The patient is an 86-year-old woman with a history of right breast
infiltrative lobular carcinoma 16 years before presentation.
She underwent right total mastectomy and axillary lymph node dissection
and was found to have an extensive cancer, involving all quadrants of the right
breast, ER-positive 50%, PR-positive 75%, with 23 of 39 metastatic lymph nodes.
She then completed adjuvant chemotherapy with cyclophosphamide,
methotrexate and 5-FU (CMF) and radiotherapy. She did not receive endocrine
treatment.
She presented with an episode of hematemesis but denied abdominal pain,
nausea, weight loss or dysphagia.
Her medical history included diabetes mellitus, hypertension and
coronary artery disease with mitral valve replacement. She had a history of
bilateral knee replacement for degenerative disease, hysterectomy for uterine
fibroids and L4-L5 laminectomy for disc disease.
Home medications included atorvastatin, pregabalin, olmesartan,
tolterodine, metoprolol, furosemide, aspirin, repaglinide and insulin. She
denied use of alcohol, tobacco or drugs.
Family history was significant for a sister who had breast cancer and
subsequently died from leukemia.
The patient had hyperplastic polyp on screening colonoscopy. Her
physical examination was otherwise unrevealing.
Endoscopy revealed abnormal gastric folds, and a biopsy of the gastric
body revealed metastatic carcinoma, consistent with breast origin (lobular
carcinoma).
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Figure 1.
Selected axial images from the CT with oral and IV contrast (a), axial PET (b),
fused PET-CT (c), and fused PET-CT with regions of interest targeting an
abnormal lymph node (d). There is diffuse wall thickening of the distal stomach
with diffuse low-grade metabolic activity (arrowheads). There were multiple
enlarged lymph nodes around the stomach with minimal associated hypermetabolic
activity, including a 2.1-cm non-hypermetabolic lymph node adjacent to the
posterior stomach wall (long arrow) with maximum SUV 1.6.
Photos courtesy M. Ghesani, MD
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Immunohistochemical studies showed the tumor cells to be positive for
ER, mammoglobin and cytokeratin AE 1/3 but negative for PR, CD56, CD45RB and
HER-2/neu by fluorescence in situ hybridization.
Laboratory workup showed leukocyte count of 10 ×
103/uL, hemoglobin, 9.3g/dL and platelet count, 260
×103/uL. Kidney and liver functions were normal. Alkaline
phosphatase was 43 IU/L, CA 27.29 was elevated at 49 U/mL, CEA slightly
elevated at 2.8 ng/mL.
A CT scan of the chest, abdomen and pelvis showed gastric wall
thickening consistent with the known malignancy, in addition to extensive bony
metastases. A CT scan of the head revealed no mass lesion, but the skull base
had a mottled, sclerotic appearance that may indicate metastatic disease.
A PET/CT scan showed a uniform mural thickening of the distal body of
the stomach and gastric antrum with low-grade, diffuse metabolic activity,
maximum standardized uptake value (SUV) 2.4.
The patient had gastrohepatic ligament lymph nodes, the largest being
2.1 cm, with no associated hypermetabolic activity.
There were also extensive mixed lytic and blastic lesions scattered
throughout the skeleton, including the pelvis, cervical, thoracic and lumbar
spine, scapulae, clavicles and ribs, SUV max up to 2.34.
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Figure 2. Selected axial CT (left column) and PET (right
column) images of the shoulders (top row), lower thoracic spine (middle row)
and pelvis (bottom row) demonstrating extensive diffuse mixed lytic and blastic
bone metastases with variable low hypermetabolic activity (maximum SUV up to
2.4 in the thoracic spine). For example, there is expansion, sclerosis and
lytic permeation of the right clavicle and acromion (top row), vertebral bodies
(middle row), sacrum and pelvis (bottom row).
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The patient was started on an aromatase inhibitor with bisphosphonate
therapy.
Because malignant tumors have more specific transporter proteins with
greater glucose affinity compared with normal tissues, cancer cells have more
glucose uptake. The higher the SUV, the more likely the mass is malignant.
PET scans use fluorine-18 fluorodeoxyglucose (FDG) to demonstrate
abnormal metabolic activity in otherwise morphologically normal organs.
However, a PET scan alone is limited in the workup of suspected recurrent
malignancy. Tumors smaller than 1 cm are rarely picked up with a PET scan
because it is limited by spatial resolution. Also, there is limited sensitivity
of PET imaging for tumors with low glucose avidity, such as lobular carcinoma.
Combined PET and CT scans provide increased overall sensitivity and
specificity for both the functional and anatomic localization of lesions.
PET/CT scan is used for diagnosis, evaluating lymph node involvement,
preoperative staging, response to neo-adjuvant therapy and detection of
metastasis/recurrences in breast cancer.
Normal physiologic FDG uptake may be seen in the central nervous system,
myocardium and the genitourinary tract. Areas of inflammation, infection and
postoperative wound healing also increase uptake. These benign conditions and
normal tissues have lesser uptake than neoplasms. However, areas of overlap
often are seen.
Occasionally, FDG uptake can be observed in the breast. Lactating and
denser breasts have a higher uptake. The reported sensitivity of PET/CT in
detecting breast cancers range between 80% and 96% and specificity between 83%
and 100%.
Breast cancer commonly spreads to the bones, lungs and liver. Metastasis
to the upper gastrointestinal tract is seldom seen, with incidence reported at
2% to 18%. This may occur many years after the diagnosis and treatment of
primary breast cancer. The clinical manifestations often overlap, including
abdominal pain, weight loss, early satiety, dyspepsia, anorexia, vomiting and
bleeding.
Radiologic and endoscopic tools are unable to differentiate between
primary gastric cancer and breast cancer metastasis. A study by Taal and
colleagues found that 83% of the gastric metastases were lobular breast
carcinoma. They usually present as diffuse infiltration of the submucosa and
muscularis with a linitis plastica pattern.
Invasive lobular carcinomas are more difficult to diagnose with imaging
procedures owing to their diffuse growth pattern and lower microvessel density
almost equivalent to the surrounding breast parenchyma. They are extremely
difficult to detect mammographically and account for false negative results in
MRI and PET scans. Lobular cancers have a significantly lower FDG uptake than
ductal breast cancers, as reported by Buck and colleagues.
Histology plays a role in defining glycolytic uptake.
Well-differentiated tumors, carcinoma in situ and slow-growing tumors, such as
tubular carcinoma, have lesser FDG avidity. Invasive lobular carcinomas, in
contrast to carcinomas with ductal histologies, have lower tumor cell density
and diffuse infiltration of surrounding tissues, possibly explaining its lower
metabolic activity. A high index of suspicion is warranted in a patient such as
ours with borderline SUV and a remote history of breast cancer. Histologic
analysis with immunohistochemical studies and morphologic comparison with
previous breast cancer pathology will aid in the diagnosis.
Irene Dy, MD, is a fellow in hematology and oncology at St.
Luke’s-Roosevelt Hospital Center.
Iwao Tanaka, MD, is a resident in radiology at St.
Luke’s-Roosevelt Medical Center.
Rami Daya, MD, is a medical oncologist in private practice in
Brooklyn, N.Y.
Munir Ghesani, MD, is an attending radiologist at St.
Luke’s-Roosevelt Hospital Center and associate clinical professor of
radiology at Columbia University College of Physicians and Surgeons.
For more information:
- Avril N. J Clin Oncol. 2000;18:3495-3502.
- Buck A. Eur J Nucl Med Mol Imaging. 2002;29:1317-1323.
- Jones GE. World J Surg Oncol. 2007;5:75.
- Lim HS. Radiographics. 2007;27:S197-213.
- Taal BG. Gastrointest Endosc. 1992;38:130-135.