DIAGNOSIS IN ONCOLOGY

Arthur Skarin, MD, Consultant Editor

Unusual Aspects of Breast Cancer

CASE 1. ANGIOSARCOMA OF THE BREAST
A 23-year-old unmarried, nulliparous woman presented with a chief complaint of left breast enlargement of 10 months’
duration. On physical examination, a hard mass was located in the left breast, which measured 12 ⫻ 12 cm and was
accompanied by edema and hyperemia in the overlying skin, without regional node involvement (Fig 1). Tumor markers,
including carcinoembryonic antigen, CA 15-3, and CA 19-9, were all within normal limits. A mammary echogram showed
a low echoic heterogenous mass that measured 8 ⫻ 8 cm in the left breast with involvement of the skin on mammography.
Thoracic computed tomography (Fig 2) and breast magnetic resonance imaging revealed a large mass in the left breast with
cystic components, partly invading the underlying pectoralis major muscle, but without invasion into the thorax. An
incisional biopsy of the mass was performed. Many dilated capillaries were found, including an irregular network of
vasculature with proliferation of cells, suggestive of an angiogenic tumor, the cells of which were immunohistochemically
weakly positive for factor VIII with presence of necrosis (Fig 3). The patient had a left mastectomy with biopsy of axillary
lymph nodes, which were negative, accompanied by breast reconstruction using a latissimus dorsi flap. There was a complete
resection with negative margins. No adjuvant therapy was given. Multiple lung, liver, and bone metastases were detected
approximately 9 months later and she succumbed from respiratory failure caused by progressive pulmonary metastases.
Angiosarcoma of the breast occurs mainly during the third and fourth decades of life, in contrast to breast carcinoma,
which generally arises later.1 This malignant tumor occurs primarily in young women, with 6% to 12% of the cases found
during pregnancy, implying a hormonal effect. In most cases, the tumor size is more than 4 cm in diameter, which does not
correlate with survival.2 Preoperative diagnosis of angiosarcoma of the breast by aspiration cytology and biopsy is often
difficult, with a false-negative biopsy rate of 37% in one large review.3 Ultrastructural examination can reveal the vascular
nature of angiosarcoma and demonstrate the existence of diagnostic Weibel-Palade bodies and pinocytic vesicles.4
Immunostaining for factor VIII–related antigen is helpful for the diagnosis of angiosarcoma of the breast.5 The histologic
features are classified into three groups and the features in our patient are compatible with those of group III.4 Other attempts
to correlate histologic features with clinical behavior were made in a series of 10 cases, where an unfavorable prognosis was
related to a high mitotic count.6 Angiosarcoma has a high mortality rate, with only 10% to 21% of patients remaining
disease-free after 5 years.2 Although some individuals seem to benefit from adjuvant chemotherapy, available treatment for
patients with disseminated disease is of minimal benefit.4
Hamid Mansouri, Abdeloahed Jalil, Leila Choho, Abdelilah Souadka, and Brahim El Gueddari
Rabat University School of Medicine, Rabat, Morocco
Copyright © 2001 American Society of Clinical Oncology

Fig 1. Fig 2.

2570 Journal of Clinical Oncology, Vol 19, No 9 (May 1), 2001: pp 2570-2574

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DIAGNOSIS IN ONCOLOGY 2571

Fig 3.

REFERENCES
1. Melhouf M, Amrani N, Lafontaine J, et al: Les angiosarcomes du
sein. Bull Cancer 84:218-222, 1997
2. Rosen PR, Kimmel M, Ernsberger D: Mammary angiosarcoma.
Cancer 62:2145-2151, 1988
3. Chenk KTK, Kirkegaard DD, Bocian JJ: Angiosarcoma of the
breast. Cancer 46:268-271, 1980
4. Masatoshi O, Yutaka T, Soichi K, et al: Angiosarcoma of the
breast. Jap J Clin Oncol 27:91-95, 1997
5. Gupta RK, Naran S, Dowle C: Needle aspiration cytology and
immunohistochemical study in a case of angiosarcoma of the breast.
Diagn Cytopathol 7:363-365, 1991
6. Liberman L, Dershaw DD, Kaufman RJ, et al: Angiosarcoma of
the breast. Radiology 183:649-654, 1992

CASE 2. SYNCHRONOUS BILATERAL LUNG AND BREAST CANCERS

A 53-year-old postmenopausal woman with a history of smoking, hypertension, and arthritis was evaluated for bilateral chest
radiograph findings and bilateral findings on screening mammography. The lung findings included a small peripheral left
upper lobe lesion and a more centrally located lesion in the right upper lobe. Thoracoscopic wedge resection of a left lung
nodule and mediastinal lymph node sampling revealed bronchioloalveolar adenocarcinoma, without involvement of mediastinal
lymph nodes (Fig 1A, stage T1N0). Subsequent right upper lobectomy and node dissection disclosed poorly differentiated
non–small-cell carcinoma with adenosquamous features (Fig 1B, stage T1N0) but with negative nodes. Mammography revealed
an area of architectural distortion with spiculated margins in the left breast and fine linear punctate calcifications in the right breast.
Both these findings were new compared with previous mammograms obtained the prior year. Stereotactic core biopsy of the left
breast revealed invasive lobular cancer moderately differentiated (Fig 1C), which was subsequently found to affect multiple axillary
lymph nodes (stage T2N1). Stereotactic core biopsy of the right breast identified ductal carcinoma in situ cribriform type, low
nuclear grade, with a focus of microinvasion (⬍ 0.1 cm; stage TmicN0; Fig 1D; arrow indicates microinvasion). The four
synchronous tumors had distinct histologic features. Immunohistochemistry showed that the invasive lobular breast tumor was
positive for estrogen and progesterone receptors and negative for HER2/neu. The invasive component of the contralateral breast
tumor was too small to further characterize by immunohistochemistry, and the lung cancers were negative for all three markers.
There was no evidence of metastatic disease on staging serum chemistry and tumor marker tests, bone scan, or head/chest/
abdomen/pelvis computed tomography scans. The patient’s mother had died of lung cancer at age 73; there was no other history
of cancer in first- or second-degree relatives.
The diagnosis of synchronous primary tumors, as opposed to metastatic disease, can be a clinical challenge. Synchronous
primary lung cancer occurs in approximately 0.5% of lung cancer patients.1,2 Criteria for distinguishing second primary lung
cancers include different histology, and in instances of similar histology, tumors arising in different areas of lung
parenchyma, especially with areas of carcinoma-in-situ. The incidence of synchronous primary breast cancers is generally
estimated at 1%.3,4 For breast tumors, histology can be used to distinguish synchronous and metachronous primaries from
metastatic disease. Other important criteria for distinguishing primary breast tumors include the presence of in situ disease
and different patterns of expression of hormone receptors. Synchronous lung and breast cancer is rare, affecting fewer than

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2572 BURSTEIN ET AL

Fig 1.

0.5% of patients diagnosed with breast cancer.5 These malignancies do not share known predisposing etiologic or hereditary
factors.
Pulmonary nodules arising in women with histories of breast cancer may reflect metastatic disease, primary lung cancers,
or other benign etiologies. Several large institutions have reported historic experience in evaluating solitary pulmonary
nodules among women with prior or synchronous breast cancer.5-7 Among such women, the pulmonary nodule represented
metastatic breast cancer in 37% of the patients, a primary lung cancer in 55% of the cases, and a benign lesion in 8%. Women
with breast cancer and a solitary nodule merit pathologic evaluation of the pulmonary lesion, as more than half of such
women will not have metastatic breast cancer and may be treated with curative intent. Distinguishing metastatic breast
carcinoma from a new primary lung cancer can be difficult if the tumors are adenocarcinomas or poorly differentiated
carcinomas that share histologic features. Immunohistochemistry may be useful for discriminating between different
adenocarcinomas.8
Patients with synchronous or metachronous primary lung cancers or lung and breast cancers seem to have a worse prognosis
than patients with a single tumor, principally because of excess mortality from lung cancer.9,10 Nonetheless, patients with
potentially curable tumors may benefit from definitive lung surgery and consideration of curative adjunctive treatments.

Harold J. Burstein, Scott J. Swanson, Roger L. Christian, and Mairin E. McMenamin

Dana-Farber Cancer Institute, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA

Copyright © 2001 American Society of Clinical Oncology

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DIAGNOSIS IN ONCOLOGY 2573

REFERENCES
1. Ferguson MK: Synchronous primary lung cancers. Chest 103:
398S-400S, 1993
2. Martini N, Melamed M: Multiple primary lung cancers. J Thorac
Cardiovasc Surg 70:606-612, 1975
3. Donovan AJ: Bilateral breast cancer. Surg Clin North Am
70:1141-1149, 1990
4. Gollamudi SV, Gelman RS, Peiro G, et al: Breast-conserving
therapy for stage I-II synchronous bilateral breast carcinoma. Cancer
79:1362-1369, 1997
5. Casey JJ, Stempel BG, Scanlon EF, et al: The solitary
pulmonary nodule in the patient with breast cancer. Surgery
96:801-805, 1984
6. Cahan WG, Castro EB: Significance of a solitary lung shadow in
patients with breast cancer. Ann Surg 181:137-143, 1974
7. Adkins PC, Wesselhoeft CW, Newman W, et al: Thoracotomy on
the patient with previous malignancy: Metastasis or new primary?
J Thorac Cardiovasc Surg 56:351-361, 1968
8. Raab SS, Berg LC, Maj MC, et al: Adenocarcinoma in the lung in
patients with breast cancer: A prospective analysis of the discriminatory
value of immunohistology. Am J Clin Pathol 100:27-35, 1993
9. Cahan WG, Castro EB, Huvos AG: Primary breast and lung carcinoma
in the same patient. J Thorac Cardiovasc Surg 68:546-555, 1974
10. Rosengart TK, Martini N, Ghosn P, et al: Multiple primary lung
carcinomas: Prognosis and treatment. Ann Thorac Surg 52:773-779, 1991

CASE 3. BLUE HIVES DURING LYMPHATIC MAPPING FOR BREAST CANCER

A 75-year-old woman who had undergone lumpectomy for a 1.4-cm invasive ductal cancer 5 weeks earlier underwent
lymphatic mapping and sentinel lymph node biopsy after injection of 5 mL of 1% isosulfan blue dye around the lumpectomy
site. Two sentinel lymph nodes were identified, both of which were found to be free of metastases on pathologic examination.
Forty minutes after injection of isosulfan blue, the patient exhibited diffuse severe blue urticaria (Fig 1) and systemic
hypotension. These symptoms responded rapidly to epinephrine, diphenhydramine, and corticosteroids.
Anaphylaxis is a severe systemic allergic reaction that generally manifests clinically as respiratory difficulty and
hypotension. It results from massive release of preformed mediators such as histamine from mast cells and basophils. Release
of these mediators is caused by either direct cellular triggering by a drug (anaphylactoid reaction) or cellular binding of
specific immunoglobulin E antibodies (type 1 anaphylactic allergic reaction). This release produces capillary leakage and
mucosal edema that may result in urticaria, laryngeal edema, bronchospasm, asthma, and hypotension. Isosulfan blue is a
2,5-disulfonated patent blue dye that was initially approved by the United States Food and Drug Administration for selective
localization of the lymphatic system before radiocontrast procedures. Patent blue is used as a dye in some cosmetics, textiles,
and detergents. Previous reports have indicated that approximately 1.5% of patients injected with isosulfan blue have an
allergic reaction to this compound.1,2
Sentinel node biopsy is a major advance in the evaluation and treatment of breast cancer. However, no advance is without
potential complications. Surgeons performing lymphatic mapping must be aware that severe allergic reactions may occur

Fig 1.

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2574 KUERER ET AL

with the use of isosulfan blue, must recognize any reactions early, and must be prepared to treat the potentially
life-threatening signs and symptoms that can occur with this compound.
Henry Mark Kuerer, Kelly K. Hunt, S. Eva Singletary, and Frederick C. Ames
The University of Texas M.D. Anderson Cancer Center, Houston, TX

Copyright © 2001 American Society of Clinical Oncology

REFERENCES
1. Longnecker SM, Guzzardo MM, Van Voris LP: Life-threatening 2. Leong SP, Donegan E, Heffernon W, et al: Adverse reactions to
anaphylaxis following subcutaneous administration of isosulfan blue isosulfan blue during selective sentinel lymph node dissection in
1%. Clin Pharm 4:219-221, 1995 melanoma. Ann Surg Oncol 7:361-366, 2000

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