We present an interesting image of a strikingly intense radioiodine accumulation of a
histologically proven pancreatic adenocarcinoma mimicking metastasis of differentiated thyroid
cancer in a 63-year-old woman with recurrence of papillary thyroid carcinoma undergoing radioiodine
therapy. This interesting image should draw attention to considering pancreatic adenocarcinoma in
radioiodine-positive pancreatic lesions

Burgard, Caroline

Ezziddin, Samer

Khreish, Fadi

Linxweiler, Maximilian

Rosar, Florian

Stahl, Phillip R.

Diagnostics

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PubMed

We present an interesting image of a strikingly intense radioiodine accumulation of a histologically proven pancreatic adenocarcinoma mimicking metastasis of differentiated thyroid cancer in a 63-year-old woman with recurrence of papillary thyroid carcinoma undergoing radioiodine therapy. This interesting image should draw attention to considering pancreatic adenocarcinoma in radioiodine-positive pancreatic lesions

PubMed Central

Strongly Radioiodine-Positive Pancreatic Adenocarcinoma Mimicking Metastasis of Differentiated Thyroid Cancer

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Citation: Rosar, F.; Burgard, C.;Linxweiler, M.; Stahl, P.R.; Khreish, F.;Ezziddin, S. StronglyRadioiodine-Positive PancreaticAdenocarcinoma MimickingMetastasis of Differentiated ThyroidCancer. Diagnostics 2022, 12, 1934.https://doi.org/10.3390/diagnostics12081934Academic Editors: Keiji Hanada andHyung-kwon ByeonReceived: 14 July 2022Accepted: 10 August 2022Published: 11 August 2022Publisher’s Note: MDPI stays neutralwith regard to jurisdictional claims inpublished maps and institutional affil-iations.Copyright: © 2022 by the authors.Licensee MDPI, Basel, Switzerland.This article is an open access articledistributed under the terms andconditions of the Creative CommonsAttribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).diagnosticsInteresting ImagesStrongly Radioiodine-Positive Pancreatic AdenocarcinomaMimicking Metastasis of Differentiated Thyroid CancerFlorian Rosar 1 , Caroline Burgard 1 , Maximilian Linxweiler 2 , Phillip R. Stahl 3, Fadi Khreish 1and Samer Ezziddin 1,*1 Department of Nuclear Medicine, Saarland University, 66421 Homburg, Germany2 Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University, 66421 Homburg, Germany3 Department of Pathology, Saarland University, 66421 Homburg, Germany* Correspondence: samer.ezziddin@uks.eu; Tel.: +49-6841-16-22201Abstract: We present an interesting image of a strikingly intense radioiodine accumulation of ahistologically proven pancreatic adenocarcinoma mimicking metastasis of differentiated thyroidcancer in a 63-year-old woman with recurrence of papillary thyroid carcinoma undergoing radioiodinetherapy. This interesting image should draw attention to considering pancreatic adenocarcinoma inradioiodine-positive pancreatic lesions.Keywords: radioiodine therapy; iodine-131; scintigraphy; pancreatic adenocarcinoma; thyroid carcinomaA 63-year-old woman with a history of papillary thyroid carcinoma (PTC) treated withthyroidectomy and ablative radioiodine (RAI) therapy presented with local recurrence andipsilateral cervical lymph node metastases of PTC. After resection of these tumor mani-festations, the patient underwent subsequent radioiodine (RAI) therapy with 3.8 GBq 131I.Whole-body scintigraphy revealed a suspicious and intense RAI-positive abdominal lesion(Figure 1A), while no pathological uptake was observed in residual cervical lymph nodessuspicious for metastases on ultrasound. Complementary [18F]FDG PET/CT (Figure 1B,C)and contrast-enhanced CT (Figure 1D) showed a corresponding mass in the pancreatic headwith intense glucose metabolism, irregular margin and decreased contrast enhancement,respectively, suspicious for a malignant pancreatic tumor. In addition, intense [18F]FDGuptake was seen in cervical lymph nodes on the left side, considered as RAI-negative lymphnode metastases. After completion of neck dissection with histopathological confirmationof PTC metastases, we tried to clarify the pancreatic mass using fine needle aspiration,but without representative results. The CA-19-9 serum concentration of >2000 IU/mLwas highly elevated. An interdisciplinary tumor board recommended the Whipple proce-dure, which was subsequently performed. On histopathological examination (Figure 2),the lesion was cytokeratin 7 (CK7)-positive, thyroglobulin-negative, thyroid transcriptionfactor-1(TTF1)-negative and classified as pancreatic adenocarcinoma.For decades, RAI therapy has been an integral part of the treatment of patients withdifferentiated thyroid cancer. RAI is used both for the ablation of remnant tissue andto detect or treat RAI-positive metastases [1,2]. The key mechanism of using RAI is theiodine uptake of thyroid tissue by the sodium-iodide symporter (NIS), whose expression ismainly retained in well-differentiated thyroid cancer cells [3]. Some extrathyroidal tissuessuch as the salivary glands and the stomach also show physiological uptake due to NISexpression [4]. Unexpected RAI uptake has been found in benign lesions and also inmalignant non-thyroid neoplasms, e.g., lung cancer, breast cancer and other malignan-cies [5–7]. It is presumed that RAI-positivity results from the functional expression of NISand tumoral inflammatory changes. We assume that this is also the explanation in ourcase of RAI-positive pancreatic adenocarcinoma. A possible differential diagnosis wouldalso have been a pancreatic metastasis of a PTC, which seems to be very rare [8,9]. ClearDiagnostics 2022, 12, 1934. https://doi.org/10.3390/diagnostics12081934 https://www.mdpi.com/journal/diagnosticsDiagnostics 2022, 12, 1934 2 of 3differentiation of pancreatic adenocarcinoma from pancreatic metastases of thyroid cancerappears to be challenging on imaging. CT signs such as irregular boundary or decreasedcontrast enhancement seem to be more indicative of pancreatic adenocarcinoma [10,11].Diagnostics 2022, 12, x FOR PEER REVIEW 2 of 4   expression [4]. Unexpected RAI uptake has been found in benign lesions and also in ma-lignant non-thyroid neoplasms, e.g., lung cancer, breast cancer and other malignancies [5–7]. It is presumed that RAI-positivity results from the functional expression of NIS and tumoral inflammatory changes. We assume that this is also the explanation in our case of RAI-positive pancreatic adenocarcinoma. A possible differential diagnosis would also have been a pancreatic metastasis of a PTC, which seems to be very rare [8,9]. Clear dif-ferentiation of pancreatic adenocarcinoma from pancreatic metastases of thyroid cancer app ars to be challenging on i aging. CT signs such as irregular boundary or decreased contrast enhancement seem to be more indicative of pancreatic adenocarcinoma [10,11]. This interesting image should draw attention to considering pancreatic adenocarci-noma in RAI-positive pancreatic lesions.  Figure 1. Strongly radioiodine (RAI)-positive and [18F]FDG-positive pancreatic adenocarcinoma. (A): 131I whole-body scintigraphy after administration of 3.8 GBq 131I, (B): MIP (maximum intensity projection) of [18F]FDG PET, (C): transversal slice of [18F]FDG PET/CT fusion and (D): transversal slice of contrast-enhanced CT. Red arrows point to RAI-positive and [18F]FDG-positive pancreatic adenocarcinoma; green arrow points to RAI-negative and [18F]FDG-positive lymph nodes metasta-ses of papillary thyroid carcinoma in the left neck. Figure 1. Strongly radioiodine (RAI)-positive and [18F]FDG-positive pancreatic adenocarcinoma.(A): 131I whole-body scintigraphy after administration of 3.8 GBq 131I, (B): MIP (maximum intensityprojection) of [18F]FDG PET, (C): transversal slice of [18F]FDG PET/CT fusion and (D): transversalslice of contrast-enhanced CT. Red arrows point to RAI-positive and [18F]FDG-positive pancreaticadenocarcinoma; green arrow points to RAI-negative and [18F]FDG-positive lymph nodes metastasesof papillary thyroid carcinoma in the left neck.Diagnostics 2022, 12, x FOR PEER REVIEW 3 of 4    Figure 2. Histopathologic images showing pancreatic adenocarcinoma. (A): Hematoxilin-Eosin (H&E) stain, magnification 100×; (B): Immunohistochemistry: tumor cells show strong positive staining for CK7, magnification 100×; (C): Immunohistochemistry: tumor cells are negative for thy-roglobulin, magnification 100×; (D): Immunohistochemistry: tumor cells are negative for TTF1, mag-nification 100×. Author Contributions: Conceptualization, F.R., C.B., F.K. and S.E.; investigation, F.R., C.B., M.L., P.R.S., F.K. and S.E.; writing—original draft preparation, F.R. and C.B.; writing—review and edit-ing, M.L., P.R.S., F.K. and S.E.; visualization, F.R., C.B. and P.R.S.; supervision, F.K. and S.E. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Institutional Review Board Statement: Ethical review and approval were waived for this study due to retrospective case report. Informed Consent Statement: Written informed consent has been obtained from the patient to pub-lish this paper. Data Availability Statement: The datasets used and analyzed in this paper are available from the corresponding author on reasonable request. Conflicts of Interest: The authors declare no conflict of interest. References 1. Haugen, B.R.; Alexander, E.K.; Bible, K.C.; Doherty, G.M.; Mandel, S.J.; Nikiforov, Y.E.; Pacini, F.; Randolph, G.W.; Sawka, A.M.; Schlumberger, M.; et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2016, 26, 1–133. https://doi.org/10.1089/thy.2015.0020. A BC DFigure 2. Histopathologic ima es showing pancreatic adenocarcinoma. (A): Hematoxilin-Eosin(H&E) stain, magnification 100×; (B): Immunohistochemistry: tumor cells show strong positivestaining for CK7, magnification 100×; (C): Immunohistochemistry: tumor cells are negative forthyroglobulin, magnification 100×; (D): Immunohistochemistry: tumor cells are negative for TTF1,magnification 100×.Diagnostics 2022, 12, 1934 3 of 3This interesting image should draw attention to considering pancreatic adenocarci-noma in RAI-positive pancreatic lesions.Author Contributions: Conceptualization, F.R., C.B., F.K. and S.E.; investigation, F.R., C.B., M.L.,P.R.S., F.K. and S.E.; writing—original draft preparation, F.R. and C.B.; writing—review and editing,M.L., P.R.S., F.K. and S.E.; visualization, F.R., C.B. and P.R.S.; supervision, F.K. and S.E. All authorshave read and agreed to the published version of the manuscript.Funding: This research received no external funding.Institutional Review Board Statement: Ethical review and approval were waived for this study dueto retrospective case report.Informed Consent Statement: Written informed consent has been obtained from the patient topublish this paper.Data Availability Statement: The datasets used and analyzed in this paper are available from thecorresponding author on reasonable request.Conflicts of Interest: The authors declare no conflict of interest.References1. Haugen, B.R.; Alexander, E.K.; Bible, K.C.; Doherty, G.M.; Mandel, S.J.; Nikiforov, Y.E.; Pacini, F.; Randolph, G.W.; Sawka,A.M.; Schlumberger, M.; et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with ThyroidNodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules andDifferentiated Thyroid Cancer. Thyroid 2016, 26, 1–133. [CrossRef] [PubMed]2. Schmidbauer, B.; Menhart, K.; Hellwig, D.; Grosse, J. Differentiated Thyroid Cancer—Treatment: State of the Art. Int. J. Mol. Sci.2017, 18, 1292. [CrossRef] [PubMed]3. Morari, E.C.; Marcello, M.A.; Guilhen, A.C.T.; Cunha, L.L.; Latuff, P.; Soares, F.A.; Vassallo, J.; Ward, L.S. Use of Sodium IodideSymporter Expression in Differentiated Thyroid Carcinomas. Clin. Endocrinol. 2011, 75, 247–254. [CrossRef] [PubMed]4. Portulano, C.; Paroder-Belenitsky, M.; Carrasco, N. The Na+/I− Symporter (NIS): Mechanism and Medical Impact. Endocr. Rev.2014, 35, 106–149. [CrossRef] [PubMed]5. Oh, J.-R.; Ahn, B.-C. False-Positive Uptake on Radioiodine Whole-Body Scintigraphy: Physiologic and Pathologic VariantsUnrelated to Thyroid Cancer. Am. J. Nucl Med. Mol. Imaging 2012, 2, 362–385. [PubMed]6. Oral, A.; Yazıcı, B.; Eraslan, C.; Burak, Z. Unexpected False-Positive I-131 Uptake in Patients with Differentiated ThyroidCarcinoma. Mol. Imaging Radionucl. Ther. 2018, 27, 99–106. [CrossRef] [PubMed]7. Yano, E.; Nakajo, M.; Jinguji, M.; Tani, A.; Kitazono, I.; Yoshiura, T. I-131 False-Positive Uptake in a Thymic Cyst with Expressionof the Sodium-Iodide Symporter: A Case Report. Medicine 2022, 101, e29282. [CrossRef] [PubMed]8. Davidson, M.; Olsen, R.J.; Ewton, A.A.; Robbins, R.J. Pancreas Metastases from Papillary Thyroid Carcinoma: A Review of theLiterature. Endocr. Pract. 2017, 23, 1425–1429. [CrossRef] [PubMed]9. Stein, R.; Harmon, T.S.; Harmon, C.E.; Kuo, E.; Ozdemir, S. Pancreatic Metastasis from Papillary Thyroid Carcinoma: Case Reportand Literature Review. Hell. J. Nucl. Med. 2021, 24, 140–148. [CrossRef] [PubMed]10. Dallongeville, A.; Corno, L.; Silvera, S.; Boulay-Coletta, I.; Zins, M. Initial Diagnosis and Staging of Pancreatic Cancer IncludingMain Differentials. In Seminars in Ultrasound, CT and MRI; WB Saunders: Philadelphia, PA, USA, 2019; Volume 40, pp. 436–468.[CrossRef]11. 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Strongly Radioiodine-Positive Pancreatic Adenocarcinoma Mimicking Metastasis of Differentiated Thyroid Cancer

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