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Part IV
Preoperative Diagnosis and Surgical
Indications
Chapter 11
Benign, Premalignant, andMalignant
Duodenal Neoplasms
MatthewHernandez, PaulWong, andLalehMelstrom
Introduction
Benign tumors of the duodenum represent 10–20% of all duodenal lesions and present asymptomatically in most patients [1]. However, depending on their anatomical
location and etiology, these lesions may produce a variety of symptoms, including
acute and chronic bleeding, abdominal pain, weight loss, nausea, and gastric outlet
obstruction. Over the years, there has been an increased incidence of benign duodenal tumors that can be attributed to the recent improvements and greater use of
gastrointestinal endoscopy.
Lesions ofEpithelial Origin
Duodenal Adenomas
Duodenal adenomas are the most frequently seen polyp of the duodenum and derive
their origins either sporadically or in conjunction with a hereditary genetic condition (e.g., familial adenomatous polyposis and MUTYH-associated polyposis).
These adenomas have been reported in 0.3–4.6% of patients undergoing upper gastrointestinal endoscopy and are classied by their locations as ampullary or nonampullary [2]. Duodenal adenomas are often asymptomatic and found incidentally
on endoscopy. However, for ampullary adenomas, these lesions may be associated
with obstruction of the biliary or pancreatic duct, leading to jaundice, cholangitis,
M. Hernandez (*) · P. Wong · L. Melstrom
Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
e-mail: matthernandez@coh.org; lmelstrom@coh.org
Switzerland AG 2025
E. P. Ceppa et al. (eds.), The SAGES Manual of Evolving Techniques in
Pancreatic Surgery, https://doi.org/10.1007/978-3-031-78409-5_11
173© The Author(s), under exclusive license to Springer Nature
174
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M. Hernandez et al.
and pancreatitis. Other non-obstructive symptoms for duodenal adenomas may
include bleeding, nausea, vomiting, weight loss, and abdominal pain.
Endoscopy remains the prominent diagnostic tool for duodenal adenomas, especially asymptomatic non-ampullary neoplasms. The diagnosis of duodenal adenomas is made based on the lesion’s endoscopic appearance and histology. Duodenal
adenomas are generally present as at, small, white-colored lesions that appear
slightly elevated when contrasted with the surrounding mucosa. Side-viewing
endoscopy is required to obtain a complete evaluation of the lesion, and the features
of benign lesions include regular borders, no ulceration, no spontaneous bleeding,
and soft texture [3–5]. The histology of duodenal adenomas is classied based on
the mucin phenotype, with intestinal type polyps representing 89% of cases and
gastric type composing 11% [6, 7]. These phenotypes can be further stratied.
Intestinal type polyps are subdivided into tubular and villous adenomas, and gastric
type polyps are subclassied into pyloric gland and foveolar adenomas. Furthermore,
similar to traditional serrated adenomas (TSA) in the colon, there have been reports
of serrated adenomas possessing TSA-like features which possess an aggressive
morphology that carries signicant risk for malignancy [6, 8, 9].
Resection is often recommended for ampullary and non-ampullary duodenal
adenomas given the malignant potential of these neoplasms. However, there are
considerations for the method of resection that include size, location, morphology,
and pathology of the adenoma. Endoscopic resection is preferred because less invasive, but surgical resection is considered if the adenoma is ≥2 cm, demonstrates
severe dysplasia, suspicious carcinomatous inltration, and recurrence after prior
endoscopic resection [10, 11]. There has not been a consensus regarding the optimal
endoscopic technique for resection, but the various methods include snare polypectomy, endoscopic mucosal resection, endoscopic submucosal dissection, and argon
plasma coagulation ablation. While endoscopic resection provides a less invasive
approach to remove the lesion, it comes with a risk of recurrence and complications,
namely perforation and bleeding, due to the extensive arterial blood supply and thin
walls of the duodenum [10]. Figure 11.1 demonstrates an ampullary adenoma
before (a) and after (b) endoscopic resection. Following endoscopic resection,
Fig. 11.1 Ampullary adenoma before (a) and after (b) endoscopic resection
11 Benign, Premalignant, andMalignant Duodenal Neoplasms
175
surveillance endoscopy should be performed at 3–6months which can be extended
to 6–12months if recurrence is not detected, after which patients should be followed with annual endoscopy for at least 2years after initial endoscopic resection
[10, 12–14].
If endoscopic resection is not feasible due to technical challenges of large and
anatomically complex adenomas, surgical treatment of these lesions is the standard.
Surgical approaches to resect these adenomas include pancreaticoduodenectomy,
ampullectomy, and pancreas-preserving duodenectomy, transduodenal adenoma
resections, and segmental duodenal resection but are associated with higher cost
and greater risk for morbidity and mortality [15, 16]. Patients who receive surgical
ampullectomy are recommended to undergo follow-up endoscopy due to the possibility of recurrence but those who undergo pancreaticoduodenectomy do not require
further surveillance [5]. Lastly, noninvasive methods, such as non-steroidal antiinammatory drugs (NSAIDs) may be employed to treat duodenal adenomas, specically in patients with familial adenomatous polyposis. In a randomized control
trial consisting of 49 post-colectomy patients, there was signicant reduction in
duodenal polyposis seen after 6months of treatment with celecoxib compared to a
placebo [17].
In patients with familial adenomatous polyposis (FAP), extra caution should be
given to ampullary and non-ampullary duodenal adenomas due to the increased risk
of malignancy. Duodenal adenomas have been found in up to 90% of FAP patients,
and these patients have demonstrated up to a 330-fold higher risk of developing
duodenal cancer from these adenomas [16, 18]. In order to stratify risk for duodenal
cancer in patients with FAP, the Spigelman Classication, which incorporates number and size of polyps, histology, and dysplasia, is utilized to identify frequency of
endoscopic surveillance and need for prophylactic duodenectomy [19] (Table11.1).
Based on the Spigelman criteria, proposed surveillance strategies have advised
patients with Stage 0 receive to repeat surveillance endoscopy every 4years, those
Table 11.1 Spigelman Classication for duodenal adenomas in patients with Familial
Adenomatous Polyposis (FAP)
Variables 1 point 2 points 3 points
Number of polyp 1–4 5–20 >20
Size of polyp (mm) 1–4 5–10 >10
Histology Tubular Tubulovillous Villous
Dysplasia Mild Moderate Severe
Spigelman score Stage Surveillance frequency
0 0 Every 4years
1–4 I Every 2–3years
5–6 II Every 2–3years
7–8 III Every 6–12months, with surgical consideration
9–12 IV Referral for surgery
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M. Hernandez et al.
with Stage I and II undergo endoscopy every 2–3years, Stage III patients to receive
endoscopy every 6–12months with surgical consideration, and Stage IV patients to
be referred for surgery [18, 20].
Duodenal Adenocarcinomas
The most common location for small bowel adenocarcinoma is the duodenum,
which accounts for <1% of all gastrointestinal cancers [21]. The most common site
within the duodenum is D2, followed by D3/4 [22]. Duodenal cancers in the rst
portion are quite rare [22, 23]. The clinical presentation is most often associated
with pain, bleeding, and obstruction [23]. Patients may also present with weight loss
and jaundice if there is ampullary obstruction.
Imaging is most often done in the form of contrast-enhanced computed tomography. Figure 11.2 demonstrates the inltrative nature of duodenal adenocarcinomas that may lead to bleeding or obstruction. Endoscopy and endoscopic ultrasound
further characterize these tumors and determine resectability. CDX2 on pathology
which is a sensitive marker for colorectal cancer is more frequently expressed in
duodenal adenocarcinomas [24]. Surgical management includes segmental resection and pancreaticoduodenectomy pending the location of the lesions. The importance of lymphadenectomy with a minimum pathologic evaluation of six lymph
nodes is associated with improved survival [23, 25]. Adjuvant therapy most often
involves systemic chemotherapy and the role of adjuvant radiotherapy has not been
Fig. 11.2 Duodenal adenocarcinoma (a) axial and (b) coronal computed tomography view of
invasive duodenal adenocarcinoma in the third portion of the duodenum
11 Benign, Premalignant, andMalignant Duodenal Neoplasms
177
well dened [23]. In patients who are able to undergo resection, 10year OS can be
as high as 41% in some series [26].
Duodenal Neuroendocrine Tumors (D-NETs)
Duodenal neuroendocrine tumors (D-NETs) encompass 1–3% of NETs and specically 11% of small intestinal NETs [27, 28], with most of these lesions being found
in the rst or second portions of the duodenum [29, 30]. These lesions can either
form sporadically or are associated with familial multiple endocrine neoplasia, type
1 (MEN-1). Sporadic D-NETs are more likely to be solitary lesions, whereas multiple tumors usually raise suspicion of lesions arising in the context of MEN-1 [31].
Like other benign duodenal lesions, the majority of D-NETs are found incidentally on endoscopy. However, symptoms associated with D-NETs include abdominal pain, fatigue, and weight loss, but jaundice or pancreatitis can also be observed
in ampullary or periampullary tumors [27]. In addition, excess hormonal expression
can be indicative of functional tumors and is associated with clinical syndromes,
such as Zollinger-Ellison Syndrome (ZES), carcinoid syndrome, and Cushing’s disease [6, 30]. Specically, ampullary and periampullary D-NETs often present at
more advanced stages of disease and portend a worse survival than tumors found in
other anatomical locations of the duodenum [30–32].
On endoscopic diagnosis, D-NETs possess a submucosal appearance as white or
yellow-colored polyps with central dimpling or ulceration [28]. Endoscopic ultrasound (EUS) should also be conducted in order to conrm the size of the tumor and
depth of invasion. Also, since lymph node involvement and liver metastases may be
more frequently seen with the gastrinoma type of D-NETs, CT, and/or MRI can be
conducted in order to assess the burden of disease [28, 32]. Based on histology
subclassications, 50–60% of D-NETs are gastrinomas, 15% are somatostatinproducing tumors, 19–27% nonfunctional serotonin-containing tumors, <3% are
poorly differentiated neuroendocrine carcinomas, and <2% are gangliocytic paragangliomas [27]. Furthermore, histological grading of these lesions is essential for
their diagnosis and management. The current standard for NET grading is from the
World Health Organization (WHO), and it utilizes mitotic index and Ki-67 proliferation index to assess the relative risk of the tumor (Table11.2).
Considerations for treatment are dependent on the size and location of the tumor,
histological grade, and tumor type. While there is no consensus on the management
of D-NETs, proposed algorithms have been based on the ENETS guidelines [27,
Table 11.2 World Health Organization (WHO) classication of neuroendocrine tumor grades
Grade Mitotic rate (per 10 high power elds) Ki-67 index
G1, Low <2 <3%
G2, Intermediate 2–20 3–20%
G3, High >20 >20%
178
M. Hernandez et al.
32]. For non-ampullary or sub-centimeter Grade 1 lesions, endoscopic resection is
recommended. Patients with periampullary D-NETs or lesions larger than 2cm are
recommended to receive surgical resection. In addition, D-NETs of any size with
lymph node involvement should be considered for surgical resection. However, the
management of lesions between 1 and 2cm remains controversial, and the risks and
benets of endoscopic versus surgical resection should be weighed for these tumors.
Fig.11.3 demonstrates a 1.7cm ampullary D-NET on MRI (a), endoscopy (b) and
during robotic-assisted transduodenal resection.
For postoperative follow-up, the ENETS guidelines recommend abdominal
ultrasound, EGD, or CT surveillance and plasma chromogranin A (CgA) levels at 6,
24, and 36 months for patients who underwent endoscopic resection [32]. For
patients with surgically resected D-NETs, the recommended strategy includes CT
scan, somatostatin receptor scintigraphy or 68Ga-DOTATATE PET/CT, and plasma
CgA levels at 6- and 12-months following surgery, and then annually for a minimum of 3years [32]. NCCN guidelines recommend surveillance of resected patients
at 3–12months, and then subsequent follow-ups every 6–12months for 10years.
Other Non-neoplastic Epithelial Lesions
Non-neoplastic lesions may also be present in the duodenum. The histological classications of these lesions include Brunner’s gland hyperplastic polyps, hamartomas, and cysts, along with ectopic gastric mucosa, pancreatic heterotopia,
hyperplastic polyps, and inammatory polyps [6]. Some lesions, such as hamartomatous polyps, are syndromic and have been shown to be associated with PeutzJeghers syndrome, Cronkhite-Canada syndrome, Cowden syndrome, and juvenile
polyposis syndrome [6]. Endoscopic or surgical resection should be considered if
these lesions become large, symptomatic, or demonstrate dysplastic
characteristics.
abc
Fig. 11.3 Ampullary D-NET 1.7cm ampullary D-NET on MRI (a), endoscopy (b) and during
robotic-assisted transduodenal resection (c)
11 Benign, Premalignant, andMalignant Duodenal Neoplasms
179
Lesions ofMesenchymal Origin
Duodenal Gastrointestinal Stromal Tumors (DGISTs)
Duodenal gastrointestinal stromal tumors (DGISTs) are rare neoplasms arising
from interstitial cells of Cajal and are associated with high rates of malignancy [33].
While GISTs are the most common mesenchymal tumor found in the gastrointestinal tract, only 4–5% of these lesions are in the duodenum [34]. Most cases of
DGISTs occur sporadically, but these tumors have also been linked to hereditary
conditions, namely neurobromatosis type 1 and Carney triad, in 5–10% of patients
[35, 36]. These tumors may be found incidentally, especially if they are small in
size, but common clinical presentations of DGISTs include gastrointestinal bleeding and nonspecic abdominal pain.
Preoperative diagnosis of DGISTs most commonly involves gastrointestinal
endoscopy with forceps biopsy, especially for tumors possessing intramural growth
or ulceration [37]. For extraluminal tumors, CT scans or MRI are most frequently
utilized to diagnose the tumors. Endoscopic ultrasound (EUS) with ne-needle
aspiration (FNA) was found to have signicantly greater sensitivity and positive
predictive value in the diagnosis of DGISTs than CT or MRIs [36].
Immunohistochemistry can also be utilized to discern the diagnostic difference
between DGISTs and other mesenchymal lesions, as DGISTs are positive for c-Kit
(CD117) and CD34, but negative for S-100 [34]. Notably, the histologic subtypes of
DGISTs do not differ from GISTs found in other gastrointestinal locations, as these
tumors usually present with spindle cell differentiation; the mitotic count of DGISTs
has been shown to be lower than its gastric and small bowel counterparts [32].
In terms of treatment, traditional chemotherapy and radiation are not effective
against DGISTs, and thus, surgical resection remains the treatment of choice.
Current options for surgical resection of DGISTs include pancreaticoduodenectomy
or limited resection (i.e., segment or wedge duodenectomy), but there remains controversy over the preferred method. Compared to limited resection, performing a
pancreaticoduodenectomy allows for a wider resection margin that would mitigate
the risk of positive margins and local recurrence [38, 39]. On the other hand, limited
resection provides patients the opportunity to preserve pancreatic and gastrointestinal function, which would greatly reduce postoperative complications in the setting
of non-dilated biliary and pancreatic ducts [40]. Because of the technical challenges
and necessity for clear margins associated with DGISTs, endoscopic resections are
generally not performed, but hybrid endo-laparoscopic surgical techniques may
provide a less invasive approach to performing safe and effective resections for
these tumors [41–43].
In addition to surgery, tyrosine kinase inhibitors (TKIs), such as imatinib mesylate, have shown great efcacy as neoadjuvant and adjuvant treatments to reduce
morbidity and mortality associated with DGISTs. Specically, the vascular tumors
are transformed into cystic lesions and in some cases with reduction of size as well.
Figure11.4 demonstrates a large DGIST with a signicant response to neoadjuvant
180
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Fig. 11.4 Duodenal GIST as seen on CT on presentation (a) and after 6months of neoadjuvant
imatinib (b) with marked response and regression of tumor
M. Hernandez et al.
imatinib. One of the major limitations of imatinib mesylate is tumor resistance; this
is due to the development of additional c-KIT mutations in the tumor over time in
the setting of continued Imatinib use for persistent disease [34].
The recommended follow-up strategies for patients following DGIST resection
are dependent on patients’ respective risk of recurrence and treatment conditions.
For patients with less than intermediate risk of recurrence, annual abdominal CT
scans are sufcient for surveillance [44]. In high-risk patients being treated with
TKIs, follow-up imaging is suggested at 6-month intervals during treatment [44,
45]. Following the end of treatment, it is recommended for patients to receive imag-
ing every 3–4months during the rst 2years after adjuvant therapy, and then this
interval is extended to every 6–12months for up to 10years. Patients who do not
receive adjuvant therapy are recommended to obtain follow-up imaging every
3–4months during the rst few years following their surgery [45].
Leiomyoma
Leiomyomas of the duodenum are rare, benign neoplasms that arise from the
smooth muscle. These tumors may present asymptomatically as incidental ndings
on radiological scans, but common manifestations of symptoms include gastrointestinal hemorrhage, abdominal pain, and obstruction [46]. Upper endoscopy plays a
role in visualizing the lesion, and endoscopic biopsy can be utilized to obtain a
histologic diagnosis. In addition, immunohistochemistry is essential in the diagnosis of these lesions, as leiomyomas are positive for smooth muscle actin and desmin
but negative for S-100 protein [38]. The preferred treatment of choice for these
tumors is surgery, with either local tumor excision, segmental duodenectomy, or
pancreaticoduodenectomy. Less invasive techniques, such as endoscopic band ligation, may also play a role in providing a safe and effective resection for leiomyomas [47].
11 Benign, Premalignant, andMalignant Duodenal Neoplasms
181
Lipoma
Lipomas of the duodenum are benign, slow-growing tumors that predominantly
arise from the submucosa (90% of lesions) [48]. In addition, these lipomas are generally localized in the second portion of the duodenum and are often incidentally
found on endoscopy or surgery [48, 49]. On endoscopy, these tumors are characterized as being round or ovoid-shaped soft masses, accompanied with regular or lobulated contours [50]. While most cases present asymptomatically, symptoms do
occur depending on the lipoma’s size and location, as lesions larger than 4cm have
been shown to lead to intussusception, bleeding, or obstruction [48]. Based on the
size of the lipoma and associated symptoms, the recommended treatment is either
endoscopic or surgical resection. Small, solitary lipomas have been shown to be
effectively excised endoscopically through snare or endoloop-assisted polypectomy
[49, 50]. Surgical resection is preferred for larger lesions due to technical challenges
of endoscopy and potential risks of bleeding and perforation.
Neurogenic andVascular Lesions
Neurogenic and vascular lesions of the duodenum are characterized as masses arising from the nerves or blood and lymph vessels, respectively. Neuromas constitute
3–6% of all small intestine tumors and may occur in patients with neurobromatosis [51, 52]. These nerve tissue-derived lesions include neurobromas, schwannomas, and gangliomas. On the other hand, vascular lesions predominantly feature
hemangiomas and lymphangiomas. Neurogenic and vascular lesions are conventionally treated surgically with partial duodenectomy, but less invasive treatment
strategies, such as endoscopic resection, may be employed to effectively treat these
lesions [53].
Choledochal Cysts
Choledochal cysts represent a group of biliary cystic dilations of the extrahepatic
duct, intrahepatic duct, or both [54]. These can cause considerable patient-related
morbidity and mortality unless identied at an early stage and managed appropriately. Choledochal cysts are an uncommon congenital anomaly of the bile duct. The
incidence of this is 1in 100,000–150,000 live births worldwide [55]. However, the
incidence has been reported to be as high as 1in 13,500 individuals in the United
States and nearly as high as 1in 15,000in Australia [55]. The incidence of a choledochal cyst is higher in the Asian population with an incidence of nearly 1in 1000
individuals [55]. The majority of cases are reported to be from Japan.