# Pancreas as Delayed Site of Metastasis from  Papillary Thyroid Carcinoma

Authors: Mutahir A. Tunio; Mushabbab AlAsiri; Khalid Riaz; Wafa AlShakweer
Journal: Case Reports in Gastrointestinal Medicine
 (2013)

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## Abstract

Introduction. Follicular variant (FV) papillary thyroid carcinoma (PTC) has aggressive biologic behavior as compared to classic variant (CV) of PTC and frequently metastasizes to the lungs and bones. However, metastasis to the pancreas is extremely rare manifestation of FV-PTC. To date, only 9 cases of PTC have been reported in the literature. Pancreatic metastases from PTC usually remain asymptomatic or manifest as repeated abdominal aches. Associated obstructive jaundice is rare. Prognosis is variable with reported median survival from 16 to 46 months. Case Presentation. Herein we present a 67-year-old Saudi woman, who developed pancreatic metastases seven years after total thyroidectomy and neck dissection followed by radioactive iodine ablation (RAI) for FV-PTC. Metastasectomy was performed by pancreaticoduodenectomy followed by sorafenib as genetic testing revealed a BRAF V600E mutation. She survived 32 months after the pancreatic metastasis diagnosis. Conclusion. Pancreatic metastases are rare manifestation of FV-PTC and are usually sign of extensive disease and conventional diagnostic tools may remain to reach the diagnosis.


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## Body

## 1. Introduction

Thyroid cancer is the commonest endocrine malignancy, presenting with 23 500 new cases per year in the United States and European Union, respectively [1, 2]. Differentiated thyroid carcinoma (DTC) is the most frequently diagnosed cancer among women in the Middle East, behind only breast cancer, and accounting for more than 10% of all cancers among women in Saudi Arabia [3].Papillary thyroid carcinoma (PTC) is the most frequent form of DTC and the follicular variant of PTC (FV-PTC) is more aggressive than the classic variant of PTC. It differs from classical PTC in being follicular growth pattern, higher prevalence of tumor encapsulation, angiovascular invasion, and poorly differentiated areas and a lower rate of lymph node metastases [4].Pancreas is an extremely rare site of metastasis of PTC. To date, only 9 cases of pancreatic metastasis secondary to PTC have been reported in the literature.Herein we present a 67-year-old Saudi woman, who developed pancreatic metastasis seven years after total thyroidectomy and neck dissection followed by sorafenib for FV-PTC.


## 2. Case Presentation

In November 2009, a 67-year-old Saudi woman presented in our clinic for her routine visit with the complaints of abdominal pain and indigestion.  She had noticed these complaints for 2 months and these have been occurring frequently over 2 weeks, for which she was taking antispasmodics and nonsteroidal anti-inflammatory drugs (NSAIDs), but with minimal improvement. Her previous medical history revealed hypertension and diabetes since last 20 years which were controlled on medications. She had no history of smoking and her weight was stable.  Her past surgical history showed that she underwent total thyroidectomy and lymph node dissection for follicular variant papillary thyroid carcinoma pT2N1cM0 (Figure1) in March 2002, followed by radioactive iodine (RAI) ablation 150 mCi in May 2002, and RAI ablation 150 mCi in July 2003 for raised serum thyroglobulin levels (39.3 ng/mL).Computed tomography of neck showing diffuse enlargement of right lobe of thyroid, came out as papillary follicular cell variant thyroid carcinoma pT2N1.
(a)
(b)On physical examination, she was in good general condition and her vitals were stable. Per abdomen examination revealed deep tenderness in epigastrium; however, there was no palpable mass or visceromegaly. There was no other palpable cervical lymphadenopathy and examination of chest, heart, nervous system, and pelvic was normal. Clinical differential diagnosis was chronic pancreatitis, primary pancreatic adenocarcinoma, or metastasis.  Her hematological, renal, and liver function tests, tuberculin, serum electrolytes, and thyroid stimulating hormone (TSH) and thyroxin (T4) were found within normal limits. Serum tumor markers, carcinoembryonic antigen (CEA), and cancer antigen 19-9 were also normal; however, serum TG levels were raised, that is, 672.8 ng/mL (normal: 5–25 ng/mL). Computed tomography (CT) of abdomen showed decreased  enhancement  of  the  neck,  body,  and  tail  of  the  pancreas;  while  enhancement  of the  pancreatic head appeared  normal and there were bilateral multiple pulmonary metastases.  Whole body iodine scintigraphy was noniodine avid. Magnetic Resonance Cholangiopancreatography (MRCP) revealed  a  small  hypovascular  lesion  in  the  pancreatic  neck  measuring1.8×1.5 cm. It showed  low  signal  intensity  in  both  T1  and  T2  with  no  enhancement  in  the  arterial  phase  and  faint  enhancement  in  delayed  sequences. Mass was  abutting  the  superior mesenteric vein (SMV) and  caused  narrowing  to  its  caliber  below  the  confluence  with  splenic  vein; however, superior mesenteric artery (SMA) was found normal  in  caliber  with  no  sign  of  invasion (Figure 2). CT guided fine needle aspiration cytology of the mass was performed and it showed papillary nests of eosinophilic tumor cells with intranuclear inclusions. The patient underwent pancreaticoduodenectomy. Histopathology showed 1.6×1.4 cm metastatic deposit in the neck of the pancreas and immunohistochemistry examination showed the positivity for TG and thyroid transcription factor-1 (TTF-1) and made confirmed diagnosis of pancreatic metastasis consistent with FV-PTC (Figure 3). Genetic testing revealed a BRAF V600E mutation.  After surgical resection, she was started on sorafenib 400 mg twice daily, which she tolerated well. At time of submission of case report the patient was alive at 36 months postoperatively and was doing fine with partial response in lungs, without recurrence in neck and serum TG levels 39.8 ng/mL.Figure 2
Magnetic Resonance Cholangiopancreatography (MRCP) showing a  small  hypovascular1.8×1.5 cm mass in  the  pancreatic  neck, invading  the  superior mesenteric vein.(a) Infiltrating clusters of papillary tumor cells in pancreatic tissue parenchyma (H&E ×100) and (b) follicular pattern with abundant cytoplasm (H&E ×200).
(a)
(b)


## 3. Discussion

Pancreas is rare site metastasis. Common malignancies which metastasize to pancreas are renal cell carcinoma, lung, medullary carcinoma of the thyroid, lymphomas, alveolar rhabdomyosarcoma, and esophagus [11]. Metastases to the pancreas from papillary thyroid carcinoma are extremely rare. To date, only 9 cases have been reported in the literature with initial diagnosis of PTC [5–10, 12] in Table 1. Exact pathogenesis is not well known; however, hematogenous route is well supported.Table 1
Cases of pancreatic metastasis secondary to papillary thyroid carcinoma reported from 1991 to 2012.
Author
Age
From time of initial treatment
Variant
Treatment
Survival after diagnosis of pancreatic metastasis
Zhu et al. [4]
NA
NA
Tall cell
Surgical resection
NA
Sugimura  et al. [5]
53 years
7 years after TT + RAI
Classical
Surgical resection
NA
Jobran et al. [6]
53 years male
NA
Tall cell
Surgical resection
NA
Angeles-Angeles et al. [7]
72 years male
NA
Classical
Surgical resection
NA
Borschitz et al. [8]
34 years female
9 years after TT + RAI
Classical
Surgical resection
42 months
46 years male
2 years after TT + RAI
Follicular
Chen and Brainard [9]
82 years male
5 years after TT + RAI
Classical
Surgical resection
NA
Alzahrani et al. [10]
56 years male
6 years after TT + RAI
Classical
Sorafenib
20 months
Present case
67 years
7 years after TT + RAI
Tall cell
Surgical resection and RAI
Alive at 32 months
TT: total thyroidectomy, RAI: radioactive iodine therapy, NA: not mentioned.Pancreatic metastases remain asymptomatic for long period before diagnosis or manifest as symptoms like chronic pancreatitis as seen in our patient.  At time of presentation, pancreatic metastases are usually sign of extensive disease seen in our patient. Conventional diagnostic tools (CT, WBS) may remain fail to reach the diagnosis. However, positron emission tomography-computed tomography (PET-CT) and endoscopic ultrasound (EUS) have shown the sensitivity or detecting pancreatic lesions up to 94–100%, though not performed in our case due to unavailability in institute [13].Surgical treatment in the form of pylorus sparing pancreaticoduodenectomy relieves the symptoms and may increase the disease free survival (DFS) for isolated pancreatic metastasis. However, adjunct and multikinase inhibitors (sorafenib or sunitinib) may slow the disease progression especially in patients with BRAF V600E mutation in tumor cell lines [14].In conclusion, pancreatic metastases are rare in FV-PTC and they remain asymptomatic or are associated with nonspecific complaints. Improved diagnostic tools (MRCP, PET-CT, and EUS) and immunohistochemistry can be helpful for prompt diagnosis and treatment by means of pancreaticoduodenectomy followed by sorafenib which is associated with increased DFS.



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