Deceptive presentation of metastatic lobular breast carcinoma

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.

Patient history

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).

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

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.

Scanning results

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.

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).

The patient was started on an aromatase inhibitor with bisphosphonate therapy.

Discussion

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.