Occult Breast Cancer Initially Presenting with Axillary Lymph Node Metastasis: A Case Report

Abstract

Occult breast cancer presenting with axillary lymph node metastasis refers to carcinoma of unknown primary origin that is consistent with metastatic breast cancer initially presenting with axillary metastasis, without clinical or imaging evidence of a definitive primary breast tumor. The standardized treatment and prognosis of occult breast cancer remain unknown owing to its rarity. Herein, we report a case of a 59-year-old woman with occult breast cancer who presented with axillary metastasis. A comprehensive evaluation, including a thorough review of breast examination findings such as mammography and ultrasonography, breast MRI, lymph node biopsy with immunohistochemistry analysis, additional whole-body PET-CT, and testing for other tumor markers, can be crucial in diagnosing occult breast cancer. Therefore, effective communication among clinicians, radiologists, and pathologists throughout the diagnostic process, along with clear explanations to patients, is crucial for diagnosing this rare occult breast cancer.

INTRODUCTION

Occult breast cancer presenting with axillary lymph node metastasis is a type of carcinoma of unknown primary origin. This condition is consistent with metastatic carcinoma originating from the breast, manifesting as axillary metastasis in the absence of clinical or imaging evidence of a definitive underlying primary breast tumor (1). At present, standardized treatment and prognosis for this condition remain unclear owing to its low incidence rate, which ranges from 0.04% to 0.09% in breast cancer cases (2,3). Herein, we report a case of a 59-year-old woman with occult breast cancer who initially presented with axillary metastasis.

CASE REPORT

In January 2024, a 59-year-old woman visited the clinic for a follow-up breast screening examination. She had a history of a benign lesion in her right breast, an intraductal papilloma, which had been excised 9 years previously. The patient did not report any specific symptoms at the time of her recent visit. No abnormalities were observed on follow-up full-field digital mammography. On subsequent supplemental screening ultrasonography (US), in addition to the expected postoperative changes in the right breast, no abnormalities were observed in either breast. However, multiple round or oval hypoechoic masses were identified in the left axilla, specifically at lymph node levels I–III. The largest mass, located at level I, measured 3.5 cm along its longest axis and showed diffusely increased vascularity on Doppler US (Fig. 1A, B). Differential diagnoses included metastatic lymphadenopathy or lymphoproliferative diseases such as lymphoma. A US-guided core needle biopsy using a 14-G needle was performed on the left axillary mass, and histological analysis revealed findings consistent with those of metastatic carcinoma. Based on the immunohistochemical staining results, metastatic lobular carcinoma originating from the breast was suspected. Breast MRI was performed to detect occult breast cancer; it revealed multiple enlarged lymph nodes with circumscribed margins and heterogeneous enhancement in the left axilla, as well as a subtle, unexpected 5-mm enhancing focus in the left upper center breast, classified as Breast Imaging-Reporting and Data System category 4A, indicating a low suspicion of malignancy (Fig. 1C, D) (4). However, second-look US revealed no correlation with the suspicious lesions in the left upper central breast. Therefore, follow-up management was recommended for the unexpected enhancing focus on MRI. Imaging studies, including chest CT, abdominal CT, and whole-body PET-CT, were conducted to eliminate primary malignancies other than breast cancer as potential sources of metastasis. These scans revealed no specific findings apart from the previously identified left axillary metastasis.

Fig. 1. A 59-year-old woman with occult breast cancer presenting as axillary metastasis.

A. US shows oval hypoechoic masses (arrow, arrowhead) in the left axilla (level I), with the largest mass (arrow) measuring up to 3.5 cm along the longest axis.

B. Doppler US shows diffusely increased vascularity in the lesions (arrow, arrowhead). Histological analysis confirmed that this lesion was metastatic carcinoma, consistent with metastatic lobular carcinoma originating from the breast.

C, D. Contrast-enhanced subtracted imaging of the breast MRI shows enlarged lymph nodes (C, arrows) with circumscribed margins and heterogeneous enhancement in the left axilla, as well as a subtle, unexpected 5-mm enhancing focus (D, arrow) in the left upper central breast, assessed as BI-RADS category 4A.

E. Repeat second-look US after left ALND revealed a small mass (arrow) measuring at the 12-o’clock position in the left breast, corresponding to the lesion observed on breast MRI. The mass was confirmed as a lobular carcinoma in situ measuring 0.2 × 0.1 cm and intraductal papilloma with florid ductal hyperplasia.

F. A photomicrograph shows an axillary lymph node with its architecture effaced by discohesive tumor cells arranged in a diffuse solid sheet pattern (hematoxylin and eosin staining, ×100). Immunohistochemical staining results (not shown) revealed positivity for cytokeratin 7, estrogen receptor, GATA3, and GCDFP-15 and negativity for E-cadherin, consistent with metastatic lobular carcinoma from the breast.

ALND = axillary lymph node dissection, BI-RADS = Breast Imaging-Reporting and Data System, GATA3 = GATA binding protein 3, GCDFP-15 = gross cystic disease fluid protein 15, US = ultrasonography

Left axillary lymph node dissection (ALND) was performed, and the resulting histopathological analysis revealed metastatic carcinoma in 19 of 20 dissected lymph nodes, which was consistent with metastatic lobular carcinoma originating from the breast (Fig. 1F). The metastatic cancer cells showed positivity for estrogen receptor (ER) and negativity for progesterone receptor (PR) and human epidermal growth factor receptor 2. The metastatic cancer cells exhibited low Ki-67 expression (10.53%). They were positive for GATA binding protein 3 (GATA3), gross cystic disease fluid protein-15 (GCDFP-15), and cytokeratin 7 and negative for E-cadherin, indicating lobular carcinoma from the breast.

Repeat second-look US after left ALND revealed a small, indistinct, hypoechoic mass measuring approximately 5 mm at the 12-o’clock position in the left breast, corresponding to the lesion observed on breast MRI (Fig. 1E). US-guided needle localization and surgical excision of the left breast lesion were performed. The mass was confirmed as a lobular carcinoma in situ measuring 0.2 × 0.1 cm and intraductal papilloma with florid ductal hyperplasia. The patient was diagnosed as having occult breast cancer with axillary metastasis. The patient was evaluated by a multidisciplinary board who decided to initiate adjuvant systemic chemotherapy consisting of four cycles of adriamycin and cyclophosphamide, followed by weekly doses of paclitaxel, along with subsequent radiation and hormone therapy.

This study was approved by our Institutional Review Committee (IRB No. 2024-05-045). The requirement for informed consent was waived owing to the retrospective nature of this study.

DISCUSSION

Occult breast cancer is uncommon, representing 0.3%–1% of all breast cancer diagnoses, and frequently manifests through metastasis to the lymph nodes, bones, and skin (5). In 0.04%–0.09% of breast cancer cases, axillary metastasis is the first presentation of an occult breast malignancy, which can pose diagnostic and therapeutic difficulties (2,3). Adenocarcinoma or carcinoma detected in the axillary lymph nodes of women is a strong indicator of primary breast carcinoma. In such cases, mammography and breast US are recommended for further evaluation. If no abnormal findings are detected in either breast on mammography and US, percutaneous biopsy and histopathological analysis of the axillary lymph nodes should be performed. Accurate histopathological assessment of the biopsied material is crucial as it can help determine the primary site of cancer, including the breast. Immunohistochemical staining for specific markers, including ER, PR, cytokeratin 7/20, GATA3, and GCDFP-15, is important for this investigation (6). For patients with histopathological evidence of breast cancer but with inconclusive mammography and US results, contrast-enhanced breast MRI should be considered for a more detailed examination. Breast MRI can be performed for many indications, including preoperative staging, screening for high-risk women, and resolving inconclusive imaging from conventional imaging such as mammography and breast US. Therefore, breast MRI can be performed in patients with occult primary breast cancer. Moreover, when breast MRI detects certain enhancing lesions in patients with occult primary breast cancer, they can be treated with conserving surgery rather than mastectomy (7,8). Patients with MRI-positive findings for breast disease should be evaluated using US- or MRI-guided biopsy and treated based on the clinical stage of breast cancer. An accurate diagnosis becomes challenging when no suspicious lesions are found on breast MRI or if MR- or US-guided biopsy yields negative results. In such cases, additional tests such as CT or whole-body PET-CT should be considered to identify primary malignancies other than breast cancer. Given the complexity and difficulty of the aforementioned diagnostic process, it is essential that all clinicians, radiologists, and pathologists thoroughly review and discuss the test results.

Currently, ALND is the standard treatment for patients diagnosed with occult breast cancer. However, the optimal approach for the treatment of the ipsilateral breast cancer remains controversial and variable. A recent meta-analysis showed that even though there may be undetectable lesions in the breast, breast surgery, including modified radical mastectomy (MRM), breast-conserving surgery (BCS), and radiation therapy (RT), provides superior survival and prognostic benefits compared to ALND alone. Furthermore, for patients who have undergone ALND alone or ALND plus breast surgery, additional RT significantly improves overall survival. Hence, the meta-analysis suggested that the best locoregional treatment for patients with occult breast cancer may be a combination of breast surgery and RT (9). For systemic therapy, chemotherapy, endocrine therapy, and targeted therapy are recommended based on the patient’s molecular type and clinical stage (9). Recently, the National Comprehensive Cancer Network recommended two treatment approaches based on nodal status for patients diagnosed with occult breast cancer presenting with axillary metastasis and MRI-negative disease. Patients with T0N1M0 disease can be treated with either MRM with ALND or ALND combined with whole-breast RT, with or without nodal RT. Systemic chemotherapy, endocrine therapy, or trastuzumab can be administered based on stage II or III disease recommendations. Alternatively, in patients with T0N2–3M0 disease, neoadjuvant chemotherapy, trastuzumab, and endocrine therapy should be considered before undergoing ALND and MRM, similar to the treatment for those with locally advanced disease (10).

In the present case, the patient had axillary metastasis despite the absence of any evidence of primary cancer, including breast cancer, upon evaluation (physical examination, mammography, US, and PET-CT). Histopathological analysis of axillary lymph nodes was the sole method used to identify metastatic lobular carcinoma originating from the breast. Although a small suspicious enhancing focus was detected on breast MRI, surgical excision and histopathological examination confirmed it as lobular carcinoma in situ and intraductal papilloma. Therefore, the precise origin of the left axillary metastatic carcinoma from the breast remains unclear. Because mastectomy was not performed, there was a possibility of occult breast cancer in other areas of the left breast beyond the excision site. Additionally, although less likely, there is a possibility of occult breast cancer being present in the contralateral breast. After undergoing ALND and BCS, our patient is currently receiving adjuvant chemotherapy, RT, and hormone therapy without evidence of further deterioration. We anticipate favorable treatment outcomes as the patient is receiving well-planned therapies that are known to be effective for occult breast cancer.

An unexpected 5-mm enhancing focus was observed on breast MRI in our case; however, no correlating lesion was visible on second-look US. Consequently, we did not proceed with additional MRI-guided biopsy of the MRI-detected lesion after consultation with a clinician. At that time, we deemed the MRI-detected lesion too small for MRI-guided biopsy and opted for follow-up after ALND. However, in similar situations, considering the possibility of breast surgery such as MRM and the appropriateness of the lesion’s size and location, attempting an MRI-guided biopsy could also be a suitable option.

In summary, we report a case of occult breast cancer presenting with axillary metastasis. In such cases, clinicians, radiologists, and pathologists should maintain an open approach to all possible diagnostic avenues before making the final decision. A comprehensive evaluation, including a thorough review of breast examination findings, such as mammography, US, breast MRI, lymph node biopsy with immunohistochemistry analysis, additional whole-body PET/CT, and testing for other tumor markers, is invaluable for the diagnosis of occult breast cancer.