ANZ J. Surg.

2002;

72

: 531–533

CASE REPORT

Case report

NEUROENDOCRINE TUMOURS OF THE AMPULLA OF VATER

M

EHRDAD

N

IKFARJAM

* C

ATRIONA

M

C

L

EAN

,

†

V

IJYARAGAVAN

M

URALIDHARAN

*

AND

C

HRIS

C

HRISTOPHI

*

*Monash University Department of Surgery and

†

Department of Pathology, Alfred Hospital, Melbourne, Victoria, Australia

Key words: carcinoid tumour, local resection, neuroendocrine carcinoma, pancreaticoduodenctomy.

Abbreviation

: ERCP, endoscopic retrograde cholangiopancreatography.

INTRODUCTION

Neuroendocrine tumours of the ampulla of Vater are extremelyrare, comprising no more than 2% of ampullary malignancies.They have a better prognosis than adenocarcinomas, withgood results reported for both local resection and pancreatico-duodenectomy.

1

We report two patients with ampullary neuro-endocrine tumours and discuss the specific features of thesetumours and their prognostic significance.

CASE REPORTS

Case 1

A 45-year-old man with von Recklinghausen’s neurofibromatosispresented with 6 weeks of intermittent epigastric pain. Liverfunction tests showed marked elevations in alkaline phos-phatase and

γ

-glutamine transferase. Common bile duct dilatationwas seen on ultrasound, without evidence of gallstones. Endo-scopic retrograde cholangiopancreatography (ERCP) demon-strated an enlarged friable major duodenal papilla. The lesionwas considered malignant despite normal biopsies. A pylorus-preserving pancreaticoduodenal resection was performed. Histo-logical findings were that of a 2.5-cm carcinoid tumour arisingfrom the ampulla of Vater, invading into the duodenal wall(Fig. 1). One of five nodes examined was positive for carcinoidtumour. He made a complete recovery and was without evidenceof disease 60 months postoperatively.

Case 2

A 74-year-old man with no significant past medical history pre-sented with fever, jaundice and abdominal pain. Ultrasound andcomputed tomography of the abdomen demonstrated a dilatedcommon bile duct without gallstones or periampullary lesions.Endoscopic retrograde cholangiopancreatography performed2 days later showed a small, ulcerated, pale lesion at the majorduodenal papilla. Biopsies disclosed a poorly differentiated car-cinoma. A transduodenal local excision of the tumour was under-taken. Histopathological examination demonstrated a 2-cm non-small cell neuroendocrine carcinoma arising from the ampulla

of Vater, extending to the deep resection margins of the duode-num (Fig. 2). The patient made an uncomplicated recovery, butwas hospitalized 12 months postoperatively with recurrent dis-ease. At laparotomy, there was a large obstructing duodenalmass and extensive retroperitoneal lymphadenopathy. A pallia-tive bypass procedure was performed. He died from metastaticdisease 16 months after initial surgery.

DISCUSSION

Neuroendocrine cell micronests are found in the major duodenalpapilla of up to 10% of the population.

2

The incidence of malignanttransformation is uncommon. About 100 cases of ampullary neuro-endocrine tumours are reported in international literature, with atwo- to threefold male predominance.

1,3,4

These account for lessthan 0.3% of all gastrointestinal neuroendocrine tumours

5

and canbe classified into three prognostically distinct categories: carcinoidtumours, small cell neuroendocrine carcinomas, and non-small cellneuroendocrine carcinomas.

6

Jaundice (60%) and abdominal pain (40%) are the most frequentpresenting symptoms. Weight loss is reported in about 10% ofcases. Pancreatitis and upper gastrointestinal bleeding areuncommon presentations.

4

Computed tomography scan and ERCPmay identify the lesion, but the correct diagnosis generally followshistological and immunochemical examination of surgical speci-mens. Preoperative diagnosis is correct in a distinct minority ofpatients. Hatzitheoklitos

et al

., in a review of patients with ampul-lary carcinoid tumours, found that only 14% (10 of 71) had accu-rate preoperative diagnosis.

4

Carcinoids are the most common primary neuroendocrinetumour of the ampulla of Vater and are associated with von Reck-linghausen’s neurofibromatosis in 25% of cases.

3

Histologically,they are composed of nests of uniform cells with central roundnuclei and coarse chromatin. Although previously consideredbenign, subsequent reports demonstrate that they have metastaticand lethal potential.

Ampullary carcinoids progress slowly and long-term survival isreported even when metastases are present at the time of diagno-sis.

7

Overall 5-year survival approaches 90%.

4,5

Some authors claim that transduodenal local resection is jus-tified for ampullary carcinoids when possible, given goodtumour prognosis combined with the safety of this procedure.

8

However, even for tumours less than 2 cm that are technicallylocally resectable, lymph node metastases approach 50% andwould provide inadequate clearance in many cases.

5

Hatzithe-oklitos

et al

. found that lymph node metastases was present in47% (14 of 30) of patients with tumours less than 2 cm, and in46% (11 of 24) of those with tumours above 2 cm.

4

M. Nikfarjam

MB BS;

C. McLean

MD, FRCPA;

V. Muralidharan

FRACS;

C. Christophi

MD, FRACS.

Correspondence: M. Nikfarjam, Department of Surgery, Monash University,Alfred Hospital, Commercial Road, Prahran, Victoria 3181, Australia.Email: mnikfarjam@optusnet.com.au

Accepted for publication 11 February 2002.

532 NIKFARJAM

ET AL

.

Depth of tumour invasion is a good predictor of regional spreadfor adenocarcinomas, and can be assessed by preoperative endo-scopic ultrasound.

9,10

Unfortunately, the relationship of tumourinvasion and lymph node spread has not been verified for neuroen-docrine tumours. Moertel, in a study of 168 patients with smallbowel carcinoids, found that locoregional tumour clearance hadsurvival benefit.

11

In that study, 10 years survival for those withregionally resected disease was about 60% (

n

= 64) compared with40% (

n

= 16) where regional disease was not resected. If we makeinferences from this study, pancreaticoduodenctomy is the proce-dure of choice in most patients with ampullary carcinoids.

11

Small cell ampullary neuroendocrine carcinomas are extra-ordinarily rare, with fewer than 10 reported cases. Typically, theyare composed of sheets and irregular groups of pleomorphic cells,with appearances akin to bronchogenic small cell carcinomas. Themean survival for patients with these tumours is about 9 months.

6

The high incidence of lymph node spread suggests that pancreatic-oduodenectomy is required to achieve adequate clearance. Whetherthis impacts prognosis is unknown.

Non-small cell neuroendocrine carcinomas have endocrinearchitectural features. They are arranged in nests and rosettes,with cells that have glandular cytoplasm, mild to moderatenuclear pleomorphism, frequent mitoses and increased nuclear tocytoplasmic ratio. The first reported case was a 1-cm lesion in a67-year-old man with regional lymph node metastases, treatedby pancreaticoduodenal resection. The patient was alive withoutevidence of distant metastases at 38 months follow up.

6

As far asis known, our case is only the second reported in international lit-erature. These tumours appear to have better prognosis than theirsmall cell counterparts.

Ampullary neuroendocrine tumours are exceedingly rare. Theygenerally have a better prognosis than adenocarcinomas and fallinto three distinct categories. Carcinoids are the most commonvariety and have the best prognosis. Small cell and non-small cellneuroendocrine carcinomas make up the remainder and have apoorer prognosis. Pancreaticoduodenal resection appears to bethe procedure of choice for all neuroendocrine tumours, giventhe high incidence of lymph node involvement and inability to

Fig. 1.

(a) Carcinoid tumour composed of nests of uniform cells with central round nuclei (haemotoxylin and eosin). (b) The cells show gran-ular cytoplasmic immunoreactivity for neurosecretory granules (chromagranin immunoreaction).

Fig. 2.

(a) Non-small cell neuroendocrine carcinoma forming broad nests within which small gland-like structures are present. The cells havea glandular cytoplasm and exhibit mild to moderate nuclear pleomorphism (haemotoxylin and eosin). (b) Strong focal cytoplasmic immuno-reactivity with chromagranin is demonstrated (chromagranin immunoreaction).

AMPULLARY NEUROENDOCRINE TUMOURS 533

accurately predict regional spread preoperatively. Local excisionshould be confined to patients unable to tolerate more extensivesurgery.

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6. Emory RE, Emory TS, Goellner JR, Grant CS, Nagorney DM.Neuroendocrine ampullary tumor: Spectrum of disease includingfirst report of a neuroendocrine carcinoma of non-small cell type.

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1987;

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the criteria for local resection of ampullary neoplasms.

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Gastrointest. Endosc.

1999;

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: 27–33.10. Beger HG, Treitschke F, Gansauge F, Harada N, Hiki N,

Mattfeldt T. Tumor of the ampulla of Vater: Experience withlocal or radical resection in 171 consecutively treated patients.

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land of small tumors.

J. Clin. Oncol.

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Upper Gastrointestinal Surgery. A Companion to Special-ist Surgical Practice

, 2nd edition. Edited by S. M

ICHAEL

G

RIFFIN

and S

IMON

A. R

AIMES

. London: Harcourt PublishersLtd, 2001. Illustrated; 455 pages, Includes index. ISBN07020 2587 9. Price: $198.55.

This second edition of

Upper Gastrointestinal Surgery

is onevolume of a series of

Companion(s) to Specialist Surgical Prac-tice

. The second edition has appeared 3 years after the first,which is testament to the editors’ desire to provide up-to-dateinformation in an area of rapid change. The editors of this volumeare Michael Griffin and Simon Raimes, both of whom are practis-ing surgeons and recognized authorities on upper gastrointestinal(GI) surgery in general, and the management of upper GI malig-nancies in particular. Each contribute a chapter and have selecteda superb panel of contributing authors for the other chapters.

In addition to chapters on management of benign and mal-ignant oesophageal and gastric disorders, there is an excellentchapter on pathology and another on epidemiology. Oesophagealemergencies, the treatment of complications of upper GI surgeryand bariatric surgery are also covered. The information is as up-to-date as is possible with a textbook. There has also been anattempt to identify the strength of evidence underpinning variousstatements and recommendations. Throughout the text, a ‘scalpel’signal indicates statements for which there is thought to be astrong evidence base or sometimes to highlight the fact that thereis no satisfactory data in a particular area. The reader is thenreferred to the appropriate reference(s). This is a useful approach,which can hopefully be expanded upon further in subsequenteditions. There is, however, some inconsistency with how this is

used between chapters. The citations are extensive and up-to-date. The style is clear and readable. There is a judicious use ofdiagrams and photos, which are generally clear and relevant. Thebook is well presented with high-quality paper and binding.

It is inevitable that any reader with knowledge of this area willhave some quibbles with a text of this nature. The section onsurgery of oesophageal cancer reflects an aggressive surgicalapproach and dismisses the possibility that any other form oftherapy has the potential for cure. Fortunately, the balance isrestored somewhat in the section on radiotherapy and chemo-therapy, which presents the data on radical and adjuvant chemo-radiation. In the section on oesophageal emergencies, there is nomention of the use of a Celestin tube for treatment of oesophagealrupture, although this must be one of the commonest treatmentsused in Australia. In the overall context of a volume of thisnature, however, such criticisms are minor ones. Indeed, I foundmuch that was of interest in every chapter. The summary of theconflicting data on the contentious subject of radical lym-phadenectomy for gastric cancer was particularly good.

As the title indicates, this text is aimed at specialist surgeons,practising upper GI surgery. It would also be ideal reading forany general surgical trainee. If a surgical trainee knew this bookthoroughly, the exam would hold few fears as far as upper GIsurgery is concerned. I wholeheartedly commend it to anyonepractising surgery of this nature.

S

IMON

W

OODS

, FRACS

Monash University Departmentof Surgery at CabriniSuite 44, Cabrini Medical CentreMalvern, Victoria, Australia

ANZ J. Surg.

2002;

72

: 533

BOOK REVIEW