1. Imaging Mimics of Lymphoma on PET/CT
葉加祿醫師 新光醫院

2. Lymphadenopathy (1)
Lymphadenopathy is a common clinical finding with a broad differential diagnosis, and is frequently benign.
In one series of 543 patients for further evaluation of lymphadenopathy,
only 17.5% had an underlying malignant disorder (11.4% : lymphoproliferative disorder and 6.1% : metastatic solid tumor.
The other had benign reactive lymphadenopathy and miscellaneous non-neoplastic diseases.
Br J Cancer 2003;88:354–361

3. Lymphadenopathy (2) Localized lymphadenopathy
may suggest a local infection
supraclavicular, axillary, or epitrochlear LNs have a greater probability of malignancy
Metastatic solid tumors
Generalized lymphadenopathy
particularly concerning for lymphoma or a systemic disease that mimics lymphoma

4. Causes of Lymphadenopathy: CHICAGO
Cancers
Hypersensitivity syndromes
Infections
Connective tissue diseases
Atypical lymphoproliferative disorders
Granulomatous disorders
Other unusual causes of lymphadenopathy

5. Cancers Hematologic malignancies:
Hodgkin disease, non-Hodgkin lymphoma, acute and chronic leukemia, multiple myeloma
Metastatic “solid” tumors:
breast, lung, renal cell, prostate, other

6. Hypersensitivity syndromes
Drug sensitivity:
Anticonvulsants: phenytoin, carbamazepine,
Antibiotics: Sulfas, penicillins, erythromycin
Aspirin    
Allopurinol
Silicone reaction
Vaccination related
Graft-vs-host disease

7. Infections
Viral:
infectious mononucleosis (Epstein-Barr virus), cytomegalovirus, infectious hepatitis, adenovirus, herpes zoster, HIV
Bacterial:
cutaneous infections (staphylococcus, streptococcus), cat-scratch fever, tuberculosis, atypical mycobacteria, syphilis
Chlamydial: lymphogranuloma venereum
Protozoan: toxoplasmosis
Mycotic: histoplasmosis, coccidioidomycosis

8. Connective tissue diseases (Autoimmune diseases)
Rheumatoid arthritis,
Systemic lupus erythematosus,
Dermatomyositis,
Mixed connective tissue disease
Sjögren syndrome

9. Atypical lymphoproliferative disorders (with potential evolution to a more aggressive malignancy)
Angiofollicular (giant) lymph node hyperplasia (Castleman disease)
Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)
Lymphomatoid granulomatosis
Lymphomatoid papulosis

10. Granulomatous disorders
Sarcoidosis
Tuberculosis
Histoplasmosis
Mycobacterial infections
Cryptococcus
Silicosis
Berylliosis
Cat-scratch fever

11. Other unusual causes of lymphadenopathy (BENIGN REACTIVE LYMPHOPROLIFERATIVE DISORDERS)
Inflammatory pseudotumor of lymph nodes
Histiocytic necrotizing lymphadenitis (Kikuchi’s disease)
Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)
Vascular transformation of sinuses
Progressive transformation of germinal centers

12. Case 1

13. 39 y/o, male
Palpable nodules over bilateral neck
Flu-like symptom in recent days

15. (according to excisional Bx of left neck LN)
Lymphoma ?
Lymphoid hyperplasia !
(according to excisional Bx of left neck LN)

16. Nodal FDG uptake is non-specific finding and could be seen in
lymphoid hyperplasia
lymphadenitis
benign and atypical lymphoproliferative disorder
malignancy
Radiologic findings shown by the CT images of FDG PET/CT may be helpful.

17. Radiologic sign (1) Signs suggestive of a benign etiology:
measures < 1 cm in diameter
has a smooth, well defined border
shows homogeneous density
Normal reniform shape : C-shape thin & even cortex and intact central fatty hilum

18. Reniform shape

19. Radiologic sign (2) Signs suggestive of a malignant etiology:
Nodal size > 2 cm (insensitive)
Loss of the central fatty hilum or eccentric hilum
Eccentric cortical thickening/lobulation
Abnormal lymph node shape: Round node
Central nodal necrosis: A central area of low “water” attenuation
Extracapsular spread : Irregular nodal margin with infiltration around

20. Case 1 – Lymphoid hyperplasia

21. Case 2

22. 51 y/o, male
Bilateral hilar enlargement noted incidentally by CXR

23. CXR

24. Lymphoma ?
Sarcoidosis !
according to mediastinoscopic Bx of mediastinal LN :
(Noncaseating granulomatous inflammation)
&
regular clinical F/U

25. Case 3

26. 50 y/o. female
Non-specific medical history

27. Lymphoma ? Sarcoidosis ! according to excisional Bx of right neck LN :
(chronic granulomatous inflammation)
&
regular clinical F/U)

28. Case 4

29. 29 y/o, male
With clinical Hx of sarcoidosis

33. Lymphoma ? Sarcoidosis ! according to his clinical history:
sarcoidosis diagnosed with F/U at VGH

34. Sarcoidosis (1)
An inflammatory multisystem granulomatous disease of unknown etiology
Formation of noncaseating epithelioid granulomas in tissues without another known cause for granulomatous disease.
-- a diagnosis of exclusion.
Diagnosis is established when the clinical and radiographic findings are supported by histologic evidence.

35. Sarcoidosis (2)
Most present with bilateral hilar lymphadenopathy, lung parenchymal disease, and eye or skin lesions.
At diagnosis, 50% are asymptomatic, 25% complain of cough or dyspnea, 25% have eye symptoms or skin lesions.
Can affect any organ :
lung (90%), lymph node (75~90%), liver (60~90%), spleen (50~60%), joint (25~50%), bone marrow (15~40%), salivary gland (10%), heart (5%), nervous system (5%), and kidney (rare).

36. Sarcoidosis (3)- Radiologic findings
Typical finding:
bilateral hilar and/or mediastinal LAPs
Atypical finding:
mediastinal LAPs unaccompanied by hilar LAP, isolated unilateral hilar LAP
Dytrophic calcification of involved LNs (related to duration of disease). -- amorphous, punctate, popcorn-like, eggshell.

37. Case 5

38. 26 y/o, female
Right neck palpable nodes

39. Lymphoma ? Kikuchi’s disease ! (Histiocytic necrotizing lymphadenitis)
according to excisional Bx of neck LN

40. Kikuchi’s disease (1) A self-limited, benign, reactive lymphadenitis
Clinically, characterized most commonly by
posterior cervical lymphadenopathy
flu-like prodrome with fever (50%)
resolve spontaneously within several weeks to months
The etiology of Kikuchi’s disease remains unclear

41. Kikuchi’s disease (2)
Diagnosis is confirmed only by excisional biopsy of lymph node.
Histological findings,
necrosis with nuclear debris (karyorrhexis)
proliferation of histiocytes with crescentic nuclei.
Treatment is generally conservative. Steroids may be used for severe symptoms.

42. Kikuchi’s disease (3) Lymphadenopathy of Kikuchi’s disease:
One location in 83% of patients, although multiple nodal chains may be occasionally involved
Cervical nodes are affected in 80% of patients (60~70% involve posterior triangle cervical nodes)
Less commonly affected nodes : axillary, mediastinal, celiac, abdominal, inguinal location.
The nodes tend to be 2~3 cm in diameter, although larger lymph nodes may be seen

43. Case 6

44. 57 y/o, female
Fever of unknown origin
BWL, general weakness

46. Lymphoma ? Tuberculosis ! according to sputum TB culture : (+) and
post anti-TB treatment follow up PET : markedly interval resolution

47. 1st PET before anti-TB treatment
F/U PET After anti-TB treatment for 2 months

48. Case 7

49. 57 y/o, female

50. Systemic lupus erythematosus (SLE) !
Lymphoma ?
Systemic lupus erythematosus (SLE) !
(according to clinical history and follow up at our hospital)

51. Case 8

52. 42 y/o, female

53. Systemic lupus erythematosus (SLE) !
Lymphoma ?
Systemic lupus erythematosus (SLE) !
(according to clinical history and follow up at our hospital)

54. Case 9

55. 65 y/o, female,
(1) history of left breast cancer s/p MRM 1+ month ago,
(2) history of RA for 20+ years ago with regular medical control and s/p operation for RA joints

56. Lymphoma ? Rheumatoid arthritis (RA)
(according to clinical history and follow up at our hospital)

57. Autoimmune diseases Most common associated with lymphadenopathy
Rheumatoid arthritis
Systemic lupus erythematosus
Sjogren’s syndrome
Lymph node pathology generally shows reactive lymphoid hyperplasia

58. Case 10

59. 44 y/o, female

61. Infectious mononucleosis !
Lymphoma ?
Infectious mononucleosis !
(according to clinical diagnosis and follow up at other hospital)

62. Infectious mononucleosis (1)
Most common cause : Epstein-Barr virus infection.
Most patients are asymptomatic. Non-specific symptoms include fatigue, malaise, fever, sorethroat, nausea and anorexia.
Early signs: fever, lymphadenopathy, pharyngitis, rash, and/or periorbital edema.
Late signs: hepatomegaly, splenomegaly, palatal petechiae.
Presence of typical syndrome and positive result on a heterophilic antibody test (Monospot test) confirm the diagnosis.

63. Infectious mononucleosis (2)
Lymphadenopathy in infectious mononucleosis:
Any or all chains may be enlarged, bilateral posterior cervical adenopathy is most common
Always bilateral and symmetrical
Splenomegaly is usually accompanied by lymphadenopathy
Generalized adenopathy with prominent splenomegaly should include EBV infectious mononucleosis in the differential diagnosis.

64. Hypermetabolic adenopathy seen frequently in the FDG PET images – Imaging mimics of lymphoma
In the case of more generalized lymphadenopathy, in addition to the more common lymphomas, benign etiologies & benign and atypical lymphoproliferative disorders need to be considered.
Diagnosis only on basis of PET findings is almost impossible. Clinical, laboratory, radiologic and histopathologic findings should be included for final diagnosis.

65. Thanks for attention !