Vol. 117 No. 1 January 2014

Pancreatic adenocarcinoma presenting as mandibular tumor: case report Nicola R. Jaffa, BDS, MFDS,a Danny Adam, BDS, MFDS,a Shakeel Akhtar, BDS, FDS RCS, MB ChB, FRCS, (OMFS),b and Panayiotis A. Kyzas, PhD, BDS, MBBS, MRCS, FRCS (OMFS)c Royal Preston Hospital, Preston, Lancashire, United Kingdom

Context. Pancreatic adenocarcinoma metastasizing to the mandible is extremely rare, with only 4 previous cases reported in the literature. Here, we present a patient with a metastatic lesion in the mandible as the initial manifestation of pancreatic adenocarcinoma. We also review the incidence, diagnosis, and management of this rare occurrence. Case report. A 45-year-old man with a 5-week history of pain, following a tooth extraction, was referred to our Oral & Maxillofacial Department and presented with a nonhealing socket in the mandibular premolar region. He was investigated by use of imaging and an urgent biopsy. The diagnosis of pancreatic neoplasm was made. At this stage, the disease was fairly extensive and management was palliative. Conclusion. This case demonstrates the importance of a full investigation when a patient presents with a nonhealing socket and pain after tooth extraction. Mandibular metastases from distant primaries often have poor prognosis, with most patients getting palliative support. A multidisciplinary team approach is required for the management of these rare cases. (Oral Surg Oral Med Oral Pathol Oral Radiol 2014;117:23-26)

Head and neck malignant neoplasms account for 5% of all malignancies. However, intraoral metastatic disease is much rarer. The body of the mandible, especially the premolar-molar region, is the most common site of metastatic disease.1 The most frequent primary sites are breast (21.8%), followed by lung (12.6%), adrenal (8.7%), kidney (7.9%), bone (7.4%), colon (6.6%), and prostate (5.6%).1 Most intraoral metastases present late in the context of the progression of a known advanced primary cancer.1 Occasionally, however, the discovery of intraoral metastatic deposits may be the first or only symptom of an unknown underlying malignancy elsewhere in the body.1 Arriving at a diagnosis can often be challenging when there is no previous history of malignant disease. Histology and immunochemistry play an important role in differentiating whether a lesion in the mandible is a primary neoplasm or a distant metastasis. In the current report, we present a case of metastatic adenocarcinoma of the pancreas, which presented with a metastatic lesion in the mandible as the initial manifestation.

CASE REPORT A 45-year-old man presented to the Accident & Emergency department with pain and swelling intraorally, in the right a

Senior House Officer, Department of Oral and Maxillofacial Surgery, Royal Preston Hospital, Lancashire Teaching Hospital Trust. b Consultant, Department of Oral and Maxillofacial Surgery, Royal Preston Hospital, Lancashire Teaching Hospital Trust. c Specialty Registrar, Department of Oral and Maxillofacial Surgery, Royal Preston Hospital, Lancashire Teaching Hospital Trust. Received for publication May 25, 2013; accepted for publication Aug 11, 2013. Ó 2014 Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter http://dx.doi.org/10.1016/j.oooo.2013.08.009

lower premolar region (RL45), following a dental extraction. He mentioned that he had extraction of the second right lower premolar 5 weeks previously, which was still causing him significant pain. The patient also had a 3-week history of shortness of breath, which he attributed to his known history of asthma. His shortness of breath was dealt with initially as community-acquired pneumonia, and his general practitioner had treated him with antibiotics. He also mentioned weight loss of 15 kg over 12 weeks, but he attributed this to intentional diet and exercise. Apart from his asthma and wellcontrolled type 2 diabetes, the patient’s previous medical history was generally unremarkable. The patient was a heavy smoker of 25 pack-years. The patient was admitted under the care of the physicians for intravenous antibiotic therapy for the treatment of suspected atypical pneumonia. An HIV test was negative. A chest radiograph showed extensive abnormal chronic change of a diffuse nature in all lung zones, and an urgent chest clinic referral was made. Subsequently, the patient was referred to the Oral & Maxillofacial Surgery Department to address the patient’s main complaint: pain and swelling intraorally in the right mandible. Clinical examination revealed a 3  4-cm lobulated, indurated mass, arising from the RL5 socket and occupying most of the parasymphysis area of the right mandible. The lesion demonstrated contact bleeding. He also had right lower lip paresthesia. An enlarged left level I node was also palpable. An orthopanoramic radiograph (Figure 1) showed an unusual soft tissue irregular opacity in the RL45 region, with motheaten bone margins, suggestive of a malignant process. A biopsy was taken, and pathology confirmed a moderately differentiated adenocarcinoma. The origin of the adenocarcinoma was not clear on the hematoxylin-eosin staining, and a differential diagnosis of primary minor salivary gland adenocarcinoma or a distant metastasis from an unknown primary site was made. Following immunohistochemical staining, the specimen was strongly positive for cytokeratin 7 (CK7) and negative for cytokeratin 20 (CK20) and thyroid transcription factor 1 (TTF1) (lung). A panel of

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Fig. 1. (a) Chest radiograph on admission, showing diffuse radiopacity in all lung zones. (b) Chest computed tomography scan, demonstrating innumerable small cavitating nodules. (c) Abdomen computed tomography scan, showing dilatation of the main pancreatic duct and a 17-mm lesion in the uncinate process, in keeping with a primary adenocarcinoma.

tumor markers was run, and the patient’s carbohydrate antigen 19-9 (CA19-9) levels were extremely high. This suggested a primary adenocarcinoma of the pancreas or gastrointestinal tract. Urgent full-body computed tomography (CT) and magnetic resonance imaging (MRI) scans were then organized. The CT chest scan showed diffusely abnormal lungs with innumerable small cavitating nodules. In the abdomen, dilatation of the main pancreatic duct was noted along with a 17mm lesion in the uncinate process of the pancreas. Multiple para-aortic lymph nodes with suspicious radiologic features were also noted. In addition, several metastatic liver lesions were seen. The head and neck MRI (Figure 2) showed a 3  2.1-cm mass in the RL45 region, with clear evidence of

mandibular involvement. In addition, a large left level Ib nodal mass and an abnormal soft tissue swelling into the superior mediastinum were shown. After multidisciplinary team discussion, the consensus reached was that the patient had a very advanced metastatic primary adenocarcinoma of the pancreas. Palliative care was offered, and the patient succumbed shortly after being transferred to a hospice.

DISCUSSION To our knowledge, this is the first report of a case in which the discovery of an intraoral metastasis led to the identification of an unknown primary pancreatic

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CASE REPORT Jaffa et al. 25

Fig. 2. (a) Orthopanoramic radiograph showing soft tissue radiopacity in the nonhealing region of the right lower premolars. (b) Head and neck magnetic resonance imaging scan showing a soft tissue mass in the right lower premolar region (coronal view). (c) Head and neck magnetic resonance imaging scan showing a soft tissue mass in the right lower premolar region (axial view).

adenocarcinoma. There are only 4 reported cases of mandibular metastasis from malignant pancreatic neoplasms.2-5 The incidence of pancreatic neoplasm is 10.3/ 100,000 males and 7.9/100,000 females in the United Kingdom. In general, it is an aggressive malignancy, with only 20% to 30% of cases localized and potentially curable when diagnosed.6 Several studies have examined the distribution of metastases of carcinoma of the pancreas.6,7 Metastases most often involve regional lymph nodes rather than distant organs.8 In terms of hematogenous spread, the liver (64% to 80%) and the lung (27% to 50%) are usually affected, whereas peritoneum deposits are not uncommon (40% to 55%).8 The incidence of oral metastatic tumors is very low. However, a significant number may go undetected owing to the fact that micrometastasis is rarely detected by the commonly employed staging scans (CT, MRI). Patients with terminal-stage disease often succumb before presenting to a clinician, and the head and neck region is not often included in detailing the staging scans for abdominal malignancies. Therefore, the exact incidence of metastatic diseases that affect the mandible is still unknown.

The premolar-molar region of the mandible is usually the area that harbors metastatic disease. This region is rich in hemopoietic tissue. Even though the exact mechanism of metastatic dissemination is unclear, a hematogenous spread is suggested. The mechanisms of angiogenesis, vascular invasion, and metastasis have been previously described.1,9 Most head and neck metastases originate from the lungs, breasts, and kidneys.1,8,9 It is understandable that metastatic disease in the mandible from pancreatic adenocarcinoma can cause diagnostic confusion clinically and pathologically owing to the extreme rarity of such lesions. Clinically there is a wide variety of presentations of oral metastatic lesions that include pain, swelling, tooth mobility, paresthesia, pathologic fracture, and, as in this case, a mass arising from a nonhealing socket after tooth extraction.1 Most of these symptoms can be signs of malignant disease. Trying to determine the primary source in this case was a challenge, because there was no previous history of any malignant disease. This is where histology and immunochemistry play a vital role in enabling us to precisely identify the primary neoplasm. CK7, CK20, TTF1, and CDX2 stains and CA19-9 tumor marker are of particular importance in the diagnosis of metastatic

ORAL AND MAXILLOFACIAL SURGERY 26 Jaffa et al.

pancreatic adenocarcinoma. CA19-9 has the highest sensitivity as a tumor marker for pancreatic adenocarcinoma,10 but its specificity is limited, because it can be raised in a number of intra-abdominal malignancies. TTF1 rules out lung as a primary source, and Duval et al.10 have recently reported that the majority of pancreatic carcinomas were positive for CK7 and negative for CK20. In our case, the combination of the immunohistochemical markers and the elevated CA19-9, combined with the results of the intraoral biopsy and the findings of the MRI and CT scans, led to the confident identification of the primary tumor. An argument favoring the use of positron emission tomographyeCT (PET-CT) in this case could be made, but the cost-benefit ratio was not favorable. Generally, oral metastases are evidence of widespread disease. Therefore, metastatic disease to the mandible arising from pancreatic adenocarcinoma is a poor prognostic indicator. Due to the rare nature of this presentation, there are no studies reporting the incidence or treatment of mandible metastasis from pancreatic adenocarcinoma. In the very few reported cases, detection of metastases from pancreatic neoplasms marked limited short-term survival, and the patients died within months after discovery of an oral lesion. The mean survival time was 6 months.1 Even if such late discovery is the case, patients with advanced malignant disease will require palliative treatment for pain control, nutritional support, control of bleeding, and, generally, help to improve the quality of life. The management of such cases should always be in the context of a multidisciplinary team. Metastatic disease of the mandible could potentially originate from anywhere in the body. This is the first report of metastatic pancreatic adenocarcinoma with a mandibular deposit as a first presentation. Because the exact incidence of mandibular metastatic disease is still unknown, all medical and dental clinicians must include metastatic disease in the differential diagnosis of oral complaints, because this could be the initial presentation. This case particularly emphasizes the importance of a clinical suspicion for patients presenting with a nonhealing socket following tooth extraction.

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Management strategies in these rare cases cannot be guided by published data and therefore should be approached by a multidisciplinary team. There will never be randomized data to clearly define management in these rare cases, but pooling of cases may lend insight into the most efficacious therapy. Future studies should focus on quality of life, as it is reasonable to assume these cases to be palliative. REFERENCES 1. Hirshberg A, Leibovich P, Buchner A. Metastatic tumors to the jawbones: analysis of 390 cases. J Oral Pathol Med. 1994;23: 337-341. 2. Hayes RL, Pinson TJ, Leffall LD. Adenocarcinoma of the pancreas metastatic to the mandible. Oral Surg Oral Med Oral Pathol. 1966;21:61-66. 3. Freilich RE. Adenocarcinoma of the pancreas metastatic to the mandible. J Oral Maxillofac Surg. 1986;44:735-737. 4. Vähätalo K, Ekfors T, Syrjänen S. Adenocarcinoma of the pancreas metastatic to the mandible. J Oral Maxillofac Surg. 2000;58:110-114. 5. Stecher JA, Mostofi R, True LD, Indresano AT. Pancreatic carcinoma metastatic to the mandibular gingiva. J Oral Maxillofac Surg. 1985;43:385-390. 6. Halpert B, Makk L, Jordan GL. A retrospective study of 120 patients with carcinoma of the pancreas. Surg Gynecol Obstet. 1965;121:91. 7. Cubilla AL, Fitzgerald PJ. Cancer of the exocrine pancreas: the pathologic aspects. Cancer. 1985;35:2. 8. Scipio JE, Murti PR, Al-Bayaty HF, Matthews R, Scully C. Metastasis of breast carcinoma to mandibular gingiva. Oral Oncol. 2001;37:393-396. 9. Zacchariades N. Neoplasms metastatic to mouth, jaws and surrounding tissues. J Cranio Maxillofac Surg. 1983;17:283. 10. Duval JY, Savas L, Banner BF. Expression of cytokeratins 7 and 20 in carcinomas of the extrahepatic biliary tract, pancreas and gallbladder. Arch Pathol Lab Med. 2000;124:1196-1200.

Reprint requests: Panayiotis A. Kyzas Department of Oral and Maxillofacial Surgery Royal Preston Hospital Sharoe Green Lane North Preston PR2 9HT United Kingdom [email protected]

Pancreatic adenocarcinoma presenting as mandibular tumor: case report.

Pancreatic adenocarcinoma metastasizing to the mandible is extremely rare, with only 4 previous cases reported in the literature. Here, we present a p...
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