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From the Archives of the AFIP

Abdominal Neoplasms in Patients with Neurofibromatosis Type 1: Radiologic-Pathologic Correlation¹

¹ From the Departments of Radiologic Pathology (A.D.L., R.M.A.), Hepatic and Gastrointestinal Pathology (N.D., L.H.S), and Soft Tissue Pathology (M.M.), Armed Forces Institute of Pathology, Alaska and Fern Sts NW, Washington, DC 20306-6000; Department of Medical Education, Washington Hospital Center, Washington, DC (N.P.); Department of Radiology, University of Maryland School of Medicine, Baltimore (R.M.A.); and Department of Radiology and Nuclear Medicine, Uniformed Services University of the Health Sciences, Bethesda, Md (A.D.L., R.M.A.). Received September 1, 2004; accepted September 20. All authors have no financial relationships to disclose. Address correspondence to A.D.L. (e-mail: levya{at}afip.osd.mil).

	Abstract

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction General Clinical Features Neurogenic Tumors Neuroendocrine Tumors Gastrointestinal Stromal Tumor Embryonal Tumors Adenocarcinoma Final Considerations for... References

 
Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders. NF1 is a complex disease resulting from a spectrum of mutations that may occur at many locations along the large, complex NF1 gene, which is located on chromosome 17. Mutations of the NF1 gene lead to abnormal tumor suppression. Consequently, patients with NF1 have an increased prevalence of benign and malignant neoplasms throughout the body. There are five categories of NF1 tumors that occur in the abdomen: neurogenic, neuroendocrine, nonneurogenic gastrointestinal mesenchymal, embryonal, and miscellaneous. Many of these tumors are age related, occur at specific anatomic locations, and have unique imaging features. Notably, many patients have a variety of organs affected because there is a high prevalence of multiple tumors occurring in the same patient. Neurofibromas are the most common benign neoplasms and may occur in the retroperitoneum or visceral organs. Malignant peripheral nerve sheath tumor is an aggressive malignancy that is the most common malignant tumor of the abdomen in patients with NF1. Interpreting abdominal imaging studies in patients with NF1 can be challenging because of the wide spectrum and diverse nature of tumors that occur in this disease.

Abbreviations: H-E = hematoxylin-eosin, MPNST = malignant peripheral nerve sheath tumor, NF1 = neurofibromatosis type 1

	LEARNING OBJECTIVES FOR TEST 6

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction General Clinical Features Neurogenic Tumors Neuroendocrine Tumors Gastrointestinal Stromal Tumor Embryonal Tumors Adenocarcinoma Final Considerations for... References

 
After reading this article and taking the test, the reader will be able to:

• Identify the clinical features of NF1.
  
• Describe the pathologic and radiologic features of abdominal neoplasms occurring in patients with NF1.
  
• Discuss the imaging evaluation of the abdomen in patients with NF1.
  

	Introduction

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction General Clinical Features Neurogenic Tumors Neuroendocrine Tumors Gastrointestinal Stromal Tumor Embryonal Tumors Adenocarcinoma Final Considerations for... References

 
Neurofibromatosis type 1 (NF1) is one of the most fascinating and common human mendelian disorders, affecting approximately one in 3000 persons (1). From the initial artist renderings of patients with NF1 in the 15th century and the earliest medical reports in 18th century, to the complex molecular genetic studies of the late 20th century, physicians and lay persons alike have been fascinated with this disease because of its diverse manifestations and the unusual and bizarre physical appearances associated with the disease. Also known as peripheral neurofibromatosis or von Recklinghausen disease, NF1 is inherited in an autosomal dominant pattern. The disease bears the name of Friedrich von Recklinghausen (1833–1910), a German pathologist, who was not the first to report the disease but was the first to recognize that the characteristic peripheral neurofibromas developed from nervous tissue (2).

Patients with NF1 are afflicted with a diverse group of lesions that are predominantly neuroectodermal or mesenchymal in origin. The large and complex NF1 gene, located on chromosome 17, encodes a protein named neurofibromin that works to control cellular proliferation through complex interactions with ras oncogenes (3). The resulting hyperplasias, hamartomas, and neoplasms (benign and malignant) occur in a variety of tissues and organs as a result of abnormal tumor suppression.

The clinical expression of NF1 is extremely variable. The cutaneous manifestations range from small nodular or pedunculated dermal neurofibromas and pigmentation abnormalities to large and grotesque diffuse and plexiform neurofibromas and bone dysplasias that interfere with organ function or alter the overall appearance of an individual through deformation or overgrowth of portions of the body. Many of the clinical and neoplastic manifestations of NF1 are age dependent, and they may vary among the affected members of a single family, emphasizing the need for physicians to be familiar with the entire disease spectrum.

Benign and malignant neoplasms may arise in the abdomen in both pediatric and adult patients with NF1. The abdominal neoplasms in NF1 can be divided into five basic categories: neurogenic tumors, neuroendocrine tumors, nonneurogenic gastrointestinal mesenchymal tumors, embryonal tumors, and miscellaneous tumors (Table 1).

	General Clinical Features

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NF1 belongs to a group of disorders referred to as phakomatoses. These disorders (NF1, neurofibromatosis type 2, tuberous sclerosis, Sturge-Weber syndrome, and neurocutaneous melanosis) have selective involvement of tissues of ectodermal origin (central nervous system, eye, and skin). All of these disorders, with the exception of Sturge-Weber syndrome, have an autosomal dominant inheritance pattern.

NF1 affects all races and both sexes equally, occurring in the population with a prevalence of approximately one in 3000 persons (1). Only 50% of patients with NF1 have a positive family history. In the remaining 50% of patients, the disorder represents a sporadic new mutation, a reflection of the high mutation rate of the NF1 gene (4). Although NF1 has high penetrance, expression is quite variable. Many patients with NF1 are only mildly affected.

The diagnosis of NF1 is largely based on clinical criteria established by the National Institutes of Health Consensus Development Conference (Table 2) (5). The most common clinical manifestations are café au lait spots, neurofibromas, Lisch nodules, and axillary or inguinal freckling. Café au lait spots are one of the earliest manifestations of NF1 and may be present at birth. Café au lait spots are pigmented cutaneous macules that are often oval in configuration (Fig 1). Freckling in NF1 occurs on intertriginous skin, and the finding of freckles less than 5 mm in size in the axillary, inguinal, submammary, or neck regions is so highly suggestive of NF1 that it may permit the diagnosis of NF1 in a young child whose only other manifestation is café au lait spots (5). In general, skin fold freckling appears between the ages of 3 and 5 years (5).

View larger version (126K): [in this window] [in a new window] [Download PPT slide]   Figure 1a.  Café au lait spots. (a) Clinical photograph of a 42-year-old woman with NF1 who had abdominal pain from mesenteric and small intestinal neurofibromas shows multiple café au lait spots (black arrows) and sessile cutaneous neurofibromas (white arrow) on the anterior abdomen. (b) Clinical photograph of a 24-year-old man with NF1 and MPNST metastatic to the peritoneal cavity shows a long, oval café au lait spot on his leg.

View larger version (115K): [in this window] [in a new window] [Download PPT slide]   Figure 1b.  Café au lait spots. (a) Clinical photograph of a 42-year-old woman with NF1 who had abdominal pain from mesenteric and small intestinal neurofibromas shows multiple café au lait spots (black arrows) and sessile cutaneous neurofibromas (white arrow) on the anterior abdomen. (b) Clinical photograph of a 24-year-old man with NF1 and MPNST metastatic to the peritoneal cavity shows a long, oval café au lait spot on his leg.

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure 2.  Lisch nodules. Clinical photograph of the iris in a patient with NF1 shows yellow and brown nodules (arrows) that are elevated above the iris surface and affect the entire area of the iris.

View larger version (124K): [in this window] [in a new window] [Download PPT slide]   Figure 3.  Innumerable cutaneous neurofibromas in a 74-year-old woman with NF1 who presented with melena and hematemesis from retroperitoneal MPNST invading the duodenum. Clinical photograph shows a pattern of sessile and pedunculated neurofibromas that is more typical of cutaneous neurofibromas affecting the trunk.

	Neurogenic Tumors

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Neurofibroma and Plexiform Neurofibroma
Clinical Features.— Neurofibromas are benign nerve sheath tumors and the hallmark lesion of NF1. Neurofibromas begin to appear during adolescence and may involve the skin, soft tissues, or viscera. Localized and plexiform neurofibromas of the paraspinal and sacral region are the most common abdominal neoplasm in NF1. The majority (65% of cases) are asymptomatic (8). Symptoms of abdominal neurofibromas include a palpable abdominal mass or pain along the distribution of a nerve.

Gastrointestinal involvement in NF1 is reported to occur in 10%–25% of patients (9). Neurofibromas are the most common neoplasm of the gastrointestinal tract in patients with NF1. The majority of gastrointestinal neurofibromas in NF1 are clinically occult. Symptomatic tumors are most common in the stomach and jejunum (10). The clinical manifestations vary depending on the location of the neurofibroma and the extent of mucosal involvement. Mucosal involvement may lead to occult or profound (hematemesis, melena, or hematochezia) gastrointestinal bleeding. Nausea, vomiting, and abdominal distension may be the presenting signs for patients who have intestinal obstruction from intussusception or volvulus secondary to gastrointestinal neurofibromas (11).

Genitourinary neurofibromas are rare. The bladder is the most common genitourinary organ affected by neurofibromas. Most patients with bladder involvement present with symptoms such as urinary frequency, incontinence, urgency, or abdominal pain (12). Asymptomatic bladder neurofibromas are uncommon.

Pathologic Features.— Neurofibromas are categorized as localized, plexiform, or diffuse. Localized intraneural neurofibromas are well-defined fusiform or diffuse lesions that appear confined to the affected nerve at gross inspection (7). They appear gray to tan on cut sections and may have focal areas of heterogeneity reflecting variable collagen content. At microscopic analysis, neurofibromas are composed of Schwann cells and fibroblasts in a myxoid or mucinous matrix with surrounding collagen. Residual myelinated nerve fibers may be present within the tumor and can be demonstrated with immunostaining for S-100 protein.

Plexiform neurofibromas are congenital lesions that occur exclusively in patients with NF1. Although the natural history of plexiform neurofibromas has not been clearly elucidated, they do have potential for malignant transformation to MPNST. Plexiform neurofibromas involve a nerve plexus or multiple fascicles in a medium- to large-sized nerve. The involved nerves retain their original configuration and anatomy and are altered into complex, tortuous masses. The term ropelike has been applied to the macroscopic appearance of plexiform neurofibromas that involve nonbranching nerves, and the term bag of worms has been used to refer to plexiform neurofibromas of highly branching nerves (7).

The fascicles of plexiform neurofibromas may have a rubbery texture from their myxoid matrix or may be firm when they contain abundant collagen (7). The majority of neurofibromas affecting the abdominal viscera and mesentery in patients with NF1 are plexiform neurofibromas. Plexiform neurofibromas share the same basic histologic features seen with intraneural neurofibromas, but they are organized into multiple fascicular units (Fig 4). A myxoid matrix is typical of plexiform neurofibromas; however, as these tumors enlarge, they become more cellular and collagenous (7).

View larger version (176K): [in this window] [in a new window] [Download PPT slide]   Figure 4a.  Histologic features of plexiform neurofibroma. (a) Photomicrograph (original magnification, x10; hematoxylin-eosin [H-E] stain) shows the fascicular arrangement of the tumor. Some fascicles are mucin rich (arrow). (b) Photomicrograph at higher magnification (original magnification, x16; H-E stain) shows dense, spindle-shaped curved nuclei mixed with eosinophilic collagen and basophilic myxoid matrix.

View larger version (193K): [in this window] [in a new window] [Download PPT slide]   Figure 4b.  Histologic features of plexiform neurofibroma. (a) Photomicrograph (original magnification, x10; hematoxylin-eosin [H-E] stain) shows the fascicular arrangement of the tumor. Some fascicles are mucin rich (arrow). (b) Photomicrograph at higher magnification (original magnification, x16; H-E stain) shows dense, spindle-shaped curved nuclei mixed with eosinophilic collagen and basophilic myxoid matrix.

Diffuse neurofibromas may also occur in NF1. They are most common in the subcutaneous tissues and rarely involve intraabdominal structures. They are typically plaquelike masses that contain diffuse microscopic fat (14). One of the most important microscopic features of all forms of neurofibromas is evidence of soft-tissue infiltration. Even though neurofibromas may appear as well-defined masses at gross inspection, they frequently infiltrate into adjacent adipose, muscle, or viscera. Thus, local recurrences are common after surgical resection.

Radiologic Features.— The most common abdominal locations for neurofibromas are the paraspinal and presacral regions in the distribution of the lumbosacral plexus (15). Lumbosacral neurofibromas are usually of the plexiform type. On sonograms, retroperitoneal and paraspinal neurofibromas are typically heterogeneous in echotexture with variable through transmission (Fig 5) (16). On computed tomographic (CT) scans, paraspinal neurofibromas are hypoattenuating, symmetric or asymmetric masses within or adjacent to the psoas muscles (Fig 5). They may involve single or multiple vertebral body levels. Enlargement of the adjacent neural foramen is present in 30% of patients with paraspinal lesions (Fig 6) (8).

View larger version (89K): [in this window] [in a new window] [Download PPT slide]   Figure 5a.  Bilateral psoas neurofibromas in a 32-year-old woman with NF1 who presented to the emergency department with right lower abdominal pain and nausea. (a) Longitudinal sonogram of the right lower quadrant shows a 10-cm oval heterogeneously hypoechoic mass. (b, c) Intravenous contrast material–enhanced CT scans show a hypoattenuating mass (arrow in b) containing focal areas of high attenuation arising from the right psoas muscle and a smaller hypoattenuating mass (arrowhead in c) in the left psoas muscle. (d) Photograph of the cut surface of the resected specimen from the right psoas muscle shows an oval, rubbery, tan mass surrounded by a thin fibrous capsule.

View larger version (106K): [in this window] [in a new window] [Download PPT slide]   Figure 5b.  Bilateral psoas neurofibromas in a 32-year-old woman with NF1 who presented to the emergency department with right lower abdominal pain and nausea. (a) Longitudinal sonogram of the right lower quadrant shows a 10-cm oval heterogeneously hypoechoic mass. (b, c) Intravenous contrast material–enhanced CT scans show a hypoattenuating mass (arrow in b) containing focal areas of high attenuation arising from the right psoas muscle and a smaller hypoattenuating mass (arrowhead in c) in the left psoas muscle. (d) Photograph of the cut surface of the resected specimen from the right psoas muscle shows an oval, rubbery, tan mass surrounded by a thin fibrous capsule.

View larger version (108K): [in this window] [in a new window] [Download PPT slide]   Figure 5c.  Bilateral psoas neurofibromas in a 32-year-old woman with NF1 who presented to the emergency department with right lower abdominal pain and nausea. (a) Longitudinal sonogram of the right lower quadrant shows a 10-cm oval heterogeneously hypoechoic mass. (b, c) Intravenous contrast material–enhanced CT scans show a hypoattenuating mass (arrow in b) containing focal areas of high attenuation arising from the right psoas muscle and a smaller hypoattenuating mass (arrowhead in c) in the left psoas muscle. (d) Photograph of the cut surface of the resected specimen from the right psoas muscle shows an oval, rubbery, tan mass surrounded by a thin fibrous capsule.

View larger version (108K): [in this window] [in a new window] [Download PPT slide]   Figure 5d.  Bilateral psoas neurofibromas in a 32-year-old woman with NF1 who presented to the emergency department with right lower abdominal pain and nausea. (a) Longitudinal sonogram of the right lower quadrant shows a 10-cm oval heterogeneously hypoechoic mass. (b, c) Intravenous contrast material–enhanced CT scans show a hypoattenuating mass (arrow in b) containing focal areas of high attenuation arising from the right psoas muscle and a smaller hypoattenuating mass (arrowhead in c) in the left psoas muscle. (d) Photograph of the cut surface of the resected specimen from the right psoas muscle shows an oval, rubbery, tan mass surrounded by a thin fibrous capsule.

View larger version (125K): [in this window] [in a new window] [Download PPT slide]   Figure 6a.  Bilateral plexiform neurofibromas of the lumbosacral plexus in a 25-year-old man with a family history of NF1. He presented to the emergency department complaining of abdominal pain following a motor vehicle accident. Intravenous contrast-enhanced CT scans show bilateral psoas masses. The mass on the right is large, lobular, and hypoattenuating with patchy contrast enhancement. It enlarges and extends into the adjacent neural foramen (arrow in a). Multiple branches of the inferior right lumbosacral plexus (arrowheads) are involved, including the femoral nerve adjacent to the external iliac vessels. The lower sacral foramina (curved arrow in c) are enlarged bilaterally.

View larger version (125K): [in this window] [in a new window] [Download PPT slide]   Figure 6b.  Bilateral plexiform neurofibromas of the lumbosacral plexus in a 25-year-old man with a family history of NF1. He presented to the emergency department complaining of abdominal pain following a motor vehicle accident. Intravenous contrast-enhanced CT scans show bilateral psoas masses. The mass on the right is large, lobular, and hypoattenuating with patchy contrast enhancement. It enlarges and extends into the adjacent neural foramen (arrow in a). Multiple branches of the inferior right lumbosacral plexus (arrowheads) are involved, including the femoral nerve adjacent to the external iliac vessels. The lower sacral foramina (curved arrow in c) are enlarged bilaterally.

View larger version (121K): [in this window] [in a new window] [Download PPT slide]   Figure 6c.  Bilateral plexiform neurofibromas of the lumbosacral plexus in a 25-year-old man with a family history of NF1. He presented to the emergency department complaining of abdominal pain following a motor vehicle accident. Intravenous contrast-enhanced CT scans show bilateral psoas masses. The mass on the right is large, lobular, and hypoattenuating with patchy contrast enhancement. It enlarges and extends into the adjacent neural foramen (arrow in a). Multiple branches of the inferior right lumbosacral plexus (arrowheads) are involved, including the femoral nerve adjacent to the external iliac vessels. The lower sacral foramina (curved arrow in c) are enlarged bilaterally.

The nerves of the mesenteric, subserosal, and myenteric plexuses give rise to neurofibromas and plexiform neurofibromas of the mesentery and gastrointestinal tract. Mesenteric plexiform neurofibromas manifest as multiple discrete nodules or infiltrating lesions that extend from the root of the mesentery to the wall of the intestine (16,19–21). On sonograms, they appear as well-defined masses that are homogeneously or heterogeneously hypoechoic in echotexture. On CT scans, the lesions are iso- or hypoattenuating compared with adjacent soft tissue. Those lesions occurring in the perirectal region often manifest as infiltration of the perirectal fat and may extend to involve adjacent pelvic structures such as the vagina or uterus (8).

Mesenteric neurofibromas may encroach on the adjacent intestine, producing mass effect on the serosal surface, or may infiltrate into the intestinal wall, producing submucosal or mucosal masses (19). Conventional barium examination of the intestine may reveal displacement of the intestine, mural rigidity, external mass effect, sub-mucosal or mucosal masses or polyps, and mucosal ulcers (Figs 7, 8). Neurofibromas that infiltrate through the intestinal wall appear as focal or diffuse soft-tissue attenuation mural thickening.

View larger version (110K): [in this window] [in a new window] [Download PPT slide]   Figure 7a.  Plexiform neurofibroma of the mesentery in a 10-year-old girl with NF1 who complained of chronic abdominal pain. (a–c) Intravenous contrast-enhanced CT scans show a large, multilobulated hypoattenuating mass arising from the sigmoid mesentery (* in a). There are extensive plexiform neurofibromas involving the lumbosacral plexus (arrows). (d) Image from an air contrast barium enema study shows leftward displacement and scalloping of the medial margin of the sigmoid colon (arrows). (e) Photograph of the cut surface of the resected mesenteric mass shows a lobulated mass composed of numerous mucoid plexiform neurofibromas. Cystic degeneration is also present. The mass partially encircles the sigmoid colon (arrow).

View larger version (120K): [in this window] [in a new window] [Download PPT slide]   Figure 7b.  Plexiform neurofibroma of the mesentery in a 10-year-old girl with NF1 who complained of chronic abdominal pain. (a–c) Intravenous contrast-enhanced CT scans show a large, multilobulated hypoattenuating mass arising from the sigmoid mesentery (* in a). There are extensive plexiform neurofibromas involving the lumbosacral plexus (arrows). (d) Image from an air contrast barium enema study shows leftward displacement and scalloping of the medial margin of the sigmoid colon (arrows). (e) Photograph of the cut surface of the resected mesenteric mass shows a lobulated mass composed of numerous mucoid plexiform neurofibromas. Cystic degeneration is also present. The mass partially encircles the sigmoid colon (arrow).

View larger version (121K): [in this window] [in a new window] [Download PPT slide]   Figure 7c.  Plexiform neurofibroma of the mesentery in a 10-year-old girl with NF1 who complained of chronic abdominal pain. (a–c) Intravenous contrast-enhanced CT scans show a large, multilobulated hypoattenuating mass arising from the sigmoid mesentery (* in a). There are extensive plexiform neurofibromas involving the lumbosacral plexus (arrows). (d) Image from an air contrast barium enema study shows leftward displacement and scalloping of the medial margin of the sigmoid colon (arrows). (e) Photograph of the cut surface of the resected mesenteric mass shows a lobulated mass composed of numerous mucoid plexiform neurofibromas. Cystic degeneration is also present. The mass partially encircles the sigmoid colon (arrow).

View larger version (159K): [in this window] [in a new window] [Download PPT slide]   Figure 7d.  Plexiform neurofibroma of the mesentery in a 10-year-old girl with NF1 who complained of chronic abdominal pain. (a–c) Intravenous contrast-enhanced CT scans show a large, multilobulated hypoattenuating mass arising from the sigmoid mesentery (* in a). There are extensive plexiform neurofibromas involving the lumbosacral plexus (arrows). (d) Image from an air contrast barium enema study shows leftward displacement and scalloping of the medial margin of the sigmoid colon (arrows). (e) Photograph of the cut surface of the resected mesenteric mass shows a lobulated mass composed of numerous mucoid plexiform neurofibromas. Cystic degeneration is also present. The mass partially encircles the sigmoid colon (arrow).

View larger version (159K): [in this window] [in a new window] [Download PPT slide]   Figure 7e.  Plexiform neurofibroma of the mesentery in a 10-year-old girl with NF1 who complained of chronic abdominal pain. (a–c) Intravenous contrast-enhanced CT scans show a large, multilobulated hypoattenuating mass arising from the sigmoid mesentery (* in a). There are extensive plexiform neurofibromas involving the lumbosacral plexus (arrows). (d) Image from an air contrast barium enema study shows leftward displacement and scalloping of the medial margin of the sigmoid colon (arrows). (e) Photograph of the cut surface of the resected mesenteric mass shows a lobulated mass composed of numerous mucoid plexiform neurofibromas. Cystic degeneration is also present. The mass partially encircles the sigmoid colon (arrow).

View larger version (126K): [in this window] [in a new window] [Download PPT slide]   Figure 8a.  Ileal plexiform neurofibromas discovered in a routine pelvic examination of a 40-year-old asymptomatic woman with NF1. (a) Image from a small bowel barium study shows irregular narrowing of a long segment of distal ileum caused by intramural and intraluminal neurofibromas. The affected segment of ileum is displaced into the pelvis and separated from adjacent segments of intestine. (b) Intravenous contrast-enhanced CT scan shows homogeneous circumferential mural thickening (arrows) of the involved ileal segment. (c) Photograph of the opened resected ileum shows multiple intraluminal polypoid nodules of varying size on the mucosal surface.

View larger version (120K): [in this window] [in a new window] [Download PPT slide]   Figure 8b.  Ileal plexiform neurofibromas discovered in a routine pelvic examination of a 40-year-old asymptomatic woman with NF1. (a) Image from a small bowel barium study shows irregular narrowing of a long segment of distal ileum caused by intramural and intraluminal neurofibromas. The affected segment of ileum is displaced into the pelvis and separated from adjacent segments of intestine. (b) Intravenous contrast-enhanced CT scan shows homogeneous circumferential mural thickening (arrows) of the involved ileal segment. (c) Photograph of the opened resected ileum shows multiple intraluminal polypoid nodules of varying size on the mucosal surface.

View larger version (127K): [in this window] [in a new window] [Download PPT slide]   Figure 8c.  Ileal plexiform neurofibromas discovered in a routine pelvic examination of a 40-year-old asymptomatic woman with NF1. (a) Image from a small bowel barium study shows irregular narrowing of a long segment of distal ileum caused by intramural and intraluminal neurofibromas. The affected segment of ileum is displaced into the pelvis and separated from adjacent segments of intestine. (b) Intravenous contrast-enhanced CT scan shows homogeneous circumferential mural thickening (arrows) of the involved ileal segment. (c) Photograph of the opened resected ileum shows multiple intraluminal polypoid nodules of varying size on the mucosal surface.

View larger version (167K): [in this window] [in a new window] [Download PPT slide]   Figure 9a.  Plexiform neurofibromas of the mesentery and small intestine in a 42-year-old woman with NF1 who was being evaluated for cervical carcinoma. (a) Image from a small bowel barium study shows scalloping of the mesenteric border of the small intestine and intraluminal polyps (arrows). The affected segment of small intestine is displaced into the pelvis away from the root of the small bowel mesentery. (b) Photograph of opened resected small intestine shows multiple mural masses and mucosal polyps (arrows).

View larger version (130K): [in this window] [in a new window] [Download PPT slide]   Figure 9b.  Plexiform neurofibromas of the mesentery and small intestine in a 42-year-old woman with NF1 who was being evaluated for cervical carcinoma. (a) Image from a small bowel barium study shows scalloping of the mesenteric border of the small intestine and intraluminal polyps (arrows). The affected segment of small intestine is displaced into the pelvis away from the root of the small bowel mesentery. (b) Photograph of opened resected small intestine shows multiple mural masses and mucosal polyps (arrows).

View larger version (108K): [in this window] [in a new window] [Download PPT slide]   Figure 10a.  Plexiform neurofibromatosis of the colon in a 9-year-old boy with previously unrecognized NF1 who was being evaluated for an asymptomatic palpable abdominal mass. (a–c) Intravenous contrast-enhanced CT scans (obtained at successively lower levels) show mural thickening (arrows) of the transverse (a), descending (b), and rectosigmoid (c) colon. (d) Photograph of the opened resected colon shows the complex, tortuous, "wormlike," plexiform neurofibromas (arrows) expanding the submucosal layers of the colonic wall.

View larger version (120K): [in this window] [in a new window] [Download PPT slide]   Figure 10b.  Plexiform neurofibromatosis of the colon in a 9-year-old boy with previously unrecognized NF1 who was being evaluated for an asymptomatic palpable abdominal mass. (a–c) Intravenous contrast-enhanced CT scans (obtained at successively lower levels) show mural thickening (arrows) of the transverse (a), descending (b), and rectosigmoid (c) colon. (d) Photograph of the opened resected colon shows the complex, tortuous, "wormlike," plexiform neurofibromas (arrows) expanding the submucosal layers of the colonic wall.

View larger version (107K): [in this window] [in a new window] [Download PPT slide]   Figure 10c.  Plexiform neurofibromatosis of the colon in a 9-year-old boy with previously unrecognized NF1 who was being evaluated for an asymptomatic palpable abdominal mass. (a–c) Intravenous contrast-enhanced CT scans (obtained at successively lower levels) show mural thickening (arrows) of the transverse (a), descending (b), and rectosigmoid (c) colon. (d) Photograph of the opened resected colon shows the complex, tortuous, "wormlike," plexiform neurofibromas (arrows) expanding the submucosal layers of the colonic wall.

View larger version (118K): [in this window] [in a new window] [Download PPT slide]   Figure 10d.  Plexiform neurofibromatosis of the colon in a 9-year-old boy with previously unrecognized NF1 who was being evaluated for an asymptomatic palpable abdominal mass. (a–c) Intravenous contrast-enhanced CT scans (obtained at successively lower levels) show mural thickening (arrows) of the transverse (a), descending (b), and rectosigmoid (c) colon. (d) Photograph of the opened resected colon shows the complex, tortuous, "wormlike," plexiform neurofibromas (arrows) expanding the submucosal layers of the colonic wall.

View larger version (129K): [in this window] [in a new window] [Download PPT slide]   Figure 11a.  Plexiform neurofibroma of the rectosigmoid colon in a 5-year-old girl with a 3-year history of constipation and previously unrecognized NF1. (a) Coronal T1-weighted MR image shows a thick hypointense thickening of the rectal wall. (b) Axial T2-weighted MR image shows a ringlike pattern (black arrows) to the hyperintense plexiform neurofibroma. The tumor also encircles the vagina and urethra. A plexiform neurofibroma of the left sacral plexus is also present (white arrow). (c) Photograph of the resected specimen shows the nodular cut surface of the plexiform neurofibroma that arose from the rectal wall.

View larger version (124K): [in this window] [in a new window] [Download PPT slide]   Figure 11b.  Plexiform neurofibroma of the rectosigmoid colon in a 5-year-old girl with a 3-year history of constipation and previously unrecognized NF1. (a) Coronal T1-weighted MR image shows a thick hypointense thickening of the rectal wall. (b) Axial T2-weighted MR image shows a ringlike pattern (black arrows) to the hyperintense plexiform neurofibroma. The tumor also encircles the vagina and urethra. A plexiform neurofibroma of the left sacral plexus is also present (white arrow). (c) Photograph of the resected specimen shows the nodular cut surface of the plexiform neurofibroma that arose from the rectal wall.

View larger version (134K): [in this window] [in a new window] [Download PPT slide]   Figure 11c.  Plexiform neurofibroma of the rectosigmoid colon in a 5-year-old girl with a 3-year history of constipation and previously unrecognized NF1. (a) Coronal T1-weighted MR image shows a thick hypointense thickening of the rectal wall. (b) Axial T2-weighted MR image shows a ringlike pattern (black arrows) to the hyperintense plexiform neurofibroma. The tumor also encircles the vagina and urethra. A plexiform neurofibroma of the left sacral plexus is also present (white arrow). (c) Photograph of the resected specimen shows the nodular cut surface of the plexiform neurofibroma that arose from the rectal wall.

View larger version (117K): [in this window] [in a new window] [Download PPT slide]   Figure 12a.  Degenerating hepatic neurofibroma in a 23-year-old man with NF1 who complained of nausea and vomiting. (a) Longitudinal sonogram of the right lobe of the liver shows a solitary, complex, and echogenic mass. (b) Intravenous contrast-enhanced CT scan shows a heterogeneously hypointense mass with ill-defined borders in the right lobe of the liver.

View larger version (137K): [in this window] [in a new window] [Download PPT slide]   Figure 12b.  Degenerating hepatic neurofibroma in a 23-year-old man with NF1 who complained of nausea and vomiting. (a) Longitudinal sonogram of the right lobe of the liver shows a solitary, complex, and echogenic mass. (b) Intravenous contrast-enhanced CT scan shows a heterogeneously hypointense mass with ill-defined borders in the right lobe of the liver.

View larger version (137K): [in this window] [in a new window] [Download PPT slide]   Figure 13a.  Periportal plexiform neurofibromas and bilateral pheochromocytomas in a 44-year-old man with NF1 and uncontrolled hypertension. Intravenous contrast-enhanced CT scans (a obtained at a higher level than b) show a low-attenuation plexiform neurofibroma infiltrating through the hepatic hilum and periportal spaces throughout the liver (arrowheads). There are bilateral mixed-attenuation pheochromocytomas (arrows).

View larger version (138K): [in this window] [in a new window] [Download PPT slide]   Figure 13b.  Periportal plexiform neurofibromas and bilateral pheochromocytomas in a 44-year-old man with NF1 and uncontrolled hypertension. Intravenous contrast-enhanced CT scans (a obtained at a higher level than b) show a low-attenuation plexiform neurofibroma infiltrating through the hepatic hilum and periportal spaces throughout the liver (arrowheads). There are bilateral mixed-attenuation pheochromocytomas (arrows).

View larger version (123K): [in this window] [in a new window] [Download PPT slide]   Figure 14a.  Diffuse abdominal and retroperitoneal plexiform neurofibromatosis in an 11-year-old boy who complained of increasing abdominal girth. Intravenous contrast-enhanced CT scans (a obtained at a higher level than b) show low-attenuation plexiform neurofibromas infiltrating throughout the hepatic hilum, paraaortic regions, small bowel mesentery, greater omentum, and retrocrural space.

View larger version (113K): [in this window] [in a new window] [Download PPT slide]   Figure 14b.  Diffuse abdominal and retroperitoneal plexiform neurofibromatosis in an 11-year-old boy who complained of increasing abdominal girth. Intravenous contrast-enhanced CT scans (a obtained at a higher level than b) show low-attenuation plexiform neurofibromas infiltrating throughout the hepatic hilum, paraaortic regions, small bowel mesentery, greater omentum, and retrocrural space.

View larger version (80K): [in this window] [in a new window] [Download PPT slide]   Figure 15a.  Plexiform neurofibroma of the bladder in an 8-year-old girl with café au lait spots and inguinal freckling who presented with hematuria. (a) Sonogram of the bladder shows heterogeneous thickening of the posterior bladder wall (*). (b, c) Intravenous contrast-enhanced CT scans show a low-attenuation mass along the posterior wall of the bladder (* in b). The mass extends into the posterior pelvis and encircles the vagina and rectum (arrows in c).

View larger version (101K): [in this window] [in a new window] [Download PPT slide]   Figure 15b.  Plexiform neurofibroma of the bladder in an 8-year-old girl with café au lait spots and inguinal freckling who presented with hematuria. (a) Sonogram of the bladder shows heterogeneous thickening of the posterior bladder wall (*). (b, c) Intravenous contrast-enhanced CT scans show a low-attenuation mass along the posterior wall of the bladder (* in b). The mass extends into the posterior pelvis and encircles the vagina and rectum (arrows in c).

View larger version (93K): [in this window] [in a new window] [Download PPT slide]   Figure 15c.  Plexiform neurofibroma of the bladder in an 8-year-old girl with café au lait spots and inguinal freckling who presented with hematuria. (a) Sonogram of the bladder shows heterogeneous thickening of the posterior bladder wall (*). (b, c) Intravenous contrast-enhanced CT scans show a low-attenuation mass along the posterior wall of the bladder (* in b). The mass extends into the posterior pelvis and encircles the vagina and rectum (arrows in c).

View larger version (111K): [in this window] [in a new window] [Download PPT slide]   Figure 16a.  Plexiform neurofibroma of the bladder in an 18-year-old man with known NF1 who developed renal insufficiency from chronic bilateral ureteral obstruction. (a) Unenhanced CT scan shows a low-attenuation mass thickening the posterior and left lateral bladder wall. There are high-attenuation septa (arrow) and nodules in the mass from the collagenous septa within the neurofibroma. (b) Photograph of the cut surface of the resected bladder specimen shows innumerable nodules (arrow) from cross sectioning the plexiform neurofibroma.

View larger version (96K): [in this window] [in a new window] [Download PPT slide]   Figure 16b.  Plexiform neurofibroma of the bladder in an 18-year-old man with known NF1 who developed renal insufficiency from chronic bilateral ureteral obstruction. (a) Unenhanced CT scan shows a low-attenuation mass thickening the posterior and left lateral bladder wall. There are high-attenuation septa (arrow) and nodules in the mass from the collagenous septa within the neurofibroma. (b) Photograph of the cut surface of the resected bladder specimen shows innumerable nodules (arrow) from cross sectioning the plexiform neurofibroma.

View larger version (121K): [in this window] [in a new window] [Download PPT slide]   Figure 17a.  Plexiform neurofibromas of the bladder and prostate in a 21-year-old man with NF1 who was being evaluated for infertility. (a) Sagittal T1-weighted MR image shows a large hypointense mass (*) infiltrating the posterior bladder wall. The mass extends inferiorly to involve the prostate (arrow) and perineum. (b) Axial T2-weighted MR image shows a ringlike (arrow) and septated pattern, consistent with the fascicular pattern of plexiform neurofibromas.

View larger version (133K): [in this window] [in a new window] [Download PPT slide]   Figure 17b.  Plexiform neurofibromas of the bladder and prostate in a 21-year-old man with NF1 who was being evaluated for infertility. (a) Sagittal T1-weighted MR image shows a large hypointense mass (*) infiltrating the posterior bladder wall. The mass extends inferiorly to involve the prostate (arrow) and perineum. (b) Axial T2-weighted MR image shows a ringlike (arrow) and septated pattern, consistent with the fascicular pattern of plexiform neurofibromas.

When MPNST develops in patients with NF1, the tumor is diagnosed when the patients are younger (mean, 26 years) and has a poorer prognosis, compared with MPNSTs in patients without NF1 (30). Moreover, those tumors that arise in central locations such as the paraspinal region of the retroperitoneum are associated with lower 5-year survival rates, higher recurrence rates, and higher frequency of metastasis compared with tumors in other body sites (31,32).

MPNST arising in an extremity most commonly manifests as a painful mass (33). In contrast, those tumors that arise in the abdomen and retroperitoneum are often clinically silent (30). MPNST may also produce neurologic deficits in the distribution of the affected nerve.

Pathologic Features.— MPNST is a large, globular or fusiform mass that frequently exceeds 5 cm in diameter (7). The associated nerve of origin or preexisting plexiform neurofibroma may or may not be evident at gross inspection. The majority of tumors have fibrous pseudocapsules. On the cut surface, necrosis is present in 60% of cases (7).

At histologic analysis, the tumor is composed of spindle cells organized in fascicles, in a herring-bone pattern, or less commonly without a pattern (Fig 18). Necrosis and vascular proliferation are often present (14). MPNST is typically a high-grade tumor with a high mitotic rate (14). In rare cases, the MPNST may be called a malignant triton tumor because it has histologic evidence of rhabdomyosarcomatous differentiation.

View larger version (159K): [in this window] [in a new window] [Download PPT slide]   Figure 18.  Spindled MPNST. Photomicrograph (original magnification, x10; H-E stain) shows a spindle cell MPNST arising from an intra-neural neurofibroma (*). There is geographic necrosis (arrow) within the highly cellular MPNST.

View larger version (127K): [in this window] [in a new window] [Download PPT slide]   Figure 19a.  MPNST in a 20-year-old woman with NF1 who presented with right lower extremity pain and weakness. Unenhanced CT scans (a obtained at a higher level than b) show a large right pelvic mass (*) contiguous with the right iliopsoas muscle. The mass contains multiple areas of low-attenuation necrosis. There are plexiform neurofibromas of the sacral plexus (arrows) that widen the sacral foramina bilaterally and extend anteriorly into the pelvis.

View larger version (126K): [in this window] [in a new window] [Download PPT slide]   Figure 19b.  MPNST in a 20-year-old woman with NF1 who presented with right lower extremity pain and weakness. Unenhanced CT scans (a obtained at a higher level than b) show a large right pelvic mass (*) contiguous with the right iliopsoas muscle. The mass contains multiple areas of low-attenuation necrosis. There are plexiform neurofibromas of the sacral plexus (arrows) that widen the sacral foramina bilaterally and extend anteriorly into the pelvis.

View larger version (118K): [in this window] [in a new window] [Download PPT slide]   Figure 20a.  Retroperitoneal MPNST with rhabdomyosarcomatous differentiation (triton tumor) in a 22-year-old man with NF1 who complained of left thigh pain and a 20-pound weight loss over 3 months. (a) Coronal T1-weighted MR image shows a large hypointense left retroperitoneal mass (*). (b) Coronal T2-weighted MR image shows a mixed-signal-intensity mass that has a central area of higher signal intensity representing necrosis (arrow). (c) Gadolinium-enhanced T1-weighted image shows heterogeneously enhancing peripheral viable tumor and low-signal-intensity central necrosis (arrow). (d) Photograph of the resected, sectioned mass shows focal areas of necrosis and cyst formation. There is a thin, fibrous pseudocapsule (arrow).

View larger version (123K): [in this window] [in a new window] [Download PPT slide]   Figure 20b.  Retroperitoneal MPNST with rhabdomyosarcomatous differentiation (triton tumor) in a 22-year-old man with NF1 who complained of left thigh pain and a 20-pound weight loss over 3 months. (a) Coronal T1-weighted MR image shows a large hypointense left retroperitoneal mass (*). (b) Coronal T2-weighted MR image shows a mixed-signal-intensity mass that has a central area of higher signal intensity representing necrosis (arrow). (c) Gadolinium-enhanced T1-weighted image shows heterogeneously enhancing peripheral viable tumor and low-signal-intensity central necrosis (arrow). (d) Photograph of the resected, sectioned mass shows focal areas of necrosis and cyst formation. There is a thin, fibrous pseudocapsule (arrow).

View larger version (126K): [in this window] [in a new window] [Download PPT slide]   Figure 20c.  Retroperitoneal MPNST with rhabdomyosarcomatous differentiation (triton tumor) in a 22-year-old man with NF1 who complained of left thigh pain and a 20-pound weight loss over 3 months. (a) Coronal T1-weighted MR image shows a large hypointense left retroperitoneal mass (*). (b) Coronal T2-weighted MR image shows a mixed-signal-intensity mass that has a central area of higher signal intensity representing necrosis (arrow). (c) Gadolinium-enhanced T1-weighted image shows heterogeneously enhancing peripheral viable tumor and low-signal-intensity central necrosis (arrow). (d) Photograph of the resected, sectioned mass shows focal areas of necrosis and cyst formation. There is a thin, fibrous pseudocapsule (arrow).

View larger version (130K): [in this window] [in a new window] [Download PPT slide]   Figure 20d.  Retroperitoneal MPNST with rhabdomyosarcomatous differentiation (triton tumor) in a 22-year-old man with NF1 who complained of left thigh pain and a 20-pound weight loss over 3 months. (a) Coronal T1-weighted MR image shows a large hypointense left retroperitoneal mass (*). (b) Coronal T2-weighted MR image shows a mixed-signal-intensity mass that has a central area of higher signal intensity representing necrosis (arrow). (c) Gadolinium-enhanced T1-weighted image shows heterogeneously enhancing peripheral viable tumor and low-signal-intensity central necrosis (arrow). (d) Photograph of the resected, sectioned mass shows focal areas of necrosis and cyst formation. There is a thin, fibrous pseudocapsule (arrow).

View larger version (120K): [in this window] [in a new window] [Download PPT slide]   Figure 21a.  MPNST of the mesentery in a 36-year-old man with NF1 who presented with an enlarging left upper quadrant mass. Intravenous contrast-enhanced CT scans show a mass (* in a) in the small bowel mesentery that invades the left abdominal wall (black arrowheads). The mass has a large area of low-attenuation necrosis and is surrounded by a thin capsule (black arrow in a). The patient also has subcutaneous neurofibromas (white arrowheads) and parapsoas plexiform neurofibromas (white arrows in a).

View larger version (125K): [in this window] [in a new window] [Download PPT slide]   Figure 21b.  MPNST of the mesentery in a 36-year-old man with NF1 who presented with an enlarging left upper quadrant mass. Intravenous contrast-enhanced CT scans show a mass (* in a) in the small bowel mesentery that invades the left abdominal wall (black arrowheads). The mass has a large area of low-attenuation necrosis and is surrounded by a thin capsule (black arrow in a). The patient also has subcutaneous neurofibromas (white arrowheads) and parapsoas plexiform neurofibromas (white arrows in a).

Ganglioneuroma and Ganglioneuromatosis
Clinical Features.— Ganglioneuromas are rare, benign neoplasms that arise from sympathetic ganglia. They may occur anywhere along the paravertebral sympathetic plexus; in the adrenal gland; and, in rare cases, in the gastrointestinal tract. Gastrointestinal ganglioneuromas may manifest as focal polypoid lesions (ganglioneuromas), multifocal polyps (ganglioneuromatous polyposis), or diffuse infiltrating lesions (ganglioneuromatosis) (36). The latter two patterns occur more commonly in the colon and rectum in patients with NF1 or with multiple endocrine neoplasia type 2b (36).

Focal ganglioneuromas are most often asymptomatic, particularly when they involve the para-vertebral sympathetic plexus or adrenal gland. In rare cases, ganglioneuromas may be hormonally active and may produce catecholamines, androgens, or vasoactive intestinal polypeptides. Correspondingly, ganglioneuromas of the gastrointestinal tract are most often asymptomatic. However, patients with polypoid tumors may present with gastrointestinal bleeding or signs and symptoms of intestinal obstruction. Diffuse ganglioneuromatosis may cause disturbances in gastrointestinal motility (10). Constipation is the most common clinical complaint, and in some patients, the motility disturbance may be severe enough to lead to a Hirschsprung-like condition in children and chronic colonic pseudo-obstruction and megacolon in adults (37,38).

Pathologic Features.— Ganglioneuromas are typically well-circumscribed, round or oval masses that occur at the locations of sympathetic ganglia, most commonly in the mediastinum, retroperitoneum, and pelvis. In the gastrointestinal tract, focal ganglioneuromas are generally small, sessile, or pedunculated polyps, whereas diffuse ganglioneuromatosis produces irregular, nodular thickening of the intestinal wall. At histologic analysis, ganglioneuromas are composed of mature autonomic ganglion cells and their axonal fibers, ensheathing Schwann cells, and satellite cells (Fig 22) (7).

View larger version (190K): [in this window] [in a new window] [Download PPT slide]   Figure 22.  Ganglioneuromatous intestinal polyp. Photomicrograph (original magnification, x40; H-E stain) shows scattered ganglion cells (arrow) and spindle cells in the intestinal mucosa.

View larger version (130K): [in this window] [in a new window] [Download PPT slide]   Figure 23a.  Jejunal ganglioneuroma, gastrointestinal stromal tumor, and adenocarcinoma in a 52-year-old man who presented with signs and symptoms of a small bowel obstruction and a known history of NF1. (a, b) Intravenous contrast-enhanced CT scans show a left adrenal pheochromocytoma (arrow in a), multiple subcutaneous neurofibromas, a plexiform neurofibroma in the right psoas muscle (arrow in b), and a homogeneous low-attenuation oval mass (arrowhead in b) that represented a jejunal ganglioneuroma leading an intussusception. (c) Photograph of the opened, resected specimen shows the jejunal ganglioneuroma (arrowheads), adenocarcinoma (black arrow), and exophytic gastrointestinal stromal tumor (white arrow).

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure 23b.  Jejunal ganglioneuroma, gastrointestinal stromal tumor, and adenocarcinoma in a 52-year-old man who presented with signs and symptoms of a small bowel obstruction and a known history of NF1. (a, b) Intravenous contrast-enhanced CT scans show a left adrenal pheochromocytoma (arrow in a), multiple subcutaneous neurofibromas, a plexiform neurofibroma in the right psoas muscle (arrow in b), and a homogeneous low-attenuation oval mass (arrowhead in b) that represented a jejunal ganglioneuroma leading an intussusception. (c) Photograph of the opened, resected specimen shows the jejunal ganglioneuroma (arrowheads), adenocarcinoma (black arrow), and exophytic gastrointestinal stromal tumor (white arrow).

View larger version (145K): [in this window] [in a new window] [Download PPT slide]   Figure 23c.  Jejunal ganglioneuroma, gastrointestinal stromal tumor, and adenocarcinoma in a 52-year-old man who presented with signs and symptoms of a small bowel obstruction and a known history of NF1. (a, b) Intravenous contrast-enhanced CT scans show a left adrenal pheochromocytoma (arrow in a), multiple subcutaneous neurofibromas, a plexiform neurofibroma in the right psoas muscle (arrow in b), and a homogeneous low-attenuation oval mass (arrowhead in b) that represented a jejunal ganglioneuroma leading an intussusception. (c) Photograph of the opened, resected specimen shows the jejunal ganglioneuroma (arrowheads), adenocarcinoma (black arrow), and exophytic gastrointestinal stromal tumor (white arrow).

	Neuroendocrine Tumors

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Patients with periampullary carcinoids may present with jaundice from biliary obstruction; fever and sepsis from cholangitis; nausea, vomiting, and abdominal pain from pancreatitis or intestinal obstruction; or hemorrhage from tumor ulceration (10,43). Even though periampullary carcinoids in patients with NF1 often contain somatostatin, reports of clinical symptoms and disorders from excess somatostatin, such as diarrhea, dyspepsia, diabetes mellitus, and cholelithiasis, are rare (10).

Pathologic Features.— Periampullary carcinoids are firm, nonnecrotic, solid, polypoid or infiltrative tumors. At microscopic analysis, they are composed of a uniform population of small cells with eosinophilic cytoplasm and round nuclei, which have a finely dispersed, salt-and-pepper chromatin pattern. The cells are organized in insular, tubuloglandular, or trabecular architectural patterns (Fig 24). By immunohistochemical criteria, the majority of duodenal carcinoids occurring in NF1 can be classified as somatostatinomas (42,43). Somatostatinomas are derived from somatostatin-producing D cells. They may have prominent psammoma bodies and, therefore, are often referred to as psammomatous somatostatinomas (Fig 24b).

View larger version (170K): [in this window] [in a new window] [Download PPT slide]   Figure 24a.  Duodenal psammomatous somatostatinoma from a patient with NF1. (a) Photomicrograph (original magnification, x16; H-E stain) shows nests of small cells organized in a glandular pattern (arrows) in the duodenal mucosa. (b) Photomicrograph (original magnification, x40; H-E stain) shows basophilic psammoma bodies (arrow) within the tumor.

View larger version (156K): [in this window] [in a new window] [Download PPT slide]   Figure 24b.  Duodenal psammomatous somatostatinoma from a patient with NF1. (a) Photomicrograph (original magnification, x16; H-E stain) shows nests of small cells organized in a glandular pattern (arrows) in the duodenal mucosa. (b) Photomicrograph (original magnification, x40; H-E stain) shows basophilic psammoma bodies (arrow) within the tumor.

Radiologic Features.— To our knowledge, only two case reports in the English language radiology literature have described the appearance of duodenal carcinoids in patients with NF1 (45,46). We have seen five patients with NF1 and gastrointestinal carcinoids. All of the tumors were periampullary in location. Four of the five patients had evidence of biliary and pancreatic ductal obstruction on CT scans. The tumors ranged from 1.5 cm to 4.0 cm in maximal diameter. Although all tumors had an intramural location pathologically, three of the tumors had a predominant polypoid appearance on barium and CT images (Figs 25, 26). The two remaining patients had tumors that manifested as nodular and lobular thickening of the medial duodenal wall on CT scans. The CT attenuation in all cases was homogeneous. Both Hamissa et al (45) and Mendes Ribeiro and Woodham (46) reported marked enhancement of the tumor on contrast-enhanced CT scans. Our cases showed little to no enhancement of the tumor on CT scans (Figs 25, 26).

View larger version (146K): [in this window] [in a new window] [Download PPT slide]   Figure 25a.  Duodenal carcinoid in NF1. (a) Image from an upper gastrointestinal tract barium study of a 54-year-old woman with vague abdominal pain shows a well-defined intraluminal polypoid mass (arrow) in the second portion of the duodenum. (b) Intravenous contrast-enhanced CT scan, obtained during the late phase of contrast enhancement in a 34-year-old woman with NF1 who presented with jaundice, shows a well-defined, round, nonenhancing polypoid mass (arrow) in the second portion of the duodenum.

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure 25b.  Duodenal carcinoid in NF1. (a) Image from an upper gastrointestinal tract barium study of a 54-year-old woman with vague abdominal pain shows a well-defined intraluminal polypoid mass (arrow) in the second portion of the duodenum. (b) Intravenous contrast-enhanced CT scan, obtained during the late phase of contrast enhancement in a 34-year-old woman with NF1 who presented with jaundice, shows a well-defined, round, nonenhancing polypoid mass (arrow) in the second portion of the duodenum.

View larger version (132K): [in this window] [in a new window] [Download PPT slide]   Figure 26a.  Duodenal carcinoid in a 26-year-old woman who presented to the emergency department with right flank pain. Elevated values for her liver function tests were found during the evaluation. (a, b) Intravenous contrast-enhanced CT scans show pancreatic duct and biliary duct dilatation extending caudally to a focal, round mass in the second portion of the duodenum (arrow in b). A cutaneous neurofibroma is also present (arrowhead in b). (c) Endoscopic photograph shows an intraluminal polypoid mass (arrow) in the periampullary region of the duodenum.

View larger version (120K): [in this window] [in a new window] [Download PPT slide]   Figure 26b.  Duodenal carcinoid in a 26-year-old woman who presented to the emergency department with right flank pain. Elevated values for her liver function tests were found during the evaluation. (a, b) Intravenous contrast-enhanced CT scans show pancreatic duct and biliary duct dilatation extending caudally to a focal, round mass in the second portion of the duodenum (arrow in b). A cutaneous neurofibroma is also present (arrowhead in b). (c) Endoscopic photograph shows an intraluminal polypoid mass (arrow) in the periampullary region of the duodenum.

View larger version (122K): [in this window] [in a new window] [Download PPT slide]   Figure 26c.  Duodenal carcinoid in a 26-year-old woman who presented to the emergency department with right flank pain. Elevated values for her liver function tests were found during the evaluation. (a, b) Intravenous contrast-enhanced CT scans show pancreatic duct and biliary duct dilatation extending caudally to a focal, round mass in the second portion of the duodenum (arrow in b). A cutaneous neurofibroma is also present (arrowhead in b). (c) Endoscopic photograph shows an intraluminal polypoid mass (arrow) in the periampullary region of the duodenum.

Pheochromocytoma and Paraganglioma
Clinical Features.— Pheochromocytoma is a catecholamine-secreting tumor that arises from the chromaffin cells of the sympathoadrenal system. The term pheochromocytoma is used for tumors arising from the adrenal medulla, whereas extraadrenal pheochromocytoma refers to pheochromocytomas arising from the organs of Zuckerkandl, and the term paraganglioma is used for this same tumor in other anatomic locations such as the retroperitoneum, bladder, or gastrointestinal tract. Pheochromocytoma is more common in patients with NF1 compared with the general population, occurring in 0.1%–5.7% of patients with NF1 and in 20%–50% of NF1 patients with hypertension (48).

Sixty-one percent of patients with NF1-associated pheochromocytoma have symptoms attributable to the tumor (48). Hypertension is the most common symptom of catecholamine release from the tumor. Patients may also present with a triad of headache, palpitations, and diaphoresis. Pheochromocytomas are more common in adults than in children. Hypertension in children with NF1 is most commonly associated with NF1 vasculopathy (renal artery stenosis, renal artery aneurysm, or aortic coarctation) and less commonly with pheochromocytoma.

There is a curious association between pheochromocytoma and duodenal carcinoids in patients with NF1. Not uncommonly, these tumors are diagnosed at the same time in a patient who is being evaluated for symptoms from the other tumor (49,50). The explanation for the association between these two neoplasms is unclear. It has been postulated that certain NF1 mutations may have a propensity to produce both neoplasms or there may be an unrecognized hormonal association between the two tumors (4).

Pathologic Features.— NF1-associated pheochromocytoma is solitary and unilateral in the majority of patients (84%), bilateral in 9.6%, and extraadrenal in 6.1% (48). The tumors are spherical, encapsulated masses that expand the adrenal medulla and are surrounded by yellow, compressed adrenal cortical tissue. Frequently, the adjacent normal adrenal gland in patients with NF1-associated tumors will be multilobular because of medullary hyperplasia (51). On sectioning, the tumors are brown. Hemorrhage, necrosis, and cyst formation are common in large tumors. Calcification may occur.

At histologic analysis, the cells of pheochromocytoma are polygonal with eosinophilic cytoplasm, resembling those of the normal adrenal medulla. They are arranged in an organoid pattern separated into compartments by thin septa. The compartments may be round (Zellballen), trabecular, or irregular (14,51) (Fig 27). The histologic features of paragangliomas of the retroperitoneum, gastrointestinal tract, and urinary bladder are similar to those of adrenal pheochromocytomas. In rare cases, composite tumors of pheochromocytoma and ganglioneuroblastoma or ganglioneuroma may occur in patients with NF1 (52).

View larger version (150K): [in this window] [in a new window] [Download PPT slide]   Figure 27.  Histologic features of pheochromocytoma. Photomicrograph (original magnification, x40; H-E stain) shows a small nesting pattern of growth with typical Zellballen (arrow) appearance.

View larger version (128K): [in this window] [in a new window] [Download PPT slide]   Figure 28a.  Incidentally discovered retroperitoneal paraganglioma in a 49-year-old woman with NF1 who complained of an enlarging right flank mass. Unenhanced (a) and gadolinium-enhanced (b) T1-weighted MR images show a large, multilobulated, heterogeneously enhancing plexiform neurofibroma of the right flank (black arrows). The round, enhancing mass anterior to the inferior vena cava (white arrow) was asymptomatic and proved to be a paraganglioma. There are numerous cutaneous neurofibromas.

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure 28b.  Incidentally discovered retroperitoneal paraganglioma in a 49-year-old woman with NF1 who complained of an enlarging right flank mass. Unenhanced (a) and gadolinium-enhanced (b) T1-weighted MR images show a large, multilobulated, heterogeneously enhancing plexiform neurofibroma of the right flank (black arrows). The round, enhancing mass anterior to the inferior vena cava (white arrow) was asymptomatic and proved to be a paraganglioma. There are numerous cutaneous neurofibromas.

	Gastrointestinal Stromal Tumor

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Pathologic Features
Gastrointestinal stromal tumors associated with NF1 are histologically and immunophenotypically identical to those that occur in patients without NF1. The distinguishing features of gastrointestinal stromal tumors in NF1 are their predominant location in the small intestine and their tendency for multiplicity (56,57). Gastrointestinal stromal tumors arise in or near the muscularis propria of the gastrointestinal tract wall and may have intramural, intraluminal, or extraluminal growth. Intratumoral hemorrhage, necrosis, and degeneration are common. At histologic analysis, gastrointestinal stromal tumors of the small intestine are most often spindle cell tumors (Fig 29). The cells are usually arranged in a pattern of interlacing fascicles. They may contain extracellular collagenous skenoid fibers (Fig 29b). Immunoreactivity with CD117 (KIT) and CD34 distinguishes gastrointestinal stromal tumors from leiomyomas and leiomyosarcomas (58). The biologic behavior of gastrointestinal stromal tumors in patients with NF1 does not appear to be different than that of such tumors in patients without NF1. The tumors may be benign, be malignant, or have uncertain malignant potential based on the current understanding of gastrointestinal stromal tumors.

View larger version (189K): [in this window] [in a new window] [Download PPT slide]   Figure 29a.  Histologic features of gastrointestinal stromal tumors in NF1. (a) Photomicrograph (original magnification, x40; H-E stain) shows a spindle cell gastrointestinal stromal tumor with uniform cigar-shaped elongated nuclei (arrow). (b) Photomicrograph (original magnification,x 80; H-E stain) shows skenoid fibers (arrow).

View larger version (189K): [in this window] [in a new window] [Download PPT slide]   Figure 29b.  Histologic features of gastrointestinal stromal tumors in NF1. (a) Photomicrograph (original magnification, x40; H-E stain) shows a spindle cell gastrointestinal stromal tumor with uniform cigar-shaped elongated nuclei (arrow). (b) Photomicrograph (original magnification,x 80; H-E stain) shows skenoid fibers (arrow).

View larger version (133K): [in this window] [in a new window] [Download PPT slide]   Figure 30a.  Gastrointestinal stromal tumor of the small intestine in a 36-year-old man with NF1 and gastrointestinal bleeding. Intravenous contrast-enhanced CT scans show a large, heterogeneous-attenuation, intraluminal small bowel mass (* in a). The inferior portion of the mass has cystic degeneration (white arrow in b). There are extensive plexiform neurofibromas of the lumbosacral plexus (black arrows) and enlargement of the sacral foramina. (Case courtesy of Francis J. Scholz, MD, Lahey Clinic, Burlington, Mass.)

View larger version (130K): [in this window] [in a new window] [Download PPT slide]   Figure 30b.  Gastrointestinal stromal tumor of the small intestine in a 36-year-old man with NF1 and gastrointestinal bleeding. Intravenous contrast-enhanced CT scans show a large, heterogeneous-attenuation, intraluminal small bowel mass (* in a). The inferior portion of the mass has cystic degeneration (white arrow in b). There are extensive plexiform neurofibromas of the lumbosacral plexus (black arrows) and enlargement of the sacral foramina. (Case courtesy of Francis J. Scholz, MD, Lahey Clinic, Burlington, Mass.)

View larger version (123K): [in this window] [in a new window] [Download PPT slide]   Figure 31a.  Multiple gastrointestinal stromal tumors in a 23-year-old woman with NF1 who presented with syncope from severe anemia. (a, b) Intravenous contrast-enhanced CT scans show a lobulated, proximal jejunal gastrointestinal stromal tumor (arrow in a) and two large gastrointestinal stromal tumors in the middle abdomen. There is a mixed solid and cystic gastrointestinal stromal tumor adjacent to a predominantly cystic gastrointestinal stromal tumor (* in b). (c) Photograph of the unopened, resected upper jejunum shows innumerable gastrointestinal stromal tumors extending through to the serosal surface of the jejunum.

View larger version (113K): [in this window] [in a new window] [Download PPT slide]   Figure 31b.  Multiple gastrointestinal stromal tumors in a 23-year-old woman with NF1 who presented with syncope from severe anemia. (a, b) Intravenous contrast-enhanced CT scans show a lobulated, proximal jejunal gastrointestinal stromal tumor (arrow in a) and two large gastrointestinal stromal tumors in the middle abdomen. There is a mixed solid and cystic gastrointestinal stromal tumor adjacent to a predominantly cystic gastrointestinal stromal tumor (* in b). (c) Photograph of the unopened, resected upper jejunum shows innumerable gastrointestinal stromal tumors extending through to the serosal surface of the jejunum.

View larger version (95K): [in this window] [in a new window] [Download PPT slide]   Figure 31c.  Multiple gastrointestinal stromal tumors in a 23-year-old woman with NF1 who presented with syncope from severe anemia. (a, b) Intravenous contrast-enhanced CT scans show a lobulated, proximal jejunal gastrointestinal stromal tumor (arrow in a) and two large gastrointestinal stromal tumors in the middle abdomen. There is a mixed solid and cystic gastrointestinal stromal tumor adjacent to a predominantly cystic gastrointestinal stromal tumor (* in b). (c) Photograph of the unopened, resected upper jejunum shows innumerable gastrointestinal stromal tumors extending through to the serosal surface of the jejunum.

	Embryonal Tumors

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction General Clinical Features Neurogenic Tumors Neuroendocrine Tumors Gastrointestinal Stromal Tumor Embryonal Tumors Adenocarcinoma Final Considerations for... References

	Adenocarcinoma

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction General Clinical Features Neurogenic Tumors Neuroendocrine Tumors Gastrointestinal Stromal Tumor Embryonal Tumors Adenocarcinoma Final Considerations for... References

 
The association between adenocarcinoma and NF1 is unclear. Adenocarcinomas of the esophagus (63), stomach (64), colon (65,66), small intestine (67–72), pancreas (72,73), gallbladder (74), and bile ducts (74,75) have been reported in patients with NF1. Taking into consideration the prevalence of these cancers in the general population, the association of adenocarcinomas in the colon, esophagus, stomach, biliary tract, and pancreas with NF1 may be incidental. On the other hand, the reports of adenocarcinomas of the small intestine in patients with NF1 are more difficult to dismiss as coincidental because of the number of reported cases for an uncommon neoplasm (13,70).

The majority of the small intestinal adenocarcinomas occurring in patients with NF1 are periampullary in location (68,70). Williams et al (76) remarked that the association between adenocarcinoma of the small intestine and NF1 should be considered tenuous because of the well-established association between carcinoids and NF1 and the difficulty in distinguishing between adenocarcinoma and carcinoid histopathologically. Nevertheless, as radiologists we should be cognizant of the possibility of small intestinal adenocarcinoma when evaluating a small intestinal mass in a patient with NF1.

On images, small intestinal adenocarcinomas are most commonly annular lesions located in the proximal small intestine. Those that occur in the periampullary region may be polypoid intraluminal masses or infiltrating lesions that extend into the adjacent pancreas.

	Final Considerations for Abdominal Imaging in Patients with NF1

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction General Clinical Features Neurogenic Tumors Neuroendocrine Tumors Gastrointestinal Stromal Tumor Embryonal Tumors Adenocarcinoma Final Considerations for... References

 
Interpreting abdominal imaging studies in patients with NF1 can be challenging because a variety of organs may be affected with a diverse group of neoplasms. Furthermore, disease manifestations vary from patient to patient. Optimizing imaging techniques and careful patient preparation before imaging will maximize lesion detection. Complete abdominal and pelvic scanning with intravenous and oral contrast material administration should be done in each patient, even if the primary abnormality is suspected to be in the retroperitoneum, because patients with NF1 frequently have additional asymptomatic neoplasms in other organs.

The most frequent abdominal neoplasm in patients with NF1 is a neurofibroma arising in the retroperitoneum or in the paraspinal or presacral regions. The differential diagnosis for neurofibromas of the retroperitoneum includes lymphadenopathy and soft-tissue sarcomas. Multiplanar or curvilinear multidetector CT reconstructions or MR imaging may be a useful adjunct to demonstrate the relationship of a suspected neurofibroma to the lumbosacral spine and lumbosacral neural plexus. Occasionally, plexiform neurofibromas of the retroperitoneum and mesentery are so extensive and characterized by low attenuation that they are difficult to distinguish from the adenopathy typical of lymphoma, tuberculosis, or Whipple disease (Fig 14) (77). Plexiform neurofibromas may be differentiated from adenopathy by identifying the characteristic fascicular ringlike or septated pattern on MR images.

Lastly, it is noteworthy that patients with NF1 may have multiple gastrointestinal neoplasms. It is clinically prudent to evaluate the entire gastrointestinal tract thoroughly for additional lesions when a solitary lesion is diagnosed because neurofibromas and gastrointestinal stromal tumors are often multifocal in patients with NF1. In addition, gastrointestinal stromal tumors frequently occur in association with other gastrointestinal neoplasms. Consideration should be given to performing detailed preoperative radiologic evaluation of the small bowel with enteroclysis if the patient is discovered to have a small intestinal mass at CT or routine small bowel barium study.

In summary, altered tumor suppression in patients with NF1 results in a variety of benign and malignant abdominal neoplasms of neuroectodermal or mesenchymal origin. Neurofibromas are the most common benign neoplasms and may occur in the retroperitoneum or visceral organs. MPNST is an aggressive malignancy that is the most common malignant tumor of the abdomen in patients with NF1.

	Footnotes

 
The opinions and assertions contained herein are the private views of the authors and are not to be construed as official nor as reflecting the views of the Departments of the Army, Air Force, or Defense.

	References

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1. Huson SM, Compston DA, Clark P, Harper PS. A genetic study of von Recklinghausen neurofibromatosis in south east Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity. J Med Genet 1989; 26:704–711.[Abstract/Free Full Text]
2. von Recklinghausen FD. Ueber die multiplen fibrome der haut und ihre beiehung zu den multi-plen neuromen. Berlin, Germany: Hirschwald, 1882.
3. Xu GF, O’Connell P, Viskochil D, et al. The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell 1990; 62:599–608.[CrossRef][Medline]
4. Friedman JM, Riccardi VM. Neurofibromatosis: phenotype, natural history, and pathogenesis. 3rd ed. Baltimore, Md: Johns Hopkins University Press, 1999.
5. Gutmann DH, Aylsworth A, Carey JC, et al. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA 1997; 278:51–57.[Abstract/Free Full Text]
6. Lubs ML, Bauer MS, Formas ME, Djokic B. Lisch nodules in neurofibromatosis type 1. N Engl J Med 1991; 324:1264–1266.[Medline]
7. Scheithauer BW, Woodruff JM, Erlandson RA. Tumors of the peripheral nervous system. Washington, DC: Armed Forces Institute of Pathology, 1999.
8. Tonsgard JH, Kwak SM, Short MP, Dachman AH. CT imaging in adults with neurofibromatosis-1: frequent asymptomatic plexiform lesions. Neurology 1998; 50:1755–1760.[Abstract]
9. Riccardi VM. Neurofibromatosis: phenotype, natural history, and pathogenesis. 2nd ed. Baltimore, Md: Johns Hopkins University Press, 1992.
10. Fuller CE, Williams GT. Gastrointestinal manifestations of type 1 neurofibromatosis (von Recklinghausen’s disease). Histopathology 1991; 19:1–11.[Medline]
11. Petersen JM, Ferguson DR. Gastrointestinal neurofibromatosis. J Clin Gastroenterol 1984; 6:529–534.[CrossRef][Medline]
12. Miller WB Jr, Boal DK, Teele R. Neurofibromatosis of the bladder: sonographic findings. J Clin Ultrasound 1983; 11:460–462.[Medline]
13. Riddell RH, Petras RE, Williams GT, Sobin LH. Tumors of the intestines. Washington, DC: Armed Forces Institute of Pathology, 2003.
14. Miettinen M. Diagnostic soft tissue pathology. New York, NY: Churchill Livingstone, 2003.
15. Bass JC, Korobkin M, Francis IR, Ellis JH, Cohan RH. Retroperitoneal plexiform neurofibromas: CT findings. AJR Am J Roentgenol 1994; 163: 617–620.[Abstract/Free Full Text]
16. Sato M, Ishida H, Konno K, et al. Abdominal involvement in neurofibromatosis 1: sonographic findings. Abdom Imaging 2000; 25:517–522.[CrossRef][Medline]
17. Coleman BG, Arger PH, Dalinka MK, Obringer AC, Raney BR, Meadows AT. CT of sarcomatous degeneration in neurofibromatosis. AJR Am J Roentgenol 1983; 140:383–387.[Abstract/Free Full Text]
18. Kumar AJ, Kuhajda FP, Martinez CR, Fishman EK, Jezic DV, Siegelman SS. Computed tomography of extracranial nerve sheath tumors with pathological correlation. J Comput Assist Tomogr 1983; 7:857–865.[Medline]
19. Fukuya T, Lu CC, Mitros FA. CT findings of plexiform neurofibromatosis involving the ileum and its mesentery. Clin Imaging 1994; 18:142–145.[CrossRef][Medline]
20. Fenton LZ, Foreman N, Wyatt-Ashmead J. Diffuse, retroperitoneal mesenteric and intrahepatic periportal plexiform neurofibroma in a 5-year-old boy. Pediatr Radiol 2001; 31:637–639.[CrossRef][Medline]
21. Jain R, Sawhney S, Berry M. Mesenteric plexiform neurofibroma: computed tomography appearance. Australas Radiol 1996; 40:158–159.[Medline]
22. Matsuki K, Kakitsubata Y, Watanabe K, Tsukino H, Nakajima K. Mesenteric plexiform neurofibroma associated with Recklinghausen’s disease. Pediatr Radiol 1997; 27:255–256.[CrossRef][Medline]
23. Partin JS, Lane BP, Partin JC, Edelstein LR, Priebe CJ Jr. Plexiform neurofibromatosis of the liver and mesentery in a child. Hepatology 1990; 12(3 pt 1):559–564.[CrossRef][Medline]
24. Kakitsubata Y, Kakitsubata S, Sonoda T, Watanabe K. Neurofibromatosis type 1 involving the liver: ultrasound and CT manifestations. Pediatr Radiol 1994; 24:66–67.[CrossRef][Medline]
25. Pessin JI, Bodian M. Neurofibromatosis of the pelvic autonomic plexuses. Br J Urol 1964; 36: 510–518.[Medline]
26. Shonnard KM, Jelinek JS, Benedikt RA, Kransdorf MJ. CT and MR of neurofibromatosis of the bladder. J Comput Assist Tomogr 1992; 16:433–438.[Medline]
27. Bhargava R, Parham DM, Lasater OE, Chari RS, Chen G, Fletcher BD. MR imaging differentiation of benign and malignant peripheral nerve sheath tumors: use of the target sign. Pediatr Radiol 1997; 27:124–129.[CrossRef][Medline]
28. Ros PR, Eshaghi N. Plexiform neurofibroma of the pelvis: CT and MRI findings. Magn Reson Imaging 1991; 9:463–465.[CrossRef][Medline]
29. D’Agostino AN, Soule EH, Miller RH. Primary malignant neoplasms of nerves (malignant neurilemomas) in patients without manifestations of multiple neurofibromatosis (von Recklinghausen’s disease). Cancer 1963; 16:1003–1014.[CrossRef][Medline]
30. King AA, Debaun MR, Riccardi VM, Gutmann DH. Malignant peripheral nerve sheath tumors in neurofibromatosis 1. Am J Med Genet 2000; 93: 388–392.[CrossRef][Medline]
31. Ducatman BS, Scheithauer BW, Piepgras DG, Reiman HM, Ilstrup DM. Malignant peripheral nerve sheath tumors: a clinicopathologic study of 120 cases. Cancer 1986; 57:2006–2021.[CrossRef][Medline]
32. Kourea HP, Bilsky MH, Leung DH, Lewis JJ, Woodruff JM. Subdiaphragmatic and intrathoracic paraspinal malignant peripheral nerve sheath tumors: a clinicopathologic study of 25 patients and 26 tumors. Cancer 1998; 82:2191–2203.[CrossRef][Medline]
33. Murphey MD, Smith WS, Smith SE, Kransdorf MJ, Temple HT. Imaging of musculoskeletal neurogenic tumors: radiologic-pathologic correlation. RadioGraphics 1999; 19:1253–1280.[Abstract/Free Full Text]
34. Levine E, Huntrakoon M, Wetzel LH. Malignant nerve-sheath neoplasms in neurofibromatosis: distinction from benign tumors by using imaging techniques. AJR Am J Roentgenol 1987; 149: 1059–1064.[Abstract/Free Full Text]
35. Hammond JA, Driedger AA. Detection of malignant change in neurofibromatosis (von Recklinghausen’s disease) by gallium-67 scanning. Can Med Assoc J 1978; 119:352–353.[Medline]
36. Shekitka KM, Sobin LH. Ganglioneuromas of the gastrointestinal tract: relation to von Recklinghausen disease and other multiple tumor syndromes. Am J Surg Pathol 1994; 18:250–257.[Medline]
37. Saul RA, Sturner RA, Burger PC. Hyperplasia of the myenteric plexus: its association with early infantile megacolon and neurofibromatosis. Am J Dis Child 1982; 136:852–854.[Abstract/Free Full Text]
38. Staple TW, McAlister WH, Anderson MS. Plexiform neurofibromatosis of the colon simulating Hirschsprung’s disease. Am J Roentgenol Radium Ther Nucl Med 1964; 91:840–845.[Medline]
39. Rha SE, Byun JY, Jung SE, Chun HJ, Lee HG, Lee JM. Neurogenic tumors in the abdomen: tumor types and imaging characteristics. RadioGraphics 2003; 23:29–43.[Abstract/Free Full Text]
40. Hirata K, Kitahara K, Momosaka Y, et al. Diffuse ganglioneuromatosis with plexiform neurofibromas limited to the gastrointestinal tract involving a large segment of small intestine. J Gastroenterol 1996; 31:263–267.[CrossRef][Medline]
41. Lockhart ME, Smith JK, Canon CL, Morgan DE, Heslin MJ. Appendiceal ganglioneuromas and pheochromocytoma in neurofibromatosis type 1. AJR Am J Roentgenol 2000; 175:132–134.[Free Full Text]
42. Burke AP, Sobin LH, Shekitka KM, Federspiel BH, Helwig EB. Somatostatin-producing duodenal carcinoids in patients with von Recklinghausen’s neurofibromatosis: a predilection for black patients. Cancer 1990; 65:1591–1595.[CrossRef][Medline]
43. Dayal Y, Tallberg KA, Nunnemacher G, DeLellis RA, Wolfe HJ. Duodenal carcinoids in patients with and without neurofibromatosis: a comparative study. Am J Surg Pathol 1986; 10:348–357.[CrossRef][Medline]
44. Burke AP, Federspiel BH, Sobin LH, Shekitka KM, Helwig EB. Carcinoids of the duodenum: a histologic and immunohistochemical study of 65 tumors. Am J Surg Pathol 1989; 13:828–837.[Medline]
45. Hamissa S, Rahmouni A, Coffin C, Wolkenstein P. CT detection of an ampullary somatostatinoma in a patient with von Recklinghausen’s disease. AJR Am J Roentgenol 1999; 173:503–504.[Medline]
46. Mendes Ribeiro HK, Woodham C. CT demonstration of an unusual cause of biliary obstruction in a patient with peripheral neurofibromatosis. Clin Radiol 2000; 55:796–798.[CrossRef][Medline]
47. Buck JL, Elsayed AM. Ampullary tumors: radiologic-pathologic correlation. RadioGraphics 1993; 13:193–212.[Abstract]
48. Walther MM, Herring J, Enquist E, Keiser HR, Linehan WM. von Recklinghausen’s disease and pheochromocytomas. J Urol 1999; 162:1582–1586.[CrossRef][Medline]
49. Wheeler MH, Curley IR, Williams ED. The association of neurofibromatosis, pheochromocytoma, and somatostatin-rich duodenal carcinoid tumor. Surgery 1986; 100:1163–1169.[Medline]
50. Griffiths DF, Williams GT, Williams ED. Duodenal carcinoid tumours, phaeochromocytoma and neurofibromatosis: islet cell tumour, phaeochromocytoma and the von Hippel-Lindau complex: two distinctive neuroendocrine syndromes. Q J Med 1987; 64:769–782.
51. Page DL, DeLellis RA, Hough AJ. Tumors of the adrenal. Washington, DC: Armed Forces Institute of Pathology, 1986.
52. Chetty R, Duhig JD. Bilateral pheochromocytoma-ganglioneuroma of the adrenal in type 1 neurofibromatosis. Am J Surg Pathol 1993; 17: 837–841.[Medline]
53. Francis IR, Korobkin M. Pheochromocytoma. Radiol Clin North Am 1996; 34:1101–1112.[Medline]
54. Boldorini R, Tosoni A, Leutner M, et al. Multiple small intestinal stromal tumours in a patient with previously unrecognised neurofibromatosis type 1: immunohistochemical and ultrastructural evaluation. Pathology 2001; 33:390–395.[Medline]
55. Giuly JA, Picand R, Giuly D, Monges B, Nguyen-Cat R. Von Recklinghausen disease and gastrointestinal stromal tumors. Am J Surg 2003; 185:86–87.[CrossRef][Medline]
56. Levy AD, Patel N, Abbott RM, Dow N, Miettinen M, Sobin LH. Gastrointestinal stromal tumors in patients with neurofibromatosis: imaging features with clinicopathologic correlation. AJR Am J Roentgenol 2004; 183:1629–1636.[Abstract/Free Full Text]
57. Miettinen M, Kopczynski J, Makhlouf HR, et al. Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the duodenum: a clinicopathologic, immunohistochemical, and molecular genetic study of 167 cases. Am J Surg Pathol 2003; 27:625–641.[CrossRef][Medline]
58. Fletcher CD, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol 2002; 33:459–465.[CrossRef][Medline]
59. Hayflick SJ, Hofman KJ, Tunnessen WW, Jr, Leventhal BG, Dudgeon DL. Neurofibromatosis 1: recognition and management of associated neuroblastoma. Pediatr Dermatol 1990; 7:293–295.[Medline]
60. Matsui I, Tanimura M, Kobayashi N, Sawada T, Nagahara N, Akatsuka J. Neurofibromatosis type 1 and childhood cancer. Cancer 1993; 72:2746–2754.[CrossRef][Medline]
61. Stay EJ, Vawter G. The relationship between nephroblastoma and neurofibromatosis (von Recklinghausen’s disease). Cancer 1977; 39:2550–2555.[CrossRef][Medline]
62. Hartley AL, Birch JM, Marsden HB, Harris M, Blair V. Neurofibromatosis in children with soft tissue sarcoma. Pediatr Hematol Oncol 1988; 5:7–16.[Medline]
63. Desigan G, Dunn GD, Halter S. Adenocarcinoma of the esophagus associated with neurofibromatosis. J Tenn Med Assoc 1985; 78:138–140.[Medline]
64. Basu S, Majumdar J, Mitra R, Chowdhury JR. Primary adenocarcinoma of the stomach associated with peripheral neurofibromatosis: report of a case. Surg Today 1997; 27:57–59.[CrossRef][Medline]
65. Jenkins DH, Gill W. A case of carcinoma of the colon in association with neurofibromatosis. Br J Surg 1972; 59:322–323.[Medline]
66. Shousha S, Smith PA. Colonic ganglioneuroma: report of a case in a patient with neurofibromatosis, multiple colonic adenomas and adenocarcinoma. Virchows Arch A Pathol Anat Histol 1981; 392:105–109.[CrossRef][Medline]
67. Colarian J, Pietruk T, LaFave L, Calzada R. Adenocarcinoma of the ampulla of Vater associated with neurofibromatosis. J Clin Gastroenterol 1990; 12:118–119.[CrossRef][Medline]
68. Costi R, Caruana P, Sarli L, Violi V, Roncoroni L, Bordi C. Ampullary adenocarcinoma in neurofibromatosis type 1: case report and literature review. Mod Pathol 2001; 14:1169–1174.[CrossRef][Medline]
69. Jones TJ, Marshall TL. Neurofibromatosis and small bowel adenocarcinoma: an unrecognised association. Gut 1987; 28:1173–1176.[Abstract/Free Full Text]
70. Joo YE, Kim HS, Choi SK, Rew JS, Park CS, Kim SJ. Primary duodenal adenocarcinoma associated with neurofibromatosis type 1. J Gastroenterol 2002; 37:215–219.[CrossRef][Medline]
71. Kingston RD. Neurofibromatosis and small bowel adenocarcinoma: an unrecognised association (letter). Gut 1988; 29:134.[Free Full Text]
72. Niv Y, Abu-Avid S, Oren M. Adenocarcinoma of pancreas and duodenum associated with cutaneous neurofibromatosis. Am J Med 1987; 82:384–385.[CrossRef][Medline]
73. Keller RT, Logan GM, Jr. Adenocarcinoma of the pancreas associated with neurofibromatosis. Cancer 1977; 39:1264–1266.[CrossRef][Medline]
74. Ching CK, Greer AJ. Metachronous biliary tract cancers in a patient with von Recklinghausen’s disease. Am J Gastroenterol 1993; 88:1124–1125.[Medline]
75. Sprengers DP, Knockaert DC, Van Steenbergen W, Penninckx F. Primary bile duct cancer and von Recklinghausen disease (letter). Ann Intern Med 1987; 106:772.
76. Williams GT, Griffiths DF, Williams ED. Small intestinal adenocarcinoma, duodenal carcinoid tumour, and von Recklinghausen’s neurofibromatosis (letter). Gut 1988; 29:553.[Free Full Text]
77. Fortman BJ, Kuszyk BS, Urban BA, Fishman EK. Neurofibromatosis type 1: a diagnostic mimicker at CT. RadioGraphics 2001; 21:601–612.[Abstract/Free Full Text]

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