pancreatic adenocarcinoma presenting as mandibular tumor: case report

4
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 me- tastatic deposits may be the rst 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 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 signicant 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 inten- tional diet and exercise. Apart from his asthma and well- controlled type 2 diabetes, the patients 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 sus- pected 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 patients 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 demon- strated contact bleeding. He also had right lower lip pares- thesia. 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 moth- eaten bone margins, suggestive of a malignant process. A biopsy was taken, and pathology conrmed a moder- ately differentiated adenocarcinoma. The origin of the adenocarcinoma was not clear on the hematoxylin-eosin staining, and a differential diagnosis of primary minor sali- vary gland adenocarcinoma or a distant metastasis from an unknown primary site was made. Following immunohisto- chemical 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 a Senior House Ofcer, 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 23 Vol. 117 No. 1 January 2014

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Vol. 117 No. 1 January 2014

Pancreatic adenocarcinoma presenting as mandibular tumor:case reportNicola 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% ofall malignancies. However, intraoral metastatic diseaseis much rarer. The body of the mandible, especially thepremolar-molar region, is the most common site ofmetastatic disease.1 The most frequent primary sites arebreast (21.8%), followed by lung (12.6%), adrenal(8.7%), kidney (7.9%), bone (7.4%), colon (6.6%), andprostate (5.6%).1

Most intraoral metastases present late in the context ofthe progression of a known advanced primary cancer.1

Occasionally, however, the discovery of intraoral me-tastatic deposits may be the first or only symptom ofan unknown underlying malignancy elsewhere in thebody.1 Arriving at a diagnosis can often be challengingwhen there is no previous history of malignant disease.Histology and immunochemistry play an important rolein differentiating whether a lesion in the mandible isa primary neoplasm or a distant metastasis.

In the current report, we present a case of metastaticadenocarcinoma of the pancreas, which presentedwith a metastatic lesion in the mandible as the initialmanifestation.

CASE REPORTA 45-year-old man presented to the Accident & Emergencydepartment with pain and swelling intraorally, in the right

aSenior House Officer, Department of Oral and Maxillofacial Surgery,Royal Preston Hospital, Lancashire Teaching Hospital Trust.bConsultant, Department of Oral and Maxillofacial Surgery, RoyalPreston Hospital, Lancashire Teaching Hospital Trust.cSpecialty Registrar, Department of Oral and Maxillofacial Surgery,Royal Preston Hospital, Lancashire Teaching Hospital Trust.Received for publication May 25, 2013; accepted for publication Aug11, 2013.� 2014 Elsevier Inc. All rights reserved.2212-4403/$ - see front matterhttp://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 lowerpremolar 5 weeks previously, which was still causing himsignificant pain. The patient also had a 3-week history ofshortness of breath, which he attributed to his known historyof asthma. His shortness of breath was dealt with initially ascommunity-acquired pneumonia, and his general practitionerhad treated him with antibiotics. He also mentioned weightloss of 15 kg over 12 weeks, but he attributed this to inten-tional diet and exercise. Apart from his asthma and well-controlled type 2 diabetes, the patient’s previous medicalhistory was generally unremarkable. The patient was a heavysmoker of 25 pack-years.

The patient was admitted under the care of the physiciansfor intravenous antibiotic therapy for the treatment of sus-pected atypical pneumonia. An HIV test was negative. Achest radiograph showed extensive abnormal chronic changeof a diffuse nature in all lung zones, and an urgent chest clinicreferral was made.

Subsequently, the patient was referred to the Oral &Maxillofacial Surgery Department to address the patient’s maincomplaint: pain and swelling intraorally in the right mandible.Clinical examination revealed a 3 � 4-cm lobulated, induratedmass, arising from the RL5 socket and occupying most of theparasymphysis area of the right mandible. The lesion demon-strated contact bleeding. He also had right lower lip pares-thesia. An enlarged left level I node was also palpable. Anorthopanoramic radiograph (Figure 1) showed an unusualsoft tissue irregular opacity in the RL45 region, with moth-eaten bone margins, suggestive of a malignant process.

A biopsy was taken, and pathology confirmed a moder-ately differentiated adenocarcinoma. The origin of theadenocarcinoma was not clear on the hematoxylin-eosinstaining, and a differential diagnosis of primary minor sali-vary gland adenocarcinoma or a distant metastasis from anunknown primary site was made. Following immunohisto-chemical staining, the specimen was strongly positive forcytokeratin 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 mainpancreatic duct and a 17-mm lesion in the uncinate process, in keeping with a primary adenocarcinoma.

ORAL AND MAXILLOFACIAL SURGERY OOOO

24 Jaffa et al. January 2014

tumor markers was run, and the patient’s carbohydrateantigen 19-9 (CA19-9) levels were extremely high. Thissuggested a primary adenocarcinoma of the pancreas orgastrointestinal tract. Urgent full-body computed tomog-raphy (CT) and magnetic resonance imaging (MRI) scanswere then organized.

The CT chest scan showed diffusely abnormal lungs withinnumerable small cavitating nodules. In the abdomen, dila-tation of the main pancreatic duct was noted along with a 17-mm lesion in the uncinate process of the pancreas. Multiplepara-aortic lymph nodes with suspicious radiologic featureswere also noted. In addition, several metastatic liver lesionswere 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 Ibnodal mass and an abnormal soft tissue swelling into thesuperior mediastinum were shown.

After multidisciplinary team discussion, the consensusreached was that the patient had a very advanced metastaticprimary adenocarcinoma of the pancreas. Palliative care wasoffered, and the patient succumbed shortly after being trans-ferred to a hospice.

DISCUSSIONTo our knowledge, this is the first report of a casein which the discovery of an intraoral metastasis ledto the identification of an unknown primary pancreatic

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).

OOOO CASE REPORT

Volume 117, Number 1 Jaffa et al. 25

adenocarcinoma. There are only 4 reported casesof mandibular metastasis from malignant pancreaticneoplasms.2-5

The incidence of pancreatic neoplasm is 10.3/100,000 males and 7.9/100,000 females in the UnitedKingdom. In general, it is an aggressive malignancy,with only 20% to 30% of cases localized and potentiallycurable when diagnosed.6

Several studies have examined the distribution ofmetastases of carcinoma of the pancreas.6,7 Metastasesmost often involve regional lymph nodes rather thandistant organs.8 In terms of hematogenous spread, theliver (64% to 80%) and the lung (27% to 50%) areusually affected, whereas peritoneum deposits are notuncommon (40% to 55%).8

The incidence of oral metastatic tumors is very low.However, a significant number may go undetectedowing to the fact that micrometastasis is rarely detectedby the commonly employed staging scans (CT, MRI).Patients with terminal-stage disease often succumbbefore presenting to a clinician, and the head and neckregion is not often included in detailing the stagingscans for abdominal malignancies. Therefore, the exactincidence of metastatic diseases that affect the mandibleis still unknown.

The premolar-molar region of the mandible is usuallythe area that harbors metastatic disease. This regionis rich in hemopoietic tissue. Even though the exactmechanism of metastatic dissemination is unclear,a hematogenous spread is suggested. The mechanismsof angiogenesis, vascular invasion, and metastasis havebeen previously described.1,9 Most head and neckmetastases originate from the lungs, breasts, andkidneys.1,8,9 It is understandable that metastatic diseasein the mandible from pancreatic adenocarcinoma cancause diagnostic confusion clinically and pathologicallyowing to the extreme rarity of such lesions.

Clinically there is a wide variety of presentations oforal metastatic lesions that include pain, swelling, toothmobility, paresthesia, pathologic fracture, and, as in thiscase, a mass arising from a nonhealing socket aftertooth extraction.1 Most of these symptoms can be signsof malignant disease.

Trying to determine the primary source in this casewas a challenge, because there was no previous historyof any malignant disease. This is where histology andimmunochemistry play a vital role in enabling us toprecisely identify the primary neoplasm. CK7, CK20,TTF1, and CDX2 stains and CA19-9 tumor marker areof particular importance in the diagnosis of metastatic

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26 Jaffa et al. January 2014

pancreatic adenocarcinoma. CA19-9 has the highestsensitivity as a tumor marker for pancreatic adenocar-cinoma,10 but its specificity is limited, because it can beraised in a number of intra-abdominal malignancies.TTF1 rules out lung as a primary source, and Duvalet al.10 have recently reported that the majority ofpancreatic carcinomas were positive for CK7 andnegative for CK20. In our case, the combination ofthe immunohistochemical markers and the elevatedCA19-9, combined with the results of the intraoralbiopsy and the findings of the MRI and CT scans, ledto the confident identification of the primary tumor.An argument favoring the use of positron emissiontomographyeCT (PET-CT) in this case could be made,but the cost-benefit ratio was not favorable.

Generally, oral metastases are evidence of widespreaddisease. Therefore, metastatic disease to the mandiblearising from pancreatic adenocarcinoma is a poor prog-nostic indicator. Due to the rare nature of this presenta-tion, there are no studies reporting the incidence ortreatment of mandible metastasis from pancreatic adeno-carcinoma. In the very few reported cases, detection ofmetastases from pancreatic neoplasms marked limitedshort-term survival, and the patients died within monthsafter discovery of an oral lesion. The mean survival timewas 6 months.1 Even if such late discovery is the case,patients with advanced malignant disease will requirepalliative treatment for pain control, nutritional support,control of bleeding, and, generally, help to improve thequality of life. The management of such cases shouldalways be in the context of a multidisciplinary team.

Metastatic disease of the mandible could potentiallyoriginate from anywhere in the body. This is the firstreport of metastatic pancreatic adenocarcinoma witha mandibular deposit as a first presentation. Becausethe exact incidence of mandibular metastatic disease isstill unknown, all medical and dental clinicians mustinclude metastatic disease in the differential diagnosisof oral complaints, because this could be the initialpresentation. This case particularly emphasizes theimportance of a clinical suspicion for patients present-ing with a nonhealing socket following tooth extraction.

Management strategies in these rare cases cannot beguided by published data and therefore should beapproached by a multidisciplinary team. There willnever be randomized data to clearly define managementin these rare cases, but pooling of cases may lendinsight into the most efficacious therapy. Future studiesshould focus on quality of life, as it is reasonable toassume these cases to be palliative.

REFERENCES1. 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 thepancreas metastatic to the mandible. Oral Surg Oral Med OralPathol. 1966;21:61-66.

3. Freilich RE. Adenocarcinoma of the pancreas metastatic to themandible. J Oral Maxillofac Surg. 1986;44:735-737.

4. Vähätalo K, Ekfors T, Syrjänen S. Adenocarcinoma of thepancreas metastatic to the mandible. J Oral Maxillofac Surg.2000;58:110-114.

5. Stecher JA, Mostofi R, True LD, Indresano AT. Pancreaticcarcinoma metastatic to the mandibular gingiva. J Oral Max-illofac Surg. 1985;43:385-390.

6. Halpert B, Makk L, Jordan GL. A retrospective study of 120patients with carcinoma of the pancreas. Surg Gynecol Obstet.1965;121:91.

7. Cubilla AL, Fitzgerald PJ. Cancer of the exocrine pancreas: thepathologic aspects. Cancer. 1985;35:2.

8. Scipio JE, Murti PR, Al-Bayaty HF, Matthews R, Scully C.Metastasis of breast carcinoma to mandibular gingiva. OralOncol. 2001;37:393-396.

9. Zacchariades N. Neoplasms metastatic to mouth, jaws andsurrounding tissues. J Cranio Maxillofac Surg. 1983;17:283.

10. Duval JY, Savas L, Banner BF. Expression of cytokeratins 7 and20 in carcinomas of the extrahepatic biliary tract, pancreas andgallbladder. Arch Pathol Lab Med. 2000;124:1196-1200.

Reprint requests:

Panayiotis A. KyzasDepartment of Oral and Maxillofacial SurgeryRoyal Preston HospitalSharoe Green Lane NorthPreston PR2 9HTUnited [email protected]