AJR 2004; 182:1579-1586
© American Roentgen Ray Society
PET–CT of Extranodal Lymphoma
Ur Metser1,
Odelia Goor2,
Hedva Lerman1,
Elizabeth Naparstek2 and
Einat Even-Sapir1
1 Department of Nuclear Medicine, Tel-Aviv Sourasky Medical Center, Sackler
Faculty of Medicine, Tel-Aviv University, 6 Weizman St., Tel-Aviv 64239,
Israel.
2 Department of Hematology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of
Medicine, Tel-Aviv University, Tel-Aviv 64239, Israel.
Received July 18, 2003;
accepted after revision October 21, 2003.
Address correspondence to U. Metser.
Lymphoma, mainly non-Hodgkin's lymphoma, may be extranodal in origin in
approximately 40% of patients. Extranodal involvement may also be due to
regional spread of nodal disease or hematogenous dissemination
[1]. FDG positron emission
tomography (PET) imaging has been shown to be an important technique for both
staging and follow-up of nodal and extranodal lymphoma
[2]. PET–CT systems,
which enable the performance of PET and CT data acquisition at the same
setting without changing the patient's positioning, have been recently
introduced in clinical practice
[3]. Lesions are characterized
on the fused PET–CT images by both their metabolic status and their
anatomic details. Such fusion can also assist in the differentiation of
physiologic and tumoral sites of FDG uptake. Our aim is to show the use of FDG
PET–CT imaging in extranodal lymphoma involving various structures and
organs. The relevant CT, PET, and fused PET–CT images of each
illustrative case will be presented.
Thorax
Lung
Secondary involvement of the lungs is three times more frequent in
Hodgkin's disease than in non-Hodgkin's lymphoma, usually because of extension
of disease from involved hilar and mediastinal nodes. Peripheral subpleural
masses or consolidations without mediastinal adenopathy can occur in both
Hodgkin's disease and non-Hodgkin's lymphoma
[4].
Pleura and Pericardium
Pleural effusion is common but rarely indicates pleural involvement.
Pleural-based lymphomatous masses are less common
[1] and are frequently
overlooked on conventional imaging. Pericardial disease arises from lymphatic
or hematogenous spread or by direct extension of mediastinal tumor
[1].
Thymus
Although 30–50% of patients with Hodgkin's disease have thymic
enlargement at presentation, actual involvement of the thymus with lymphoma is
rare and difficult to assess on imaging.
Chest Wall
Anterior mediastinal adenopathy, especially in the internal mammary chain,
may extend into the chest wall (Fig.
1A). Thoracic spine involvement is often secondary to posterior
extension of posterior mediastinal adenopathy.
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Fig. 1A. —23-year-old man with extranodal chest and peritoneal
involvement of Hodgkin's lymphoma. PET–CT scan was obtained at
presentation. Later findings resolved on follow-up PET–CT after
chemotherapy. Fusion PET–CT axial image shows consolidation due to
lymphoma in both lungs (arrowhead), with chest wall extension
(thick arrow) and pleural mass (thin arrow).
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Breast
Primary breast lymphoma accounts for only 0.1–0.5% of all breast
tumors [5]. The diagnosis of
primary breast lymphoma depends on the absence of concurrent widespread
lymphoma (with the exception of ipsilateral axillary nodes) and no previous
diagnosis of extramammary lymphoma. Otherwise, it is considered secondary
involvement. No imaging criteria are available to distinguish primary breast
lymphoma from other neoplasms of the breast (Fig.
2A,
2B).
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Fig. 2B. —27-year-old woman with stage IV non-Hodgkin's lymphoma and
presumed lymphomatous mass in breast. Corresponding FDG PET axial image shows
presumed lymphomatous breast mass (arrowhead). Follow-up scan (not
shown) obtained 4 months later, after chemotherapy, showed resolution of
findings.
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Abdomen and Pelvis
Spleen
The spleen is frequently involved in non-Hodgkin's lymphoma and in one
third of patients with Hodgkin's disease
[6]. It may be the only site of
abdominal disease in 10% of patients with Hodgkin's disease. Splenomegaly is
not a reliable indicator of disease because the organ's size is normal in one
third of patients with splenic
disease.
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Fig. 9C. —64-year-old man with non-Hodgkin's lymphoma and extranodal
involvement of skeleton (biopsy proven) and adrenal glands. Coronal fused
PET–CT image shows diffuse patchy bone marrow involvement in axial and
peripheral skeleton (e.g., T11 vertebral body [arrow]). Note
abnormally increased uptake of FDG (arrowhead) in center of pelvis
shown to be in segment of normal-appearing bowel on CT. Therefore, this uptake
was presumed to represent physiologic FDG uptake in bowel.
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Liver
Only 5% of patients with Hodgkin's disease have liver involvement, almost
always with splenic involvement, but up to 15% of patients with non-Hodgkin's
lymphoma have liver disease
[7]. Hepatomegaly is suggestive
of diffuse liver infiltration, and focal liver disease may resemble metastatic
disease on imaging (Fig. 3).
Occasionally, lymphomatous infiltration may be seen extending from the porta
hepatis along the margins of the portal veins (Fig.
4A,
4B).
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Fig. 3. —74-year-old man with non-Hodgkin's lymphoma involving liver
and spleen. Coronal fused PET–CT image shows focal deposit in liver
(arrowhead) and diffuse increased FDG uptake in spleen
(arrow), indicating splenic involvement. Findings were confirmed on
contrast-enhanced CT (not shown).
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Fig. 4A. —52-year-old man with histologically proven non-Hodgkin's
lymphoma involving nodes above and below diaphragm, with infiltration of tumor
along liver ligaments. Axial FDG PET image shows lymphomatous mass
(arrowhead) in region of liver. Also note focal right pleural
involvement.
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Fig. 4B. —52-year-old man with histologically proven non-Hodgkin's
lymphoma involving nodes above and below diaphragm, with infiltration of tumor
along liver ligaments. Axial fused PET–CT image shows tumor mass
(arrowhead) extending along ligamentum venosum.
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Pancreas
Lymphomatous involvement of the pancreas is unusual but is well documented
in the literature [1]. On
imaging, a large mass may be seen with extrapancreatic extension. When below
the renal vessels, associated lymphadenopathy is far more common in lymphoma
than in adenocarcinoma of the pancreas.
Gastrointestinal Tract
The gastrointestinal tract is the most common site of primary extranodal
non-Hodgkin's lymphoma, accounting for up to 10% of extranodal disease at
diagnosis [8]. A single segment
of gut is involved without distant lymph node involvement, except for lymph
nodes draining the involved segment. Secondary involvement of the
gastrointestinal tract is common (Fig.
5A,
5B), usually extending from
adjacent nodal masses. Multiple segments may be involved.
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Fig. 5A. —55-year-old man with non-Hodgkin's lymphoma secondarily
involving bowel. Axial CT image shows soft-tissue attenuating mass
(arrows) encasing segment of small bowel in right lower quadrant of
abdomen.
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Fig. 5B. —55-year-old man with non-Hodgkin's lymphoma secondarily
involving bowel. Corresponding fusion PET–CT image shows abnormal uptake
of FDG in soft-tissue mass (arrows), indicating lymphomatous
involvement. Findings resolved on followup PET–CT (not shown) after
chemotherapy.
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Peritoneum and Omentum
Peritoneal or omental infiltration by lymphoma is seen almost exclusively
in non-Hodgkin's lymphoma. Peritoneal lymphoma mimics peritoneal
carcinomatosis with ascites, peritoneal nodules, and occasionally omental
infiltration (Fig. 1B).
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Fig. 1B. —23-year-old man with extranodal chest and peritoneal
involvement of Hodgkin's lymphoma. PET–CT scan was obtained at
presentation. Later findings resolved on follow-up PET–CT after
chemotherapy. Fusion PET–CT axial image obtained in upper abdomen shows
subtle peritoneal mass (arrow) anterior to liver, indicating
peritoneal involvement.
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Genitourinary Tract
Genitourinary tract involvement is unusual at presentation. The most common
organs involved are the testes, followed by the kidneys. Although only 3% of
patients have renal involvement at diagnosis, the incidence in recurrent
high-grade non-Hodgkin's lymphoma is higher. There are four CT imaging
patterns, the most frequent of which is multiple hypodense nodules (which may
be hyperdense on unenhanced CT) followed by extension from retroperitoneal
adenopathy (Fig. 6). A
solitary mass indistinguishable from renal cell carcinoma
(Fig. 7) and diffuse
infiltration are less commonly seen
[9].
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Fig. 6. —44-year-old woman with recurrent non-Hodgkin's lymphoma
involving retroperitoneal lymph nodes. Axial fusion PET–CT image shows
invasion of left kidney through left renal hilum (arrowhead),
confirmed on contrast-enhanced CT (not shown).
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Fig. 7. —77-year-old man with non-Hodgkin's lymphoma. Coronal
PET–CT image shows FDG-avid soft-tissue attenuating left renal masses
(arrows). Note abnormal FDG uptake in retroperitoneal lymph nodes.
Renal findings resolved on follow-up scan (not shown) obtained after
chemotherapy.
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Testicular lymphoma accounts for 5% of testicular tumors and is the most
common testicular tumor in patients older than 60 years. The testes may be the
only site of disease or a site of recurrence. Bilateral involvement may be
seen in up to 38% of cases. Concomitant involvement of the epididymis and
spermatic cord (Fig. 8A,
8B) and the skin and central
nervous system is common
[1].
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Fig. 8A. —76-year-old man with non-Hodgkin's lymphoma involving
retroperitoneal nodes, spermatic cord, and testis.
Maximum-intensity-projection PET view shows retroperitoneal lymphadenopathy
and lymphomatous involvement of serpentine structure in right groin and
scrotum, conforming to path of right spermatic cord, epididymis
(arrows), and testis (arrowhead).
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Fig. 8B. —76-year-old man with non-Hodgkin's lymphoma involving
retroperitoneal nodes, spermatic cord, and testis. Sagittal fused PET–CT
image confirms location of abnormality in spermatic cord, epididymis
(arrows), and testis (arrowhead). Absence of bowel in
scrotal sac depicted on CT excludes hernia with loops of bowel in it as
possible cause for abnormal FDG uptake. Findings were confirmed on sonography
(not shown).
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Adrenal Gland
The adrenal gland is involved in 4% of patients with non-Hodgkin's
lymphoma. Adrenal lymphoma is bilateral in 50% of these cases
(Fig. 9A) and may cause
adrenal insufficiency [10].
Nonlymphomatous bilateral adrenal hyperplasia has been described in
association with lymphoma and should be differentiated from tumoral
involvement.
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Fig. 9A. —64-year-old man with non-Hodgkin's lymphoma and extranodal
involvement of skeleton (biopsy proven) and adrenal glands. Axial fused
PET–CT image shows bilateral lymphomatous deposits (arrowheads)
in adrenal glands. Adrenal masses resolved after therapy (not shown). Note
involvement of L1 vertebral body (arrow).
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Musculoskeletal System
Bone and bone marrow involvement may occur in both Hodgkin's disease and
non-Hodgkin's lymphoma. The skeleton is a frequent site of relapse. Bone
marrow infiltration may be a site of a primary disease (stage IE) or more
often part of a disseminated disease (stage IV), found in up to 40% of
patients with non-Hodgkin's lymphoma at presentation
(Fig. 9B). Bone marrow
involvement in Hodgkin's disease at presentation is rare but may be seen in
5–34% of patients later during the course of disease.
Primary lymphoma of bone is almost exclusively due to non-Hodgkin's
lymphoma, usually involving a single bone
[1] (Fig.
10A,
10B). Secondary involvement of
bones, mostly the axial skeleton, may be seen in both non-Hodgkin's lymphoma
and Hodgkin's disease. The use of PET obviates performing bone scintigraphy
[11]. The disease may extend
into the adjacent soft tissue or present as a separate intramuscular mass.
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Fig. 10B. —39-year-old man with histologically proven non-Hodgkin's
lymphoma of bone. Corresponding PET image shows lymphomatous involvement of
left iliac bone (arrow). Follow-up scan (not shown) obtained after
chemotherapy 3 months later showed resolution of findings on PET and CT.
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Head and Neck
Unlike Hodgkin's disease, extranodal lymphoma of the head and neck region
is relatively common in non-Hodgkin's lymphoma, accounting for approximately
5% of head and neck tumors. The most common site of involvement is Waldeyer's
ring: the lymphoid tissue in the nasopharynx, oropharynx, and tonsils. The
parotid gland is the most commonly involved salivary gland
(Fig. 11). Most cases of
thyroid non-Hodgkin's lymphoma arise in a background of Hashimoto's
thyroiditis. It may be difficult to distinguish between lymphoma and
thyroiditis on the basis of fine-needle aspirates. Mediastinal and
retrosternal extension is associated with a worse prognosis
[1].
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Fig. 11. —74-year-old woman with non-Hodgkin's lymphoma. Fused
PET–CT axial image shows lymphomatous deposit in right parotid gland
(arrowhead) and in small right neck nodes (arrow). Findings
resolved on follow-up PET–CT scan (not shown) obtained after
chemotherapy.
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Nervous System
Primary central nervous system lymphoma occurs almost exclusively in the
brain's white matter (Fig.
12). Increase in its incidence has been coupled with the rise in
frequency of immunocompromised conditions. Secondary lymphoma occurs in up to
15% of patients with non-Hodgkin's lymphoma but is rare in Hodgkin's disease.
The extracerebral spaces and the epidural and subarachnoid spinal spaces may
be involved [1]. Compression of
the spinal cord or cauda equina may be seen because of extension of nodal
disease through the intervertebral foramina
[12] (Fig.
13A,
13B).
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Fig. 13A. —60-year-old man with non-Hodgkin's lymphoma and spinal cord
compression. Axial CT image shows right paravertebral mass
(arrowheads) extending through right thoracic intervertebral foramen
to invade epidural space.
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Fig. 13B. —60-year-old man with non-Hodgkin's lymphoma and spinal cord
compression. Fused PET–CT image shows abnormal FDG uptake in right
paraspinal and epidural mass (arrowheads), indicating tumor
involvement.
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Non-Hodgkin's lymphoma of the orbit is the most common primary orbital
malignancy in adults (Fig.
14A,
14B). Retrobulbar lymphoma is
an infiltrative process, causing ophthalmoplegia and proptosis
[1]. Secondary orbital lymphoma
may be seen in up to 5% of patients with lymphoma.
Infiltration of the peripheral or cranial nerves is a rare condition,
termed "neurolymphomatosis." Clinically, patients may present with
peripheral or cranial neuropathy. CT or MRI may show nerve enlargement or
enhancement beyond the dural sleeve. Recently, a case of neurolymphomatosis
was diagnosed using PET–CT
[13] (Fig.
15A,
15B,
15C,
15D,
15E,
15F).
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Fig. 15A. —32-year-old woman with history of uterine lymphoma 8 years
earlier, who presented with progressive paraparesis (more on left) and
progressing dysphagia, diagnosed as biopsy-proven neurolymphomatosis. After
chemotherapy, patient improved clinically, and findings resolved on subsequent
PET–CT scan. Axial PET image of brain shows increased FDG uptake
(arrow) in left cerebellopontine angle.
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Fig. 15B. —32-year-old woman with history of uterine lymphoma 8 years
earlier, who presented with progressive paraparesis (more on left) and
progressing dysphagia, diagnosed as biopsy-proven neurolymphomatosis. After
chemotherapy, patient improved clinically, and findings resolved on subsequent
PET–CT scan. Sagittal PET image shows increased FDG uptake
(arrow) in upper neck on left.
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Fig. 15C. —32-year-old woman with history of uterine lymphoma 8 years
earlier, who presented with progressive paraparesis (more on left) and
progressing dysphagia, diagnosed as biopsy-proven neurolymphomatosis. After
chemotherapy, patient improved clinically, and findings resolved on subsequent
PET–CT scan. Fused PET–CT image shows extension of FDG uptake
(arrow) through jugular foramen. MRI findings (not shown) were
normal. Because of clinical history of dysphagia and path of increased FDG
uptake on fusion PET–CT images, this uptake was presumed to represent
lymphomatous infiltration along left tenth cranial nerve.
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Fig. 15D. —32-year-old woman with history of uterine lymphoma 8 years
earlier, who presented with progressive paraparesis (more on left) and
progressing dysphagia, diagnosed as biopsy-proven neurolymphomatosis. After
chemotherapy, patient improved clinically, and findings resolved on subsequent
PET–CT scan. Coronal fused PET–CT image shows abnormal FDG uptake
(arrow) along thoracolumbar spine and along origins of intervertebral
nerves, representing lymphomatous involvement.
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Fig. 15E. —32-year-old woman with history of uterine lymphoma 8 years
earlier, who presented with progressive paraparesis (more on left) and
progressing dysphagia, diagnosed as biopsy-proven neurolymphomatosis. After
chemotherapy, patient improved clinically, and findings resolved on subsequent
PET–CT scan. Axial PET image (L3–L4) shows abnormal FDG uptake
(arrows) in paravertebral location (more on left). This uptake was
proven by fusion image (not shown) to be along origins of intervertebral
nerves.
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Fig. 15F. —32-year-old woman with history of uterine lymphoma 8 years
earlier, who presented with progressive paraparesis (more on left) and
progressing dysphagia, diagnosed as biopsy-proven neurolymphomatosis. After
chemotherapy, patient improved clinically, and findings resolved on subsequent
PET–CT scan. Corresponding axial CT image shows relative thickening of
left nerve root (arrow).
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