Vanessa Murad1, 2, E. Edmund Kim3, 4, Jin-Chul Paeng1, Camilo Barragan5 and Gi-Jeong Cheon1
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
Department of Diagnostic Imaging, Fundacion Santa Fe de Bogotá University Hospital, Bogota, Colombia
Department of Radiological Sciences, University of California, Irvine, School of Medicine, Orange, CA, USA
Department of Nuclear Medicine and Department of Molecular Medicine, Graduate School of Convergence Science and Technology, Seoul National University College of Medicine, Seoul, Republic of Korea
Joint Department of Medical Imaging, University Health Network, University of Toronto, Toronto, ON, Canada
PET/CT is a combined system of positron emission tomography (PET) and computed tomography (CT) scanners. PET can detect abnormal metabolic activity in organs or lesions even before they show morphological changes and CT enables precise localization, so co-registration of functional and anatomic information is achieved in the same study, obtained on the same scanner . This technology, available now for at least 10 years, has allowed great advances especially in the field of oncology, and every day it opens more fields to explore in this and other multiple pathologies . Nowadays there is also the possibility of carrying out total body PET studies, which encompasses the entire body within the field of view of the scanner, allowing imaging of all the tissues and organs simultaneously. The increase in geometric coverage of total body PET and multiple adjusted parameters make the whole-body image a very sensitive study with major implications for medical imaging.
PET/CT is currently widely available in the world and many guidelines already recommend it as part of the diagnosis, staging, follow-up, or re-evaluation of various pathologies. As for PET/MR, nonspecific 18F-FDG is the most widely used an available radiotracer for PET/CT studies, and thus many other new tracers are available or under investigation, to offer better possibilities to patients and not only in the field of oncology [2, 3]. Indications for FDG PET/CT are continuously evolving according to the advances that current research allows; however, in oncology it can be useful in various stages of the disease depending on the pathology: initial diagnosis, staging, therapeutic approach, evaluation of response to treatment and recurrence. A great example, and perhaps one of the most frequently used with multiple indications is lymphoma [3, 4]. Other frequent scenarios in which it has a diagnostic utility are the evaluation of a solitary pulmonary nodule, multiple myeloma, and search for a primary tumor of unknown origin [5–7]. Its usefulness in staging due to the ability to evaluate the whole body, detect lymph node or distant metastasis, and offer some prognostic information can be extended to almost all cancer pathology, but it has been evaluated with better results in melanoma, head and neck, lung, colorectal, gynecological and esophageal cancers among others, as well as in bone and soft tissue sarcomas [3, 8–11]. Likewise, in some cases such as lung, esophageal, and colorectal cancers, it has shown great utility in radiotherapy planning with excellent results [12, 13]. Response assessment utility depends on the characteristics of the primary tumor and stage, but in lung, esophageal, and colorectal cancers, the results have been promising [10, 13, 14]. Finally, in the evaluation of recurrence, its diagnostic accuracy may also be subject to the characteristics of the primary tumor, but since a large part of the metastases are more aggressive and metabolically active, it represents a good tool for almost all tumors, especially for head and neck, lung, gynecological, and bone and soft tissue tumors. It is important to bear in mind that although it is not indicated for the diagnosis or staging of a series of non-FDG avid tumors (stomach, pancreas, hepatoma, genitourinary tract, ovary, among others), when there is a suspicion of relapse it may play an important role [3, 15, 16].
As in PET/MRI, the availability of multiple novel radiotracers has allowed great advances, especially in neuroendocrine tumors, prostate cancer, and neuro-oncology and degenerative diseases, having the same tracers previously described available for PET/CT studies .
In this chapter, we present multiple demonstrative examples of the different uses of FDG and non-FDG PET/CT, with the most relevant anatomical references for each case.
1 18F-FDG PET/CT
1.1 Head and Neck
1.1.1 Case 1
A 56-year-old female patient with frontal headaches during the last 3 months. Brain 18F-FDG PET/CT was performed for malignancy work-up. Images showed mild and irregular increased activity in the cingulate cortex and corpus callosum, at a lobulated and calcified extra axial mass, and later proved to be a meningioma (WHO grade I). The increased activity in this case may represent an artifact due to the dense and irregular calcification, rather than a definite uptake by the mass (Figs. 1 and 2).
1.1.2 Case 2
A 65-year-old woman with a history of lung squamous cell carcinoma undergoing chemotherapy, who attended her routine follow-up completely asymptomatic. 18F-FDG PET/CT was performed finding a newly developed focal hypometabolic lesion in the left parietal cortex with peripheral mild, diffuse hypometabolism, which was confirmed to be a metastatic lesion with surrounding edema on contrast MRI (Figs. 3 and 4) .
1.1.3 Case 3
A 17-year-old male patient with persistent headache and obstructive hydrocephalus on brain CT. 18F-FDG PET/CT was performed finding two lesions, one located in the suprasellar region and the other in the pineal region. Both lesions showed very low FDG uptake and heterogeneous density with cystic components and calcifications. Biopsy revealed the diagnosis of bifocal germinoma, which can be found in 2–18% of cases. It remains unclear if this represents synchronous tumors or metastatic disease, but it is known that these patients have a worse prognosis (Fig. 5) .
1.1.4 Case 4
A 64-year-old man with occasional headache. Initial brain CT revealed an expansive heterogeneous lesion in the clivus, so 18F-FDG PET/CT was performed to determine its nature. Images showed minimal diffusely increased activity in an expansive, well-defined, lytic lesion in the superior and central aspect of the clivus. These findings favored the diagnosis of a chordoma, which differs from chondrosarcoma because the latter generally presents greater FDG uptake and a chondroid matrix with typical calcifications in rings and arcs (Fig. 6) .
1.1.5 Case 5
A 65-year-old man with progressive hoarseness. In otolaryngology consultation, physical examination and laryngoscopy revealed a tiny lesion in the right side of the glottis. Biopsy confirmed a squamous cell carcinoma, so 18F-FDG PET/CT scan was requested for staging. Images showed focal increased uptake in the right side of the glottis, at the site of the primary tumor, which represents a metabolic change without an evident anatomical abnormality. No hypermetabolic lymph nodes or distant metastases were found  (Figs. 7 and 8).
1.1.6 Case 6
A 45-year-old woman with progressive enlargement of the thyroid gland and occasional pain. Ultrasound and ultrasound-guided biopsy confirmed the diagnosis of diffuse, large B-cell lymphoma, so 18F-FDG PET/CT was performed for staging. Images showed marked increased activity in the diffusely enlarged thyroid gland. No hypermetabolic lymph nodes or distant metastasis were noted (Fig. 9) .
1.1.7 Case 7
An 85-year-old man with odynophagia. Physical examination revealed enlargement and ulceration of the right palatine tonsil and biopsy confirmed the diagnosis of a squamous cell carcinoma, so FDG was performed for staging. Images showed focal increased activity in the right palatine tonsil at the primary tumor, as well as two hypermetabolic metastatic lymph nodes in the right upper neck, level II. Note the obliteration of the right parapharyngeal space, which is one of the indirect signs of lesions at this location (Fig. 10) .
1.2.1 Case 1
A 25-year-old man with rapid weight loss. Initial studies showed high alpha-fetoprotein (AFP) and a mediastinal mass in the chest X-ray, so 18F-FDG PET/CT was performed on suspicion of a germ cell tumor. Images showed a well-defined, cystic-necrotic anterior mediastinal mass, with a peripheral hypermetabolic solid component, which suggested a more aggressive behavior favoring a non-seminomatous tumor. Posterior biopsy confirmed the diagnosis of a yolk sac tumor (Fig. 11).
1.2.2 Case 2
A 43-year-old woman with occasional dyspnea and chest tightness. Chest X-ray and CT were performed, finding a mediastinal mass and considering lymphoma or thymoma as differential diagnoses, so 18F-FDG PET/CT was performed. Images showed an irregular, well-defined anterior mediastinal mass, with an adequate cleavage plane with the vascular structures, with mild homogeneous FDG uptake. With these findings, the diagnosis of low-grade thymoma was suggested and biopsy confirmed a type AB thymoma (Fig. 12) .
1.2.3 Case 3
A 50-year-old man with progressive dyspnea and chest pain. Chest X-ray and CT showed an anterior mediastinal mass, so 18F-FDG PET/CT was performed. Images showed a large, irregular, but not infiltrative, mild, metabolically active anterior mediastinal mass with dystrophic calcifications. Extensive pleural invasion with the same mild, diffuse uptake as the primary tumor was observed. The findings suggested a low-grade thymoma and later biopsy confirmed a thymoma type B1 (Fig. 13) .
1.2.4 Case 4
A 58-year-old patient with atypical and occasional chest pain who underwent an echocardiogram, finding a poorly defined mediastinal lesion. Contrast CT and 18F-FDG PET/CT revealed a poorly defined infiltrative mediastinal lesion with high and homogeneous FDG uptake, as well as a right inferior pleural seeding. The findings were suspicious of a high-grade thymoma, and postsurgical pathology of the pleural lesion confirmed the diagnosis of a thymoma type B3 (Fig. 14) .
1.2.5 Case 5
A 58-year-old female patient with a history of diffuse, large B-cell lymphoma with lymph node involvement, treated with chemotherapy achieving complete metabolic response. In the last 18F-FDG PET/CT checkup, multiple new hypermetabolic mediastinal lymph nodes were noted, with a distribution in bilateral hilar, subcarinal, and right paratracheal areas (lambda sign). Also, diffusely increased activity was detected in the soft tissues of the lower lumbar region and left gluteal region. Given the suspicion of lymphoma recurrence, biopsy of both the lymph nodes and the soft tissue lesions was performed, where chronic granulomatous changes consistent with sarcoidosis were reported (Fig. 15).
1.2.6 Case 6
A 51-year-old man with dyspnea and chest pain, with normal chest X-ray. Suspecting pulmonary embolism (PE), chest CT angiography was requested, finding an extensive filling defect in the pulmonary trunk, the entire right pulmonary artery and the branch for the superior lobe, as well as in the proximal left pulmonary artery. However, the filling defect was irregular and showed enhancement, indicating that it was more likely a soft tissue lesion or a tumor thrombus, so 18F-FDG PET/CT was performed. Images showed marked increased activity in the irregular intravascular lesion without other findings. A primary angiosarcoma of the pulmonary artery was suggested as the diagnosis, which was later confirmed with biopsy (Fig. 16) .
1.2.7 Case 7
A 28-year-old woman with occasional chest pain. Chest X-ray was performed finding a mediastinal mass, so 18F-FDG PET/CT was ordered for further evaluation. Initial images (superior) showed intense FDG uptake in a bulky anterior mediastinal mass, as well as metabolically active enlarged lymph nodes at the lower neck and right cardiophrenic and left retroperitoneal areas. The diagnosis of primary mediastinal B-cell lymphoma was confirmed and first-line chemotherapy was started. Two cycles later, in the follow-up 18F-FDG PET/CT, complete metabolic resolution of the previously visualized lesions was observed. This unique and rare subtype of non-Hodgkin lymphoma occurs in only 2–3% of cases (Fig. 17) .
1.2.8 Case 8
A 54-year-old woman with diagnosis of infiltrating ductal carcinoma of the left breast and suspected axillary lymph node metastases. As part of staging, 18F-FDG PET/CT was performed. Images showed diffuse, increased activity in the left breast, predominantly toward the lower outer quadrant, where the primary lesion was confirmed. Furthermore, multiple metabolically active lymph node metastases were observed at all left axillary levels, supraclavicular region, and mediastinum. In the normal right breast parenchyma, diffuse FDG uptake is perceived, which represents normal physiologic activity frequently seen in premenopausal women (Figs. 18 and 19) .
1.2.9 Case 9
A 48-year-old woman with progressive pain, redness, and hardening of the left breast, associated with bloody nipple discharge. Ultrasound and biopsy were performed confirming the diagnosis of an inflammatory carcinoma and 18F-FDG PET/CT was requested for staging. Images showed a metabolically active multifocal left breast cancer with increased activity at marked skin thickening. Multiple hypermetabolic metastatic lymph nodes were also observed, predominantly in the axillary level I, as well as same-side interpectoral area and internal mammary chain (Fig. 20) .
1.2.10 Case 10
An 80-year-old male patient with history of scalp angiosarcoma, treated with surgery and chemotherapy. Follow-up 18F-FDG PET/CT was performed 8 months after surgery and showed multiple new lesions, including a small left upper lobe pneumothorax chamber, increased activity at a right middle lobe ground glass opacity, and multiple randomly distributed, thin-walled cystic lesions, some with peripheral FDG uptake. Hypermetabolic lymph nodes were also noted in the subcarinal and bilateral hilar areas. Ultrasound-guided endobronchial biopsy revealed the suspected diagnosis: angiosarcoma metastasis (Fig. 21) .
1.2.11 Case 11
A 43-year-old male patient, currently smoker, who presented with persistent productive cough with occasional drops of blood. 18F-FDG PET/CT was performed, finding multiple metabolically active solid nodules with random distribution in both lungs, with two dominant lesions at the right lung, one of them with central cavitation. Ultrasound-guided endobronchial biopsy confirmed the diagnosis of primary pulmonary melanoma at the right upper lobe, with multiple bilateral metastases. Additionally, a metastatic mediastinal lymph node conglomerate with necrotic components was found involving levels 7, 10R, and 11R, as well as a right neck level II metabolically active lymph node (Figs. 22 and 23) .
1.2.12 Case 12
A 74-year-old woman with significant weight loss. Chest X-ray showed a mediastinal mass, so 18F-FDG PET/CT was performed. Images revealed a high metabolically active left hilar mass with multiple mediastinal and lower neck metastatic lymph nodes, as well as a retroperitoneal lymph node. The diagnosis of a primary lung cancer was suggested, but transbronchial biopsy confirmed a diffuse, large B-cell lymphoma. Findings that favor the diagnosis of lymphoma include the presence of a bulky mass with bulky lymph nodes, which surrounds or encases the bronchial and vascular structures, without compressing or invading them. Also, the presence of lymph nodes in other locations can give a clue, although there is no definitive finding to differentiate them from metastasis of a primary lung tumor (Fig. 24) .
1.2.13 Case 13
A 75-year-old female patient with history of breast cancer and recent diagnosis of small cell lung cancer, in treatment with immunotherapy (atezolizumab). Follow-up 18F-FDG PET/CT showed increased size of metabolically active primary tumor in the left upper lobe, with a peripheral area of necrosis, as well as increased activity in two lesions that were previously not so evident, one in the left diaphragmatic crus and other in the right perirenal area. At this time, the possibility of a pseudo-progression due to the ongoing treatment was considered, which was confirmed with the following follow-up, where metabolic response of all the described lesions was observed (Fig. 25) .
1.2.14 Case 14
A 59-year-old woman with a history of breast cancer 25 years ago. She attended due to progressive dyspnea and chest radiograph showed diffuse opacity of the left lung, so 18F-FDG PET/CT was performed. Images showed marked increased activity in diffuse nodular pleural thickening of the left lung, with involvement of the major fissure; there was no significant pleural effusion or mediastinal lymph nodes. Pleural mesothelioma was initially suspected, but biopsy confirmed the diagnosis of pleural metastases from breast carcinoma. Although it is not the most frequent site of metastasis, the pleura can be the only manifestation of recurrent disease in up to 40% of cases (Fig. 26) .
1.2.15 Case 15
A 54-year-old woman with dyspnea and fatigue for several months. Chest X-ray was performed, finding bilateral pleural effusion and cardiomegaly. Given the suspicion of pulmonary embolism, contrast-enhanced CT was performed, finding a soft tissue mass involving the right ventricle, superior vena cava, and innominate veins, as well as mild pericardial effusion. 18F-FDG PET/CT was performed for whole body evaluation, observing moderate, diffuse, increased activity in the soft tissue lesion described in tomography. Final diagnosis was consistent with a superior vena cava angiosarcoma (Fig. 27) .
1.2.16 Case 16
A 34-year-old male patient with progressive odynophagia and night sweats. 18F-FDG PET/CT was performed finding a metabolically active mass in the oropharynx, consistent with biopsy-confirmed diffuse, large B-cell lymphoma; no other hypermetabolic lesion suggestive of lymphoma involvement was found. However, two incidental cardiac findings were found: (1) diffuse increase in FDG uptake at the right ventricular wall, secondary to pulmonary hypertension and (2) focal FDG uptake at the upper portion of the interventricular septum, protruding into the left ventricle. The last finding corresponds to an asymmetric or isolated septal hypertrophy, also known as interventricular septal bulge (Fig. 28) .
1.2.17 Case 17
An 18-year-old man with diagnosis of Hodgkin lymphoma with inguinal lymph nodes involvement, undergoing treatment with first-line chemotherapy. After the second cycle, follow-up 18F-FDG PET/CT was performed, where complete resolution of the previously visualized lymph nodes was observed. However, as a new finding, increased activity was found at the aortic root, consistent with inflammatory changes (aortitis), more likely related to the established treatment (Fig. 29) .
1.2.18 Case 18
A 32-year-old man diagnosed with Hodgkin lymphoma with nodal involvement. 18F-FDG PET/CT was performed for end-of-therapy follow-up, where complete resolution of previously identified lymph nodes was found, consistent with metabolic complete response. However, increased activity was found in the bilateral neck, supraclavicular fossae, and thoracic paravertebral areas, corresponding in the CT to fat with no underlying lesion. This finding represents metabolically active adipose tissue or brown fat and is a common finding specially related to cold temperatures (Fig. 30) .
1.2.19 Case 19
A 71-year-old man with progressive fatigue, weight loss, and dyspnea, as well as fever in the last 3 weeks. Chest X-ray and CT did not show any remarkable findings, so 18F-FDG PET/CT was performed to rule out occult malignancy. Images showed multiple hypermetabolic mediastinal lymph nodes in paratracheal and bilateral hilar areas, as well as markedly increased activity in the enlarged spleen. Widespread FDG uptake was noted in both lungs without any CT abnormality. Transbronchial lymph node biopsy confirmed the diagnosis of diffuse, large B-cell lymphoma. Although the initial bronchoalveolar lavage only showed increased alveolar macrophages, without evidence of abnormal lymphocytes, in the follow-up study all pulmonary findings disappeared as did the lymph nodes and splenomegaly. There are some cases with similar lung findings reported in the literature, where the histopathologic diagnosis of intravascular large B-cell lymphoma has been confirmed with the presence of large atypical lymphocytes in the lumina of the capillary vessels, so in this case, these findings and their evolution most likely represent lymphoma involvement (Fig. 31) .
1.2.20 Case 20
A 62-year-old woman with a history of Takayasu arteritis, who consulted for acute thoracoabdominal pain. Other possible causes of pain were ruled out, and 18F-FDG PET/CT was performed to assess disease activity and thus define treatment. Images showed generalized increased activity in the walls of the thoracoabdominal aorta, with involvement of the main cervical trunks, the iliac bifurcation, and the proximal iliac arteries. These findings indicate an active acute phase of the disease. No areas of stenosis or aneurysmal dilatation were observed (Fig. 32) .
1.2.21 Case 21
A 52-year-old male patient with a known diagnosis of Langerhans cell histiocytosis (LCH). After almost 2 years asymptomatic, he presented with lower back pain, so imaging studies including 18F-FDG PET/CT were performed. Images showed diffusely increased activity in a permetative and aggressive lytic lesion involving the left iliac bone and sacral ala, as well as a smaller lesion with same characteristics in the right iliac bone; both lesions corresponded to LCH involvement. Additionally, minimal diffuse increased uptake was observed in both lungs, with multiple small irregular cystic lesions and septal thickening, with findings also corresponding to LCH involvement (Fig. 33).
1.3 Abdomen and Pelvis
1.3.1 Case 1
A 73-year-old man with a history of occasional dysphagia and weight loss. Upper digestive tract endoscopy showed suspicious findings of malignancy, so 18F-FDG PET/CT was performed. Images showed focal increased activity at the distal third of the esophagus in a concentric solid mass, which was later confirmed to correspond to a squamous cell carcinoma. No abnormal lymph nodes or distant metastasis were noted (Fig. 34) [14, 36].
1.3.2 Case 2
A 26-year-old female patient with occasional chest pain and reflux. Chest X-ray showed a mediastinal mass, so 18F-FDG PET/CT was performed, finding markedly increased activity in a prominent wall-based mass at the distal esophagus, with exophytic growth and no lumen obstruction or mucosal involvement. The diagnosis of a gastrointestinal stromal tumor (GIST) was considered as the first possibility, which was later confirmed with biopsy (Fig. 35) .
1.3.3 Case 3
A 49-year-old man with chronic upper abdominal pain and weight loss. Endoscopic evaluation and biopsy were performed, finding an advanced gastric adenocarcinoma, so 18F-FDG PET/CT was performed for staging. Images showed increased metabolic activity in the gastric fundus and body at irregular wall thickening, consistent with the primary tumor. Metabolically active enlarged lymph nodes at the gastro-hepatic and right retrocrural areas were also noted (Figs. 36 and 37) .
1.3.4 Case 4
A 54-year-old male patient with weight loss and night sweats during the last 2 months. 18F-FDG PET/CT was performed on suspicion of malignancy, where a bulky metabolically active mass was found in the stomach, as well as multiple prominent hypermetabolic retroperitoneal lymph nodes. With these findings, a lymphoma was suggested, and the subsequent biopsy confirmed the diagnosis: diffuse, large B-cell lymphoma (Fig. 38) .
1.3.5 Case 5
A 79-year-old woman with acute abdominal pain and vomiting. Contrast-enhanced CT was performed, finding a partial low-grade bowel obstruction with transition zone at the distal ileum. After managing the acute condition, 18F-FDG PET/CT was performed, finding a metabolically active concentric mass at the distal ileum with lumen reduction, without adjacent mesenteric fat stranding or other findings. Surgical resection was performed, confirming a primary large B-cell lymphoma (Fig. 39) .
1.3.6 Case 6
A 38-year-old man who attended an annual checkup completely asymptomatic. Colonoscopy and biopsy revealed a colon adenocarcinoma. 18F-FDG PET/CT was performed for staging, finding a focal increased activity in the distal transverse colon corresponding to the primary tumor, as well as a metabolically active mesenteric lymph node metastasis. No distant metastases were noted (Fig. 40) .
1.3.7 Case 7
A 52-year-old woman with a history of constipation and occasional rectal bleeding. 18F-FDG PET/CT was performed to rule out malignancy. Images showed focal increased activity at the sigmoid colon suggesting a polypoid lesion. Colonoscopy and biopsy were performed confirming the diagnosis of sigmoid colon adenocarcinoma. No abnormal hypermetabolic lymph nodes or metastasis were detected (Fig. 41) .
1.3.8 Case 8
A 60-year-old man with a history of occasional rectal bleeding worsened in the last 2 weeks. Clinical examination and rectoscopy were performed and confirmed the presence of a mass, so 18F-FDG PET/CT was performed. Images showed a focal increased activity in the lower rectum at the primary tumor site, with no other hypermetabolic lesions suggesting metastasis. Final biopsy confirmed an adenocarcinoma (Fig. 42) .
1.3.9 Case 9
A 71-year-old man with a history of ascending colon adenocarcinoma 2 years ago, treated with laparoscopic right hemicolectomy and chemotherapy. He attended due to nodular feeling at the umbilical port scar where ultrasound showed a suspicious mass, so 18F-FDG PET/CT was performed. Images showed a metabolically active spiculated lesion involving the subcutaneous tissue and both rectus abdominis muscles. Biopsy confirmed the presence of metastatic adenocarcinoma, probably secondary to a seeding during prior surgery (Fig. 43) .