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Table 1 Patterns of uptake in benign neoplasms, post treatment changes and inflammatory processes which can mimic malignancy

From: How We Read Oncologic FDG PET/CT

Pathology

Pattern of uptake and comment

Benign neoplasms

 Thyroid Hurthle cell adenoma (see Fig. 10a)

Focal and intense thyroid uptake. Virtually diagnostic if there is a calcified egg-shell appearance on CT, but this feature is not always present.

 Renal oncocytoma (Fig. 10b)

Can have similar anatomic appearance on CT to renal cell carcinoma

 Parotid oncocytoma (Warthin’s tumours) (see Fig. 10c)

Focal and intense uptake in the parotid corresponding to a soft tissue nodule of increased density relative to normal parotid tissue

 Colorectal adenoma

These are typically focal and may be identified on CT if pedunculated. Depending on the clinical context, these generally warrant endoscopic evaluation as high FDG-avidity generally reflects at least high-grade dysplasia.

 Elastofibromi dorsi

Linear low-to-moderate uptake corresponding to muscle-like soft tissue abnormality in posterior chest wall [17]

Post treatment changes

 Post talc pleurodesis (Fig. 6)

Multi-focal intense uptake corresponding to high-density material (talc) on CT. Can be extensive and persist indefinitely. FDG-avidity should be very closely matched to the sites of CT density and if performed for prior pleural malignancy, sites of pleural uptake with corresponding CT density should be considered to be malignant deposits

 Post radiotherapy inflammatory change

Geographic (linear) change conforming to the radiation treatment field. Surrounding very low grade ‘haze’ of uptake within muscle and soft tissue can be apparent

 Fat necrosis

Most commonly located in mesenteric fat after therapy in patients with lymphoma [10]. Focal moderate-to-intense uptake corresponding to nodule with density between that of soft tissue and fat. Classic appearance of ‘donut shape’ abnormality sometimes apparent.

 High and symmetric tonsillar activity post chemotherapy

Commonly seen in patients with haematologic malignancies following chemotherapy, reflecting lymphoid repopulation/hyperplasia. This is commonly accompanied by lower grade reactive jugulodiagastric nodal activity that should not be misinterpreted as recurrent lymphoma.

 Appendiceal linear activity

Another region of rich lymphoid tissue, in which increased activity is seen post treatment, particularly in younger patients as described above.

 Dystrophic calcification

Following treatment some tumours calcify with pathologic correlate of xanthogranulomatosis inflammatory change. High metabolic activity can predate appearance of calcification on CT. Myositis ossificians is a variant of this process and should be considered for fusiform and focal intramuscular lesions, even in the absence of calcification. This can be an important diagnosis as this disease can mimic a sarcoma on MRI and even pathology.

 Immune related inflammatory response

Following treatment with anti-CTLA4 antibodies (eg. iplilumab) and much less commonly with PD1 inhibitors (eg. pembrozulimab) low-to-moderate uptake in lymph nodes in drainage sites from tumours can be observed. Associated homogenous diffuse splenic uptake can assist identify this pattern. Autoimmune thyroiditis, colitis, adrenalitis and hypohysitis can also be identified in this therapeutic setting.

Inflammatory processes

 Hilar and mediastinal nodal activity, pre-caval nodal activity (see Fig. 7)

A common finding with symmetry being the key finding pointing to an inflammatory/reactive aetiology. Symmetrical nodal activity of malignant aetiology is exceedingly rare. We have noted higher incidence of this reactive pattern in patients from rural areas. In association, it is quite frequent to visualise similar intensity metabolic abnormality in the subdiaphragmatic pre-caval region.

 Marrow uptake

Diffuse marrow uptake is a feature of a systemic inflammatory system and can be a feature of an infectious or septic process. It may be accompanied by mild diffuse increased splenic activity. This is also seen with Hodgkin’s lymphoma where only focal high intensity abnormalities should be interpreted as marrow infiltration.

Physiologic variants

 Anal sphincter activity

Midline, ring morphology, air-filled rectum (“polite sign”)

 Fallopian tube and ovary (see Fig. 8)

In mid-cycle it is frequent to observe bilateral curvilinear increased fallopian tube activity +/− focal unilateral ovarian follicular activity [18]

 Brown fat activity

Whilst typical features of symmetric cervical, supraclavicular, axillary and para-vertebral fat activity is easily identified, locations such as para-adrenal region should also be recognised. Administration of propranolol 10–20 mg orally 60 minutes prior FDG administration is effective in suppressing brown fat. Rarely, brown fat activation can be a clue to an underlying functional phaeochromocytoma or paraganglioma. Diffuse increased white fat uptake can also occur following administration of steroids [19].

 Large and small bowel activity

Diffuse increased uptake is seen in patients on metformin, which increases colonic glycolysis. Cessation of metformin for 48 h will reduce bowel related activity [20]; this can be a useful manoeuvre if is interfering with scan interpretation. In patients not on metformin, physiologic bowel activity can be seen as part of normal peristalsis.

 Ureteric activity

The ureter can follow a tortuous course which can result in apparent focal activity which can be difficult to distinguish from nodal activity. A delayed phase image after injection of intravenous contrast can assist by enabling confident localisation to the ureter.

 Gallbladder luminal activity

Uncommon finding but seen in patients with a delayed uptake phase who have eaten after initial uptake period; this typically occurs when there is equipment failure necessitating very delayed imaging [21].

 FDG ‘pulmonary emboli’

Iatrogenic micro-embolism can occur when blood is withdrawn from vein and mixed with FDG, and then re-injected. The complete absence of anatomic abnormality corresponding to focal very intense activity (SUV > 30) is very likely to represent this phenomenon.