Japanese Journal of Clinical Oncology 30:185-187 (2000)
© 2000 Foundation for Promotion of Cancer Research
Occult Breast Cancer Presenting Axillary Nodal Metastasis: A Case Report
1First Department of Surgery and 2Department of Laboratory Medicine, Shiga University of Medical Science, Shiga, Japan
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ABSTRACT |
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We report a case of a 42-year-old female with occult breast cancer presenting axillary nodal metastasis. She complained of a swelling of the right axillary lymph node, but no breast mass was palpable. Biopsy of the lymph node was performed and histological examination showed a metastatic ductal carcinoma with papillotubular formation. Estrogen receptor of the lymph node was positive. No pathological findings were obtained by mammography and ultrasonography and systemic examinations revealed no extramammary primary lesion. All these data suggested an occult carcinoma of the breast and modified radical mastectomy was performed. Pathological findings of the removed specimen failed to find the primary breast cancer lesion. The patient has been treated with hormonal therapy and she is well without evidence of disease 5 years after surgery.
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INTRODUCTION |
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Female patients who present with adenocarcinoma in an axillary lymph node as the sole clinical site of disease can be a diagnostic and therapeutic challenge. In 1907, Halsted (1) first described two patients with ‘extensive carcinomatous involvement of the axilla’ due to occult breast cancer: ‘In the course of a few months, thereafter, the mammary disease manifested itself in both patients’. Occult breast cancer is uncommon, accounting for fewer than 1% of all breast cancer patients (2–4). This paper describes a case of occult breast cancer which was diagnosed by right axillary lymph node metastasis, together with a review of the literature.
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CASE REPORT |
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A 42-year-old woman visited our clinic complaining of a 35 x 29 mm tumor in the right axilla on March 17, 1994 (Fig. 1). Clinically, no mass was palpable in the right breast and no nipple discharge was seen. No signs of abnormality were found in the breast by mammography and ultrasonography (Fig. 2). Because the patient did not wish a fine needle aspiration cytology, excisional biopsy of the tumor was performed. Histological examination showed a metastatic ductal carcinoma with papillotubular formation in the lymph node. In some parts, a comedo-like area was seen and no mucin was demonstrated (Fig. 3). The patient underwent a work-up including ultrasonography, computed tomography, esophago-gastrography, barium enema and scintigraphy for examination of the neck, chest, abdomen, pelvis and bone, which were all negative. Serum levels of CEA, CA15-3, CA19-9, CA125 and AFP were within normal ranges. Estrogen receptor (ER) analysis of the axillary lymph node using enzyme immunoassay method was positive, but progesterone receptor (PR) analysis was negative (43.8 and 4.2 fmol/mg protein, respectively). There were no mutations of c-erbB2 and p53 gene in the PCR analysis of the lymph node. Immunostaining of ER was positive, but CEA, c-erbB2, p53 and thyroglobulin were negative in the lymph node. Since occult breast cancer was the most likely diagnosis, modified radical mastectomy was performed on April 20. The removed specimen was serially sectioned in a 5 mm stepwise fashion and 96 sections were examined. Microscopy of the specimen failed to find the primary breast cancer lesion. There was no other metastasis in 28 resected axillary and infraclavicular lymph nodes and accessory breast gland was not revealed. Postoperatively, the patient has been treated with hormonal therapy. She is well without evidence of disease 5 years after surgery.
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DISCUSSION |
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A carcinoma found in the axillary lymph node may be caused by primary carcinoma of heterotopic glandular tissue or metastatic neoplasm. Carcinomas arising in the heterotopic glandular tissue should accompany the pre-existing non-neoplastic glandular component and the ectopic tissue may be present in more than one lymph node (5). In the present case, there were no heterotopic glandular tissues in the axillary lymph nodes.
Aside from breast cancer, many other adenocarcinomas have been shown to metastasize to axillary lymph nodes (6). The most common of these include lung, thyroid, stomach, colorectum and pancreas. Once a diagnosis of metastatic adenocarcinoma on an axillary lymph node has been made in a female patient, there is a tendency to subject the patient to an exhaustive investigation. However, most of these additional tests failed to identify another primary site of carcinoma. Kemeny et al. (7) reported that further diagnostic work-up was unnecessary. A thorough history, physical examination, screening blood work and chest roentogenogram are sufficient for locating other potential primary sites of carcinoma.
ER/PR analysis should be performed for two reasons (8,9). Positive findings are suggestive of breast cancer and these occur in approximately 50% of females. Negative ER/PR do not exclude the diagnosis of breast cancer, however, and it is important to remember that other malignancies (e.g. colon, ovary, endometrium, kidney and melanoma) may demonstrate detectable ER/PR activity (10,11). The second reason for obtaining ER/PR studies on the initial biopsy is that a primary tumor may never be identified or, if found, may be so small as to render ER/PR assay impracticable (9,12). Tumor marker studies such as CEA and CA15-3 can also contribute to a more reliable diagnosis. Immunohistochemical stains for lactalbumin, CEA, ER and PR are recommended for the diagnosis of breast cancer (9,11). CEA and ER are not specific for breast cancer, but their positivity unequivocally supports the diagnosis of metastatic breast cancer. In the present case, tumor markers were all negative, but analysis and stain of ER were strongly positive.
There have been reports of some cases where the primary breast tumor could not be identified even in radical mastectomy specimens as in our case. A primary breast cancer will be not found in the specimen in about one third of the cases in the western literature (3,7,12) and 16.3% in Japan (4). Occult breast cancer demonstrated an 8–20% incidence of in situ cancer as the primary lesion (3) and this is in contrast to the reported 1% incidence of axillary metastases in series of non-palpable in situ carcinoma of the breast (13). Kyokane et al. (4) reported that the primary tumors of non-palpable breast cancer presenting as an axillary mass were smaller than 5 mm in 19 of 62 cases, and 9 of 72 cases were intraductal carcinoma with or without minimal invasion. Little has been reported on spontaneous regression of the tumor of breast cancer. In the present case, the primary tumor was probably smaller than 5 mm. Ozzello and Sanpitak (14) speculated that either the thorough sampling process failed to locate the primary invasive cancer or, as seen with electron microscopy, invasion through the basement membrane may occur before detection by light microscopy. However, it is not clear that basement membrane invasion that is only detected by electron microscopy has any clinical significance.
The treatment of occult breast cancer remains controversial. Traditionally, the treatment of choice for these patients was radical or modified radical mastectomy (1,2,12). Most groups have shown long-term survival with mastectomy to be at least comparable with that for node-positive palpable breast cancer, even when no primary is found in the mastectomy specimen. Recent studies have suggested that there was no statistically significant difference in outcome between mastectomy and breast conservative treatment such as limited resection and/or radiation and/or chemotherapy (3,7,15). In recent years, radiation treatment has been an alternative to mastectomy (16). The high incidence of early lesions and the current trend toward breast conservation argue in favor of this approach.
The role of adjuvant systemic therapy in occult breast cancer has never been investigated in a prospective randomized fashion. There are two retrospective studies (3,15). However, there were only a small number of patients, which makes it difficult to detect a statistically significant improvement in survival with adjuvant chemotherapy. The most reasonable recommendation is still that these patients be treated like other node-positive breast cancer patients, with adjuvant chemotherapy or hormonal therapy. Furthermore, since patients with negative ER generally have a poor survival, this prognostic factor may be useful in determining the need for adjuvant chemotherapy.
The overall 10 year survival for patients with occult breast cancer is 50–71% (3,7,15). Survival has not been shown to be dependent on whether the primary cancer in the mastectomy specimen is found (3,12). Both the nodal and ER status have been shown to be the major prognostic variables (3,12). In the absence of good prospective randomized data, it is reasonable to treat these patients similarly to other patients with node-positive and palpable breast cancer, with adjuvant chemo-endocrine therapy.
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FOOTNOTES |
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+ For reprints and all correspondence: Hajime Abe, First Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga 520-2192, Japan. E-mail: abe@belle.shiga-med.ac.jpAbbreviations: CEA, carcinoembryonic antigen; CA15-3, carbohydrate antigen 15-3; AFP,
-fetoprotein; ER, estrogen receptor; PR, progesterone receptor; PCR, polymerase chain reaction 
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REFERENCES |
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Received August 25, 1999; accepted January 26, 2000.
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