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

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

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

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

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

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

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

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

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

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

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

Case 1

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

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

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.

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

Reniform shape

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

Case 1 – Lymphoid hyperplasia

Case 2

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

CXR

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

Case 3

50 y/o. female Non-specific medical history

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

Case 4

29 y/o, male With clinical Hx of sarcoidosis

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

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.

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).

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.

Case 5

26 y/o, female Right neck palpable nodes

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

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

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.

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

Case 6

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

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

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

Case 7

57 y/o, female

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

Case 8

42 y/o, female

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

Case 9

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

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

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

Case 10

44 y/o, female

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

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.

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.

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.

Thanks for attention !