Dr. Philips is an Assistant Professor, Dr. Restrepo is a Professor,
and Dr. Chintapalli is a Professor in the Department of Radiology at the
University of Texas Health Science Center, San Antonio, TX.
Several benign types of pathology can mimic the radiological
appearance of neoplasm. An indeterminate or incorrect diagnosis may lead
to unnecessary patient anxiety, biopsy, and even surgery. The recent
surge of imaging utilization, particularly in computed tomography (CT),
has contributed to an increase in detection of such lesions. A lack of
pertinent patient history also contributes to greater difficulty in
establishing a correct diagnosis.
In this review, the authors describe some of these benign
entities that can mimic neoplasia on imaging and discuss the
radiological features that may assist in reaching the correct diagnosis
of these findings as benign conditions. For the purposes of this
article, we have classified these benign etiologies into subgroups.
Although any organization and distribution can be controversial, our
classification aims to simplify the gamut of these lesions based on
their predominant/distinctive etiology. Table 1 lists our classification
scheme. Radiologists should be well acquainted with these pathologies
and their unique imaging appearances.
Inflammatory pseudotumor
An inflammatory pseudotumor (IPT), also termed inflammatory
myofibroblastic pseudotumor, is a rare lesion of unclear pathogenesis.
It is characterized by reactive non-neoplastic proliferation of
myofibroblastic spindle cells, accompanied by inflammatory cell
infiltration within a myxoid stroma.1 IPT can occur in nearly
every site in the body, from the central nervous system to the
gastrointestinal tract (Figures 1 and 2). Some authors believe this is a
low-grade fibrosarcoma with inflammatory cells. It is also thought to
be the result of inflammation following minor trauma/surgery.2 An immune-autoimmune mechanism and an infectious cause have also been proposed.3
Organisms, such as the Epstein-Barr virus, have been found in splenic
and nodal pseudotumors; actinomycetes and nocardiae are found in hepatic
and pulmonary pseudotumors, respectively; and mycoplasma in pulmonary
pseudotumors.4 Clinically, patients with inflammatory
pseudotumor may have varying degrees of fever, thrombocytosis, and
hypergammaglobulinemia
Pulmonary IPT is the most common primary lung mass seen in
children and accounts for approximately 50% of benign intrapulmonary
tumors seen in pediatric patients.5 Cough, fever, dyspnea, and hemoptysis are the usual presenting symptoms.6
On radiographs, it typically appears as a solitary, peripheral, sharply
circumscribed, lobulated mass most commonly within the lower lobes.5
On CT scans, inflammatory pseudotumors have a variable and nonspecific
appearance, but most commonly appear heterogeneous and show variable
enhancement (Figure 3, click here to view this image in a DICOM viewer). Calcification within the lesion occurs more
frequently in children.5,7
IPT of the liver has been recognized increasingly in children and young adults mainly in Asian countries.8
Most cases involve the right hepatic lobe and are solitary solid
tumors. However, involvement of the porta hepatis or bile ducts,
resulting in obstructive jaundice, can also be seen. Sclerosing
cholangitis, phlebitis, and retroperitoneal fibrosis have been found in
association with inflammatory pseudotumor of the liver.9 The IPT may spontaneously regress.8
On sonography, IPT in the liver can be a hypo- as well as
hyperechoic mass with transmission and visualization of multiple septa.10
On CT, they show soft-tissue attenuation with delayed and persistent
enhancement due to fibrous content, although a variety of different
enhancement patterns have been noted.8 On MR images, the mass
is usually hypointense relative to skeletal muscle on T1-weighted
images, hyperintense on T2-weighted images, and heterogeneously enhanced
after administration of contrast material (Figure 4). Cholangiography
may show biliary strictures of intra- or extrahepatic ducts.11 In addition, IPT may be associated with recurrent pyogenic cholangitis that leads to biliary stricture formation.
IPT of the urinary tract is extremely difficult to distinguish
from malignant tumors clinically, radiologically, and histologically.
Patients usually present with painless gross hematuria from exophytic
and ulcerated lesions.12 Lesions within the urinary bladder
are usually single, polypoid, intraluminal or submucosal masses with or
without extension into the perivesical fat and they tend to spare the
trigone area. (Figure 5).13 The maximum reported size has been 9 cm.14
Often IPT displays surface ulcerations and blood clots. IPT should be
considered when an enhancing tumor is surrounded by a clot, particularly
in young adults. Masses are usually hypervascular on Doppler imaging
and show strong enhancement on contrast-enhanced CT or magnetic
resonance imaging (MRI). Central necrosis may be observed within the
lesion.15 Lesions may also show an infiltrating margin and can be accompanied by extensive sclerosis.14
Idiopathic fibrosing disorders/fibromatosis
The fibromatoses consist of a group of fibroproliferative
conditions that are locally aggressive and have the capability to
infiltrate or recur. This can occur in the mediastinum, small bowel
mesentery, omentum, transverse or sigmoid mesocolon, and the
retroperitoneum.16
Fibrosing mediastinitis
Fibrosing mediastinitis, also known as sclerosing mediastinitis,
is characterized by proliferation of dense fibrous tissue within the
mediastinum. Affected patients are typically young and present with
signs and symptoms related to obstruction of vital mediastinal
structures, such as central systemic veins, the esophagus, airways, and
pulmonary arteries or veins. Two patterns of involvement have been
described on CT scans: a focal and a diffuse pattern. The common focal
form presents as a soft-tissue mass that is frequently calcified in the
right paratracheal/subcarinal/hilar regions (Figure 6). The etiology of
this form is postulated to be histoplasmosis in patients from the United
States. In contrast, the diffuse form demonstrates an infiltrating,
noncalcified mass affecting multiple compartments. This is often seen in
association with other idiopathic fibrosing disorders, such as
retroperitoneal fibrosis.
CT depicts the soft tissue mass and its extent. Intravenous
contrast is useful for depiction encasement or obstruction of vessels
with collaterals and also assessing for airway stenosis. Upper
gastrointestinal series may also show narrowing of the esophagus when
the patient presents with dysphagia (Figure 7). Two-dimensional or
3-dimensional reformation techniques may facilitate either surgical
planning or local therapy of these lesions. On MRI, the T1-weighted
magnetic resonance (MR) images show an intermediate signal mass with a
variable signal on the T2-weighted MR.17
Mesenteric fibromatosis
Mesenteric fibromatosis is a deep infiltrative fibroproliferative
process that shows no gender or race predilection and occurs across a
wide age range, 14-75 years.16 Thirteen percent of patients
with mesenteric fibromatosis are found to have familial adenomatous
polyposis (FAP), specifically, the Gardner variant.16 Prior
abdominal surgery is an important risk factor for the development of
mesenteric fibromatosis in patients with FAP. Complications of
fibromatosis include bowel obstruction, fistulization, and even
perforation. Mucosal ulceration may also occur as mesenteric
fibromatosis may compromise the vasculature.18 The CT and MR imaging appearances are variable and related to its underlying histologic characteristics and vascularity.19
A homogeneous, soft-tissue attenuation is seen in tumors with a highly
collagenous stroma, whereas a hypodense/intense appearance is common
with a myxoid stroma (Figure 8). Contrast enhancement both on CT and MRI
may vary from mild homogeneous to heterogeneous enhancement.20
Sclerosing mesenteritis
Sclerosing mesenteritis is an idiopathic disorder characterized
by tumor-like masses in the mesentery that are composed of chronic,
nonspecific inflammation, fat necrosis, and fibrosis. It usually
involves the small bowel, but can also affect the colonic mesocolon.21 The average age at presentation is 60 years with increased frequency in males.22
On imaging, a soft-tissue mass is noted in the mesentery with
retraction and shortening with kinking or fixation of the small bowel.
Punctate or coarse calcifications can be present within the mass. The
mass may envelop the mesenteric vessels and over time collateral vessels
may develop. Preservation of fat around the mesenteric vessels is
usually noted, referred to as the “fat ring sign.”23 This
finding may help distinguish sclerosing mesenteritis from other
mesenteric processes such as lymphoma, carcinoid tumor, or
carcinomatosis.
Retroperitoneal fibrosis
Retroperitoneal fibrosis (RPF) often manifests as a paraspinal, well-demarcated but irregular retroperitoneal mass.24
The fibrosis first begins near the aorta and the iliac arteries,
extending through the retroperitoneum to involve the ureters (Figure 9).
The average age at presentation is 40-60 years, and men are 2 to 3
times more likely to develop retroperitoneal fibrosis than women.25
Avid enhancement on imaging may be seen in the acute stages. There may
be little or no enhancement in the presence of advanced or chronic
disease.26
RPF may be confused on imaging with a neoplastic process, such as
lymphoma. It is important to note that RPF manifests as a plaque-like
density whereas neoplastic infiltration results in peripheral nodularity
and lobulation. In contrast to RPF, which tethers adjacent structures,
lymphoma or other malignant processes usually display mass effect and
displace the aorta and inferior vena cava anteriorly from the spine and
push the ureters laterally.27 RPF almost always occurs caudal to the renal hilum.28
Tumoral calcinosis and metastatic calcifications
Primary tumoral calcinosis
Primary tumoral calcinosis is a familial condition characterized
by solitary or multiple painless, periarticular calcified masses. On
imaging, tumoral calcinosis shows a rather typical appearance:
amorphous, cystic, and multilobulated calcification located in a
periarticular distribution. The greater trochanteric bursa is the most
common site of involvement.29 Fluid-fluid levels caused by calcium layering may be seen within the lesion and are commonly termed the sedimentation sign.30 A homogeneous lesion suggests reduced metabolic activity and diminished ability to grow.31
A distinguishing finding of tumoral calcinosis is the absence of
erosion or osseous destruction. T1-weighted MR images show low signal
intensity, whereas the T2-weighted sequences generally show
inhomogeneous high signal intensity even though there is a large amount
of calcification.32
Secondary tumoral calcinosis
Chronic renal failure is the most common cause of a periarticular
calcified mass, rather than the rarer primary tumoral calcinosis.
Massive periarticular calcification has been attributed to
hyperparathyroidism.33 Lesions of primary tumoral calcinosis and chronic renal failure show no radiologic or histologic differences (Figure 10).34 Hence, the differentiation is usually based on history, serum creatinine, and the glomerular filtration rate.
Foreign bodies and gossypibomas
The term gossypiboma is derived from the Latin word gossypium,
meaning cotton, and the Swahili word boma, meaning place of concealment.35
There are numerous case reports of retained foreign bodies in the
literature, but the true incidence is thought to be under-reported
secondary to possible legal ramifications of this oversight. A patient
with a retained laparotomy sponge can present acutely with sepsis from
abscess formation.36 Delayed presentations result from a
fibrinous response, which is usually an aseptic process that creates
adhesions and a thick capsule around the sponge. These masses are often
confused with neoplasia.37 Most retained sponges are now
impregnated with a radiopaque marker to facilitate radiographic
detection. However, older sponges do not always have this marker (Figure
11). The retained sponge may also be a surgical towel that usually does
not have any radio-opaque markers and often results in large
gossypibomas.
On imaging, the most commonly described ultrasound appearance is
that of an echogenic structure with sharply delineated posterior
acoustic shadowing due to the reflective nature of the gauze fibers.38 CT usually shows a hypodense mass with a thick peripheral rim (Figure 12).39 A whorl-like or spongiform appearance is more typical, but may not always be seen.35
The internal structure of the gauze is best depicted on MRI as wavy
low-signal intensity lines on T2-weighted images, which is a pathognomic
finding.35
Hypertrophy and normal tissues
Splenosis
Splenosis is defined as the autotransplantation of splenic tissue
resulting from the spillage of cells following splenic trauma or
surgery.40 Splenic implants are generally multiple, have no
characteristic shape, nor a hilum or a capsule. These can be located
anywhere in the peritoneal cavity and also within the thorax following a
diaphragmatic tear. On sonography, these implants have a homogeneously
hypoechoic echotexture identical to the spleen.41 At CT, the
attenuation is identical to that of normal spleen in all phases of the
intravenous contrast material enhancement (Figure 13).42,43
The major differential diagnosis for splenosis includes adenopathy,
peritoneal carcinomatosis, and lymphoma. If the diagnosis is in question
after routine cross-sectional imaging, technetium99m tagged heat-damaged red blood cell scintigraphy or technetium99m
sulfur colloid scintigraphy can be performed to confirm the diagnosis
by showing uptake of radionuclide activity in ectopic splenic tissue.44
Extramedullary hematopiesis (EMH)
EMH is most commonly seen in the spleen and liver and occasionally in lymph nodes.1
Involvement of other organs, such as the pleura, lungs,
gastrointestinal tract, breast, skin, brain, kidneys, and adrenal
glands, has also been reported.45 The most common imaging manifestations are paraspinal masses and rib expansion seen frequently in β-thalassemia.46
The active hemopoietic masses are well-marginated and show
mild-homogeneous enhancement on contrast-enhanced imaging. In contrast,
old, burnt-out lesions may show iron deposition or fatty degeneration.46
EMH involving the pulmonary interstitium and mimicking an inflammatory
or neoplastic diffuse interstitial process has been reported.47
In the abdomen, renal involvement is common, which may be parenchymal,
intrapelvic, parapelvic, or perirenal. Perirenal masses typically
present on imaging as uniform, enhancing perinephric masses that engulf
the kidneys without distorting their shape (Figure 14). This appearance
is often confused with bilateral renal lymphoma, and biopsy may be
necessary to establish the diagnosis. Masses of hemopoietic elements can
also involve the mesentery, presenting as nonspecific lesions that can
be mistaken for lymphadenopathy or metastatic disease. Pelvic
hemopoietic masses with a predilection for the presacral region are
rare; however, these should be included in the differential diagnosis
along with other presacral lesions, including chordoma. Identifying EMH
is important as treatment with steroids and external beam radiation is
effective and usually long-lasting.48
Lymphomatoid hyperplasia
Castleman disease, also known as angiofollicular or benign giant
lymph node hyperplasia, is an uncommon lymphoproliferative disorder.49
Castleman disease involves the thorax in 70% of cases; the abdomen in
10% to 15%, retroperitoneum and pelvis in 10% to 15% and the neck on
occasion. Castleman disease can present as a unicentric form or a
multicentric form. The unicentric form (90% of cases) demonstrates
hyaline-vascular histology and is amenable to surgical treatment. The
multicentric form typically occurs in an elderly population and shows
plasma cell histology and is usually associated with more complicated
systemic manifestations.50
Thoracic Castleman disease usually occurs in the mediastinum and
hilum and manifests as a rounded solitary mediastinal or hilar mass in
asymptomatic patients (Figure 15).49 The mediastinal form may mimic thymoma, lymphoma, or neurogenic tumors.49
On the basis of CT, 3 types of imaging appearances are noted, including
a well-defined solitary lesion (50% of cases); mass with
involvement/invasion of contiguous structures (40% of cases); or
confluent lymphadenopathy in a single mediastinal compartment (10% of
cases).50 Homogeneously intense contrast enhancement,
reflecting hypervascularity of the lesion, is considered to be a
characteristic CT finding. On CT, 5% to 10% of Castleman disease showed
intralesional calcifications, typically being discrete in morphology.50,51
Intrathoracic multicentric Castleman disease typically exhibits
bilateral hilar and mediastinal lymphadenopathy; centrilobular nodular
opacities (Figure16). Less common imaging appearances include
ground-glass opacities, consolidation and bronchiectasis.51
In the abdomen, multicentric Castleman disease is characterized by
diffuse lymphadenopathy, hepatomegaly, splenomegaly, ascites, and
thickening of the retroperitoneal fascia. The major differential
diagnosis is lymphoma.
Hemorrhage
Hemophilic pseudotumors
A hemophilic pseudotumor is an encapsulated, chronic, slowly
growing hematoma. This is a rare complication of hemophilia, occurring
in 1% to 2% of persons with severe disease.52 Pseudotumors
usually occur in soft tissues (often intramuscular), but occasionally
may originate in the bone or in a subperiosteal location. Pseudotumors
that occur in muscles can progress to cause severe pressure erosion of
adjacent bone.53 The bones most commonly involved are the
femur, pelvis, tibia, and bones of the hand. Compression of nerves or
pathologic fractures may produce pain or neurologic deficits.54
Pseudotumors have a variable radiographic appearance, however,
are usually lytic with a well-defined margin. Lesions may be
intramedullary or eccentric in location and are often expansile. CT and
MR images are useful for determining the extent of the pseudotumor and
for defining surrounding neurovascular structures and joints (Figure
17).55 On MRI, there are heterogeneous low- and
high-signal-intensity areas internally on both T1- and T2-weighted
images, findings that represent blood products in various stages of
evolution.53
Many bone tumors as well as infectious processes, such as
echinococcosis, may resemble pseudotumors on imaging since many of these
lesions show internal hemorrhage. Percutaneous drainage or biopsy is
contraindicated due to the high prevalence of complications, including
life-threatening bleeding, fistula formation, and infection.54 Therefore, it is vital that the radiologist make the diagnosis of pseudotumor based on patient history and imaging findings.
Endometriosis
Endometriosis is defined as the presence of endometrial glands
and/or stroma in locations outside the uterus. The prevalence has been
quoted to range around 5% to 10 % in both symptomatic and asymptomatic
women.56 The common sites of disease include the ovaries,
uterine ligaments, serosal surfaces, cul-de-sac, fallopian tubes,
rectosigmoid, and urinary bladder.57 Gastrointestinal involvement is estimated to occur in 12% to 37% of patients.58
Areas frequently involved are the rectosigmoid colon, appendix, cecum,
and distal ileum. Implants are usually serosal, but can erode through
the subserosal layers, with thickening and fibrosis of the muscularis
propria (Figure 18). Invasive endometriosis is typically found in the
rectovaginal septum and fibromuscular pelvic structures, such as the
uterine ligaments and the muscular walls of pelvic organs accompanied by
smooth muscle proliferation and fibrotic reaction. Solid masses in the
pelvis may simulate metastatic peritoneal implants (Figure 18).
Pleuropulmonary endometriosis is usually coexistent with pelvic
endometriosis and usually occurs 5 years following the diagnosis of
pelvic endometriosis. The imaging findings include pneumothorax,
hemothorax, and lung nodules. The pleural lesions are almost exclusively
right-sided, whereas lung lesions do not show any such predilection
(Figure 18).59
Miscellaneous conditions
Sarcoidosis
Sarcoidosis is a systemic disorder characterized by noncaseating
granulomas with proliferation of epithelioid cells. Young and
middle-aged patients, especially women, are most commonly affected.60
Ninety percent of patients with sarcoidosis show pulmonary involvement,
which commonly manifests as asymptomatic mediastinal adenopathy.60
Less commonly seen findings of pulmonary sarcoidosis include
multiple miliary nodules, bronchial-wall thickening, and ground-glass
attenuation. The latter may reflect the presence of microscopic
interstitial granulomas.
Sarcoidosis may also involve the abdomen, especially the liver
and spleen; however, the imaging findings usually include only
hepatosplenomegaly. Rarely coalescing granulomas become apparent as
multiple hypointense or hypoattenuating nodules.61 Splenic nodules are
larger and more common than hepatic lesions.61 Twenty-five
percent of patients have normal findings at chest radiography. Multiple
nodules in hepatic sarcoidosis are easily mistaken for more common
diseases, including metastases and lymphoma. When there is no other
clinical evidence of sarcoidosis, liver biopsy may be considered.
Rarely, renal sarcoidosis manifests as multiple low-attenuation
tumor-like nodules that can mimic lymphoma or metastatic tumors (Figure
19).62,63
Xanthogranulomatous pyelonephritis
Xanthogranulomatous pyelonephritis is an uncommon form of chronic renal parenchymal infection.64
The renal parenchyma is usually diffusely involved; however, focal
involvement is also noted. The kidney is diffusely enlarged with
replacement of the renal parenchyma by multiple low-attenuation rounded
masses with attenuation values of 10-15 HU. A “staghorn” calculus is
commonly associated.64 Extension to involve the peri- and
paranenal spaces, ipsilateral psoas muscle, diaphragm, posterior
abdominal wall, skin, and bowel may be present and mimic lymphoma or
renal cancer.
Conclusion
The increasing use of CT and MRI to establish or exclude a wide
variety of diagnoses in many different clinical settings will likely
increase recognition of non-neoplastic lesions that can simulate
malignancies. Some of these lesions are indeed benign and self-limited,
while others can be locally aggressive and require specific treatment.
It is important to recognize that many of these lesions have unique
imaging appearances that can aid in distinguishing them from malignancy.
Signs and symptoms have a major role in narrowing diagnostic
considerations. Hopefully, this article, while not comprehensive, will
help guide radiologists in distinguishing these conditions from true
malignancies.
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