissues of various sites.
In some cases, transformation to diffuse large B cell lymphoma (aggressive lymphoma, worse prognosis) occurs, and both diagnoses may be made in the same biopsy.

39. MALT lymphoma
These lymphomas can disseminate to other MALT sites, lymph nodes, or marrow in about 30 percent of cases.
In a series of 36 pts presenting with non-GI MALT lymphoma, 12 (33%) were found to have gastric involvement at the time of initial workup.
Some suggest that routine evaluation of the stomach should be a part of the initial staging workup, and at relapse, of non-GI MALT lymphomas
Clinical manifestations, pathologic features, and diagnosis of extranodal (MALT) and nodal marginal zone lymphomas. UpToDate

40. MALT lymphoma
They often arise within tissues involved by chronic inflammatory disorders of autoimmune or infectious etiology:
1. Sjogren syndrome (salivary gland MALT)
2. Helicobacter gastritis (gastric MALT)
3. Chlamydophila psittaci conjunctivitis (ocular
MALT)
4. Borelia skin infection (cutaneous MALT)
★ This neoplasm may lie on a continuum between reactive lymphoid hyperplasia and full-blown B-cell lymphoma.

41. Treatment of MALT Lymphoma
Localized disease:
Local therapy such as radiation or surgery
More extensive disease:
Single-agent chemotherapy
Coexistent diffuse large B cell lymphoma:
Combination chemotherapy

42. FDG Uptake Varies Among Different Types of Lymphoma
★ Intensity of FDG uptake determined by:
Histology
Grade
Viable tumor cell fraction
Tumor cell proliferation
Up-regulation of glucose meyabolism
Local perfusion
Presence of hypoxia
PET Imaging for Response Assessment in Lymphoma: Potential and Limitation. Radio Clin N Am 46(2008)

43. FDG Uptake Varies Among Different Types of Lymphoma
Indolent lymphoma exhibit lower glucose metabolic activity and hence FDG uptake than the more aggressive ones.
Using an SUV of 10 as a cutoff, FDG-PET seperated aggressive from indolent lymphoma with a sensitivity of 71% and a specificity of 81%.
There is (sometimes large) heterogeneity between lesions of the same histologic entitiy and sometimes overlap between tumor grades.
The Impact of Fluorodeoxyglucose-Positron Emmision Tomography in Primary Staging and Patient management in Lymphoma Patients. Radiol Clin N Am 46(2008)

44. FDG Uptake Varies Among Different Types of Lymphoma
Aggressive
Indolent
Indolent
Indolent
The Impact of Fluorodeoxyglucose-Positron Emmision Tomography in Primary Staging and Patient management in Lymphoma Patients. Radiol Clin N Am 46(2008)

45. Diagnostic accuracy of FDG-PET in patients with MALT lymphoma
Overall disease detection sensitivity:
In 5 studies (132 pts),
54.4%(18/33) to 81%(21/26, 34/42)
Site dependent:
gastric MALT : 38.9%1 & 60%2
non-gastric MALT : 75%1 & 88%2
Grade dependent:
early stage disease (I-II): 42.3%1 & 79%2
advanced disease (stage III-IV): 100% 1,2
Diagnostic accuracy of PET/CT in patients with extranodal marginal zone MALT lymphoma .Eur J Haematol Sep; 79(3): Epub 2007 Jul 27
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

46. Diagnostic accuracy of FDG-PET in patients with MALT lymphoma
Large cell transformation3:
Non-transformed SUV: 3.7 (SD 1.4)
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

47. Usefulness of FDG-PET in low grade lymphomas
F/U of MALT lymphoma: specificity PET<CT
 3 False positivie: one gastritis, two beingn lung process
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

48. 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

50. 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

51. FDG-PET v.s. Bone Marrow Biopsy
Patients of Lymphoma in SKH 5 33 2 45
Low grade lymphoma
High grade lymphoma

52. 67y,M, Malignant lymphoma, small lymphocytic type, PET bone-
: Bone, iliac crest, side not specified, biopsy
--- Malignant lymphoma with marrow involvement, B cell
:Lymph node, left neck, excisional biopsy
--- Malignant lymphoma, small lymphocytic type
67y,M, Malignant lymphoma, small lymphocytic type, PET bone-

53. 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

54. 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.

55. 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 of choice for early detection of LCT and/or selection of the optimal biopsy site when transformation is suspected.

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

57. Thank You.