DOI: 10.1148/rg.252045176
RadioGraphics 2005;25:455-480
From the Archives of the AFIP
Abdominal Neoplasms in Patients with Neurofibromatosis Type 1: Radiologic-Pathologic Correlation1
Angela D. Levy, LTC, MC, USA,
Nandini Patel, MD,
Nancy Dow, LTC, MC, USA,
Robert M. Abbott, MD,
Markku Miettinen, MD and
Leslie H. Sobin, MD
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).
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Abstract
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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
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LEARNING OBJECTIVES FOR TEST 6
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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.
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Introduction
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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).
This article summarizes the current literature and our experience with 60 patients with NF1 and abdominal neoplasia. These patients were accessioned into the Radiologic Pathology archive of the Armed Forces Institute of Pathology from September 1971 to September 2003. Our case material consists of patients with the following primary diagnoses: neurofibroma and plexiform neurofibroma of the retroperitoneum, genitourinary system, and gastrointestinal tract; malignant peripheral nerve sheath tumor (MPNST) of the retroperitoneum and mesentery; carcinoid; pheochromocytoma; extraadrenal paraganglioma; ganglioneuroma; gastrointestinal stromal tumor; and adenocarcinoma. Twenty-two of our patients (37%) had more than one abdominal neoplasm. The radiologic spectrum of abdominal neoplasms in patients with NF1 is presented herein with clinicopathologic correlation.
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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).
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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.
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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.
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Lisch nodules are melanocytic hamartomas of the iris. They are yellow or brown nodular elevations projecting from the surface of the iris (Fig 2). Multiple Lisch nodules are specific for NF1 and are found in nearly all patients over the age of 20 years (6).
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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.
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Dermal (cutaneous) neurofibromas usually appear during adolescence in patients with NF1. Nodular and pedunculated dermal neurofibromas most often affect the trunk (Fig 3). They are soft and easily compressible when touched. Dermal neurofibromas may become numerous, large, and disfiguring for some patients. Dermal neurofibromas are benign and do not undergo malignant transformation (5).
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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.
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Plexiform neurofibromas are variants of neurofibromas that involve a plexus of nerves or multiple fascicles within a larger nerve. They tend to grow to large sizes and may cause substantial disfigurement. They may have associated hyperpigmentation and deform adjacent tissues and bones. They are thought to be congenital and usually manifest early in life (7). Plexiform neurofibromas are seen exclusively in NF1 and may undergo malignant transformation to MPNSTs.
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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).
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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.
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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.
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The majority of gastrointestinal neurofibromas in NF1 are focal intraneural or plexiform neurofibromas that involve the myenteric plexus. Characteristically, there is focal glial overgrowth in addition to diffuse irregular thickening of the my-enteric plexus (13). Multiple tumors or diffusely elongated tumors are not uncommon. The tumors may extend to involve the mucosa, producing focal polypoid nodules that extend into the lumen of the intestine.
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).
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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The majority of neurofibromas are smooth, round or tubular masses that are homogeneously hypoattenuating on intravenous contrast-enhanced CT scans (8,15). The attenuation values range from 20 to 25 HU on nonenhanced scans and 30–50 HU on intravenous contrast-enhanced scans (17). The low attenuation of neurofibromas has been attributed to myxoid and mucinous stroma that can be observed microscopically within these tumors (7,18). Occasionally, focal areas of hyperattenuation are present because of excessive collagen. Tonsgard et al (8) reported observing intravenous contrast enhancement in 50% of their patients with abdominal or pelvic plexiform neurofibromas who had both nonenhanced and intravenous contrast-enhanced CT scans. Intravenous contrast enhancement may be homogeneous or heterogeneous.
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.
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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).
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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).
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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).
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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).
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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).
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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.
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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.
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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.
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Neurofibromas and plexiform neurofibromas may originate primarily in the intestinal wall, appearing as solitary or multifocal intraluminal or intramural masses without mesenteric involvement (Fig 8). We have observed several patients who have long segments of nodular mural thickening of the small intestine and colon. On conventional barium images, these segments are multinodular with scalloping of the mucosa from intramural and intraluminal components of the neurofibromas (Fig 9). There is a variable amount of luminal narrowing depending on the size of the neurofibromas. On CT scans, diffuse lobular, soft-tissue attenuation mural thickening is present (Fig 10). The ropelike gross appearance of plexiform neurofibromas is usually not visible on CT scans. However, magnetic resonance (MR) imaging may show innumerable ringlike structures on T2-weighted and gadolinium-enhanced T1-weighted images that correspond to cross sectioning of the ropelike masses (Fig 11) (22).
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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).
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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).
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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It is uncommon for neurofibromas to involve the liver and bile ducts. They may manifest as focal intrahepatic masses that have a nonspecific sonographic and CT appearance (Fig 12), or they may be extensive plexiform lesions of the periportal spaces that involve the hepatic hilum and extend throughout the liver adjacent to portal vein branches (Fig 13) (23,24). Rarely, plexiform neurofibromas can diffusely involve the periportal regions, retroperitoneum, and mesentery (20). In these cases, bulky soft-tissue masses are so extensive throughout the abdomen that they simulate malignancy (Fig 14).
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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.
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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.
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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).
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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).
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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.
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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.
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Neurofibromas of the bladder arise from the vesicoprostatic and vesicovaginal neural plexuses that enter the posterolateral aspect of the bladder near the trigone (25). The prostate, seminal vesicles, spermatic cord, and perineum may be involved when plexiform neurofibromas extend throughout the male pelvis. Similarly, the uterus, vagina, and urethra may be involved in the female pelvis. Neurofibromas and plexiform neurofibromas of the bladder focally or diffusely thicken the bladder wall. The contours of the bladder may be scalloped. Hydronephrosis may be present if there is involvement of the ureteral orifice. On sonograms, the thickened bladder wall is heterogeneous in echotexture with a lobular contour along the luminal margin (Fig 15) (12). CT scans show focal or diffuse mural thickening (26), which may have a low-attenuation ringlike or ropelike pattern that corresponds to the gross morphology of tortuous ropelike plexiform neurofibromas (Fig 16). Careful attention should be paid to the adjacent organs because these lesions may spread through the pelvis to involve other organs and the perineum (Fig 15b).
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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).
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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).
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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).
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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.
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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.
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The MR imaging features of neurofibromas are characteristic and can be helpful in confusing cases and in the evaluation of a mass in a patient with known NF1. Neurofibromas are characteristically low signal intensity on T1-weighted images and heterogeneous high signal intensity on T2-weighted images. The high T2 signal corresponds pathologically to areas of cystic degeneration or myxoid matrix, and the low T2 signal represents collagen and fibrous tissue (27). The areas of low T2 signal enhance following gadolinium administration. Plexiform neurofibromas have a characteristic ringlike or septated pattern that represents the complex fascicular arrangement typical of these tumors (Fig 17) (22,28). This pattern is best observed on T2-weighted images and gadolinium-enhanced T1-weighted images. The multiplanar capability of MR imaging is also useful for defining the extent of plexiform neurofibromas because they may grow to large sizes and involve adjacent tissue planes and organs (Fig 17a).
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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.
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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.
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Malignant Peripheral Nerve Sheath Tumor
Clinical Features.—
MPNST is a highly aggressive malignant tumor. In the setting of NF1, MPNST originates from a peripheral nerve sheath or plexiform neurofibroma (14). The term malignant peripheral nerve sheath tumor replaced the older nomenclature neurofibrosarcoma, malignant schwannoma, and neurogenic sarcoma. The lifetime risk of developing an MPNST for a person with NF1 is 4%–5% (29). The paraspinal region of the abdomen, extremities, and head and neck region are the most common locations for MPNST.
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.
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Abstract
LEARNING OBJECTIVES FOR TEST...
