18F-FDG PET/CT in oesophageal carcinoma- Seeing the full picture

Transcription

1 18F-FDG PET/CT in oesophageal carcinoma- Seeing the full picture Poster No.: C-1853 Congress: ECR 2015 Type: Educational Exhibit Authors: C. X. L. Leung, V. S. Jayaprakasam; Cardiff/UK Keywords: Education and training, Cancer, Staging, PET-CT, Nuclear medicine, Gastrointestinal tract DOI: /ecr2015/C-1853 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 56

2 Learning objectives To summarise the pathophysiology and the role of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in the management of oesophageal carcinoma To discuss the common, and less common, sites of extra-nodal oesophageal carcinoma metastases on PET/CT To review examples of uncommon sites of metastases and important synchronous conditions through PET/CT case stuides Background Oesophageal carcinoma th Oesophageal carcinoma is the 9 most common cancer in the UK, with more than new cases diagnosed each year. The major histological subtypes of oesophageal carcinoma are squamous cell carcinoma (SCC) and adenocarcinoma (ACE). SCC typically affects any part of the oesophagus whereas adenocarcinoma often develops from intestinal metaplasia to columnar epithelium (Barrett metaplasia) in the lower third secondary to gastrointestinal reflux disease (GORD). Risk factors such as alcohol and tobacco smoking have also been described. The carcinoma arises from the oesophageal mucosa, and its progression through the submucosal, muscularis mucosa and adventitia. Unlike the rest of the intestinal tract, there is a lack of outer serosa hence reduced resistance against local direct spread of invasive cancer cells to adjacent structures. In addition, there is a rich network of lymphatic channels in the submucosa supplies the oesophagus. The network drains to the cervical, tracheobronchial, mediastinal, gastric and coeliac lymph nodes. It is the same network that forms the basis of nodal metastasis. Oesophageal carcinoma staging Adequate staging of oesophageal carcinoma (Table 1) is vital in stratification of the most appropriate therapy. Unfortunately the 5-year survival for patients without nodal involvement is about 37% and falls to 18.4% with regional nodal disease and 3.1% in those with metastatic disease [1]. Surgical resection is considered in early-staged resectable disease, or following neoadjuvant chemotherapy or chemoradiotherapy in locally advanced disease. Accurate staging prevents futile surgery and the significant surgical morbidity and mortality associated. Page 2 of 56

3 The role of PET/CT In the UK, PET/CT is indicated in the staging and restaging of patients with oesophageal or oesophageal-gastric carcinoma, suitable for radical treatment, including patients who have received neoadjuvant treatment. There is a wealth of evidence demonstrating the superior assessment of remote nodal and systemic metastatic disease with PET/CT. Compared to the traditional anatomical techniques such as computed tomography (CT) and invasive technique such as endoscopic ultrasound (EUS), PET/CT is increasingly recognised to about change in disease staging, prognosis and ultimate management [2-3] with its combined functional and anatomical capability. The limitation of PET/CT is locoregional lymph node disease with a reported sensitivity of 51% and specificity of 84% [14] (Figure 2). There is difficulty in differentiating peritumoural lymph nodes from tumour itself and microscopic metastatic disease within lymph nodes may not demonstrate sufficient FDG uptake for detection. Furthermore, benign diseases can give rise to FDG avid lymph nodes. Site of distant metastases Previous research demonstrated common distant metastatic sites to be abdominal lymph nodes, followed by liver, lung and bone. Other less common sites reported include cervical/supraclavicular lymph nodes, adrenal gland, peritoneum, skin, pericardium, spleen, stomach, pancreas [5], cerebrum [6] and kidney [7]. Images for this section: Page 3 of 56

4 Table 1: 7th Edition of AJCC staging for oesophageal carcinoma Page 4 of 56

5 Fig. 1: Schematic representation of oesophageal anatomical and histological properties. Page 5 of 56

6 Findings and procedure details We reviewed all 18F-FDG PET/CT performed for staging of oesophageal carcinoma at our centre between September 2010 and end of August All sites of extra-nodal metastases and non-metastatic significant findings were recorded. The identification of incidental/synchronous significant findings in some cases altered patient prognosis and management. Non-regional nodal metastases th The revised 7 edition TNM staging redefines regional lymph nodes. Regional lymph nodes are classified as any perioesophageal lymph node from cervical to coeliac level. FDG avid lymph nodes outside this defined territory should be examined and suspected as distant metastases. It is important to consider non-malignant causes for nodal avidity. Figure 2. Maximum intensity projection (MIP) and fused axial image show a high left cervical non regional lymph node in a 68 year-old gentleman with distal oesophageal large cell carcinoma tumour. Further metastatic sites include the peritoneum, bone and liver. Common sites of extra-nodal metastases Liver and lung the most common extra-nodal metastatic sites [8]. Liver Like other gastrointestinal tract cancers, liver is a common site of metastatic disease due to dual blood supply via the hepatic artery and portal vein. Multiple deposits are more common than solitary deposits. Figure 3 and 4 are examples of hepatic metastases from oesophageal carcinoma. Lungs Pulmonary metastasis is the second most common extra-nodal metastatic site, accounting for about 20-52% of distant metastases [9]. Figure 5 and 6 are examples of pulmonary metastases in our patient cohort. Page 6 of 56

7 Less common and rare sites of extra-nodal metastases Bones Skeletal metastases are less common than hepatic and pulmonary metastases, with a reported frequency of 9-14% [9]. The metastases can be both lytic and sclerotic. The most common site is the spine. PET/CT is superior in detection of skeletal metastases before development radiographic abnormality. Figure 7 and 8 are two examples of FDG avid osteolytic metastases. Figure 9 is an example of a sclerotic metastasis. Adrenal glands Metastasis to the adrenal glands is via haematogenous or lymphatic spread. It has a quoted incidence of 3-12% from autopsy studies [10]. Figure 10 shows axial images demonstrating a FDG avid left adrenal nodular metastasis and thoracic vertebral body metastasis. Pleural fluid Malignant pleural effusions are rare in oesophageal carcinoma, but it is more common in the oesophageal adenocarcinoma subset than SCC. Diagnostic uncertainty exists as pleural disease can have similar CT appearance as other benign aetiologies. PET/CT provides a non-invasive method in the differentiation of benign and malignant pleural effusion than thoracocentesis [11]. We entercountered one patient with FDG avid pleural effusion in the presence of peritoneal disease (Figure 11). Peritoneum Peritoneal metastases contribute to approximately 2% of all distant metastases [19]. On the CT component, mesenteric or subserosal soft tissue nodules and intraperitoneal fluid can be seen. However microscopic disease can be missed on both CT and PET and peritoneal deposits may not be conspicuous in the absence of intravenous contrast. FDG PET increases the sensitivity of disease detection from 22.2% (CT alone) to 66.7% (PET/CT) [12]. Several patterns of tracer distribution have been described, namely focal and uniform FDG uptake due to presence of nodular and diffuse peritoneal disease respectively. Intense uptake near the anterior abdominal wall should raise the suspicion of peritoneal implant as the greater omentum often plays a role in direct spread and intraperitoneal seeding, as well as through ascites, lymphatic extension and embolic haematogenous spread [12]. Page 7 of 56

8 Figure 12 and Figure 13 are the two patients in our Cohort with peritoneal metastases diagnosed on FDG PET/CT. Cutaneous Cutaneous metastases are rare, affecting less than 1% of oesophageal carcinoma patients, and there have been only a few case reports [9]. Clinical finding of skin nodules should prompt skin biopsy. To our knowledge, there has been no case report describing PET/CT findings of cutaneous metastasis from oesophageal carcinoma. Our search yielded one patient with cutaneous metastasis, which was previously undiagnosed (Figure 14). Meninges Oesophageal disease can spread to the leptomeninges via cerebrospinal fluid (CSF), arachnoid vessels or extension from vertebral, subdural or epidural metastases. Diagnosis can be difficult as the range of signs and symptoms is broad. Lumbar puncture and CSF cytology is the gold standard test. Unfortunately, the diagnosis carries poor prognosis. Figure 15 is an example of a suspected case of meningeal metastasis. Retina Metastatic spread to the eye is extremely rare, however it is believed to be more frequent than primary tumour. The common primary malignancies are breast in women and lung in men [13]. A case report describes the PET/CT finding of a confirmed choreoretinal metastasis to be a soft tissue nodule and FDG avidity [14]. Figure 15 shows similar appearance with subtle soft tissue in the right fovea and mild to moderate FDG accumulation (arrow). Subsequent fundoscopy revealed a 1.5cm lesion in the peripheral retina in the 8 o'clock temporal quadrant, confirming the diagnosis. The patient is therefore upstage to T3N2M1. Figure 16 shows similar appearance with subtle soft tissue in the right fovea and mild to moderate FDG accumulation (arrow). Significant incidental findings Colonic uptake Segmental and diffuse colonic uptake can be physiological or due to metformin medication. This pattern of uptake is usually of low intensity. Incidental focal colonic uptake was noted in 11 patients. The literature describes unexpected focal colonic uptake Page 8 of 56

9 to encompass a range of colonic aetiologies, from inflammatory to premalignant and malignant lesions. Such findings warrant further evaluation with colonoscopy. Luboldt et al suggested a cut off of maximum standardised uptake value (SUVmax) of #5 for determining malignant lesions from non-malignant lesions [15]. Figure 17 is an example of an incidental proximal sigmoid colonic uptake (SUVmax 9.6). Subsequent colonoscopy and biopsy reviews a pre-malignant tubulovillous adenoma. Parotid gland Literature reports four patterns of FDG uptake in the parotid gland- normal physiologic uptake (< SUVmax 3.7), increased diffuse uptake, benign and malignant tumour uptake [16]. Benign tumours such as Warthin tumour can have high FDG uptake. Benign and malignant tumours can be further differentiated using metabolic tumour volume and total glycolytic activity. The patient in Figure 18 has an incidental intensely FDG avid lesion within the left parotid gland. Unfortunately follow up imaging was not performed as the patient deceased shortly following the PET/CT. Pancreas FDG uptake can be seen in a range of pancreatic conditions, from active, chronic pancreatitis, autoimmune pancreatitis to pancreatic cancer. Therefore, FDG uptake associated with pancreatic lesions should be worked up with contrast enhanced MDCT, EUS and fine-needle aspiration. The current indication of PET/CT in known pancreatic cancer is limited to pre-operative resectability workup [17]. Figure 19 is an example of a T2N2M0 oesophageal SCC (SUVmax 6.0). There is an incidental finding of an intensely avid focus (SUVmax 8.2) in the region of the pancreatic head. Subsequent contrast enhanced CT did not demonstrate definite pancreatic head mass and the patient was lost to follow up. Prostate gland Although focal prostatic FDG accumulation a rare finding, it has been described in prostate cancer, benign prostatic hyperplasia and prostatitis. Currently, there is no known SUV cut off to differentiate benign prostatic hyperplasia from prostatitis and the level of prostatic uptake depends on tumour differentiation. Seino et al concluded that FDG uptake with corresponding prostatic calcification is indicative of a benign lesion and that uptake in the absence of calcification in the peripheral zone suggests malignancy Page 9 of 56

10 [18]. Focal prostatic metabolic activity should therefore prompt digital rectal examination (DRE) and PSA analysis and biopsy, if necessary. We came across three patients with focal prostatic FDG uptake (Figure 20 & 21). Thyroid gland A recent review by Liu [19] describes diffuse FDG of the thyroid to be due to hypothyroidism under thyroxine therapy, thyroiditis, hyperthyroidism and Graves' disease and normal variance, particularly amongst cancer patients. In addition, focal uptake in the thyroid (incidentaloma) has a 25-50% risk of malignancy. More evidence is needed for a diffuse and focal pattern of uptake and it warrants further workup. Figure 22 is an example of thyroiditis on an oesophageal carcinoma staging FDG PET/ CT. Hypertrophic cardiomyopathy (HCM) The diagnosis of hypertrophy cardiomyopathy is commonly made on echocardiogram. Asymmetric septal hypertrophy is more common than apical hypertrophy and dilatedphase HCM. Uehara et al [20] concludes that 'myocardial glucose metabolism in the fasting state in HCM was noticeably increased in the hypertrophic potions', and 'uptake in the septal wall is significantly increased'. Our cohort contains a patient with known HCM with thickening of the ventricular septum. On the staging PET/CT, there is increased FDG accumulation over the thickened septum (Figure 23 and 24). Skeletal muscular activity Skeletal muscular uptake is typically symmetrical, linear in orientation, and of mild to moderate in intensity. Focal and unilateral uptake can create diagnostic uncertainty. The use of insulin prior injection of tracer can result in muscular activity. There are case reports of solitary and multiple metastases to skeletal muscle from oesophageal carcinoma. It is thought to be a rare site of metastasis but with increasing use of PET/CT, its detection is on the rise. Page 10 of 56

11 Our retrospective search yielded three cases of focal muscular uptake on oesophageal carcinoma staging FDG PET/CT (Figure 25-26). Metastasis to muscle was confirmed histologically in one patient (Figure 27). Images for this section: Page 11 of 56

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13 Fig. 2: Maximum intensity projection (MIP) and fused axial image show a high left cervical non regional lymph node in a 68 year-old gentleman with distal oesophageal large cell carcinoma tumour. Further M1 sites include the peritoneum, bone and liver. Page 13 of 56

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15 Fig. 3: A 68 year-old patient diagnosed with T3 oesophageal adenocarcinoma. There are multiple sites of extra-nodal metastases including the subcapsular region of right lobe of liver. Page 15 of 56

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17 Fig. 4: Solitary intensely metabolically active hepatic metastasis in a patient with T4 distal oesophageal SCC. Page 17 of 56

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19 Fig. 5: Staging PET/CT of this 71 year old oesophageal carcinoma shows a FDG avid right lung middle lobe nodule, hilar lymphadenopathy and skeletal metastases. PET/CT staging is T3N3M1. Fig. 6: 81 year-old patient with T3 oesophageal adenocarcinocarcinoma. Low dose CT thorax shows interstitial thickening in a bilateral lower lobe subpleural distribution and a right middle lobe subpleural nodule. This nodular metastasis is associated with moderate FDG uptake, and can be appreciated on the MIP image. Page 19 of 56

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21 Fig. 7: 77 year-old with adenocarcinoma. Right inferior pubic ramus lytic lesion with an associated soft tissue mass on axial low dose CT. Fusion image shows both components to be intensely FDG avid. Page 21 of 56

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23 Fig. 8: Axial images of a 49 year-old patient. There is a solitary FDG avid wellcircumscribed lytic lesion in the right inferior pubic ramus. Page 23 of 56

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25 Fig. 9: Axial images of a 75 year-old oesophageal adenocarcinoma patient. There is an oval sclerotic lesion in the left ilium, which is demonstrated to be intensely FDG avid and consistent with a metastasis. Page 25 of 56

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27 Fig. 10: Intensely FDG avid left adrenal nodule on axial images is in keeping with adrenal metastasis. In addition, there are thoracic vertebral body tracer avid metastases. PET/ CT staging is T3N3M1. Page 27 of 56

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29 Fig. 11: There is an intensively FDG avid circumferential bulky oesophageal tumour. In addition, there is a shallow right pleural effusion with mild to moderate tracer uptake. There is also metastatic peritoneal disease elsewhere. Page 29 of 56

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31 Fig. 12: There is generalised intraperitoneal fluid on the axial low dose CT image. As this is an unenhanced study, no definite peritoneal soft tissue can be identified. The PET image and fusion image clearly localise metabolic activity in the pelvic free fluid (arrow). Fig. 13: There are two foci of FDG uptake in the pelvis which are separate from pelvic small bowel loops. These are consistent with peritoneal deposits. Page 31 of 56

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33 Fig. 14: PET/CT of this T3 oesophageal carcinoma shows multiple sites of distant metastases, including non-regional lymph nodes, lungs, bones and adrenal gland. Incidental note is made of cutaneous FDG activity (SUVmax 5.9) and a subcutaneous soft tissue nodule over the right upper arm. This is consistent with cutaneous metastasis. Page 33 of 56

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35 Fig. 15: Axial fusion image and sagittal images of a patient with known osseous metastasis show several foci of FDG uptake in the thoracic (T11-12) and lumbar spinal canal (L2-3) with no definite CT correlate. The location is not typical of the central location expected in physiological uptake. This is therefore taken to be meningeal involvement. CSF analysis was not performed to confirm the diagnosis. Page 35 of 56

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37 Fig. 16: Axial CT and fusion images demonstrate subtle soft tissue in the right fovea and mild to moderate FDG accumulation (arrow). Page 37 of 56

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39 Fig. 17: MIP and axial fusion image of a T4N1M0 oesophageal carcinoma patient show focal FDG uptake in the proximal sigmoid colon (arrow, SUVmax 9.6). Subsequent colonoscopy and biopsy showed a tubulovillous adenoma. Page 39 of 56

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41 Fig. 18: Incidental intensely FDG avid lesion within the left parotid gland. There is no CT correlate on the unenhanced low dose CT. Unfortunately follow up imaging was not performed as the patient deceased shortly following the PET/CT. Fig. 19: T2N2M0 oesophageal SCC (SUVmax 6.0). There is an incidental finding of an intensely avid focus (SUVmax 8.2) in the region of the pancreatic head. Subsequent contrast enhanced CT did not demonstrate definite pancreatic head mass and the patient was lost to follow up. Page 41 of 56

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44 Fig. 20: Axial images demonstrate unexpected moderate metabolic activity in the left peripheral zone (SUVmax 4.8). There is no corresponding calcification on the low dose CT. Subsequent workup confirms the diagnosis of prostate cancer. Page 44 of 56

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46 Fig. 21: On the MIP image, there is FDG uptake to the left of the urinary bladder (arrow). Axial images demonstrate a focal metabolic activity (SUV max 12.8) and a corresponding hypodense lesion with faint calcific rim in the left peripheral zone/central gland. Unfortunately, the patient was lost to follow up. Page 46 of 56

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48 Fig. 22: There is symmetrical bilateral FDG accumulation in the thyroid gland (SUVmax 6.3) due to thyroiditis. Note is made of a metabolically active left cervical lymph node. Page 48 of 56

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50 Fig. 23: Figure 23 & 24: 64 year-old T3N0M0 oesophageal carcinoma patient with known asymmetric septal hypertrophy. MIP and axial images show increased intense metabolic activity (SUVmax 13.7) in an apparently thickened interventricular septum. Page 50 of 56

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52 Fig. 24: Figure 23 & 24: 64 year-old T3N0M0 oesophageal carcinoma patient with known asymmetric septal hypertrophy. MIP and axial images show increased intense metabolic activity (SUVmax 13.7) in an apparently thickened interventricular septum. Fig. 25: Figure 25 shows unexpected focal FDG accumulation posterior to left femoral neck (SUVmax 8.4). This is a possible metastatic deposit. MIP image shows hepatic metastasis. Page 52 of 56

53 Fig. 26: Intense FDG uptake (SUVmax 7.7) localises to the right gluteus medius muscle at level of sciatic notch. Biopsy of this area has not been performed. Further incidental finding of a FDG avid pancreatic head mass is noted. Page 53 of 56

54 Fig. 27: Histology proven right supraspinatus muscular metastasis from oesophageal carcinoma. Page 54 of 56

55 Conclusion th Oesophageal carcinoma is the 9 most common malignancy. Due to the lack of serosa and rich vascular and lymphatic supply, local and distant spread of disease is common. Conventional imaging technique such as contrast enhanced CT and EUS have been the mainstay of workup. In recent years, there is a wealth of evidence eliciting the superiority of FDG PET/CT in diagnosis of distant metastases and synchronous malignancies. We have demonstrated the common and less common sites of extra-nodal metastases through review of literature and examples from our centre. Furthermore, we have shown cases of synchronous malignancies which were undiagnosed pre-fdg PET/CT and significant findings that subsequently altered/ impacted on overall management. Personal information References Surveillance Epidemiology and End Results (SEER) [online]. Availabel at: [Accessed 19 Oct. 14] Chatterton BE, Ho Shon I, Baldey A, et al. Positron emission tomography changes management and prognostic stratification in patients with oesophageal cancer: results of a multicentre prospective study. Eur J Nucl Med Mol Imaging. 2009;36: Duong CP, Demitriou H, Weih L, et al. Significant clinical impact and prognostic stratification provided by FDG-PET in the staging of oesophageal cancer. Eur J Nucl Med Mol Imaging. 2006;33: von Westreenen HL, Westerterp M, Bossuyt, et al. Systematic review of the staging performance of 18F-fluorodeoxyglucose positron emission tomography in esophageal cancer. J Clin Oncol. 2004;22: Leslie E, Quint MD, Lisa M, et al. Incidence and distribution of distant metastases from newly diagnosed esophageal carcinoma. Cancer. 1995;76: Song Z, Lin B, Shao L, et al. Brain metastases from esophageal cancer: Clinical review of 26 cases. World Neurosurgery. 2014;81: Page 55 of 56

56 Sun Y, Yu X, Zhang Y. Renal metastasis after esophagectomy of esophageal squamous cell carcinoma: a case report and literature review. World J of Surg Oncology. 2014;12:165. Luketich JD, Friedman DM, Weigel TL, et al. Evaluation of distant metastases in esophageal cancer: 100 consecutive positron emission tomography scans. Ann Thorac Surg. 1999;68: Quint LE, Hepburn LM, Francis IR, et al. Incidence and distribution metastases from newly diagnosed esophageal carcinoma. Cancer. 1995;76(7): Dellaportas D, Lykoudis P, Gkiokas G, et al. Solitary adrenal metastasis from esophageal adenocarcinoma: A case report and review of the literature. Case Reports in Medicine. 2011, Article ID , 3 pages. Erasmus JJ, McAdams HP, Rossi SE, et al. FDG PET of pleural effusions in patients with non-small cell lung cancer. Am J Roentgenol. 2000;175: Suzuki A, Kawano T, Takahashi N, et al. Value of 18F-FDG PET in the detection of peritoneal carcinomatosis. European Journal of Nuclear Medicine and Molecular Imaging. 2004;31(10): Cangiarella JF, Suhrland MJ, Cajigas A, et al. Esophageal carcinoma metastatic to the retina. Acta Cytologica. 1996;40: Bahl A, Rao RR, Sharma JB. Carcinoma esophagus: A rare primary malignancy for ocular metastasis. Indian Journal of Cancer. 2010;47(4): Luboldt W, Volker T, Wiedemann B, et al. Detection of relevant colonic neoplasms with PET/CT: promising accuracy with minimal CT dose and a standardised PET cut-off. Eur Radiol. 2010;20(9): Hadiprodjo D, Ryan T, Truong MT, et al. Parotid gland tumors: preliminary data for the value of FDG PET/CT diagnostic parameters. American Journal of Roentgenology. 2012;198:W185-W190. Nguyen NQ, Bartholomeusz DF. 18F-FDG-PET/CT in the assessment of pancreatic caner: Is the contrast or a better trial needed? Journal of Gastroenterology and Hepatology. 2011;26(4): Seino H, Ono S, Miura H, et al. Incidental prostate 18F-FDG uptake without calcification indicates the possibility of prostate cancer. Oncology reports. 2014;31(4): Liu Y. Clinical significance of thyroid uptake on F18-fluorodeoxyglucose positron emission tomography. Annals of Nuclear Medicine. 2009;23(1): Uehara T, Ishida Y, Hayashida K, et al. Myocardial glucose metabolism in patients with hypertrophic cardiomyopathy: Assessment by F-18-FDG PET study. Annals of Nuclear Medicine. 1998;12(2): Page 56 of 56